Advances in Respiratory Medicine doi: 10.3390/arm94050063

Authors: Carina Adina Afloarei Andreea Zabara Antal David Toma Adriana Loredana Pintilie Georgiana Pitusac Raluca Tiron Tudor Birladeanu Teodor Zaharia Radu Crisan Dabija

Introduction: COPD-OSA overlap syndrome (OVS) is defined by the coexistence of chronic obstructive pulmonary disease and obstructive sleep apnea syndrome in the same patient; it affects 28.3% of patients evaluated for either condition and is associated with significantly higher mortality compared to either pathology in isolation. Current therapeutic approaches, involving PAP therapy and bronchodilation, treat this syndrome as a homogeneous entity and ignore the biological heterogeneity of this patient population. Objectives: This review proposes a systematic framework for the endotypic classification of biological interactions between COPD and OSA, integrating current literature on the pathophysiological mechanisms underlying the OVS, clinically accessible biomarkers, and emerging therapies. Methods: A narrative review based on available literature, focusing on studies published between 2010 and 2026 identified via searches in PubMed, PMC, and Dove Medical Press using the terms: COPD-OSA overlap syndrome, endotype, precision medicine, phenotype, biomarker, dupilumab, and incretin-based therapies. Results: Four clinical phenotypes (obese-metabolic, emphysematous, bronchitic-hypoxemic, and hypercapnic) and three molecular endotypes (Th2/eosinophilic, neutrophilic/oxidative, and metabolic-adipokine) are proposed, each with distinct pathophysiological mechanisms and specific therapeutic implications. The interaction between the two conditions generates a unique, pronounced hypoxemic profile. We propose the “double-hit hypoxemia” model as a conceptual framework characterized by amplified systemic inflammation and increased cardiovascular risk compared to either pathology in isolation. This proposed model has not yet been prospectively validated. Dupilumab (approved for an inflammatory phenotype in COPD patients characterized by eosinophil counts ≥ 300 cells/μL) represents a promising option, though currently unsupported in the OVS population, that could nonetheless be relevant to the Th2/eosinophilic endotype of this syndrome and tirzepatide (which reduced the AHI by up to 23.8 events/hour versus placebo in the SURMOUNT-OSA trial, conducted in patients with obesity and moderate-to-severe OSA, rather than in patients with confirmed OVS) could represent a promising therapy for the metabolic-adipokine endotype of obese patients with OVS. A minimal biomarker panel, comprising blood eosinophils, FeNO, daytime PaCO2, BMI, and T90, allows for a practical approach to identifying the dominant endotype. Conclusions: Endotyping of OVS may provide a framework for moving beyond a uniform therapeutic approach toward more individualized management based on the dominant underlying biological mechanism. Randomized clinical trials focusing on endotypic stratification and OVS cohorts remain research priorities.

Advances in Respiratory Medicine doi: 10.3390/arm94050062

Authors: Andrzej Obojski Krzysztof Kuziemski Marek Barczyk Rafał Krenke Ewa Wycinka Adam Barczyk

Background: The asthma–COPD overlap is widely recognized, but its characteristics are not fully understood. This is largely true for the clinical presentation characterized by various ACO definitions. The purpose of this study was to investigate the pattern of comorbidities among patients with ACO, defined by various criteria. Methods: The data came from the multicenter cross-sectional study conducted in a mixed population of patients with asthma and COPD. Patients were classified into five groups according to five different definitions of ACO (GINA/GOLD/30%, Spanish criteria, COPD + asthma < 40, Gibson’s criteria, clinician’s diagnosis), reference ACO groups, and a group of patients with obstructive pulmonary diseases who were not diagnosed with ACO. To demonstrate the differences between groups, we compared the prevalence of comorbidities between all ACO and non-ACO groups. Data on age, severity of airflow obstruction, and smoking history were recorded for all patients. Results: For the final analysis, 1609 patients were included. Patients belonging to the ACO groups had a higher burden of comorbidities, poorer lung function, and a higher number of pack-years of smoking history compared to patients without an ACO diagnosis. Comorbidities were significantly more prevalent in ACO groups. Compared to the non-ACO group, nine diseases were more common in the GINA/GOLD/30% group, seven in both the COPD + asthma < 40 group and the clinician’s diagnosis group, five in the Gibson’s criteria group, and two in the Spanish criteria group. The most common comorbidities in the ACO groups were hypertension, coronary artery disease, GERD, musculoskeletal disorders, diabetes, and chronic sinusitis. Chronic sinusitis was more frequent in ACO groups defined by more precise asthma criteria. Conclusions: The definitions of ACO used in clinical practice vary widely and describe different populations. ACO populations vary in terms of comorbidities, lung function, smoking history, and age. Chronic sinusitis is a comorbidity that occurs more frequently in ACO groups defined by more precise asthma criteria. Patients with ACO differ in their clinical outcomes from those with other obstructive airway diseases.

Advances in Respiratory Medicine doi: 10.3390/arm94050061

Authors: Alirio Bastidas-Goyes Luis F. Giraldo-Cadavid Eduardo Tuta-Quintero Diana Diaz-Quijano Daniel Botero-Rosas Adriana Maldonado-Franco Alejandra Vargas Paula Rincón Lina López Juan S. Hernández Juan Castro Isabella Criado Charbel Faizal-Gómez David Jiménez Ingrid Mora Juan León

Background/Objective: The morphology of the flow–volume curve has emerged as a potential source of additional functional information by enabling the analysis of concavity, slope-based metrics, area-derived measures, and mathematical models extracted from the expiratory tracing. Therefore, the aim of this study was to map and describe the available evidence on morphological analysis methods of the expiratory flow–volume curve for the identification and characterization of fixed airflow obstruction. Methods: A scoping review was conducted following the methodological frameworks proposed by Arksey and O’Malley, Levac et al., the Joanna Briggs Institute, and the PRISMA Extension for Scoping Reviews (PRISMA-ScR). Studies published between 1 January 1990, and 31 December 2025, that evaluated morphological flow–volume curve metrics for the diagnosis or characterization of Chronic Obstructive Pulmonary Disease (COPD) were included, without language restrictions. Searches were performed in PubMed/MEDLINE, Embase, Scopus, Web of Science, IEEE Xplore, OpenGrey, and Google Scholar. Study selection was conducted by independent reviewers, with disagreements resolved by consensus, and data extraction was performed using a standardized form. Results were synthesized narratively and organized according to metric families. Results: The search identified 13,577 records; after duplicate removal and screening, 24 studies met the inclusion criteria. The evidence included observational studies, diagnostic validation studies, longitudinal cohorts, and methodological modeling studies. Identified metrics were grouped into four main categories: concavity and geometric indices of the flow–volume curve, expiratory slope and flow-decay metrics, area-based or volumetric-derived measures, and mathematical or computational models applied to the tracing. Concavity indices, the β-angle, slope-ratio, Peak Index, and the D parameter showed consistent associations with airflow obstruction, emphysema, small airway disease, or functional impairment. Expiratory slope metrics and Flow Decay demonstrated high diagnostic performance in several studies, whereas area-based measures such as AEX, AEX-FV, AreaFE%, and AUC3/AT3 integrated the overall loss of expiratory flow during forced expiration. Mathematical and computational models suggested that the complete shape of the curve contains additional diagnostic and prognostic information, although methodological variability and the need for external validation remain important limitations. Conclusions: Morphological analysis of the flow–volume curve represents a promising approach to complement conventional spirometry in the identification and characterization of fixed airflow obstruction. These metrics may provide additional information regarding airflow limitation, non-uniform lung emptying, emphysema, small airway disease, hyperinflation, and clinically relevant outcomes.

Advances in Respiratory Medicine doi: 10.3390/arm94050060

Authors: Juan Manuel Velázquez-Enríquez Alma Aurora Ramírez-Hernández Jovito César Santos-Álvarez Edilburga Reyes-Jiménez Antonio Arcos-Román Jaime Arellanes-Robledo Carlos Alberto Matias-Cervantes María del Socorro Pina-Canseco Verónica Rocío Vásquez-Garzón Rafael Baltiérrez-Hoyos

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease driven by aberrant extracellular matrix deposition, with the activity of transforming growth factor-beta 1 (TGF-β1) orchestrating fibrogenesis. Current therapies are limited by severe adverse effects, highlighting the unmet need for safer treatments. In this study, the therapeutic potential of chlorogenic acid (CGA) in a murine model of pulmonary fibrosis was evaluated. Methods: Pathology was induced on day 0 via subcutaneous osmotic minipumps delivering bleomycin (BLM) for one week, followed by pump removal on day 10. Therapeutic interventions with intragastric CGA (60 mg/kg) were administered daily from days 14 to 20. Lung tissue samples obtained on day 21 were analyzed via histological, immunohistochemical, and RT–PCR methods. Results: Histological analysis via H&E and Masson’s trichrome staining revealed that CGA treatment significantly attenuated alveolar thickening, restored the alveolar space, and reduced the total cell density and Ashcroft fibrosis score. Furthermore, CGA markedly decreased collagen deposition. Quantitative RT–PCR and immunohistochemical assays revealed that CGA effectively decreased the expression of Col1a1, TGF-β1, and the myofibroblast marker alpha-smooth muscle actin (α-SMA). Conclusions: CGA exerts important therapeutic effects by decreasing the expression of TGF-β1 and the activation of myofibroblasts, indicating that this natural polyphenol is a promising candidate for mitigating the progression of pulmonary fibrosis.

Advances in Respiratory Medicine doi: 10.3390/arm94040059

Authors: Jyoti Bajpai Akshyaya Pradhan Mohammed Kaleem Ahmad Surya Kant Ajay Kumar Verma Darshan Kumar Bajaj Rishi Sethi Mario Cazzola

Purpose: Pulmonary hypertension (PH) is a serious complication of COPD associated with worse outcomes. Reliable circulating biomarkers of pulmonary vascular involvement are lacking. Angiopoietin-1 (ANGP-1) and angiopoietin-2 (ANGP-2) regulate endothelial homeostasis, but their relationship with echocardiographically estimated pulmonary pressure in COPD remains uncertain. Methods: This prospective cross-sectional study included 70 consecutively recruited adults with COPD, stratified using a study-specific echocardiographic threshold into the COPD PH group (mPAP > 20 mmHg; n = 46) and the COPD without PH (mPAP < 20 mmHg; n = 24), together with 20 additional controls. This non-invasive stratification was not considered equivalent to PH confirmed by right heart catheterization. Serum ANGP-1 and ANGP-2 were measured using ELISA. Group differences and associations with e-mPAP and right atrial pressure (RAP) were assessed. Results: Median ANGP-1 was higher in the elevated e-mPAP group [8780.06 (IQR 7955.29–9902.88) pg/mL] than in the lower e-mPAP group [3065.14 (1170.69–6200.41)] and controls [2997.19 (1292.13–3278.18); p < 0.001]. ANGP-2 showed a similar pattern [6152.92 (5380.27–8652.50), 2669.77 (1802.18–4744.00), and 2405.54 (1779.73–3751.76) pg/mL; p < 0.001]. Among COPD participants, ANGP-1 and ANGP-2 correlated with e-mPAP (r = 0.64 and r = 0.54) and RAP (r = 0.54 and r = 0.52; all Holm-adjusted p < 0.001). In multivariable models, e-mPAP and RAP were independently associated with ANGP-1, whereas RAP was independently associated with ANGP-2. Conclusions: Higher circulating ANGP-1 and ANGP-2 were associated with an elevated echo-estimated pulmonary-pressure phenotype in COPD. These findings are exploratory and require validation in larger cohorts using direct hemodynamic assessment.

Advances in Respiratory Medicine doi: 10.3390/arm94040058

Authors: Anna Michely Svenja Böll Lida Yao Regina Ben Hamza Irina Rachimow Klaus Tenbrock Christian Martin Eva Verjans

Background: Bronchial asthma is a chronic inflammatory airway disease characterized by acute bronchoconstriction and type 2-driven inflammation. This study investigated whether inhaled amitriptyline, a functional inhibitor of acid sphingomyelinase, exerts both bronchodilatory and immunomodulatory effects in experimental murine models of allergic airway inflammation (AAI) and human cellular systems. Methods: Acute AAI was induced in mice using ovalbumin (OVA) and house dust mite (HDM) protocols, respectively. Inhaled amitriptyline (3.3 mg/mL) was administered for either 20 days (short-term) or 36 days (long-term). Lung function was assessed using FlexiVent®, and inflammatory markers including IgE, eosinophils, and type 2 cytokines were measured in bronchoalveolar lavage fluid and lung tissue. Complementary experiments were included using passively sensitized PCLSs and human type 2-differentiated CD4+ T cells. Results: Inhaled amitriptyline improved lung mechanics in both the OVA and HDM models, reducing total respiratory resistance and elastance. In the OVA model, eosinophil and T cell counts in BALF were decreased, whereas immunomodulatory effects were less pronounced in the short-term HDM model. In human TH2 cells, no significant changes in cytokine production or gene expression were observed. Ex vivo, amitriptyline dose-dependently inhibited allergen-induced bronchoconstriction in PCLSs. Conclusions: Inhaled amitriptyline improves lung function across murine models of AAI, supporting its potential in exhibiting model-dependent immunomodulatory effects, and directly attenuates allergen-induced bronchoconstriction, supporting its potential as a bronchodilator with context-dependent immunomodulatory properties.

Advances in Respiratory Medicine doi: 10.3390/arm94040057

Authors: Ophir Freund Uriel Katsoff Tzlil Hershko Ayala Ron Shir Frydman Doron Cohn-Schwartz Aviv Kupershmidt Neta Mano Ariel Melloul Eyal Kleinhendler Amir Bar-Shai Avraham Unterman

Cardiovascular comorbidities complicate interstitial lung disease (ILD) and represent potential therapeutic targets, yet the prevalence and clinical impact of left ventricular diastolic dysfunction (LVDD) remain poorly characterized. We aimed to evaluate LVDD as a potential treatable trait within a prospective cohort. Using data from an ILD registry (January 2021–October 2024), we defined clinically relevant LVDD as echocardiographic grade 2 or 3 diastolic dysfunction. Out of 276 patients (median age 69, 44% female), 14% had LVDD, which was almost entirely in patients with fibrosis (97%, p = 0.045) and associated with lower diffusing capacity for carbon monoxide. Survival and clinical analyses restricted to the fibrotic ILD subgroup (n = 241) showed that LVDD was independently associated with a higher hazard for a combined adverse outcome of acute exacerbation, lung transplantation, or death (adjusted HR 1.82, 95% CI 1.03–3.38, p = 0.043), which persisted after 1:2 propensity score matching (HR 2.04). LVDD also independently predicted increased all-cause mortality (adjusted HR 2.10) and reduced 6-min walk distance (median 413 vs. 465 m, β = −0.14, p = 0.036). In conclusion, LVDD is prevalent in fibrotic ILD and carries significant prognostic implications. Given its objective measurability and actionable treatment pathways, LVDD represents a potentially important treatable trait requiring multi-disciplinary care.

Advances in Respiratory Medicine doi: 10.3390/arm94040056

Authors: Mohamad Mahdi Mortada Waleed Aman Ur Rahman Alaa Sherri Gabriela Pawlak Krystian Kowalski Anna Piłat Edyta Pietrowska Marta Popławska Iwona Dziembała-Gładysz Barbara Majkowska-Wojciechowska Marcin Kurowski

Introduction: Allergic rhinitis (AR) imposes a substantial burden on individuals worldwide. Local allergic rhinitis (LAR) patients exhibit symptoms similar to those of AR without a positive skin prick test (SPT) or the presence of sIgE specific to one or more allergens. Our study evaluated specific and total grass pollen IgE in the nasal secretions of patients with suspected LAR, examining the effects of natural pollen exposure and nasal provocation testing (NPT). Methods: Twenty-nine subjects (18 with suspected LAR and 11 with AR) were included in this study. The total nasal symptom score (TNSS) and visual analog scale (VAS) were used for subjective assessment. NPT was performed using grass pollen allergen. Nasal lavage was used to obtain nasal secretions, and the levels of sIgE and total IgE were measured. Results: During the exposure vs. the off-exposure period, the TNSS and VAS were significantly higher in LAR (p < 0.0001 and p = 0.0061, respectively). sIgE and total IgE were significantly higher in the AR group than in the LAR group during the exposure period (p = 0.0008 and p = 0.0491, respectively). LAR diagnosis was confirmed in seven subjects. TNSS and VAS scores were higher after a positive NPT. The median level of sIgE was lower in the negative and positive NPT. A higher median total IgE level was observed post-provocation in both groups. A significantly higher median relative sIgE level was noted after positive and negative provocation (p = 0.0156 and p = 0.0143, respectively). Conclusions: The assessment of local sIgE levels in nasal secretions can be used as a method for the diagnostic workup of patients with suspected LAR. Achieving a well-defined and standardized protocol for the assessment of sIgE concentrations in nasal secretions of LAR is a goal of future larger studies.

Advances in Respiratory Medicine doi: 10.3390/arm94040055

Authors: Wojciech Kuczyński Karol Pierzchała Weronika Bielska Zuzanna Boczar Aleksandra Kudrycka Piotr Białasiewicz

Obstructive sleep apnea (OSA) is associated with increased cardiovascular, respiratory, and all-cause mortality, yet the long-term survival impact of continuous positive airway pressure (CPAP) remains contested, and treatment is usually analysed as a binary exposure rather than by the quality of the response achieved. In a single-centre cohort of 4368 adults referred for polysomnography and followed for 8–20 years (prespecified subgroup with apnea–hypopnea index [AHI] ≥ 15, n = 2304), we applied cause-specific Cox and Fine–Gray competing-risks models, together with machine-learning classifiers, to characterise all-cause, cardiovascular, and pulmonary mortality. CPAP was associated with reduced all-cause (hazard ratio [HR] 0.75), cardiovascular (HR 0.75), and pulmonary mortality (HR 0.54), with the benefit confined to severe OSA (HR 0.66) and absent in moderate disease (HR 0.95). Good responders showed a significant 34% reduction in all-cause mortality (HR 0.66), whereas poor responders showed no significant reduction. Nocturnal desaturation (time with oxygen saturation < 90%) was the dominant independent predictor of pulmonary mortality, and baseline features predicted response category only moderately (macro-averaged AUC 0.76). Long-term CPAP confers a severity- and response-dependent survival benefit; nocturnal hypoxaemia is a key, modifiable driver of respiratory death.

Advances in Respiratory Medicine doi: 10.3390/arm94040054

Authors: Yang Ren Danni Chen Shiqi Xie Yawen He Xuanru Zhuang Dan Ye Zhentao Fei Lu Xia Yongjie Wang Feng Li

Background: Tuberculous meningitis (TBM) is the most severe form of central nervous system tuberculosis, associated with high mortality and neurological sequelae. Microglia-driven neuroinflammation is a key contributor to TBM pathogenesis; however, its specific effects on ependymal cells—critical for cerebrospinal fluid dynamics and barrier function—and potential therapeutic strategies remain unclear. Methods: A murine TBM model was established by tail vein injection of BCG. Although the virulence of BCG, an attenuated strain of Mycobacterium bovis, is different from that of clinically isolated human Mycobacterium tuberculosis, its induced phenotypes such as periventricular inflammatory infiltration, microglia activation, and ependymal dysfunction highly reproduce the key histopathological features of human TBM. Primary ependymal cells were cultured and treated either directly with BCG or indirectly with conditioned medium from BCG-stimulated BV2 microglial cells (BCG+BV2-CM). Transcriptomic profiling was conducted via RNA sequencing, with validation by qPCR and Western blot. Functional outcomes, including ciliary morphology and apoptosis, were assessed using immunofluorescence and flow cytometry. The therapeutic effect of sodium butyrate (NaB) was evaluated through pretreatment experiments. Results: BCG infection induced characteristic TBM pathology, with persistent bacteria in the brain and lungs, ventricular inflammation, and pulmonary damage. Transcriptomic analysis showed that direct BCG treatment altered the expression of 1036 genes in ependymal cells, whereas BCG+BV2-CM treatment induced 3558 differentially expressed genes, highlighting microglia’s role in amplifying ependymal injury. Integrated analysis identified 64 consistently dysregulated genes across in vitro and in vivo models, enriched in immune and metabolic pathways. BCG challenge significantly downregulated Hmgcs2, leading to ciliary shortening and increased apoptosis. Sodium butyrate treatment restored Hmgcs2 expression, preserved ciliary structure, and reduced apoptosis. Conclusion: Microglia profoundly exacerbate transcriptional dysregulation in ependymal cells during TBM. Sodium butyrate confers protection against BCG-induced ependymal damage by upregulating Hmgcs2, revealing a novel therapeutic target for tuberculous meningitis.

Advances in Respiratory Medicine doi: 10.3390/arm94040053

Authors: Mairi Ziaka Aristomenis Exadaktylos

Despite advances in the understanding of the pathophysiology of acute respiratory distress syndrome (ARDS), treatment options remain limited and are mainly supportive, while mortality remains high. Prone positioning (PP) has been shown to improve oxygenation and lung mechanics in ARDS by reducing the imbalance in ventilation distribution between ventral and dorsal lung regions, altering pulmonary blood flow distribution, modifying the density distribution of edematous lung tissue, and limiting areas with low ventilation–perfusion ratios. During the coronavirus disease 2019 (COVID-19) pandemic, the use of PP, referred to as awake prone positioning (APP), was extended to non-intubated patients with severe hypoxemic respiratory failure. However, several concerns remain, including worsening oxygenation following the transition from prone to supine position, the potential development of patient self-inflicted lung injury (P-SILI), and delays in endotracheal intubation and initiation of invasive mechanical ventilation. Evidence regarding the use of APP in non-COVID-19 ARDS is scarce and consists mainly of small case series and a limited number of prospective studies with small and heterogeneous populations. Therefore, in the present work, we aim to summarize the existing evidence on APP in non-COVID-19 ARDS and acute hypoxemic respiratory failure (AHRF), describe the underlying pathophysiological mechanisms, and highlight areas for future research.

Advances in Respiratory Medicine doi: 10.3390/arm94040052

Authors: Nielza Moreira de Souza Pedro Henrique Perpetuo de Lima Silva Estephane Ramos de Souza Penna Amanda Oliveira dos Anjos Alícia Sales Carneiro Walter Costa Bruna Cuoco Provenzano Ana Paula Santos Agnaldo José Lopes

Although poverty and tuberculosis are insidiously linked, knowledge of the relationship between social determinants of health (SDoHs) and post-tuberculosis lung disease (PTLD) is limited. This study aimed to analyze the association between physical function, pulmonary function, and SDoHs in individuals with PTLD (iwPTLD), considering the impact of social inequalities on physical performance. This cross-sectional study collected social data from 69 iwPTLDs using a standardized assessment form. The patients underwent pulmonary function testing via spirometry and body plethysmography, as well as respiratory muscle strength and quadriceps muscle strength (QMS) testing. They also completed the six-minute step test (6MST). The median value of steps climbed by participants on the 6MST was 88 (57–117), corresponding to 50.1% (34.9–73.2) of the predicted value. The mean QMS was 28.7 ± 11.9 kgf, with 11 participants (17.4%) showing QMS below the cutoff point. Spirometry revealed normal, obstructive, restrictive, and mixed patterns in 19 (27.5%), 20 (29%), 18 (26.1%), and 12 (17.4%) of the participants, respectively. Performance on the 6MST showed no statistically significant association with SDoHs. QMS showed a statistically significant association with treated sewage (W = 84, p = 0.026). Forced expiratory volume in one second showed significant correlations with education level (ρ = 0.248, p = 0.040), social protection (W = 207, p = 0.050, r = 0.238), and treated water (W = 24.5, p = 0.029, r = 0.264). Maximum inspiratory pressure showed significant correlations with education level (ρ = 0.246, p = 0.042) and treated water (W = 20, p = 0.021, r = 0.280). The regression model for 6MST and QMS performance showed that 12% and 45% of the variability was explained by the studied variables, respectively. In iwPTLD, impairments in physical function and damage to lung function are weakly associated with the deterioration of SDoHs. While this relationship is weak, it should not be ignored because it may operate through indirect pathways.

Advances in Respiratory Medicine doi: 10.3390/arm94040051

Authors: Palak Grover Rahul Jain Gurleen Kaur Bipneet Singh

Interstitial lung diseases (ILDs) comprise a heterogeneous group of pulmonary disorders associated with substantial morbidity and mortality. We examined mortality attributed to selected J84-coded ILDs in the United States from 1999 to 2024 using CDC WONDER underlying-cause-of-death data. Age-adjusted mortality rates (AAMRs) per 100,000 population were standardized to the 2000 U.S. population and stratified by sex and race. Joinpoint regression was used to identify changes in temporal slope and estimate annual percent change (APC), average annual percent change (AAPC), 95% confidence intervals (CIs), and p-values. After the removal of overlapping years between the CDC WONDER database series, 444,573 unique deaths occurred. Annual deaths increased from 11,358 in 1999 to 22,849 in 2024, while AAMR increased from 4.2 to 5.1 per 100,000. Overall, AAMR increased during 1999–2004 (APC 2.32%, 95% CI 1.39–3.26; p < 0.001) and more slowly during 2004–2024 (APC 0.36%, 95% CI 0.16–0.56; p = 0.001), with an overall AAPC of 0.75% (95% CI 0.60–0.90; p < 0.001). Male AAMRs remained higher than female AAMRs, while race-specific trends were heterogeneous. No temporal reduction in population mortality coincided with the introduction of antifibrotic therapies; however, this ecological analysis cannot evaluate treatment effectiveness or individual treatment exposure.

Advances in Respiratory Medicine doi: 10.3390/arm94040050

Authors: Pranvera Breznica Selmani Arlinda Daka Grapci Blerina Koshi Zana Sllamniku Dalipi Rozafa Koliqi

Drug delivery systems (DDS) may improve the therapeutic performance of chemotherapy in lung cancer, but their preclinical efficacy has not been quantitatively synthesized. We conducted a systematic review and meta-analysis of controlled in vivo mouse studies evaluating DDS-based chemotherapeutic formulations for lung cancer. Databases were searched from inception to 15 February 2025, and methodological quality was assessed using the SYRCLE risk-of-bias tool. Thirty studies comprising 47 experiments were included. Compared with corresponding free-drug treatments, DDS-based chemotherapy significantly reduced tumor volume (WMD −310.67 mm3; 95% CI: −375.51 to −245.83; p < 0.001), although substantial heterogeneity was observed. Both targeted and non-targeted DDS were associated with tumor growth inhibition, and targeted formulations showed a larger average reduction; however, this finding should be interpreted in light of differences in formulation properties, tumor models, and treatment protocols. Nanoparticle, liposomal, and micellar platforms all demonstrated significant antitumor effects, while combination DDS and docetaxel- or cisplatin-based systems showed large effects in subgroup analyses with variable sample sizes. These findings support the continued development of DDS-based chemotherapy for lung cancer, but standardized reporting of nanocarrier characterization, pharmacokinetics, biodistribution, toxicity, and rigorous animal-study design is required to improve reproducibility and translational relevance.

Advances in Respiratory Medicine doi: 10.3390/arm94040049

Authors: Esteban Kosak Lopez Luis Rodriguez Donís Justin Lam Andrew Geller Raul Leguizamon Michael Vera Ricaurte Priscilla Nethala Maria Planchart Ferretto Maria Laura Fernandez-Wever Jose M. Martinez-Manzano Enrique Pacheco Shahrzad Abdollahi

Introduction: Patients with rheumatoid arthritis (RA) have higher risk for pneumonia, interstitial lung disease (ILD) and pulmonary fibrosis (PF). However, the association between an ICD-10-coded pneumonia event (CPE) and the incidence of ILD or PF in the RA population remains unclear. Methods: We conducted a retrospective cohort study using the TriNetX database. Patients with ICD-10 for RA aged 50 or older who had a CPE within one year of RA diagnosis (CPE cohort, n = 4553) were matched 1:1 by propensity score for key factors, including demographics, comorbidities (i.e., COPD), and medication use (DMARDs, corticosteroids) to RA patients without a CPE (Control cohort, n = 4553). Cox proportional hazard models assessed the incidence of a composite ILD outcome, PF, and secondary complications over a 4-year follow-up after the index event defined as 1-year after RA diagnosis for both cohorts. Results: The CPE cohort showed an increased risk for all outcomes. Patients with CPE had a 2.48-fold increased risk for PF (HR = 2.48; 95% CI, 1.78–3.45; p < 0.01) and a 2.87-fold increased risk for the composite ILD outcome (HR = 2.87; 95% CI, 2.18–3.80; p < 0.01). The risk of rheumatoid lung disease was 4.15 times higher (HR = 4.15; 95% CI, 2.30–7.50; p < 0.01). Furthermore, the CPE group had a higher risk for all-cause mortality (HR = 1.82; 95% CI, 1.58–2.09; p < 0.01). Conclusions: The CPE within one year of RA diagnosis is associated with an increase in subsequent ILD-coded outcomes. While this retrospective design cannot establish causality, an unspecified pneumonia code in early RA may represent an early clinical manifestation of unrecognized ILD, serving as a high-risk marker that warrants pulmonary surveillance.

Advances in Respiratory Medicine doi: 10.3390/arm94040048

Authors: Guido Marchi Lorenzo Corbetta

Artificial intelligence (AI) is progressively reshaping interventional pulmonology (IP), yet its potential to erode procedural and cognitive competencies through AI-induced deskilling remains poorly characterized in this specialty. An international, observational, cross-sectional survey was conducted in May 2026 among 118 expert interventional pulmonologists from 10 different countries across 5 continents. Participants completed a structured questionnaire comprising five demographic items and 12 Likert-scale statements addressing deskilling risk perception and mitigation attitudes; percentage agreement was calculated for each item (scores 4–5). High perceived clinical value of AI was reported (87%), alongside substantial concern for procedural deskilling (73%) and upskilling inhibition (83%). Familiarity with automation bias was limited (38%), yet its clinical relevance was widely recognized after definition provision (81%)—a gap of 43 percentage points. Strong support emerged for AI-free training (84%), simulation-based training (86%), and longitudinal performance monitoring (78%). Concern for institutional fragility in the absence of AI was expressed by 74%, and governance frameworks, including minimum non-AI-assisted procedural volume requirements, were endorsed by 70%. Deskilling was identified as a high research priority by 89%. These findings indicate that AI-induced deskilling is perceived as a relevant and emerging risk by expert interventional pulmonologists internationally, even before the widespread clinical deployment of AI technologies. Although the extent to which these concerns will translate into measurable effects on procedural competence is currently uncertain, the results underscore the need for prospective research, educational initiatives, and appropriate governance frameworks to ensure the preservation of core procedural skills.

Advances in Respiratory Medicine doi: 10.3390/arm94040047

Authors: Palak Grover Rahul Jain Gurleen Kaur Niroshan Ranjan Bipneet Singh

Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CFTR gene. The sequential approval of CFTR modulators ivacaftor (2012), lumacaftor/ivacaftor (2015), tezacaftor/ivacaftor (2018), and elexacaftor/tezacaftor/ivacaftor (2019) has transformed CF care, but population-level mortality trends across therapeutic periods have not been comprehensively assessed. We conducted a retrospective analysis of CF mortality in the United States from 1999 to 2024 using CDC WONDER Underlying Cause of Death data (ICD-10 codes E84.0–E84.9). Age-adjusted mortality rates (AAMR) per 100,000 were calculated using the 2000 U.S. standard population. The study period was divided into three periods: pre-modulator (1999–2011), early modulator (2012–2018), and elexacaftor/tezacaftor/ivacaftor (2019–2024). Annual mortality trends were evaluated using segmented log-linear Poisson regression, with annual death counts as the outcome and the corresponding U.S. population as an offset. Candidate models with multiple change points were compared to identify distinct temporal segments. Annual percent changes (APCs) and 95% confidence intervals (CIs) were estimated for each segment. Prespecified therapeutic periods, including pre-modulator (1999–2011), early modulator (2012–2018), and ETI period (2019–2024), were retained for descriptive analyses. Trends were stratified by sex and U.S. Census Region. A total of 10,959 CF deaths were recorded over 26 years. In the pre-modulator period, mortality was stable at a mean of 478 deaths/year (AAMR 0.14–0.17). The early modulator period showed a modest 5.4% reduction in mean annual deaths (452/year). The period following ETI availability was associated with a decline to 263/year, a 47% reduction from the pre-modulator period (AAPC −8.6%/year). The AAMR declined from 0.17 (1999) to 0.07 (2024). The female-to-male death count ratio shifted from 1.05 to 0.97 across periods, though age-adjusted rates were identical between sexes within each period, and this finding should be interpreted cautiously. Regionally, the South’s share of CF deaths grew from 37.2% to 41.6% despite absolute declines in all regions, suggesting potential geographic disparities that warrant further investigation with individual-level data. Segmented regression identified change points in 2005 and 2015. Mortality declined significantly from 1999 through 2005 (APC, −2.70%; 95% CI, −4.01% to −1.37%), remained stable from 2006 through 2015 (APC, +0.21%; 95% CI, −0.47% to +0.90%), and declined sharply from 2016 through 2024 (APC, −9.76%; 95% CI, −10.66% to −8.84%). CF mortality in the United States has declined by more than half since the introduction of CFTR modulators. The shift in the sex-based death count ratio and the concentration of remaining deaths in the South are hypothesis-generating observations that require confirmation with individual-level data. These ecological findings cannot establish causation, as concurrent changes in supportive care, lung transplantation practices, and COVID-19 pandemic effects may have contributed to the observed trends.

Advances in Respiratory Medicine doi: 10.3390/arm94040046

Authors: Ahmed A. Zayed Mohammad Aldalahmeh Salim Barakat Georges Khattar Walid Sange Elie Bou Sanayeh Zaid Khamis Bahy Abofrekha Suzanne El-Sayegh Michel N. Chalhoub

Background/Objectives: Pulmonary hypertension (PH) is an increasingly recognized complication in patients with end-stage renal disease (ESRD) undergoing hemodialysis, particularly those utilizing arteriovenous fistulas (AVF) or grafts (AVG) for vascular access. The prevalence and clinical impact of PH in this population remain unclear due to methodological heterogeneity and variable diagnostic criteria. This systematic review and meta-analysis aimed to quantify the association between AVF/AVG use and PH prevalence in ESRD patients and to explore sources of heterogeneity. Methods: A systematic search of PubMed, Embase, Scopus, and Web of Science was conducted for studies published through 31 December 2024, without language or date restrictions. Eligible studies included adults (≥18 years) with ESRD on dialysis, comparing those with AVF/AVG access to non-AVF/AVG controls (e.g., tunneled dialysis catheters or peritoneal dialysis), and reporting PH prevalence or mean pulmonary artery pressures. Study quality was assessed using the Newcastle–Ottawa Scale, and risk of bias was evaluated. A random-effects meta-analysis calculated pooled odds ratios (OR) for PH prevalence, with heterogeneity assessed by I2 and Cochran’s Q. Sensitivity analyses and tests for publication bias (Egger’s and Begg’s) were performed. Secondary analysis compared pooled mean pulmonary artery pressures between groups. Results: Eleven observational studies (1299 dialysis patients) met the inclusion criteria; ten studies (1224 patients) contributed to the quantitative meta-analysis after exclusion of one study with a zero-event control arm. Most studies were small, predominantly cross-sectional, and of moderate methodological quality. The pooled analysis showed a statistically significant association between AVF/AVG use and PH (OR 2.06, 95% CI: 1.69–2.52), with low statistical heterogeneity (I2 = 0%). This estimate was sensitive to individual studies: in leave-one-out analysis the association lost statistical significance when the single most influential study was removed indicating that the pooled result is driven in part by a small number of studies rather than being uniformly robust. No statistical evidence of publication bias was detected. Five studies reported continuous pulmonary artery pressures, which were directionally higher in AVF/AVG patients but were not pooled because of extreme heterogeneity (I2 = 99.4%). Conclusions: In this synthesis of observational data, AVF/AVG use was associated with higher odds of pulmonary hypertension than non-AVF/AVG access. Because all included studies were observational and the pooled estimate is sensitive to individual influential studies, these findings indicate a possible association rather than a causal effect and should be interpreted with caution. They support the rationale for prospective hemodynamic studies and for evaluating—rather than presuming the benefit of—PH monitoring and individualized access strategies in higher-risk dialysis patients.

Advances in Respiratory Medicine doi: 10.3390/arm94040045

Authors: Francesca K. Martino Francesca Fioretti Lucia Federica Stefanelli Gianni Carraro Miriam Capuano Giuseppe Scaparrotta Federico Nalesso

Background: Respiratory syncytial virus (RSV) infection is a cause of respiratory morbidity in high-risk patients, including those with chronic lung disease (CLD) and those undergoing hemodialysis (HD). In HD patients, evidence on the clinical impact of RSV vaccination on respiratory complications remains limited. We aimed to assess the clinical impact of RSV vaccination in HD patients by comparing vaccinated and unvaccinated patients with a focus on CLD. Methods: We retrospectively evaluated 56 adult HD patients: 28 received the RSV vaccine in autumn 2024 and 28 did not. Clinical data were collected from electronic medical records. Outcomes included influenza-like illness (ILI), pneumonia, and respiratory infection requiring hospitalization between September 2024 and September 2025. Results: Patients had a mean age of 74.4 years and a median Charlson Comorbidity Index (CCI) of 10. The RSV-vaccinated group had a greater comorbidity burden than the unvaccinated group (CCI 11 IQR 10–12 vs. 9 IQR 8–11, p = 0.02) and a higher prevalence of CLD (46.4% vs. 25.0%, p = 0.09). During follow-up, 28 patients (50.0%) had at least one ILI episode, 23 (41.1%) developed pneumonia, and 15 (26.8%) were hospitalized for respiratory infection. The incidence of ILI was 46.4% in vaccinated patients and 53.6% in unvaccinated patients (p = 0.28), while the incidence of pneumonia was 39.3% and 42.9%, respectively (p = 0.78). Respiratory infection requiring hospitalization occurred in 14.3% of vaccinated patients and 39.3% of unvaccinated patients (p = 0.035). CLD was significantly associated with pneumonia (p = 0.001) and showed trends toward higher rates of ILI (p = 0.09) and hospitalization for respiratory infection (p = 0.1). Conclusions: In our exploratory study, RSV vaccination in HD patients was associated with fewer hospitalizations for respiratory infection, despite greater comorbidity in vaccinated patients. CLD was associated with a higher incidence of respiratory complications, particularly pneumonia. The retrospective design and small sample size do not allow definitive conclusions; future prospective studies with an adequate sample size are needed to confirm our results.

Advances in Respiratory Medicine doi: 10.3390/arm94040044

Authors: Adam Barczyk Anna Andrychiewicz Małgorzata Czajkowska-Malinowska Katarzyna Górska Bartosz Hudzik Piotr Korczyński Rafał Krenke Wojciech Naumnik Wojciech J. Piotrowski Cezary Piwkowski Jerzy Soja Artur Szlubowski Jerzy Windyga Joanna Zając Filip Mejza

This article presents recommendations aimed at reducing the risk of bleeding during bronchoscopy. The document was developed by a working group convened by the Polish Respiratory Society, which included pulmonologists experienced in bronchoscopic procedures, an anesthesiologist, a thoracic surgeon, a cardiologist, a hematologist, a nurse, and methodologists. Clinical questions were formulated according to the PICO (Population, Intervention, Comparison, Outcome) framework, followed by a systematic literature search and critical appraisal of the selected studies. Based on these data, 13 recommendations/good clinical practice points were developed addressing bronchoscopy in patients with thrombocytopenia, abnormal activated partial thromboplastin time or international normalized ratio results, and in those receiving antiplatelet agents, oral anticoagulants, or low-molecular-weight heparin.

Advances in Respiratory Medicine doi: 10.3390/arm94040043

Authors: Arjun Khanna Pradyut Waghray Ashok Kr Singh Jinay Mehta Rithik Sagar Bhagat Saiprasad Patil Hanmant Barkate

Background: Acute exacerbation of obstructive airway disease (AEOAD) is a major cause of hospitalization, morbidity, and premature mortality in India. Hospitalized patients for the same are predominantly treated with short-acting bronchodilators, which require frequent administration and are associated with systemic adverse effects. Despite the availability of nebulized long-acting muscarinic antagonists (LAMAs) with quick onset of action, such as glycopyrronium, their role in acute care remains unclear in India. Methods: A pan-India expert opinion-building initiative was conducted among 220 pulmonologists across Tier I–II cities through 13 structured advisory meetings between April 2025 and July 2025. The final expert perspectives were then categorized into recurrent insights, raised in 75% or more meetings, and variable insights, raised in <75% of all meetings. Results: Experts reported that AEOAD management commonly involved initial stabilization with SABA/SAMA followed by transition to triple therapy with nebulized glycopyrronium, formoterol, and budesonide. Nebulized glycopyrronium was perceived to provide rapid and sustained bronchodilation with fewer cardiovascular side effects compared to short-acting agents. Benefits were reported in patients with frequent exacerbations, high sputum burden, and bronchiectasis. Operational advantages included reduced dosing frequency and nursing workload. Experts also noted potential improvements in hospital stay and readmissions; however, these observations were based on clinical experience rather than controlled data. Conclusions: Indian pulmonologists agreed that early initiation of nebulized glycopyrronium (with formoterol and budesonide) in hospitalized AEOAD may improve symptom control, lower exacerbation burden, reduce reliance on short-acting bronchodilators and corticosteroids, and shorten hospital stays.

Advances in Respiratory Medicine doi: 10.3390/arm94030042

Authors: Bartłomiej Czyżak Adam Lasota Sebastian Majewski

Acute exacerbation of interstitial lung disease (AE-ILD) represents sudden, severe deterioration in patients with pre-existing ILD and is associated with high morbidity and mortality. Our work presents a case series of AE-ILD in patients with idiopathic pulmonary fibrosis (IPF), idiopathic non-specific interstitial pneumonia (iNSIP), and connective tissue disease-associated ILD (CTD-ILD) managed at our institution and provides a narrative review of AE-ILD. Across cases, AE-ILD manifested as rapid progression of dyspnea and extensive ground-glass opacities (GGOs) on imaging, often triggered by infections or immune-mediated processes. Despite treatment, all cases were fatal, confirming that mortality remains high in AE-ILD. In our literature review, we focus on dysregulated innate immunity, an altered microbiome, potential microaspiration, surgical procedures, and autoantibody-mediated inflammation as triggers, as well as the risk factors for and prevalence of AE-ILD. We also examine pharmacological and non-pharmacological interventions, with particular emphasis on the role of antifibrotic agents as a key protective factor. Evidence for and against corticosteroid use in AE-IPF and non-IPF AE-ILD is discussed, highlighting the radically different treatment approach for AE in melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (DM)-associated ILD compared to AE-IPF. Our findings underscore the heterogeneous presentation and poor prognosis of AE-ILD, emphasizing the urgent need for standardized diagnostic criteria, risk stratification, and prospective studies with larger cohorts to establish evidence-based therapeutic strategies.

Advances in Respiratory Medicine doi: 10.3390/arm94030041

Authors: Bimaje Akpa

Mucopolysaccharidosis (MPS) are a group of inherited lysosomal storage genetic disorders that affect the body’s ability to break down glycosaminoglycans (GAGs) due to the deficiency of required enzymes. This leads to depositions of these GAGs in various tissues and organs resulting in multi-systemic manifestations including pulmonary and sleep related issues. In recent years, there have been significant advancements in therapeutic options and supportive management which have led to the overall improvement in respiratory care, culminating in improved quality of life for MPS patients. Management of pulmonary and sleep disorders in mucopolysaccharidosis requires a multidisciplinary approach due to the multi-systemic affectation of the genetic disorders. Therapeutic options such as enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) have yielded varying success in mitigating respiratory complications. Emerging treatments such as gene therapies have shown exciting and promising results thus far. Supportive therapies such as airway clearance, regular vaccination and use of positive airway pressure devices are also essential. Pre-operative airway and anesthesia planning is critical to mitigate peri-operative and post-operative complications. Early diagnosis, close monitoring and a patient focused individualized approach are essential for respiratory optimization and overall improvement in clinical outcomes. This review article aims to discuss these advancements in a comprehensive format, making it accessible to medical providers who care for this subset of patients.

Advances in Respiratory Medicine doi: 10.3390/arm94030040

Authors: Bedriye Müge Sönmez İlker Şirin Gülşen Akçay Murat Özdemir Necip Gökhan Güner

Objective: Rapid assessment of early treatment-related physiological improvement in emergency department (ED) patients with respiratory failure (RF) remains challenging. Blood gas analysis is informative but invasive and not ideal for repeated use. The vertical displacement index (VDI), an ultrasound-derived parameter based on pleural motion, may provide dynamic bedside information on early physiological change. This study evaluated whether changes in VDI are associated with early physiological improvement in ED patients with RF. Methods: This prospective observational study was conducted in the EDs of two tertiary care hospitals. Adult patients presenting with dyspnea and clinical evidence of RF were included. VDI was measured by lung ultrasound at baseline and 30 min after initial treatment. The primary endpoint was the change in VDI 30 min after the initial treatment, calculated as the difference between pre-treatment and post-treatment VDI. The expected direction was a post-treatment decrease in VDI, with greater VDI reduction expected to be associated with greater early physiological improvement. Secondary analyses included comparisons of VDI changes across oxygen saturation and diagnostic groups, as well as correlations between ΔVDI and physiological changes. Patients were grouped by admission oxygen saturation (<80%, 80–90%, and ≥90%). Results: Seventy-nine patients were included. Pre-treatment VDI differed significantly between oxygen saturation groups, with the highest values in the most hypoxemic patients (p = 0.028). VDI decreased significantly after treatment in all groups (p < 0.001 for all), with the greatest reduction in the <80% group. By diagnosis, VDI decreased significantly in pulmonary edema, COPD/asthma, and pneumonia, but not in pulmonary embolism (p = 0.138). VDI reduction correlated positively with improvements in oxygen saturation (r = 0.27, p = 0.016) and pH (r = 0.24, p = 0.037), but not with CO2. Conclusions: VDI may be explored as a practical ultrasound-derived bedside parameter associated with early physiological improvement in ED patients with RF.

Advances in Respiratory Medicine doi: 10.3390/arm94030039

Authors: Oreth Montero-Ruiz Ramcés Falfán-Valencia Ivette Buendía-Roldán Daniela Valencia-Pérez Rea Gibran E. Rueda-Munive Ingrid Fricke-Galindo Salvador García-Carmona Edgar Abarca-Rojano Gloria Pérez-Rubio

Background: This study was conducted to identify genetic risk variants associated with nicotine addiction in the CHRNA5, HTR2A, DRD4, and CYP2A6 genes among electronic cigarette users who also smoke combustible cigarettes (dual users), and to assess potential genotoxic and cytotoxic damage in the oral mucosal cells of the study population. Methods: We included dual e-cig users (ECIG, n = 70), combustible cigarette smokers (CCU, n = 24), and non-smokers and non-e-cig users (NS, n = 110). Genetic variants in CHRNA5, HTR2A, DRD4, and CYP2A6 were genotyped. Micronucleus analysis was performed on oral mucosal cells to detect cellular abnormalities. Results: The ECIG group demonstrated greater nicotine addiction on the Fagerström Test for Nicotine Dependence (FTND, 5.5 vs. 1, p = 0.023). Salivary cotinine levels were significantly higher in the ECIG group compared to the CCU group (39 vs. 12 ng/mL, p < 0.001). The carriers of the A allele (rs16969968/CHRNA5) had higher FTND scores, carriers of the C allele (rs1800955/DRD4) used electronic cigarettes more frequently each day, and carriers of the T allele (rs4105144/CYP2A6) started using nicotine products at a younger age. The number of micronuclei and cellular abnormalities in the oral mucosa was higher in the ECIG and CCU groups compared to the NS group. Conclusions: Salivary cotinine levels and FTND are higher in dual e-cigarette users than in combustible cigarette users. Dual users exhibit risk alleles in the CHRNA5, DRD4, and CYP2A6 genes, which are associated with traits linked to increased nicotine addiction. Dual e-cigarette use poses comparable genotoxic risks to combustible smoking.

Advances in Respiratory Medicine doi: 10.3390/arm94030038

Authors: Aileen Hsieh Jenna Barker-Mulleder Chen Xi Yang May Fouadi Tillie-Louise Hackett

Asthma is characterized by persistent airway epithelial dysfunction and remodelling of the reticular basement membrane (RBM). In healthy airways, the RBM is primarily composed of the extracellular matrix (ECM) proteins laminin and collagen-IV, but in remodelled asthmatic airways, the RBM has increased deposition of collagen-I, -III and fibronectin. Here, we systematically compared the effects of collagen-I, -III, -IV, fibronectin, laminin, and bovine serum albumin (BSA) control on bronchial epithelial cells (BECs) from six healthy controls and seven individuals with asthma. Epithelial attachment, spreading and barrier function were assessed in real time over 72 h using electrical cell–substrate impedance sensing. Cell culture supernatants were analyzed for release of epithelial cytokines, thymic stromal lymphopoietin (TSLP), interleukin (IL)-6, IL-8, and IL-11 using ELISA. BECs from both control and asthma donors had faster cell attachment, spreading, and barrier formation on collagen-I, -III, -IV, and fibronectin compared to laminin and BSA. BECs from both control and asthma donors cultured on collagen -I and -III produced more TSLP, but had no effect on IL-6, IL-8, and IL-11 expression. In summary, remodelling of the RBM in asthma may promote epithelial barrier formation whilst simultaneously enhancing epithelial-derived Th2 inflammation through increased TSLP release.

Advances in Respiratory Medicine doi: 10.3390/arm94030037

Authors: Iga Ciesielska-Markowska Katarzyna Mycroft-Rzeszotarska Piotr Korczyński Kaja Pulik Katarzyna Górska

Chronic obstructive pulmonary disease (COPD) is a respiratory disease that progressively impairs airway function. Its aetiology and clinical presentation are very complex, resulting in an unpredictable course of the disease. The most important causes include smoking and environmental pollutants. However, upper airway microbiome dysbiosis has been linked with COPD severity. Through this review, we aim to compare the microbiome of the respiratory tract between its sites, and to see if there are any significant differences in the composition of the microbial flora of patients with COPD when compared to healthy individuals. While preparing this review, the PubMed database was searched using keywords such as bacteriome, COPD, exacerbation, and microbiome. Analysis of the airway microbiome shows that the three most abundant phyla are Firmicutes, Proteobacteria, and Bacteroidetes. The severity of the disease and the selected therapeutic methods influence the ratio of Proteobacteria and Firmicutes. It has been observed that a decrease in microbial diversity resulted in lower values of FEV1 in patients and could be related with COPD’s progress and exacerbation events. While exacerbation cases need quick treatment, COPD’s complex background makes it difficult to find a singular, microbial cause.

Advances in Respiratory Medicine doi: 10.3390/arm94030036

Authors: Stella Schellhorn Hanna Schmidt Ales Janda Doris Gülke Monika Toth Dorit Fabricius Sebastian F. N. Bode

Background: Highly effective CFTR modulation with Elexacaftor/Tezacaftor/Ivacaftor (ETI) markedly improves clinical outcomes in people with cystic fibrosis (CF). Data on its effects on physical activity, sleep, sinonasal symptoms, and parent-perceived outcomes in preschool-aged children are limited. Methods: In this prospective, observational, single-center cohort study, ten children with cystic fibrosis (aged 2–6 years) and at least one CFTR variant eligible for ETI were included. Data were collected using wrist-worn Garmin vívofit Junior 2 activity trackers and standardized questionnaires one month before ETI initiation and at 1, 3, 6, and 12 months after start of ETI. Outcomes included step count, minutes of moderate-to-vigorous physical activity, sleep parameters, sinonasal symptoms, and parental perceptions. Results: ETI was well tolerated. Sweat chloride levels decreased significantly. Physical activity improved at 3 and 6 months (step count and active minutes/day; p < 0.05) but declined to near-baseline levels at 12 months. Parental assessments of physical and sporting performance showed sustained improvement. Sleep duration remained stable, with no changes in deep or light sleep phases or nighttime awakenings. Sinonasal symptoms remained low. Discussion & Conclusions: Preliminary findings of this exploratory pilot study show that improvement in physical activity after three and six months of ETI therapy might be attributable to seasonality, as therapy was started in winter months. No changes in sleep duration or sleep patterns are reassuring in this small cohort of young children with CF. ETI therapy was safe and well tolerated. Parental appraisal of their children’s physical performance improved after start of ETI. Longitudinal, controlled studies involving larger cohorts are required to validate these findings and to account for potential confounding factors, such as age-dependent changes and individual and environmental factors such as seasonal variation.

Advances in Respiratory Medicine doi: 10.3390/arm94030035

Authors: Rina Hoffmann Franziska Rombach Jens Grimm Agmal Scherzad Stephan Hackenberg Pascal Ickrath

(1) Background: Innate lymphoid cells (ILCs) are potent cytokine producers that regulate local immune responses in tissues. Natural killer (NK) cells belong to group 1 ILCs and play an important role in tumor clearance and defense against intracellular pathogens. ILC2 and 3 have been implied in allergic responses and other chronic inflammatory diseases. The role of these cells in the pathogenesis of chronic rhinosinusitis (CRS) is not completely understood. There are changes in the cellular infiltrate in the mucosa of patients with CRS with and without polyps. The aim of this study was to characterize the number and phenotype of NK cells, ILC2s and ILC3s in patients with CRS. (2) Methods: Tissue samples were collected from patients with CRS with and without nasal polyps who were undergoing nasal sinus surgery as well as control patients who were undergoing surgery due to non-inflammatory reasons. Lymphocytes were isolated from the tissues using mechanical and enzymatic dissociation. Peripheral blood lymphocytes were obtained from the same patients. All cells were examined by multicolor flow cytometry. NK cells were analyzed for the distribution of CD56dimCD16+ and CD56brightCD16− subsets and the expression of IL18Rα, CD16, CD57, GATA3, TCF1 and NKp44. In ILC2s, GATA3 and IL18Rα expression was determined, and ILC3s as well as NKp44+ and NKp44−ILC3 subsets were analyzed for the expression of IL18Rα. (3) Results: There were significantly fewer NK cells in the nasal polyps compared to the peripheral blood of patients with CRSwNP and tissues from CRSsNP patients, which both showed higher levels of TCF1 expression. Irrespective of the disease condition, NK cells in tissues showed lower CD16 expression and a lower frequency of the CD56dimCD16+ subset compared to the peripheral blood mononuclear cells. Additionally, a smaller percentage of NK cells were terminally matured, as measured by CD16+ and CD57+ expression, in all examined nasal mucosa tissues. In the tissue ILC3s, we predominantly found cells from the NKp44− subset in all groups. ILC3s from CRSsNP patients showed the highest frequencies of IL18Rα+ cells of all examined tissues. ILC2s from the polyps ofCRSwNP patients showed higher levels of GATA3 expression than their peripheral blood counterparts. (4) Conclusions: We found that tissue-resident NK cells in mucosa from the nose and sinuses are a more heterogenous and less mature population than those in peripheral blood. Expression of the examined markers in NK cells was similar among groups. NK cell frequency, both in blood and tissue from CRSsNP patients, was higher than in the other groups, indicating that these cells might play an important role in this phenotype. Changes in the IL18Rα expression of ILC3s suggest a potential role of IL18 signaling in CRS pathogenesis.

Advances in Respiratory Medicine doi: 10.3390/arm94030034

Authors: Xuee Zhuang Mengyuan Liu Kunhong Lin Yangxin Xiao Xuyan Zhao Zifan Gai Yan Xing

Objectives: To provide an evidence-based reference for preventing and managing pediatric acute asthma exacerbations by examining epidemiology and long-term trends of hospitalized cases in a tertiary hospital in Beijing over 30 years. Methods: Retrospective analysis of clinical data from children hospitalized for acute asthma exacerbation at Peking University Third Hospital from 1994 to 2023. Data collected included demographics, onset timing, and hospital stay duration, with distribution patterns analyzed across ages, years, seasons, and months. Results: The study included 1106 patients (65.73% male, 34.27% female) with a median age of 4 years. Hospitalizations peaked in 1999 (8.40%) and declined, reaching the lowest point in 2020 (1.45%) coinciding with the COVID-19 pandemic. Most admissions occurred in autumn (34.27%), especially in October (13.29%). The average hospital stay was 5.35 ± 2.65 days, longest for toddlers. Conclusions: Over 30 years, pediatric hospitalizations for acute asthma exacerbations in this tertiary center have shown a declining trend, suggesting improved asthma management. However, the persistent autumn peak and male predominance highlight the need for targeted prevention strategies—particularly for male and preschool-aged children before the autumn school term—to further reduce acute exacerbations and hospitalizations.

Advances in Respiratory Medicine doi: 10.3390/arm94030033

Authors: Raffaella Griffo Jasmin K. Jasuja Benedikt Niedermaier Sabine Wege Janina Shala Henrike Deissner Lena Brendel Romina M. Rösch Florian Eichhorn Michael Allgäuer Elizabeth Tong Cosmas Wimmer Martin E. Eichhorn Hauke Winter Laura V. Klotz

Background: Pulmonary actinomycosis is a rare chronic infection that frequently mimics lung malignancy, often leading to delayed diagnosis due to its non-specific clinical and radiological presentation. Given the diagnostic challenges associated with this condition, the aim of this study was to evaluate the clinical presentation, diagnostic pathways, treatment strategies, and outcomes of patients diagnosed with pulmonary actinomycosis in a single center. Methods: We retrospectively reviewed patients diagnosed with pulmonary actinomycosis at our institution between January 2014 and December 2022. Diagnosis was established based on compatible clinical and radiological findings together with microbiological identification of Actinomyces by culture or polymerase chain reaction. Results: Twenty-two patients were included in the final analysis. The median age was 61.5 years and males were more frequently affected (59%). The median time from initial hospitalization to definitive diagnosis was 70 days. Actinomyces odontolyticus was the most frequently identified species. All patients received antibiotic therapy, with a median treatment duration of 45.5 days. Thirteen patients underwent surgical intervention, performed either for diagnostic purposes or for treatment of complications. Complete disease eradication through surgical management was achieved in six cases. During follow-up (median 24 months), overall survival at three years was 78%, with one death directly related to pulmonary actinomycosis. Conclusions: Pulmonary actinomycosis remains a diagnostic challenge due to its non-specific clinical presentation and low microbiological yield. Early clinical suspicion and a combined diagnostic approach including bronchoscopy and microbiological testing are essential for timely diagnosis. Surgical intervention may play an important diagnostic and therapeutic role in selected patients.

Advances in Respiratory Medicine doi: 10.3390/arm94030032

Authors: Rana Abdullah Bin Qamar Henrique Pereira Felipe Alckmin-Carvalho

This scoping review synthesized evidence on the psychosocial burden of tuberculosis (TB) and on evidence-based psychosocial interventions aimed at improving treatment adherence. Specifically, it examined: (a) the most frequent mental health problems associated with TB; (b) the main barriers to adherence; (c) the components and effects of psychosocial interventions; and (d) gaps in the literature and directions for future research. Bibliographic searches were conducted in PubMed and Scopus, covering articles published between 2005 and 2025. Nineteen studies met the inclusion criteria. Depression and anxiety were the most frequently reported mental health problems, while psychosis appeared mainly in multidrug-resistant TB (MDR-TB) populations. Across studies, stigma, fear of transmission, socioeconomic disadvantage, treatment duration, and medication side effects emerged as major barriers to adherence. Evidence-based interventions—including psychoeducation, motivational enhancement therapy, cognitive behavioral therapy, acceptance and commitment therapy, and multicomponent psychosocial support—were associated with improved psychological outcomes and, in several studies, better adherence-related indicators. Overall, the evidence suggests that psychosocial distress is common among people with TB and may compromise treatment engagement. Integrating psychosocial and mental health support into TB services may therefore strengthen adherence and improve patient-centered outcomes, although more rigorous and context-sensitive research is still needed.

Advances in Respiratory Medicine doi: 10.3390/arm94030031

Authors: Maria Kyrmanidou Ioannis Smaraidos Asterios Kampouras

Background: Air pollution is a major environmental determinant of respiratory health and a significant contributor to the global burden of childhood asthma. Although several recent narrative and systematic reviews have examined environmental triggers of asthma, highlighting air pollution as a consistent risk factor across diverse populations and study designs, recent epidemiological evidence—including multicenter cohort studies and region-specific analyses from Europe and Greece—has not been systematically synthesized. Objective: To systematically review recent epidemiological evidence (2000–2025) on the association between ambient air pollution and childhood asthma incidence and exacerbations, with emphasis on European and Greek populations. Methods: Following PRISMA guidelines, we systematically reviewed observational studies published between 2000 and 2025 in PubMed, Scopus, Web of Science, BMC, and Google Scholar. Studies evaluating quantitative exposure to PM2.5, PM10, NO2, O3, or SO2 and asthma incidence, prevalence, or exacerbations in children (≤18 years) were included. Evidence was synthesized by pollutant type, exposure window, geographic region, and study design. Results: Twenty-four studies involving more than 3.5 million children were included. Consistent associations were observed across international and European cohorts between long-term exposure to PM2.5, PM10, and NO2 and increased asthma incidence. Risk estimates typically ranged from 15% to 30% increases in asthma incidence per 10 μg/m3 increase in long-term exposure to PM2.5 or NO2, as reported across multiple cohort analyses. Early-life exposure showed the strongest effects on asthma development and lung function decline. European and Greek studies demonstrated comparable trends, highlighting increased hospitalizations and symptom burden in urban populations despite pollutant concentrations often below current regulatory thresholds. Short-term pollution peaks were additionally associated with increased asthma exacerbations and hospital admissions, particularly during seasonal episodes of elevated particulate matter and ozone concentrations. Conclusions: This review provides an updated synthesis of 21st-century evidence demonstrating that ambient air pollution is a major and modifiable determinant of childhood asthma. The consistency of findings across regions, combined with limited longitudinal evidence from Greece, highlight the importance of improved air-quality management and continued public-health efforts to reduce exposure and the need for enhanced epidemiological monitoring.

Advances in Respiratory Medicine doi: 10.3390/arm94030030

Authors: Toshiyuki Ito Hajime Fujimoto Masaaki Toda Valeria Fridman D’Alessandro Corina N. D’Alessandro-Gabazza Yurie Kogue Tatsuki Tsuruga Tomohito Okano Kazuki Furuhashi Haruko Saiki Atsushi Tomaru Esteban C. Gabazza Taro Yasuma Tetsu Kobayashi

Purpose: A high-salt extracellular environment promotes fibrosis in multiple organs by inducing oxidative stress, fibroblast activation, and extracellular matrix remodeling. In the lung, sodium accumulation may result from impaired epithelial ion transport. Transforming growth factor-β1 (TGF-β1), a key profibrotic cytokine, downregulates epithelial sodium and chloride channels, promoting sodium retention and fibrotic remodeling. This study investigated whether antifibrotic drugs can prevent TGF-β1-induced suppression of sodium channel expression in the lung epithelium. Methods: Human A549 alveolar epithelial cells and primary alveolar epithelial cells were cultured with or without TGF-β1 in the presence or absence of nintedanib or pirfenidone. Expression of epithelial sodium channel (ENaC) subunits (SCNN1A, SCNN1B, SCNN1G, SCNN1D) and CFTR was analyzed. In vivo, lung tissues from TGF-β1 transgenic mice and wild-type controls were examined following intranasal administration of pirfenidone. Results: TGF-β1 markedly reduced the expression of all ENaC subunits and CFTR in vitro. Nintedanib prevented suppression of SCNN1A, SCNN1D, and SCNN1G, whereas pirfenidone prevented suppression of SCNN1A, SCNN1B, and SCNN1G. In TGF-β1 transgenic mice, Scnn1a, Scnn1b, and Scnn1g expression was significantly decreased compared with wild-type controls. Pirfenidone administration dose-dependently restored expression of these ENaC subunits in vivo. Conclusions: Antifibrotic drugs partially prevent TGF-β1-induced suppression of epithelial sodium channels, preserving epithelial ion homeostasis. Restoration of ENaC expression may represent a novel mechanism by which antifibrotic therapy mitigates sodium-associated lung fibrosis.

Advances in Respiratory Medicine doi: 10.3390/arm94030029

Authors: Akina Nigi Keisuke Iwamoto Hidetoshi Itani Shigeto Kondou Yuki Okunishi Takahiro Ohnishi

Background: Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive interstitial lung disease (ILD) is associated with high mortality. While inflammatory markers have been linked to poor outcomes, clinical heterogeneity remains evident, as some patients survive despite marked hyperinflammation. Methods: We retrospectively analyzed consecutive patients with anti-MDA5 antibody-positive ILD treated at our institution between May 2017 and November 2025. In-hospital mortality was assessed in relation to clinical characteristics and laboratory markers, including peak anti-MDA5 antibody titers, ferritin, C-reactive protein (CRP), lactate dehydrogenase (LDH), and KL-6. Analyses were exploratory and hypothesis-generating. Continuous variables were compared using Mann–Whitney U tests, and categorical variables using Fisher’s exact test. Principal component analysis (PCA) and receiver operating characteristic (ROC) analyses were performed for descriptive purposes. Results: Seventeen patients were included (10 survivors and 7 non-survivors). Peak ferritin, C-reactive protein (CRP), and lactate dehydrogenase (LDH) levels were significantly higher in non-survivors, whereas peak anti-MDA5 antibody titers showed a non-significant trend toward higher values in non-survivors (p = 0.057). KL-6 levels did not differ significantly between groups. In ROC analyses, LDH and CRP showed the highest discriminative performance for in-hospital mortality, followed by ferritin, whereas KL-6 showed the lowest discriminative performance. Despite these overall trends, substantial overlap between survivors and non-survivors remained across all biomarkers. Principal component analysis (PCA) demonstrated partial separation of outcomes along an inflammation-dominant axis, but with persistent overlap, indicating marked outcome heterogeneity. Conclusions: Inflammatory biomarkers, particularly LDH, CRP, and ferritin, were associated with in-hospital mortality in anti-MDA5 antibody-associated ILD. However, persistent overlap between survivors and non-survivors suggests that single-biomarker assessment is insufficient for precise prognostication. These findings should be interpreted as hypothesis-generating and require validation in larger multicenter cohorts.

Advances in Respiratory Medicine doi: 10.3390/arm94030028

Authors: Guillermo Ortiz-Ruiz Manuel Garay-Fernández Eduardo Tuta-Quintero Alirio Bastidas Antonio Lara Arlen Mauricio Márquez Carolina Aponte Jairo Guevara Jonathan A. Guezguan

Background: The ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) is central to the classification of acute respiratory distress syndrome (ARDS). However, its assessment requires arterial blood gas analysis, which may be limited by availability, cost, and invasiveness. Consequently, the ratio of peripheral oxygen saturation to fraction of inspired oxygen (SpO2/FiO2) has been proposed as a non-invasive surrogate for estimating the degree of oxygenation impairment. Methods: A retrospective cross-sectional study was conducted in adult patients with COVID-19 admitted to the intensive care unit at an altitude of 2600 m above sea level (m.a.s.l.). Spearman correlation coefficients were calculated to assess the association between the SpO2/FiO2 and PaO2/FiO2 ratios and their corresponding imputation models. A generalized linear model was applied, and the diagnostic performance of the SpO2/FiO2 ratio and the imputation models for detecting severe and non-severe hypoxemia (PaO2/FiO2 cutoff value of 150) was evaluated using the area under the receiver operating characteristic curve (AUC). Results: A total of 473 patients receiving invasive mechanical ventilation were included, with a mean age of 62.4 years (SD 14.1), and a predominance of males (67.2%). An SpO2/FiO2 ratio cutoff value of ≥206 demonstrated excellent diagnostic performance, with an AUC of 0.983 (95% CI 0.97–0.99), high sensitivity (90.6%), high specificity (96.7%), and an overall correct classification rate of 93.9%. This performance remained consistent across multiple clinical scenarios. In patients with positive end-expiratory pressure > 10 cmH2O, the AUC was 0.982, with a specificity of 97.7%. In the presence of hyperbilirubinemia (total bilirubin ≥ 3 mg/dL), the AUC was 0.951. Among patients with hemoglobin levels < 10 g/dL, sensitivity reached 100%, although specificity was reduced. In the subgroup with arterial partial pressure of carbon dioxide > 35 mmHg, an SpO2/FiO2 ratio ≥ 206 showed near-perfect specificity (99.4%) and a positive likelihood ratio of 120.9. Conclusions: The SpO2/FiO2 ratio is a reliable and non-invasive surrogate of the PaO2/FiO2 ratio in mechanically ventilated patients with COVID-19 living at high altitude, particularly for the identification of non-severe hypoxemia.

Advances in Respiratory Medicine doi: 10.3390/arm94030027

Authors: Saad Al-Anazi Yasser A. Alshawakir Syed Shahid Habib Hayam Gad Asma F. Alotaibi Alanoud T. Aljasham Wajd Ahmed Althakfi Mohamed A. Mekhtiche Abeer Abdulmoati Al-Masri

Background: Surfactant Protein D (SP-D) is a critical immunomodulatory collectin maintaining alveolar homeostasis. Obstructive sleep apnea (OSA)-related intermittent hypoxia (IH) disrupts pulmonary surfactant integrity; however, severity-dependent SP-D dynamics remain incompletely characterized. This study explores SP-D as a potential indicator of IH-induced alveolar stress and evaluates whether Galectin-3 (Gal-3) inhibition modulates surfactant homeostasis. Methods: Forty adult male Sprague-Dawley rats (8 per group) were randomized to Control (normoxia), Moderate IH (MIH; 15–30 events/hour), Severe IH (SIH; 30–60 events/hour), MIH + Gal-3 inhibitor (Modified Citrus Pectin, 800 mg/kg/day), or SIH + Gal-3 inhibitor. IH exposure lasted 8 h/day for 10 days. Outcomes included circulating SP-D, Surfactant Protein B (SP-B), inflammatory markers, physiological parameters, and histopathological lung injury scores assessed via American Thoracic Society guidelines. Results: SP-D levels showed numerical reductions with increasing IH severity (Control: 1969.07 pg/mL [IQR: 262.15]; SIH: 1404.30 pg/mL [IQR: 351.88]), representing a 28.6% decrease. However, between-group variability resulted in non-significant omnibus testing (Kruskal–Wallis p = 0.187). Gal-3 inhibition elevated SP-D levels, particularly in severe IH (2133.95 pg/mL [IQR: 1240.70]), though high inter-individual variability was observed (CV = 58.1%). SP-B showed significant suppression under moderate IH (p = 0.019) with restoration by treatment. Exploratory correlation analysis revealed moderate positive associations between SP-D and heart rate (r = 0.587) and respiratory rate (r = 0.419) in severe IH, though these did not reach statistical significance (p = 0.126 and p = 0.301, respectively). Histologically, severe IH induced diffuse alveolar damage (total lung score: 19.67 ± 0.82). Gal-3 inhibition produced context-dependent effects: protective in severe IH but paradoxically exacerbating inflammation under moderate IH (29.20 ± 4.64 vs. 20.00 ± 4.34; p < 0.05). Gal-3 inhibition significantly attenuated cardiac injury (injury score: 0.00 ± 0.00 vs. 7.17 ± 0.75 in severe IH; p < 0.001, η2 = 0.859). Conclusions: SP-D demonstrates severity-associated alterations consistent with alveolar epithelial stress during IH, though high variability limits definitive biomarker validation in this sample. Gal-3 inhibition modulates surfactant homeostasis and attenuates cardiopulmonary injury in a context-dependent manner. These findings support further investigation into SP-D as a component of multimodal severity stratification in OSA and highlight Gal-3 inhibition as a context-dependent anti-inflammatory strategy, pending validation in larger cohorts with tissue-level confirmation.

Advances in Respiratory Medicine doi: 10.3390/arm94020026

Authors: Noppharath Sangkarit Weerasak Tapanya

Background: Standard spirometry fundamentally overlooks the mechanical dynamics of forced expiration. This study derived novel biomechanical parameters to establish functional phenotypes and predict clinical respiratory impairments. Methods: Utilizing 16,596 acceptable spirometry records from NHANES (2007 to 2012), parameters reflecting kinetic power, mass constraint, and airway instability were mathematically derived. Principal component analysis, K-means clustering, and a Multilayer Perceptron neural network were sequentially applied. Results: Three distinct biomechanical phenotypes emerged: Load-Constrained (45.4%), Mechanically Efficient (23.5%), and Dynamic Collapse (31.0%). Aging significantly degraded kinetic power, demonstrating a steeper functional decline in males (p < 0.001). The neural network achieved 93.2% testing accuracy in classifying spirometric abnormalities. Crucially, Dynamic Airway Collapse Ratio (100% normalized importance), BMI (89.4%), and kinetic power (86.2%) fundamentally outperformed traditional demographic predictors such as chronological age (20.4%) and biological sex (7.1%). Conclusions: Structural and dynamic kinetic factors drive pulmonary dysfunction far more accurately than conventional demographics. Classifying these mechanical phenotypes facilitates highly targeted precision cardiopulmonary rehabilitation.

Advances in Respiratory Medicine doi: 10.3390/arm94020025

Authors: Janne Marques Silveira Ana Paula Midori Nakaishi Marcos Gontijo da Silva Daniele Oliveira dos Santos Ada Clarice Gastaldi

Background/Objective: A substantial proportion of infected individuals develop persistent symptoms after the acute phase of COVID-19, regardless of initial disease severity. Long COVID (LC) remains a public health challenge characterized by impaired functional exercise capacity (FEC) and quality of life (QoL). We systematically synthesized evidence on the effects of in-person outpatient pulmonary rehabilitation (OPR) with individualized and supervised exercise in adults with LC. Methods: Following PROSPERO (CRD42023389365), this study reviewed randomized controlled trials (RCTs) and observational cohort studies (OCSs) published between November 2019 and January 2026 in MEDLINE/PubMed, Web of Science, PEDro, and EMBASE. Results: Fifteen studies (n = 803) were included. OPR improved FEC (6MWT; MD: 53.72 m, 95% CI 43.69–63.75) and 30″SST (MD: 4.68, 95% CI 3.59–5.77) and reduced exertional dyspnea. RCTs showed benefits in physical (MD: 8.04, 95% CI 3.02–13.05) and mental QoL (MD: 6.60, 95% CI 2.01–11.18) and dyspnea impact, with inconsistent PF findings. Fatigue showed a trend toward improvement but was measured using heterogeneous patient-reported tools in RCTs and OCSs. Conclusions: Supervised PR improves FEC, QoL, and dyspnea in individuals with LC. In patients with fatigue/PEM, systematic assessment and continuous symptom monitoring are essential. High-quality controlled studies are needed to strengthen evidence and clinical guide.

Advances in Respiratory Medicine doi: 10.3390/arm94020024

Authors: Akihito Okada Akiko Nakano Kohei Fujita Yoshitsugu Inoue Toshiyasu Ito Fumitaka Hashiba Masashi Fujikawa Tatsuya Tanaka Aya Mukai Keima Ito Yuta Mori Kensuke Fukumitsu Satoshi Fukuda Yoshihiro Kanemitsu Tomoko Tajiri Tetsuya Oguri Yoshiyuki Ozawa Takayuki Murase Hirotsugu Ohkubo

Background: Prognostic markers reflecting nutritional vulnerability in idiopathic pulmonary fibrosis (IPF) remain poorly defined. Methods: In this prospective cohort study, 63 stable outpatients with IPF were followed for 3 years. Sarcopenia was defined according to the 2019 Asian Working Group for Sarcopenia criteria. Serum transthyretin levels were measured concurrently. Cox proportional hazards regression, binary logistic regression, and Kaplan–Meier survival analyses were performed. Results: During follow-up, 18 patients (29%) died and 21 (33%) experienced respiratory-related hospitalization. Serum transthyretin was an independent predictor of both 3-year mortality and respiratory-related hospitalization, even after adjusting for the Gender–Age–Physiology index. Conversely, sarcopenia and low appendicular skeletal muscle mass index (ASMI) were not independently associated with either outcome. Kaplan–Meier analysis demonstrated significant differences in both mortality and hospitalization according to serum transthyretin levels. Low ASMI evaluated using sex-specific cutoffs was associated with higher mortality in the unadjusted analysis, but not with hospitalization; sarcopenia was not significantly associated with either endpoint. Conclusions: Serum transthyretin may serve as a practical biomarker of nutritional vulnerability, providing complementary prognostic information beyond muscle mass-based assessment in IPF.

Advances in Respiratory Medicine doi: 10.3390/arm94020023

Authors: Rongjian Feng Chonggui Jiang Yan Yang Mao Su Meng Qin Quan Wei

Background: Stroke-associated pneumonia (SAP) is a common complication after acute ischemic stroke and contributes to worse recovery and greater resource use. Nutritional and inflammatory dysregulation have been implicated in both SAP susceptibility and adverse prognosis. Objective: To examine whether admission inflammatory and nutritional markers are associated with the development of SAP and with short-term functional prognosis. Methods: We performed a retrospective single-centre cohort study of consecutive patients with acute ischemic stroke admitted between 1 January 2015 and 31 December 2024 (N=303;SAPn=108,non−SAPn=195). Admission laboratory indices (albumin, CRP, fibrinogen, WBC, PCT, and prealbumin) in the first 24 h and clinical variables were analysed. Multivariable logistic regression identified factors independently associated with SAP; the relationship between SAP and early functional recovery was assessed in adjusted outcome models. A nomogram integrating key predictors was developed and its apparent discrimination is reported. Results: SAP occurred in 35.6% of patients. Factors independently associated with SAP included nasogastric tube placement (OR: 7.02, 95% CI: 3.50–14.62), venous thromboembolism (OR: 3.20, 95% CI: 1.62–6.31), cognitive impairment (OR: 2.90, 95% CI: 1.32–6.36), and elevated inflammatory markers (WBC OR: 1.52, 95% CI: 1.28–1.80; fibrinogen OR: 1.37, 95% CI: 1.02–1.84; CRP OR: 1.01, 95% CI: 1.00–1.03). Higher admission serum albumin was associated with lower odds of SAP (OR: 0.92, 95% CI: 0.86–0.98). The nomogram showed strong apparent discrimination (AUC: 0.90, 95% CI: 0.86–0.94). After multivariable adjustment, SAP remained associated with poorer short-term functional improvement (adjusted OR: 6.99, 95% CI: 3.05–17.54) and greater healthcare utilization (median length of stay: 39.6 vs. 30.6 days; median cost: USD 12,836 vs. 6585). Conclusion: In this retrospective cohort, admission markers of nutritional depletion and inflammatory activation were associated not only with increased likelihood of SAP, but also with adverse early functional outcomes. These association-based findings support early risk stratification using routine admission markers; prospective studies and external validation are required before clinical implementation.

Advances in Respiratory Medicine doi: 10.3390/arm94020022

Authors: Madina B. Baurzhan Sayagul A. Kairgeldina Venera M. Almatova Alexandr E. Gulyayev Raushan S. Dosmagambetova Kanat K. Tekebayev Karashash Absatarova Karlygash S. Absattarova

Background: Pneumoconiosis remains a major occupational lung disease associated with progressive respiratory impairment, reduced functional capacity, and diminished quality of life. Non-pharmacological rehabilitation has been increasingly proposed as a supportive intervention; however, evidence regarding its effectiveness remains heterogeneous. Objective: This study aimed to systematically review and synthesize the available evidence on the effects of non-pharmacological rehabilitation interventions on functional capacity, quality of life, and psychological outcomes in patients with pneumoconiosis. Methods: A systematic literature search was conducted in major electronic databases and grey literature sources in accordance with PRISMA 2020 guidelines. Studies evaluating non-pharmacological rehabilitation interventions in adults with pneumoconiosis were eligible for inclusion. Outcomes of interest included functional capacity, health-related quality of life, and psychological well-being. Due to methodological heterogeneity across studies, a qualitative synthesis was performed. Results: Six studies met the predefined inclusion criteria and were included in the qualitative synthesis. The reviewed evidence suggests that structured rehabilitation interventions were associated with clinically meaningful improvements in functional capacity, particularly in structured rehabilitation programs, most consistently reflected by increases in six-minute walk distance exceeding established minimal clinically important differences in three studies. Improvements in health-related quality of life and selected psychological outcomes were also reported, although outcome measures and intervention protocols varied across studies. Significant improvements in exercise capacity, dyspnea severity, and health-related quality of life were reported. Conclusions: Non-pharmacological rehabilitation may provide clinically meaningful benefits for patients with pneumoconiosis, based on limited and heterogeneous evidence, particularly in terms of functional capacity and quality of life. Nevertheless, the current evidence base is limited by heterogeneity in study design and outcome reporting. Further high-quality, standardized trials are needed to strengthen the evidence and guide the clinical implementation of rehabilitation programs for occupational lung diseases.

Advances in Respiratory Medicine doi: 10.3390/arm94020021

Authors: Salah M. Zeineldine Rami Hallak Antonio Esquinas Mohamad F. El-Khatib

Patients with end-stage lung diseases awaiting lung transplant frequently experience severe hypoxemia, dyspnea, and functional limitations that may compromise survival and transplant eligibility. Optimizing noninvasive respiratory support during the waiting period is crucial to preserve oxygenation, maintain physical conditioning, and avoid escalation to invasive mechanical ventilation, which is associated with poorer transplant outcomes. High-flow nasal cannula therapy has emerged as an important noninvasive respiratory support modality capable of providing physiological and clinical benefits such as precise fractions of inspired oxygen, a low level of positive end-expiratory pressure, dead-space washout, and reduced work of breathing. This review summarizes the pathophysiology of hypoxemia in lung transplant candidates, the mechanisms of action of high-flow nasal cannulas, and the current clinical evidence supporting its use in this population during the pre-transplant period. Available evidence suggests that the use of high-flow nasal cannulas improves oxygenation, relieves dyspnea, enhances exercise tolerance, facilitates participation in pulmonary rehabilitation programs, and may reduce the need for endotracheal intubation, thereby improving the likelihood of survival to transplantation. The review also discusses patient selection, the practical implementation of high-flow nasal cannula therapy, and comparisons with other respiratory support modalities. Although the current evidence is largely observational and heterogenous, high flow appears to be a valuable supportive and bridging therapy for selected patients awaiting lung transplant. Future prospective studies are needed to define standardized protocols and evaluate transplant-specific outcomes.

Advances in Respiratory Medicine doi: 10.3390/arm94020020

Authors: Muhammad Ali Ibrahim Kazi Hasan Kamal Syed Musa Mufarrih Imran Qureshi Sanmeet Singh Adrien Mazer

Introduction: Diabetic gastroparesis increases the risk of aspiration, pneumonia, and sepsis, yet the impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on these outcomes is uncertain because of their gastric-emptying effects. Methods: We performed a retrospective cohort study using the TriNetX Global Research Network. Adults (≥18 years) with diabetes mellitus and gastroparesis were identified and divided into two cohorts based on GLP-1 RA exposure. Propensity score matching (1:1) balanced demographics, comorbidities, and antidiabetic medications, yielding 23,371 patients per cohort. Outcomes, assessed from 180 days after index, included pneumonia, pneumonitis, mechanical ventilation, ventilator-associated pneumonia, sepsis, bacteremia, empyema, lung abscess, acute respiratory distress syndrome (ARDS), and need for enteral feeding. Risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated. Results: Compared with GLP-1 users, non-GLP-1 patients had higher incidences of pneumonitis (3.6% vs. 2.5%; HR 1.76, 95% CI 1.58–1.95), pneumonia (13.2% vs. 12.2%; HR 1.34, 95% CI 1.27–1.41), mechanical ventilation (4.4% vs. 3.3%; HR 1.63, 95% CI 1.49–1.79), sepsis (12.8% vs. 11.1%; HR 1.44, 95% CI 1.37–1.52), and bacteremia (5.2% vs. 4.4%; HR 1.46, 95% CI 1.35–1.59) (all p < 0.001). Empyema and ARDS were also numerically lower among GLP-1 users, while ventilator-associated pneumonia and lung abscess were rare and similar between groups. No patients required percutaneous endoscopic gastrostomy or nasal enteral feeding. Conclusions: In patients with diabetes and gastroparesis, GLP-1 RA therapy was associated with significantly fewer pulmonary and systemic infectious complications. These data suggest that the systemic benefits of GLP-1 RAs may outweigh concerns regarding delayed gastric emptying in this high-risk population.

Advances in Respiratory Medicine doi: 10.3390/arm94020019

Authors: Paweł Zając Monika Zając Wojciech Kądziołka Andrzej Sokołowski Ewa Kaznowska

Sarcoidosis is a multisystem granulomatous disease of unknown aetiology that frequently presents with mediastinal lymphadenopathy and often requires invasive diagnostic procedures. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is widely used in this setting; however, a definitive diagnosis cannot always be established at first attempt. This study aimed to identify clinical, laboratory, and radiological factors associated with a definitive diagnosis of sarcoidosis in patients referred for EBUS-TBNA. A retrospective analysis was performed including patients undergoing first-time ever EBUS-TBNA for mediastinal lymphadenopathy over a 12-month period. Demographic data, clinical features suggestive of sarcoidosis, chest computed tomography findings, and white blood cell count, were analysed, and definitive diagnoses were established based on cytological results and available follow-up data. Younger age (≤55 years), female sex, the absence of a pulmonary mass >10 mm on imaging, normal white blood cell count, and the presence of clinical features typical of sarcoidosis were significantly associated with a definitive diagnosis of sarcoidosis. Based on these variables, two point-based diagnostic scoring models were developed, demonstrating clinically relevant discriminatory performance. Readily available pre-procedural clinical and radiological factors may assist in estimating the probability of sarcoidosis in patients undergoing EBUS-TBNA for mediastinal lymphadenopathy and may support risk stratification and clinical decision-making.

Advances in Respiratory Medicine doi: 10.3390/arm94020018

Authors: Gerard Kian-Meng Goh James A. Foster Vladimir N. Uversky

Clinical, experimental, and computational evidence of COVID-19 virulence and infectivity has been linked to SARS-CoV-2 shell disorder. A strong link was first discovered using an AI disorder-predicting tool, which detected an unusually hard (low disorder) outer shell among all SARS-CoV-2-related viruses but not in the 2003 SARS-CoV-1. This could account for the high infectivity found in SARS-CoV-2—but not in SARS-CoV-1—as it is believed that hard shells protect viral particles from the onslaught of the antimicrobial enzymes present in the respiratory system and saliva. As a result, much larger quantities of particles are shed by COVID-19 patients. Abnormally hard outer shells (M) are associated with burrowing animals, e.g., pangolins, and SARS-CoV-2 likely acquired these shells due to its long-term evolutionary interactions with pangolins. As for virulence, the inner shell of SARS-CoV-2 (N) has been found to exhibit lower disorder than that of SARS-CoV-1. This lower disorder is consistent with the fact that SARS-CoV-2 is less virulent than SARS-CoV-1, as higher disorder in the inner shell is associated with more efficient protein–protein binding during replication. The link between N/M disorder and virulence or infectivity falls under the umbrella of shell disorder models (SDMs), which can connect virulence, infectivity, and long COVID under one coherent concept. Evidence of the reliability and reproducibility of SDMs as applied to COVID-19 is examined. The hard M that is resisting the antimicrobial enzymes in the respiratory system can be extended to immunological enzymes, especially those found in phagocytes such as macrophages, which can therefore become a reservoir for the virus.

Advances in Respiratory Medicine doi: 10.3390/arm94020017

Authors: Zofia Potocka Katarzyna Górska Radosław Ciesielski Dorota Bomba-Opoń Mirosław Wielgoś Piotr Korczyński

Introduction: It is estimated that up to 75% of pregnant women complain of dyspnea at some point during pregnancy. Asthma is the most common chronic pulmonary disease complicating pregnancy. Well controlled asthma does not affect pregnancy negatively. However, asthma exacerbations are linked with several adverse perinatal outcomes. As diligent treatment of asthma significantly reduces the number of asthma exacerbations, it is important to properly detect asthmatic patients among pregnant women in order to provide them with better care. The most efficient way to diagnose asthma is to perform spirometry with a reversibility test. There are no studies that have examined the safety of performing spirometry and, more specifically, a reversibility test, during pregnancy. Objectives: In this systematic review we aimed to review current available data regarding the safety of performing spirometry and a reversibility test during pregnancy. Patients and methods: For this systematic review, we searched PubMed, Scopus and Cochrane databases. We used the following search terms: (pregnancy); (spirometry); (lung function test); (pulmonary function test); (reversibility test); (post-bronchodilator challenge); (safety). Results: We collected reports of spirometry performed on pregnant women and analyzed them for complications that occurred during the procedure. Out of 13,594 records identified for the aforementioned search words, we included 78 documents that met the inclusion criteria. In total, the studies consisted of over 33,405 spirometry attempts performed by 10,617 pregnant women. Additionally, the reversibility test was conducted in nine studies. In all of the selected articles, there were no reports of adverse events occurring while performing spirometry. Conclusions: In this systematic review we aimed to summarize the current available data about the safety of performing spirometry during pregnancy. Several studies have investigated pulmonary function tests during pregnancy. No studies reported any adverse events that occurred while performing the procedure. In order to better characterize the safety profile of spirometry, including during pregnancy, further prospective studies systematically reporting on adverse symptoms during spirometry are required.

Advances in Respiratory Medicine doi: 10.3390/arm94020016

Authors: Ihsan Topaloglu Gulfem Ozduygu Cagri Atasoy Guntug Batıhan Damla Serce Gulsah Inanc Mutlu Onur Güçsav Arif Metehan Yıldız Turker Tuncer Sengul Dogan Prabal Datta Barua

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Advances in Respiratory Medicine doi: 10.3390/arm94020015

Authors: Kazim Okan Dolu

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Advances in Respiratory Medicine doi: 10.3390/arm94020014

Authors: Lorenzo Carriera Angelo Coppola Roberto Lipsi Stefano Baglioni Pier-Valerio Mari Roberto Barone Simone Ielo Raffaele Scala Andrea Smargiassi Riccardo Inchingolo Luca Richeldi Valeria Gambacorta Alfredo Di Giovanni Eugenio De Corso

Small-airway disease (SAD) is a key feature of severe asthma and is associated with poor symptom control and frequent exacerbations. Dupilumab has demonstrated efficacy in improving lung function and reducing exacerbations, but real-world evidence on its effects in SAD remains limited. The aim of this study is to evaluate the impact of 12 months of dupilumab treatment on SAD, clinical outcomes, and type 2 inflammation. We included 21 patients. Small-airway function was assessed by impulse oscillometry (R5–R20) and spirometry FEF25–75% predicted at baseline (T0) and after 3 (T3), 6 (T6), and 12 (T12) months of treatment. Additional assessments included FEV1, the Asthma Control Test (ACT), exacerbation frequency, oral corticosteroid (OCS) use, the blood eosinophil count (BEC), and fractional exhaled nitric oxide (FeNO). At baseline, 62% of patients exhibited SAD (R5–R20 > 0.07 kPa/L/s). Dupilumab treatment led to a significant and sustained improvement in small-airway function: mean R5–R20 decreased from 0.18 ± 0.17 kPa/L/s to 0.09 ± 0.07 at T12 (p = 0.04), while predicted FEF25–75% increased from 29.5 ± 20.8% to 47.0 ± 21.1% (p < 0.001). ACT scores improved from 13.1 ± 4.9 to 19.6 ± 3.8 (p < 0.001). FeNO levels declined from 64.1 ± 50.7 ppb to 24.8 ± 20.9 ppb (p = 0.01). Improvements in R5–R20 correlated with better ACT and FeNO reductions. In this real-world cohort, dupilumab significantly improved SAD, lung function, and asthma control, while reducing exacerbations, OCS dependence, and type 2 inflammation over 12 months.

Advances in Respiratory Medicine doi: 10.3390/arm94010013

Authors: Saja Alrashedi Lama Alharbi Meshal Alotaibi Inad Alzahrani Albara Jad Qamar Aldoboke Suroor Algethami Raghda Alrabah Rana Alharbi Ali Al Nuwaiser Mohammed Al-Hariri

(1) Background: Pulmonary hypertension (PH) is characterized by respiratory muscle weakness, limited exercise tolerance, and reduced quality of life, but inspiratory muscle training (IMT) has emerged as a potential non-pharmacological strategy to improve functional outcomes in this population. This systematic review and meta-analysis evaluated the effects of isolated IMT on respiratory function, exercise capacity, symptom burden, and safety in adults with PH. (2) Methods: A systematic search was conducted in accordance with PRISMA guidelines. Randomized controlled trials involving adults with PH who underwent isolated IMT were included, and respiratory muscle strength, spirometric parameters, exercise capacity, dyspnea, fatigue, quality of life, and adverse events were the outcomes that were assessed. Data were pooled using meta-analytic techniques where appropriate. (3) Results: A total of 130 participants, assigned to five randomized controlled trials, met the inclusion criteria. IMT significantly improved maximal inspiratory pressure (MD = +24.01 cmH2O), maximal expiratory pressure (MD = +23.64 cmH2O), and six-minute walk distance (MD = +60.61 m), but no significant changes were observed in spirometric indices (FEV1%, FVC%, and FEV1/FVC). While several individual studies demonstrated clinically relevant improvements in six-minute walk distance, the pooled analysis did not demonstrate a statistically significant effect. IMT consistently reduced dyspnea and fatigue and improved quality-of-life domains. No serious adverse events were reported, and adherence was high. (4) Conclusions: IMT is a safe and feasible adjunct intervention in PH, providing meaningful improvements in respiratory muscle strength and symptom burden. Further large-scale trials are warranted to confirm its long-term clinical benefits.

Advances in Respiratory Medicine doi: 10.3390/arm94010012

Authors: Monika Burzyńska Małgorzata Pikala

Background: Respiratory diseases remain a major contributor to mortality in Europe, yet national long-term analyses rarely explore sex- and age-specific temporal patterns in detail. Large international datasets provide aggregated estimates but may obscure country-specific trend changes relevant for public health planning. The aim of the study was to assess long-term trends in mortality from chronic lower respiratory diseases (ICD-10: J40–J47) as well as pneumonia and influenza. (ICD-10: J10–J18) in Poland, with particular emphasis on sex- and age-specific trajectories and joinpoint-defined changes over time. Methods: All deaths among Polish residents aged ≥65 years were analysed using nationwide mortality registry data. Age-standardised death rates (SDRs) were calculated, and temporal trends were assessed using joinpoint regression models to estimate annual percentage changes (APC) and average annual percentage change (AAPC). Results: The proportion of deaths attributable to respiratory diseases increased in both men and women across early (65–74 years) and late (≥75 years) old age. Mortality from chronic lower respiratory diseases declined throughout the study period among men, with the most pronounced reductions observed in the early 2000s, particularly among those aged ≥75 years, while trends among women remained largely stable or showed only gradual declines. In contrast, mortality from pneumonia and influenza rose markedly across all sex and age subgroups, with distinct trend reversals observed after 2008–2009. Conclusions: Long-term respiratory mortality trends in Poland exhibit marked sex- and age-specific differences that are not fully captured by aggregated international analyses. These findings highlight the importance of country-level, stratified assessments when interpreting respiratory mortality patterns and underscore the need for caution when relying on single time-point indicators for risk assessment and policy planning.

Advances in Respiratory Medicine doi: 10.3390/arm94010011

Authors: Valentina Trimarco Paola Gallo Seyedali Ghazihosseini Alessia Izzo Paola Ida Rozza Alessandra Spinelli Stefano Cristiano Carlo De Rosa Felicia Rozza Carmine Morisco

Respiratory seasonal viral infections remain one of the most important issues in community medicine. The heterogeneity of etiological agents and the characteristics of the hosts airway antiviral defenses account for the complex management of these infections. The clinical consequence of this picture is that, despite the widespread use of vaccination as the primary prevention strategy, the rates of acute respiratory complications remain still high. In addition, they determine post-infectious fatigue and organ dysfunction. Inflammation and oxidative stress are the principal pathogenic mechanisms responsible for clinical complications during respiratory seasonal viral infections. Nowadays, a growing body of evidence indicates that adjunctive nutritional support can contribute to relieve the symptoms during the acute and subacute phases of respiratory viral infections. We assess the data in the literature regarding the combination of L-Arginine and Liposomal Vitamin C as adjuvant treatment for respiratory seasonal viral infections. The database of the National Library of Medicine (PubMed) was searched using the keywords “L-Arginine, Vitamin C, dietary supplements, seasonal respiratory viral infections”. The treatment of symptoms during acute and post-acute respiratory viral infections requires an integrated approach that includes vitamins and nutritional supplementation. The combination of L-Arginine and Liposomal Vitamin C seems to represent a nutritional support able to mitigate symptoms occurring during the acute or post-acute phase of infection.

Advances in Respiratory Medicine doi: 10.3390/arm94010010

Authors: Aleksandra Marchwińska Katarzyna Mazurek Katarzyna Białek-Gosk Elżbieta M. Grabczak Olga Truba Karolina Klimowicz Marta Dąbrowska

A chronic cough, defined as a cough persisting for more than eight weeks in adults, is a common clinical problem with a significant impact on patients’ quality of life. This study compares the etiological spectrum and treatment effectiveness of chronic cough in male and female patients. A retrospective analysis was conducted on a cohort of patients diagnosed in the cough clinic between 2017 and 2021. The response to treatment was assessed based on the reduction in cough severity measured using a 100 mm visual analogue scale (VAS). This study included 231 patients: 164 women (70.9%) and 67 men (29.1%). The median duration of cough was 48 months (IQR 24–120). There were no gender differences in age, BMI, smoking history, cough duration, or severity at the initial visit. Upper airway cough syndrome (UACS) and obstructive sleep apnea (OSA) were diagnosed more frequently in men than in women (UACS: 75% vs. 53%, p = 0.002; OSA: 21% vs. 6%, p = 0.001). Cough severity significantly decreased in both groups; the median VAS score dropped from 55 to 40 mm in women (p < 0.0001) and from 69 to 39 mm in men (p = 0.009). The effectiveness of chronic cough treatment, measured by the median reduction in VAS score, was greater in men than in women (32 mm vs. 17.5 mm, p = 0.006). These gender-specific differences in cough etiology and treatment response suggest that a “one-size-fits-all” approach may be inadequate.

Advances in Respiratory Medicine doi: 10.3390/arm94010009

Authors: Kazuki Furuhashi Hajime Fujimoto Masaaki Toda Corina N. D’Alessandro-Gabazza Atsuro Takeshita Kota Nishihama Tomohito Okano Haruko Saiki Atsushi Tomaru Valeria Fridman D’Alessandro Isaac Cann Esteban C. Gabazza Taro Yasuma Osamu Hataji Tetsu Kobayashi

Background: Corisin, a microbiota-derived proapoptotic peptide, has emerged as a key mediator of epithelial injury, inflammation, and acute exacerbation in fibrotic lung disease. Although acute corisin inhibition prevents exacerbations in experimental models, its therapeutic impact on established pulmonary fibrosis remains unclear. This study evaluated the short-term efficacy of corisin neutralization in advanced transforming growth factor-β1 (TGF-β1)-driven lung fibrosis. Methods: Male TGF-β1 transgenic mice with established fibrosis were allocated to computed tomography-matched groups and treated intraperitoneally with an anti-corisin monoclonal antibody (clone 21A) or control IgG every two days for one week. Bronchoalveolar lavage fluid (BALF) analysis, histopathology, assessment of apoptosis, Ashcroft scoring, and lung hydroxyproline quantification were performed on day 8. Results: Anti-corisin treatment significantly reduced BALF inflammatory cell counts, including macrophages and lymphocytes. Histological analyses demonstrated decreased alveolar epithelial apoptosis, reduced collagen deposition, and significantly lower Ashcroft fibrosis scores. Lung hydroxyproline content was also markedly decreased, indicating attenuation of extracellular matrix accumulation. Conclusions: Short-term neutralization of microbiota-derived corisin rapidly alleviates inflammation, epithelial injury, and fibrotic remodeling in advanced TGF-β1-induced pulmonary fibrosis. These findings identify corisin as an upstream driver of ongoing fibrogenesis and support its potential as a therapeutic target in progressive fibrotic lung disease.

Advances in Respiratory Medicine doi: 10.3390/arm94010008

Authors: Carlos Granados-Burgos Eduardo Tuta-Quintero Paula Romero Laura Gómez-Castro Alirio Bastidas Johan Rincón Sergio Torres Diego Rodríguez Kamil Faizal Juan Moreno Santiago Monsalve Estefania Couto Sofia Yanes David Torres Juan Sandoval Juan Hernández

Background: Obstructive sleep apnea (OSA) affects quality of life and increases cardiovascular risk. Nocturnal oxygen therapy (NOT) offers a potential alternative for patients intolerant to CPAP. The objective of this study was to compare NOT and continuous positive airway pressure (CPAP) by evaluating five-year survival in patients with obstructive sleep apnea. Methods: A retrospective cohort study was conducted using propensity score matching (PSM) methodology. A PSM analysis was conducted to reduce selection bias due to differences in baseline characteristics between patients using CPAP and those receiving oxygen therapy. Balance between treated and untreated groups was assessed using standardized mean differences. A PSM was estimated using a logistic regression model, matching patients adherent to CPAP therapy to those treated with NOT. Results: A total of 497 patients with a confirmed diagnosis of OSA were included in the analysis. The mean age was 62.1 years (SD13.6), and 54.3% (270/497) were male. Overall, 42.1% (209/497) of the patients were over 65 years old. Of the total, 303 patients received CPAP therapy and 194 received NOT. After PSM, a matched cohort of 370 patients (185 per group) was obtained. The CPAP-treated group showed a significantly lower residual Apnea–Hypopnea Index compared to the oxygen therapy group (3.9, IQR: 1.8–6.5 vs. 15, IQR:7.5–29.1; p < 0.001), indicating better physiological control of respiratory events. Treatment with CPAP was associated with a significantly lower risk of mortality compared with NOT across analytical approaches, including weighted logistic regression (OR = 0.11; 95% CI 0.02–0.48; p = 0.004) and PSM with bootstrap estimation (ATT = −0.12; 95% CI −0.22 to −0.01; p = 0.030). Conclusions: In this cohort, higher five-year survival was observed among patients with OSA treated with CPAP compared with those receiving supplemental oxygen. These findings indicate a favorable association between CPAP use and long-term outcomes, supporting its role as the preferred first-line therapy in patients with OSA.

Advances in Respiratory Medicine doi: 10.3390/arm94010007

Authors: Chebly Dagher Allysse Thomas Suzie Al Absi Brett Carollo Garrett Fiscus Raj Parikh

Pulmonary hypertension associated with interstitial lung disease (PH-ILD) is a progressive condition with limited treatment options and associated with high mortality rates. Inhaled treprostinil (iTre) is the only approved therapy for PH-ILD and has been shown to improve exercise capacity and delay disease progression. However, the conventional outpatient titration schedule requires 8–16 weeks to achieve therapeutic dosing, which may delay clinical benefit in those with advanced disease. We conducted a retrospective study of six patients with severe PH-ILD admitted to a tertiary academic center for initiation of iTre using a rapid inpatient uptitration protocol. iTre was started at 3 breaths four times daily (QID) and increased by 2 additional breaths every 12–24 h as tolerated, aiming for ≥9–12 breaths QID within one week under close monitoring. All six patients achieved target dosing without dose reduction or interruption. At three-month follow-up, mean pulmonary artery pressure decreased from 42 ± 5.5 to 35.2 ± 4.5 mmHg, pulmonary vascular resistance from 8.0 ± 1.2 to 6.0 ± 0.9 WU, and cardiac index increased from 2.05 ± 0.13 to 2.15 ± 0.12 L/min/m2. No readmissions occurred within 90 days. This study demonstrates that rapid inpatient uptitration of iTre in severe PH-ILD is feasible and well-tolerated, with preliminary evidence of short-term hemodynamic improvement.

Advances in Respiratory Medicine doi: 10.3390/arm94010006

Authors: Georgia Kourlaba Stylianos Ravanidis Garyfallia Stefanou Konstantinos Mathioudakis Anastasios Tsolakidis Dimitrios Zografopoulos

Background: Nintedanib and pirfenidone are two anti-fibrotic agents for diseases within the interstitial lung diseases (ILDs) spectrum. Here, we provide a comprehensive analysis regarding treatment persistence and adherence rates for the Greek territory. Methods: This was a retrospective cohort study of patients initiating anti-fibrotic treatment during the period 2019–2023, utilizing data extracted from the National Electronic Prescription Database. Treatment persistence was defined as the duration from the date of the first prescription to the end of follow-up, death, or switching to another agent. Adherence was estimated based on the Medication Possession Ratio (MPR) metric. Results: Overall, 2112 patients were analyzed. The majority were naive, male patients with a diagnosis of idiopathic pulmonary fibrosis (IPF). The overall median treatment persistence was 40.2 months (95% CI: 35.5–44.6). Women and treatment-naive patients demonstrated longer median treatment persistence compared to their counterparts, while older patients demonstrated the lowest median persistence rates. Adherence levels remained high across the follow-up period (90%). Diagnosis of IPF and gastrointestinal comorbidities were associated with a higher risk of discontinuation. Conclusions: We have generated novel data concerning the factors that affect patients’ outcomes under anti-fibrotic therapy. These findings may provide helpful insights for the therapeutic management of ILDs.

Advances in Respiratory Medicine doi: 10.3390/arm94010005

Authors: Sabrina Meng Hersh Sagreiya Negar Orangi-Fard

Introduction: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality. Early identification and timely intervention for COPD exacerbations can reduce hospitalizations and complications, as well as improve patient outcomes. Methods: To develop and evaluate predictive models for COPD exacerbations using machine learning (ML), we performed a retrospective study using intensive care unit patient records. Records including 31,667 clinical notes and 10,489 vital signs were used to train and validate two machine learning models to predict COPD exacerbations in patients with known or suspected COPD. Predictive performance was evaluated for support vector machine, quadratic discriminant analysis, and adaptive boosting algorithms using area under the receiver operating characteristic curve (AUC). Results: The clinical note-based support vector machine model achieved an AUC of 0.81 and accuracy of 84.0% in predicting COPD exacerbations. Data from patient monitors and hospital information systems provided sufficient information for accurate prediction, demonstrating the utility of combining physiological signals with clinical text data. Discussion: Clinically available patient data and vital signs can effectively predict COPD exacerbations, potentially enabling earlier interventions, improved outcomes, and reduced healthcare burden. These findings suggest that integrating unstructured clinical notes with structured vital signs using ML frameworks may improve early detection of exacerbation risk, thus enabling appropriate patient counseling, triage, and treatment based on COPD severity.

Advances in Respiratory Medicine doi: 10.3390/arm94010004

Authors: Adam Jerzy Białas Adam Barczyk Iwona Damps-Konstańska Aleksander Kania Krzysztof Kuziemski Justyna Ledwoch Krystyna Rasławska Małgorzata Czajkowska-Malinowska

Introduction: This document presents recommendations of the Polish Respiratory Society on discharge instructions following hospitalization for an exacerbation of chronic obstructive pulmonary disease (COPD). Methods: The Delphi method was applied to achieve consensus among independent experts. Results: Fourteen recommendations were formulated. Experts emphasized that discharge summaries require clear graphical and editorial design to ensure readability for both patients and healthcare professionals. The involvement of a multidisciplinary team was recommended to provide coherent and comprehensive documentation. Discharge instructions should be discussed with the patient during hospitalization and supplemented with standardized educational materials provided separately. These materials should cover inhaler technique, smoking cessation, physical activity, pulmonary rehabilitation, and vaccination. For patients with respiratory failure, home oxygen therapy or non-invasive ventilation must be addressed. Discharge recommendations should highlight modifications in baseline COPD treatment and management of comorbidities. A personalized action plan for future exacerbations is essential, and dietary consultation is advised. Finally, discharge summaries should specify follow-up appointments and include prescriptions for inhaled medications. Conclusions: The Polish Respiratory Society recommends that discharge instructions be provided to all patients hospitalized for a COPD exacerbation.

Advances in Respiratory Medicine doi: 10.3390/arm94010003

Authors: Ahmed Ehab Axel T. Kempa Ahmad Shalabi Noha Elkateb Nesrine Saad Farrag Heba Wagih Abdelwahab

Background: Elderly-onset sarcoidosis > 65 (EOS) is rare and occurs in patients over 65. Studies on its incidence, clinical features, and treatment are limited, and its link to malignancy remains complex. Objectives: In this study, we aimed to analyze the possible association between malignancy and the occurrence of sarcoidosis in elderly patients over 65 years old. Design: Monocentric, nested retrospective case–control study. Material and Methods: A retrospective study analyzed newly diagnosed sarcoidosis patients in the Loewenstein Lung Center, Baden-Württemberg, Germany, categorizing them into younger-onset (<65 years) and elderly-onset (≥65 years). Demographic data, smoking status, medical history, symptoms, diagnostic methods, and any prior malignancy history were collected. Results: A total of 447 patients were included (365 patients within the group of younger-onset sarcoidosis and 82 patients with EOS). The median age of the younger-onset group was 47 (47 [23–63] years), compared to 69 (69 [65–84] years), p ≤ 0.001. Female patients were more prevalent in the group of elderly-onsets (54.9%) compared to the younger-onset group (35.9%), corresponding to an odds ratio of 2.2 (95% CI: 1.3–3.5, p: 0.002). Regarding the past history of malignancy, patients who had a positive history of malignancy were more prevalent among the elderly-onset group (29.6%) compared to the younger-onset group (5%) [OR (95% CI): 8.1 (4.1–15.8), p ≤ 0.001]. In multivariable logistic regression analysis with malignancy as the outcome, increasing age at sarcoidosis diagnosis was independently associated with a higher likelihood of prior malignancy (adjusted OR 1.08 per year, 95% CI 1.04–1.12), whereas sex, smoking status, and cardiometabolic comorbidity (diabetes and/or hypertension) were not independently associated. Conclusions: Elderly-onset sarcoidosis (EOS) is a less frequent variant of sarcoidosis with limited data regarding the possible risk factors. The increased prevalence of malignancy observed among patients with elderly-onset sarcoidosis appeared to be largely driven by age rather than a distinct EOS-specific effect. Age-adjusted analyses are essential when interpreting malignancy risk in sarcoidosis, and future age-matched prospective studies are needed to clarify potential biological links and guide evidence-based screening strategies.

Advances in Respiratory Medicine doi: 10.3390/arm94010002

Authors: Chia Kow Syed Hasan Kaeshaelya Thiruchelvam

This systematic review and meta-analysis aimed to evaluate the efficacy and safety of carbocisteine in reducing chronic obstructive pulmonary disease (COPD) exacerbations based on evidence from randomized controlled trials (RCTs). A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. RCTs comparing carbocisteine (1500 mg/day) with placebo in COPD patients, with a minimum follow-up of six months, were included. Data on exacerbation rates and adverse events were extracted and analyzed using a random-effects model. Four RCTs involving 1746 patients met inclusion criteria. Pooled analysis showed that carbocisteine significantly reduced the annual rate of acute exacerbations compared to placebo (WMD = −0.40; 95% CI: −0.69 to −0.11), with no significant increase in adverse events (OR = 1.02; 95% CI: 0.76 to 1.37). Mechanistically, carbocisteine improves mucociliary clearance, suppresses airway inflammation, reduces oxidative stress, and may hinder bacterial colonization. Carbocisteine is associated with a significant reduction in COPD exacerbations and demonstrates a favorable safety profile. It may serve as an effective adjunctive therapy in patients with frequent exacerbations and mucus hypersecretion.

Advances in Respiratory Medicine doi: 10.3390/arm94010001

Authors: Jose Luis Estela-Zape

High-flow nasal cannula (HFNC) therapy is frequently described as a positive pressure modality, yet this classification lacks mechanistic support. This critical narrative review integrates experimental, computational, and clinical evidence to examine the established physiological mechanisms underlying HFNC, with emphasis on precise terminology. The study clarifies that labeling HFNC as “positive pressure” is conceptually inaccurate, as the system delivers transient, flow-dependent pressures characteristic of open-circuit administration. Evidence is synthesized to quantify the relative contributions of nasopharyngeal dead-space clearance versus emergent pressure generation. Unlike CPAP, HFNC produces pressures ranging from 0.2 to 13.5 cmH2O, determined by airway geometry, leak magnitude, and mouth position. Fluid dynamic modeling using Bernoulli and Darcy–Weisbach equations demonstrates oscillatory rather than sustained pressures, with magnitudes linked to nasopharyngeal Reynolds numbers (2400–6000) and turbulent energy dissipation (30–60%). Clinical efficacy persists despite variable pressures, reflecting synergistic mechanisms: inspiratory flow matching (40–50% reduction in work of breathing), dead-space clearance (CO2 reduction, r = −0.77, p < 0.05), emergent pressure effects (10–20%), and thermal humidification (10–20%). Electrical impedance tomography reveals heterogeneous alveolar recruitment, with high-potential (54%) and low-potential (46%) phenotypes. Based on these mechanistic insights, this review proposes the term “emergent hydrodynamic pressure” to accurately describe HFNC’s transient, flow-dependent pressures. This terminology differentiates HFNC from conventional positive pressure systems and aligns language with the principles of fluid dynamics and respiratory physiology.

Advances in Respiratory Medicine doi: 10.3390/arm93060058

Authors: Abdullah Almufleh Abdulrahman Altuwayjiri Abdulmalik Alshehri Abdulaziz Alzouman Abdulhadi Alotaibi Abdulrahman Alsaedy

Background/Objectives: Community-acquired pneumonia (CAP) is classified into typical and atypical forms, with Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila being the most common atypical pathogens and Streptococcus pneumoniae and Haemophilus influenzae the most common typical organisms. This study aimed to compare the prevalence, demographics, and clinical outcomes of hospitalized typical and atypical CAP patients. Methods: A cross-sectional study was conducted from January 2016 to June 2022 at two tertiary hospitals in Riyadh, Saudi Arabia. All inpatients diagnosed with CAP by imaging and clinical findings were included, excluding viral cases. Outcomes measured included pathogen testing and identification, hospitalization duration, ICU stay, and in-hospital mortality. Results: Among 1238 CAP hospitalizations, 65% underwent molecular testing, with atypical pathogens detected in 17 cases (2.09%). Mycoplasma pneumoniae was the most common organism. The cases had an almost equal male-to-female ratio. Mean hospitalization was 12 days overall versus 4 days for atypical pneumonia. Of 265 ICU admissions, none tested positive for atypical CAP. Overall mortality was 6.94%, with no deaths in atypical pneumonia positive patients. Conclusions: PCR molecular testing was performed in 65% of patients hospitalized with CAP, and atypical pneumonia organisms were uncommon in these patients, with Mycoplasma pneumoniae being the most common. Clinical outcomes were more favorable for these patients. Expanding molecular testing may improve pathogen detection and guide target management.

Advances in Respiratory Medicine doi: 10.3390/arm93060057

Authors: Anna Ziętarska Adam Dobek Piotr Białek Wojciech Szubert Sebastian Majewski Ludomir Stefańczyk

Haemoptysis arises from diverse respiratory diseases and may involve a broad spectrum of thoracic vessels. Arterial embolisation (AE) is an effective, repeatable, minimally invasive treatment option for life-threatening haemoptysis. This case series included 10 patients (mean age 34 years; six males; five with cystic fibrosis) who underwent 17 AE procedures for life-threatening haemoptysis between January 2018 and September 2025. The study assessed the role of wide-field computed tomography angiography (CTA), extending from the thoracic inlet to L2, in preprocedural planning, bleeding localisation and detection of systemic collaterals. CTA accurately predicted the culprit region in 16 out of 17 procedures. Non-bronchial systemic arteries were identified in 6 out of 10 patients, consistent with previous reports. CTA showed strong concordance with angiography and enabled the detection of uncommon collaterals, including subclavian and phrenic branches. Recurrence of hemoptysis occurred in one patient during follow-up; however, three patients were lost to follow-up. Wide-field CTA enhances the identification of systemic feeders and supports procedural planning, potentially reducing recurrence associated with missed culprit vessels. AE remains a valuable option for haemoptysis control in cystic fibrosis, with outcomes further improved following initiation of CFTR modulators. The small sample size and incomplete follow-up limit generalisability, but findings highlight the importance of CTA in guiding AE and improving clinical outcomes.

Advances in Respiratory Medicine doi: 10.3390/arm93060056

Authors: Laura Zaliene Alvina Mockute Lina Levickiene

Background: Dysfunctional breathing patterns may impair autonomic regulation and increase perceived stress. Breathing-based interventions, particularly those involving guided exercises and supportive tools, have the potential to provide non-pharmacological benefits. Methods: In this parallel two-arm randomized controlled trial, 14 women aged 35–45 years with signs of dysfunctional breathing and no comorbidities were recruited from a fitness club. Participants were randomly assigned (1:1) using a computer-generated sequence to an intervention group (n = 7) or a control group (n = 7). Blinding was not applied. Both groups completed a 6-week program of guided breathing exercises using the iBreathe app, while the intervention group additionally used mouth tape during sleep. The primary outcomes were heart rate variability (HRV) indices—root mean square of successive differences (RMSSD) and the high-frequency (HF) component. Secondary outcomes included respiratory rate, Hencho test performance, and perceived stress measured using the Perceived Stress Scale-10 (PSS-10) and a Visual Analogue Scale (VAS). All participants were included in the final analysis (no loss to follow-up). Results: The intervention group showed a significant increase in the HF component of HRV (p = 0.018) and improved Hencho test performance (p = 0.018). Both groups demonstrated significant reductions in respiratory rate (p < 0.05) and PSS scores (p < 0.05). Between-group differences were not significant for RMSSD or perceived stress. No adverse events were reported. Conclusions: A 6-week breathing intervention improved respiratory efficiency and reduced perceived stress among women with dysfunctional breathing. The additional of night-time mouth taping provided further benefits for HRV and respiratory control. Larger and longer trials are needed to confirm these findings.

Advances in Respiratory Medicine doi: 10.3390/arm93060055

Authors: Ana Karolina Mendes Moreno Rajiv Gandhi Gopalsamy Lucas Alves da Mota Santana Marina dos Santos Barreto Pedro Henrique Macedo Moura Deise Maria Rego Rodrigues Silva Túlio César Rodrigues Leite Camila de Paula Dias Breno de Melo Silva Lysandro Pinto Borges Ricardo Lemes Gonçalves

During the COVID-19 pandemic, the global focus on SARS-CoV-2 overshadowed the epidemiology of other respiratory pathogens. This study aimed to characterize the circulation of endemic human coronaviruses (HCoVs) in Brazil. We retrospectively analyzed results from 22,472 PCR tests for HCoVs (from 5183 patients) and 601,278 tests for SARS-CoV-2 (from 475,856 patients) between November 2019 and June 2021. HCoVs were detected in 160 patients (3.09%), with HCoV-NL63 as the most frequent species. HCoV circulation was intermittent, with positivity peaks up to 4% but also periods of up to six months with an absence of detections in 2020, contrasting with the sustained high positivity of SARS-CoV-2 (22.37%). Co-infections were frequent: 26.25% of HCoV-positive patients were co-infected with at least one other respiratory pathogen, most commonly Rhinovirus/Enterovirus, and cases involving up to five pathogens were observed, seven patients had co-infections between HCoVs and SARS-CoV-2. These findings reveal the persistent, often cryptic, circulation of HCoVs during the pandemic and highlight their role as key components in complex multi-pathogen infections. This underscores the critical importance of implementing comprehensive molecular diagnostic panels in routine respiratory surveillance to ensure accurate etiology, guide appropriate clinical management, and fully assess the public health burden of non-SARS-CoV-2 coronaviruses.

Advances in Respiratory Medicine doi: 10.3390/arm93060054

Authors: Beatrice Ragnoli Patrizia Pochetti Fausto Chiazza Carlotta Bertelegni Danila Azzolina Mario Malerba

Background: Obstructive sleep apnea (OSA) is recognized as a systemic disorder associated with several comorbidities, including renal dysfunction, which may improve with continuous positive airway pressure (C-PAP) therapy. Sleep fragmentation and nocturnal hypoxia characteristic of OSA have been implicated in carcinogenesis, particularly affecting hypoxia-sensitive urinary tract tissues. This study aimed to assess the prevalence of different cancer types among patients with concurrent OSA and malignancy and to characterize the clinical profiles of those with urinary tract cancer. Methods: We retrospectively analyzed 50 patients with both OSA and cancer from the Vercelli Hospital Registry. Cancer diagnoses were collected at the time of OSA diagnosis, prior to C-PAP initiation. Results: Among the cohort (70% males) of OSA-cancer patients, urinary tract cancers were the most frequent (34%), followed by breast (14%), colorectal (12%), lung (10%), laryngeal and skin (8%), intracranial (6%), hematologic and parotid (4%), and other cancers (2%); 10% had multiple cancer sites. Patients with urinary tract cancer were mainly male (88%, p = 0.0043) and displayed better respiratory indices, frequent hypertension, and higher C-PAP adherence. Conclusions: These findings suggest a possible link between OSA-related hypoxia and carcinogenesis in urinary tract tissues and support increased clinical surveillance and further research to determine potential protective effects of C-PAP therapy.

Advances in Respiratory Medicine doi: 10.3390/arm93060053

Authors: Anjali R. Nath Adesh Kumar Amit Suresh Bhate Bharat Mehrotra Deependra Kumar Rai Vijay Kumar Barge Divya Bhojwani Sagar Bhagat Sumit Bhushan Saiprasad Patil Hanmant Barkate

Chronic obstructive pulmonary disease (COPD) is a major health burden in India with limited real-world data on triple inhaler therapy. This prospective, open-label, multi-center, single-arm, phase 4 study (October 2023–August 2024) assessed the effectiveness and safety of glycopyrronium/formoterol fumarate/budesonide (GFB) triple therapy, administered as metered-dose inhaler (MDI) or dry-powder inhaler (DPI), in Indian COPD patients. Symptomatic patients aged ≥40 years with minimum one exacerbation in the past year and receiving dual or monotherapy were included. GFB was delivered as MDI or DPI based on physician and patient preference. Primary outcomes were changes from baseline in trough forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and modified medical research council (mMRC) score over 24 weeks, with assessment of exacerbations, hospitalizations, rescue medication use, and safety. In 184 patients (70.65% male, mean age 53.7 years), GFB significantly improved FEV1, FVC, and mMRC scores. Eleven mild exacerbations were reported without hospitalization; 17.39% used rescue salbutamol largely in the first 4 weeks. GFB was well tolerated, with mild-to-moderate adverse events in 14.67%, and outcomes were comparable between MDI and DPI. Our findings support GFB as safe and effective treatment in real-world COPD management.

Advances in Respiratory Medicine doi: 10.3390/arm93060052

Authors: Naoki Maki Takahiro Yanagihara Ashoka Indranatha Wijesinghe Kazuto Sugai Tomoyuki Kawamura Yusuke Saeki Shinsuke Kitazawa Naohiro Kobayashi Shinji Kikuchi Yukinobu Goto Harumi Sakamoto Keisuke Taniguchi Hideo Ichimura Yukio Sato

Introduction: Minimally invasive video-assisted thoracic surgery (VATS) for lung cancer has become a widely used approach. However, postoperative pulmonary complications (PCs) such as pneumonia, atelectasis, and lung fistula remain significant challenges, particularly in older adult patients with multiple comorbidities. The 6-minute walk test (6MWT) has been suggested as a predictor of postoperative outcomes in various surgical settings, but its relationship with postoperative complications following VATS lobectomy for lung cancer has not been thoroughly explored. The aim of this study was to determine if preoperative 6MWD predicted the occurrence of 30-day PCs among patients undergoing VATS lobectomy for non-small-cell lung cancer. Methods: This retrospective study examined 66 patients who underwent VATS lobectomy for lung cancer. Participants were categorized into two groups: those with postoperative pulmonary complications (n = 11) and those without (n = 55). The research period was from January to September 2022. The preoperative 6MWT distance, along with other clinical and demographic factors, was assessed to determine its predictive value for postoperative complications. Multivariate logistic regression analysis was performed to identify significant predictors. Results: The study found that preoperative 6MWT ≤ 450 m was a significant predictor of postoperative pulmonary complications (odds ratio: 5.674, 95% CI: 1.206–26.684, p = 0.028). Conclusions: The preoperative 6MWT distance is a useful predictor of postoperative pulmonary complications in patients undergoing VATS lobectomy for lung cancer. Patients with a 6MWT ≤ 450 m may be at higher risk for complications such as pneumonia, atelectasis, and lung fistula. Incorporating preoperative 6MWT as a risk stratification tool could help guide clinical decisions and rehabilitation efforts to improve postoperative outcomes in this patient population.

Advances in Respiratory Medicine doi: 10.3390/arm93060051

Authors: Crizaldy Tugade Jopeth Ramis

Human airways maintain homeostasis through intricate cellular interactomes combining secretome-mediated signalling and mechanotransduction feedback loops. This review presents the first unified map of bidirectional mechanobiology–secretome interactions between airway epithelial cells (AECs), smooth muscle cells (ASMCs), and chondrocytes. We unify a novel three-component regulatory architecture: epithelium functioning as environmental activators, smooth muscle as mechanical actuators, and cartilage as calcium-dependent regulators. Critical mechanotransduction pathways, particularly YAP/TAZ signalling and TRPV4 channels, directly couple matrix stiffness to cytokine release, creating a closed-loop feedback system. During development, ASM-driven FGF-10 signalling and peristaltic contractions orchestrate cartilage formation and epithelial differentiation through mechanically guided morphogenesis. In disease states, these homeostatic circuits become pathologically dysregulated; asthma and COPD exhibit feed-forward stiffness traps where increased matrix rigidity triggers YAP/TAZ-mediated hypercontractility, perpetuating further remodelling. Aberrant mechanotransduction drives smooth muscle hyperplasia, cartilage degradation, and epithelial dysfunction through sustained inflammatory cascades. This system-level understanding of airway cellular networks provides mechanistic frameworks for targeted therapeutic interventions and tissue engineering strategies that incorporate essential mechanobiological signalling requirements.

Advances in Respiratory Medicine doi: 10.3390/arm93060050

Authors: Joana Lourenço Sofia Castro David Barros Coelho André Terras Alexandre Natália Melo Patrícia Caetano Mota Hélder Novais Bastos André Carvalho António Morais

Background: Some hypersensitivity pneumonitis (HP) patients exhibit autoimmune features (HPAF). This study compared outcomes of HPAF and HP without autoimmune features, focusing on progressive pulmonary fibrosis (PPF) and response to immunosuppression. Methods: A retrospective cohort study included HP patients from a single center. HPAF was defined as HP overlapping with autoimmune disease or presenting autoimmune markers/symptoms not fulfilling connective tissue disease criteria. A control HP group without autoimmune features was randomly selected. Demographics, autoimmune profiles, and outcomes over two years were analyzed. Results: 103 patients were included (52 HPAF; 51 HP). In HPAF, the most common autoimmune diseases were rheumatoid arthritis (9.6%), while 57.7% had isolated autoimmune serology. Groups showed no baseline differences in demographics, exposures, smoking, or lung function. Fibrotic disease on high-resolution CT at diagnosis was less frequent in HPAF (71.2% vs. 88.2%; p = 0.031). At two-year follow-up, survival, transplantation, and PPF prevalence were similar. HPAF patients received immunosuppression less often (69.2% vs. 86.3%; p = 0.038). Among patients under immunosuppression, PPF was significantly lower in HPAF group (8.6% vs. 29.5%; p = 0.021). Conclusions: Within two years post-diagnosis, HPAF and HP had comparable overall outcomes. However, under immunosuppression, HPAF patients had significantly lower odds of developing PPF (adjusted OR 0.08; 95% CI 0.008–0.816; p = 0.033) compared to HP patients, suggesting a more favorable treatment response.

Advances in Respiratory Medicine doi: 10.3390/arm93060049

Authors: Rami Salim Najjar Jaishree Jagirdar Andrew T. Gewirtz

Background: Essential hypertension is associated with an increased risk of pulmonary hypertension (PH). PH is diagnosed more frequently in females. Little is known about the effects of a plant-based diet (PBD) in improving lung abnormalities in PH. Methods: We compared 28- and 40-week-old female normotensive Wistar Kyoto and spontaneously hypertensive rats (SHR), maintained from the age of 4 weeks on a control refined diet or a PBD, comprising 28% fruits, vegetables, nuts and legumes. A subset of control SHRs were switched to the PBD at 28 weeks of age. Lungs were taken for protein and histological analysis. Results: Relative to WKYs, SHRs consuming the control diet exhibited decreased lung endothelial nitric oxide synthase (eNOS). PBD consumption by SHRs prevented and reversed this phenotype. Expression of E-cadherin was also reduced in SHRs. This reduction was attenuated by PBD consumption treatment. The phosphorylation of extracellular signal-regulated kinase (ERK)1/2 in the lung was increased in SHRs and attenuated by PBD. The expression of activated transforming growth factor (TGF)-β1 was also attenuated by a PBD. Conclusions: The PBD favorably mediated hypertension-induced pulmonary molecular abnormalities in lung endothelium, epithelial junction and pro-fibrotic signaling. Future studies should assess the effects of a PBD in improving PH and lung function.

Advances in Respiratory Medicine doi: 10.3390/arm93060048

Authors: Brian Foster Sikandar Khan Ana Suarez Gonzalez Samantha Gillenwater

Pulmonary veno-occlusive disease (PVOD) is a rare and under-recognized cause of pulmonary hypertension. It is characterized by fibrotic obstruction of small pulmonary veins and venules. Its clinical presentation closely mimics pulmonary arterial hypertension (PAH), leading to frequent misdiagnosis, delayed recognition, and potentially harmful exposure to PAH-specific vasodilator therapy. This review aims to synthesize our evolving understanding of PVOD, discussing its etiologies, role of genetic underpinnings, histopathologic features, pathophysiology, clinical presentation, and characteristic imaging findings. It then discusses management strategies emphasizing early recognition, supportive care, avoidance of inappropriate PAH therapies due to poor response, and timely referral for lung transplantation. Despite advances in identification and management, PVOD remains a fatal condition with a median survival of less than two years, underscoring the importance of early recognition and multidisciplinary care.

Advances in Respiratory Medicine doi: 10.3390/arm93050047

Authors: Samiksha Jain Avneet Kaur Abdul Qadeer Victor Ghosh Shivani Thota Mallareddy Banala Jieun Lee Gayathri Yerrapragada Poonguzhali Elangovan Mohammed Naveed Shariff Thangeswaran Natarajan Jayarajasekaran Janarthanan Jayavinamika Jayapradhaban Kala Samuel Richard Saai Poornima Vommi Shiva Sankari Karuppiah Anjani Muthyala Vivek N. Iyer Scott A. Helgeson Dipankar Mitra Shivaram P. Arunachalam

Systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) is a life-threatening vascular complication of SSc, marked by high morbidity and mortality. Early diagnosis remains a major challenge due to nonspecific symptoms and the limitations of conventional tools such as echocardiography (ECHO), pulmonary function tests (PFTs), and serum biomarkers. This review evaluates the emerging role of artificial intelligence (AI), particularly machine learning (ML) and deep learning (DL), in improving the diagnostic landscape of SSc-PAH. A comprehensive literature search was conducted across PubMed, Scopus, IEEE Xplore, Embase and Google Scholar to identify studies involving AI applications in SSc, pulmonary arterial hypertension (PAH), and their intersection. Evidence indicates that AI models can assist interpretation across modalities, including heart sounds, ECGs, chest X-rays (CXRs), ECHOs, CT pulmonary angiography (CTPA), and omics-based biomarkers. While several models show encouraging diagnostic performance, their accuracy varies by dataset and modality, and most require external validation against right heart catheterization (RHC)-confirmed cohorts. Integrating multimodal data through AI frameworks may enhance early recognition and individualized risk stratification; however, these tools remain exploratory. Future work should emphasize harmonized hemodynamic definitions, transparent validation protocols, and SSc-specific datasets to ensure clinical applicability and reproducibility.

Advances in Respiratory Medicine doi: 10.3390/arm93050046

Authors: Wojciech Kuczyński Aleksandra Kudrycka Karol Pierzchała Izabela Grabska-Kobyłecka Michael Pencina Sebastian Sakowski Piotr Białasiewicz

Obstructive sleep apnea (OSA) is associated with increased risks of systemic comorbidities, leading to significant morbidity and mortality. This study investigates predictors of all-cause mortality, emphasizing the interplay of clinical symptoms, polysomnographic findings, and comorbidities. The aim of this study was to identify and compare respiratory predictors of all-cause mortality over 5, 10, and 15 years. A single-center study was conducted at a Sleep Medicine Department between 2005 and 2019, 4025 patients with suspected OSA who underwent polysomnography were admitted, 853 died during the study. We performed Cox regression analyses with dynamic hazard ratios to evaluated predictors of mortality. Prevalence of OSA was high—75.6% in the cohort: 929 patients with mild OSA (23.1%), 770 with moderate OSA (19.1%), and 1343 with severe OSA (33.4%). Survival rates were 89.7%, 81.9%, and 78.8% at 5, 10, and 15 years, respectively. Cardiovascular causes dominated mortality (33.3%), followed by cancer (26.5%). AHIREM was associated with higher mortality risk in 0–5, 0–10, 0–15 years of observation in contrast to AHINREM and AHITST. The hazard ratio analysis showed that mortality risk changed over time depending on sleep stage and event type: risk increased for AHIREM and AHITST, while it stayed the same or decreased for AHINREM and most central apneas.

Advances in Respiratory Medicine doi: 10.3390/arm93050045

Authors: Gabriel Román-Ríos Gabriel Rosario-Ortiz Marcos J. Ramos-Benitez Ricardo A. Mosquera Wilfredo De Jesús-Rojas

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Advances in Respiratory Medicine doi: 10.3390/arm93050044

Authors: Dekel Shlomi Bernice Oberman Yehonatan Halevy Shiri Kushnir Hadas Meir Yael Reichenberg

Background: The core management of most individuals with asthma and COPD is daily treatment with inhalers such as inhaled corticosteroids (ICS) and long-acting bronchodilators. The two main types of inhalers used are pressurized metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs). Different studies have shown low adherence to inhaler treatments among subjects with asthma and COPD. In this study, we explored the differences in adherence between pMDIs and DPIs of combined ICS and long-acting β2-agonist inhalers (ICS + LABA) in a large cohort, free from commercial biases. Methods: In this historical prospective study, we included all adult subjects with asthma and/or COPD who acquired at least one ICS + LABA inhaler between 2016 and 2019. We carried out propensity score matching and then compared the maximal number of pMDIs and DPIs purchased in any continuous 12 months during the study period. We also compared once-a-day DPIs with twice-a-day DPIs. Results: Of the 36,998 matched subjects, 5897 (15.9%) purchased pMDIs. The overall median [IQR] inhalers purchased for pMDIs and DPIs were 1 [1, 4] and 3 [1, 8], respectively; for subjects with asthma, 1 [1, 3] and 2 [1, 6]; for subjects with COPD, 1 [1, 3] and 3 [1, 10]; and for subjects with asthma–COPD overlap, 2 [1, 7] and 6 [2, 12]. For all the comparisons, p < 0.001. The once-a-day DPI group had a slight but significantly better adherence than the twice-a-day DPI group. Conclusions: For ICS + LABA therapy, the number of DPIs purchased was significantly greater than the number of pMDIs purchased, as well as the once-a-day DPI relative to the other DPIs. Overall, subjects with asthma and/or COPD had low adherence to all inhalers, with the highest adherence observed among subjects with asthma–COPD overlap.

Advances in Respiratory Medicine doi: 10.3390/arm93050043

Authors: Ovidiu Cristian Chiriac Corina Sporea Daniela Miricescu Ana Raluca Mitrea Ileana Adela Vacaroiu Raluca Grigore Adriana Sarah Nica

COVID-19 signs and symptoms varied among patients, with the most common being fever, fatigue, sore throat, cough, anorexia, and shortness of breath. (1) Background: This study aimed to assess effort, dyspnea, and cooperation scores in patients with mild and moderate post-COVID-19 forms, both at baseline and after completing a structured physical recovery program. (2) Methods: Our study included 160 post-COVID-19 patients who had experienced mild or moderate disease. (3) Results: Effort and dyspnea scores were significantly lower (p < 0.01), while cooperation scores were significantly higher after the rehabilitation program. Both men and women demonstrated significant increases in cooperation scores after recovery. Additionally, both groups showed statistically significant reductions in effort and dyspnea scores (p < 0.001). Among patients aged under and over 60 years, effort and dyspnea scores decreased after rehabilitation, and cooperation scores increased significantly (p < 0.001). No statistically significant differences were observed between genders in any of the three scores. Similarly, no significant differences by age were found in cooperation or dyspnea scores. A significant negative correlation was observed between cooperation and effort scores: patients with higher cooperation scores tended to report lower effort scores, and vice versa (p < 0.001, R = −0.571). (4) Conclusions: The improved cooperation demonstrated by patients during the physical recovery program was significantly associated with reductions in perceived effort and dyspnea, indicating a positive impact on post-COVID-19 rehabilitation outcomes.

Advances in Respiratory Medicine doi: 10.3390/arm93050042

Authors: Mihrican Yeşildağ Taha Tahir Bekçi

Background and Objectives: Hematological parameters are increasingly being investigated as readily accessible biomarkers for the diagnosis of obstructive sleep apnea syndrome (OSAS). In our study, we aimed to investigate the relationship between OSAS and albumin indices and the uric acid-to-HDL ratio (UHR). Methods: The demographic and laboratory data and AHI (apnea–hypopnea index) values of 613 patients who underwent polysomnography were obtained retrospectively from their files. Blood parameters such as white blood cells (WBCs), red blood cell distribution width (RDW), red blood cells (RBCs), hemoglobin (Hb), hematocrit (Hct), platelets (PLTs), C-reactive protein (CRP), albumin, blood urea nitrogen (BUN), and high-density lipoproteins (HDLs) were obtained from the files. Laboratory indices such as the BUN-to-albumin ratio (BAR), neutrophil-to-albumin ratio (NAR), RDW-to-albumin ratio (RAR), CRP-to-albumin ratio (CAR), and UHR were calculated. OSAS was categorized as simple snoring (SS) (control) (AHI < 5), mild (5 ≤ AHI < 15), moderate (15 ≤ AHI < 30), and severe (AHI ≥ 30). The patients were also grouped as severe (AHI ≥ 30) and non-severe (5 > AHI < 30) OSAS and compared in terms of laboratory parameters and indices. Results: Of the 613 participants, 366 (59.7%) were men, and the average age of participants was 55.22 ± 11.13 years. The biomarkers such as RBCs, Hb, Htc, CRP, BUN, creatinine, uric acid, HDLs, CAR, RAR, BAR, and UHR showed significant differences between OSAS patients and controls. WBCs, basophils, RBCs, RDW, Htc, PLTs, HDLs, uric acid, RAR, NAR, and UHR indices were significantly different between the severe OSAS and non-severe OSAS groups (p < 0.05). BAR (OR = 1.151; CI = 1.056 − 1.256; p = 0.001) and UHR (OR = 2.257; 95% CI = 1.507 − 3.382; p < 0.001) were the most important indices predicting OSAS, while RAR (OR = 1.844; CI = 1.224 − 2.778; p = 0.003) and UHR (OR = 2.203; 95% CI = 1.496 − 3.243; p < 0.001) were the strongest indices associated with severe OSAS. Conclusion: In our study, RAR, BAR, and UHR indices were closely associated with the presence and severity of OSAS. These indices can be considered low-cost, readily available methods for predicting OSAS patients.

Advances in Respiratory Medicine doi: 10.3390/arm93050041

Authors: Garrett Fiscus Chebly Dagher David O’Sullivan Brett Carollo Kristen Swanson Harrison W. Farber Raj Parikh

Background: Pulmonary hypertension (PH) is a frequent complication in patients with interstitial lung disease (ILD); its occurrence results in significant morbidity and mortality. Currently approved treatment options for PH-ILD include inhaled prostacyclin therapy, although this approach may be insufficient in patients who have developed simultaneous right ventricular failure. Moreover, there is no available treatment algorithm regarding the optimal therapy and timing of lung transplant referral for PH-ILD patients based on disease severity. Design/Methods: In this study, we created such a tool to guide PH-specific therapy in PH-ILD patients, especially as further treatment strategies are developed. We developed a 4-point PH-ILD Severity score that integrated both subjective and objective information (WHO FC, CI, TAPSE, PVR) from retrospective analysis of 57 PH-ILD patients. Results: A score of 3 or greater in the PH-ILD Severity score yielded an AUC of 0.831 (p < 0.001) for the composite endpoint of clinical worsening (hospitalization due to a cardiopulmonary indication; decrease in 6 min walk distance by >15% at 2 consecutive visits; all-cause mortality; lung transplantation). Conclusions: Further confirmation and evolution of this PH-ILD Severity score will assist in the development of optimal treatment plans in ILD patients diagnosed with concomitant PH.

Advances in Respiratory Medicine doi: 10.3390/arm93050040

Authors: Antonio Maiorano Anna Ferrante Bannera Chiara Lupia Daniela Pastore Emanuela Chiarella Giovanna Lucia Piazzetta Angelantonio Maglio Alessandro Vatrella Girolamo Pelaia Corrado Pelaia

Background: Uncontrolled asthma remains a significant clinical challenge, often linked to impaired lung function and increased diaphragmatic workload. Recent studies have shown promising results using a triple inhaled therapy comprising beclomethasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G). This study assessed the real-world efficacy of BDP/FF/G on lung function and diaphragmatic workload in patients with uncontrolled asthma. Methods: A prospective observational study enrolled 21 adult patients diagnosed with uncontrolled asthma despite high-dose ICS/LABA therapy. Patients underwent lung function tests and right diaphragmatic ultrasound assessments at baseline and after three months of treatment with BDP/FF/G (172/5/9 mcg, administered as two inhalations every 12 h). Results: After three months, significant improvements were observed in FEV1 (from 57.75 ± 12.30% to 75.10 ± 18.94%, p < 0.001) and FEF25–75 (from 47.80 ± 19.23% to 75.10 ± 36.06%, p < 0.001). Additionally, during the same period, we recorded significant reductions in residual volume (from 130.10 ± 28.20% to 92.55 ± 21.18%, p < 0.001) and total airway resistance (Rtot) (from 164.60 ± 83.21% to 140.70 ± 83.25%, p < 0.05). The mean asthma control test (ACT) score increased by 5.6 points (p < 0.001), surpassing the established minimal clinically important difference (MCID) of 3 points and raising the cohort mean above the well-controlled threshold. The right diaphragmatic workload was significantly decreased, as shown by a reduction in thickening fraction (TF) (from 63.86 ± 17.67% to 40.29 ± 16.65%, p < 0.01). Correlation analysis indicated significant associations between diaphragmatic function and some lung function parameters (FEV1, FEF25–75, and Rtot). Conclusions: In this real-world pilot, triple BDP/FF/G was linked to improvements in airflow, hyperinflation, symptoms, and a reduction in diaphragmatic thickening fraction, indicating potential physiological benefit. Due to the small sample size, single-centre design, and 3-month follow-up, these results should be viewed as hypothesis-generating and need to be confirmed in larger, controlled, multicentre studies with longer follow-up.

Advances in Respiratory Medicine doi: 10.3390/arm93050039

Authors: Anass Benfares Badreddine Alami Sara Boukansa Mamoun Qjidaa Ikram Benomar Mounia Serraj Ahmed Lakhssassi Mohammed Ouazzani Jamil Mustapha Maaroufi Hassan Qjidaa

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Accurate determination of epidermal growth factor receptor (EGFR) mutation status is essential for selecting patients eligible for tyrosine kinase inhibitors (TKIs). However, invasive genotyping is often limited by tissue accessibility and sample quality. This study presents a non-invasive machine learning model combining clinical data, CT morphological features, and radiomic descriptors to predict EGFR mutation status. A retrospective cohort of 138 patients with confirmed EGFR status and pre-treatment CT scans was analyzed. Radiomic features were extracted with PyRadiomics, and feature selection applied mutual information, Spearman correlation, and wrapper-based methods. Five Random Forest models were trained with different feature sets. The best-performing model, based on 11 selected variables, achieved an AUC of 0.91 (95% CI: 0.81–1.00) under stratified five-fold cross-validation, with an accuracy of 0.88 ± 0.03. Subgroup analysis showed that EGFR-WT had a performance of precision 0.93 ± 0.04, recall 0.92 ± 0.03, F1-score 0.91 ± 0.02, and EGFR-Mutant had a performance of precision 0.76 ± 0.05, recall 0.71 ± 0.05, F1-score 0.68 ± 0.04. SHapley Additive exPlanations (SHAP) analysis identified tobacco use, enhancement pattern, and gray-level-zone entropy as key predictors. Decision curve analysis confirmed clinical utility, supporting its role as a non-invasive tool for EGFR-screening.

Advances in Respiratory Medicine doi: 10.3390/arm93050038

Authors: Valmir N. Rastely-Junior Hosanea S. N. Rocha Mitermayer G. Reis

Respiratory infections and chronic lung disease are major contributors to morbidity in children. Aztreonam lysine for inhalation (AZLI) delivers high local antibiotic concentrations while limiting systemic exposure; however, its safety in younger patients remains uncertain. This systematic review and meta-analysis searched MEDLINE, CENTRAL, and Google Scholar for randomized and observational studies reporting adverse events in children and adolescents (≤18 years) receiving AZLI, with no date limit. Fourteen studies were included. Most studies were moderate-to-high quality. Comparative analysis showed no clinically relevant increase in common adverse events relative to placebo or other inhaled antibiotics. The pooled relative risk for severe respiratory disorders (grade 3/4) was 1.65 (95% CI 1.07–2.57), suggesting a higher incidence of serious respiratory events, while a protective effect against decline in pulmonary function was observed (RR 0.70, 95% CI 0.54–0.90). Adverse events were generally mild; serious adverse events and hospitalizations were infrequent and comparable between groups. Cumulative prevalence estimates indicated that respiratory irritation occurred in 10–25% of patients, whereas systemic effects were uncommon. Overall, AZLI appears to have an acceptable tolerability and safety profile in children and adolescents, though careful monitoring is warranted, especially for severe respiratory events.

Advances in Respiratory Medicine doi: 10.3390/arm93050037

Authors: Vitaliano Nicola Quaranta Andrea Portacci Leonardo Maselli Marta Tornesello Maria Granito Gennaro Rociola Silvano Dragonieri Giovanna Elisiana Carpagnano

Background: Several studies focused on the importance of managing small airways disease in the treatment of severe asthma, whose improvement can improve respiratory symptoms, lung function, and airways inflammation, potentially reaching the objective of clinical remission. Methods: Twenty-five patients with severe asthma and without bronchiectasis were enrolled. They were started on biological therapies with Omalizumab, Dupilumab, Benralizumab or Mepolizumab. Follow-up evaluations were conducted at baseline (T0) and after one year of biological therapy (T1). Assessments included clinical evaluations, spirometry, questionnaires, and inflammatory markers. Results: Predictive analysis identified baseline FeNO 350 mL/s levels as a significant predictor of clinical remission in both univariable and multivariable analysis. Higher FeNO 350 mL/s levels at T0 were associated with an increased likelihood of achieving remission (p = 0.012). The optimal cutoff value for FeNO 350 mL/s was determined to be 18 ppb, based on the Younden Index. Conclusions: Following patients with severe asthma on biological therapy for one year, FeNO 350 mL/s could be used as a predictive factor of clinical remission, highlighting its importance as inflammatory marker not only in small airways disease, but also in predicting clinical remission in severe asthmatic patients.

Advances in Respiratory Medicine doi: 10.3390/arm93050036

Authors: Nicolas Raoul Lucie Laurent Ophélie Ritter Pauline Roux-Claudé Faraj Al Freijat Nadine Magy-Bertrand Virginie Westeel Cindy Barnig

Airway involvement in eosinophilic disorders other than asthma is not well-defined, and the symptoms may be overshadowed by other more prominent eosinophilic extra-respiratory manifestations. This study aimed to evaluate the utility of fractional exhaled nitric oxide (FeNO) in diagnosing eosinophilic airway involvement in patients with persistent eosinophilia (>0.5 × 109/L). We conducted a retrospective analysis of adult patients with confirmed peripheral blood eosinophilia (>0.5 × 109/L) on at least two occasions one month apart. Patients with blood eosinophilia associated with known eosinophilic airway inflammatory diseases were excluded from the study. Pulmonary function testing, spirometry, and FeNO measurement were conducted. A total of 14 patients with various eosinophil-related disorders were identified, with a mean age of 65.7 years. Increased FeNO levels were associated with airflow obstruction and clinical symptoms such as coughing and wheezing. Notably, eosinophil levels were not predictive of eosinophilic airway involvement. FeNO could be a useful diagnostic tool for detecting bronchial eosinophilic airway inflammation in non-asthmatic disorders, thereby enabling appropriate treatment. Further studies with larger cohorts are needed to validate these findings.

Advances in Respiratory Medicine doi: 10.3390/arm93050035

Authors: Anna Ziętarska Adam Dobek Anna Sawina Piotr Białek Sebastian Majewski Ludomir Stefańczyk

Haemoptysis is an alarming symptom of a wide spectrum of underlying diseases, ranging from indolent chronic conditions to life-threatening states. Among the strategies to manage pulmonary bleeding is bronchial artery embolisation (BAE), an interventional radiology procedure. The objective of this scoping review was to map the current evidence on embolic agents used in BAE for haemoptysis management, with a focus on their clinical applications, and decision-making factors. Studies published between 2019 and 2024 were included if they specified the embolic material used and reported outcomes of BAE in adult patients. Data were extracted from PubMed and charted according to embolic agent type, recurrence rate, and clinical context. Thirty-one studies met the eligibility criteria. Polyvinyl alcohol (PVA) remains the most widely studied agent, comparable in efficacy to more homogeneous microspheres. Gelatin sponges (GS), though biodegradable, are well-documented and affordable, making them a common choice. N-butyl-2-cyanoacrylate (NBCA) is highly effective for small vessels and may offer lower recurrence rates. Coils are valuable in proximal embolisation and severe cases. This review highlights the need for individualised embolisation strategies and updated guidelines for material selection, considering clinical context, vascular anatomy, and recurrence rates. The findings aim to support evidence-based decision-making in interventional radiology practice.

Advances in Respiratory Medicine doi: 10.3390/arm93050034

Authors: Yongchao Li Lei Cai Jia Huang Hongbin Gao Zhongqiang Huang Yalun Guan Yunfeng Li Shuhua Liu Shi Liang Summer Xiatian Li Hongzhou Lu Ge Li Yijiang Li Yu Zhang

Since extracorporeal membrane oxygenation (ECMO) is primarily used for patients in a high-risk state and is an invasive procedure, its unique application scenarios make it difficult to recruit suitable cases for clinical trials. Therefore, large animal models have become one of the most important models for preclinical evaluation of the safety and effectiveness of ECMO. This study aims to assess the safety and performance of a novel portable ECMO device with Small-tail Han sheep. Fifteen sheep were divided into a test group (LIFEMOTION, Chinabridge, Shenzhen, China) and control group (NOVALUNG XLUNG kit 230, Xonis, Heilbronn, Germany) with veno-venous ECMO (VV-ECMO) and veno-arterial ECMO (VA-ECMO) modes. Tracheal intubation, arteriovenous access, and ECMO support were performed. Vital signs and blood laboratory tests of the subjects were monitored and recorded. The main organs were examined pathologically at the end of day fourteen. The serum protein expression profile was analyzed by protein quantification techniques. All sheep were successfully weaned from ECMO without transfusion or cannula complications. No significant differences were observed between the two groups in terms of vital signs, oxygenation, hemodynamic stability, and physiological function (p > 0.05). According to the serum protein expression profile, no significant biomarkers associated with ECMO clinical complications were identified. The LIFEMOTION ECMO device demonstrated good safety and efficacy.

Advances in Respiratory Medicine doi: 10.3390/arm93050033

Authors: Patchareeya Amput Weerasak Tapanya Sirima Wongphon Krittin Naravejsakul Thanakorn Sritiyot

Background: This study aims to determine test–retest reliability and to calculate minimal detectable change (MDC) scores for the functional capacity of the 6-minute step test (6MST) and 1 min sit-to-stand test (1-min-STST), and compare these outcomes with the 6-minute walk test (6MWT) in post-COVID-19 patients. Methods: A total of 42 post-COVID-19 patients aged 18 years or older were recruited for this study. The post-COVID-19 patients were investigated for cardiovascular response parameters induced by a 6MWT, 6MST, and 1-min-STST on two different days, with a five-day interval between the first and second days. Results: The test–retest reliability obtained between the initial measurement and the measurement recorded five days later in the post-COVID-19 patients was excellent for all three of the 6MWT, 6MST, and 1-min-STST. The ICC of the 6MWT was 0.97 with MDC95 at 5.57%. The ICC of the 6MST was 0.93 with MDC95 at 12.21%, while, the ICC of the 1-min-STST was 0.96 with MDC95 at 3.61%. Conclusions: The 6MST and 1-min-STST were valid and acceptable for the evaluation of functional capacity in post- COVID-19 patients and can be used to investigate whether each post-COVID-19 patient had made significant improvement in a clinical setting.

Advances in Respiratory Medicine doi: 10.3390/arm93050032

Authors: Ihsan Topaloglu Gulfem Ozduygu Cagri Atasoy Guntug Batıhan Damla Serce Gulsah Inanc Mutlu Onur Güçsav Arif Metehan Yıldız Turker Tuncer Sengul Dogan Prabal Datta Barua

Introduction: Asthma is a chronic airway inflammatory disease characterized by variable airflow limitation and intermittent symptoms. In well-controlled asthma, auscultation and spirometry often appear normal, making diagnosis challenging. Moreover, bronchial provocation tests carry a risk of inducing acute bronchoconstriction. This study aimed to develop a non-invasive, objective, and reproducible diagnostic method using machine learning-based lung sound analysis for the early detection of asthma, even during stable periods. Methods: We designed a machine learning algorithm to classify controlled asthma patients and healthy individuals using respiratory sounds recorded with a digital stethoscope. We enrolled 120 participants (60 asthmatic, 60 healthy). Controlled asthma was defined according to Global Initiative for Asthma (GINA) criteria and was supported by normal spirometry, no pathological auscultation findings, and no exacerbations in the past three months. A total of 3600 respiratory sound segments (each 3 s long) were obtained by dividing 90 s recordings from 120 participants (60 asthmatic, 60 healthy) into non-overlapping clips. The samples were analyzed using Mel-Frequency Cepstral Coefficients (MFCCs) and Tunable Q-Factor Wavelet Transform (TQWT). Significant features selected with ReliefF were used to train Quadratic Support Vector Machine (SVM) and Narrow Neural Network (NNN) models. Results: In 120 participants, pulmonary function test (PFT) results in the asthma group showed lower FEV1 (86.9 ± 5.7%) and FEV1/FVC ratios (86.1 ± 8.8%) compared to controls, but remained within normal ranges. Quadratic SVM achieved 99.86% accuracy, correctly classifying 99.44% of controls and 99.89% of asthma cases. Narrow Neural Network achieved 99.63% accuracy. Sensitivity, specificity, and F1-scores exceeded 99%. Conclusion: This machine learning-based algorithm provides accurate asthma diagnosis, even in patients with normal spirometry and clinical findings, offering a non-invasive and efficient diagnostic tool.

Advances in Respiratory Medicine doi: 10.3390/arm93040031

Authors: Bartłomiej Czyżak Sebastian Majewski

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease (ILD) with poor prognosis and limited therapeutic options. The introduction of antifibrotic agents has improved survival outcomes in IPF patients, which has led to more frequent recognition of comorbidities, particularly lung cancer (LC). This review summarizes current evidence on the epidemiology and pathogenesis of LC in the context of IPF, with particular emphasis placed on shared molecular, cellular, genetic, and epigenetic alterations. Diagnostic approaches and available treatment modalities, including surgical, systemic, and radiation therapies, are outlined, and their limitations in patients with IPF-LC are discussed. Acute exacerbations (AEs), as a life-threatening complication influencing diagnostic and treatment strategies, are specifically addressed. Moreover, studies indicating a possible protective effect of antifibrotic agents against LC development in IPF are reviewed. Further research is warranted into the shared mechanisms of IPF and LC to identify novel therapeutic targets. Establishing standardized, multidisciplinary clinical guidelines is essential for optimizing patient management, reducing AE risk, and improving patient outcomes.

Advances in Respiratory Medicine doi: 10.3390/arm93040030

Authors: Alexandr E. Gulyayev Karlygash S. Absattarova Sayagul A. Kairgeldina Raushan S. Dosmagambetova Kanat K. Tekebayev Madina B. Baurzhan Nazym Sagandykova Gaukhar Sh. Dauletova

Background: Occupational bronchopulmonary diseases (OBPDs)—including pneumoconiosis, silicosis, and occupational COPD—remain a pressing public health issue, especially in regions with intensive mining, metallurgy, and construction industries. Caused by chronic inhalation of fibrogenic dusts, these conditions are often diagnosed at late stages, resulting in irreversible lung damage and diminished work capacity. Methods: A scoping review was performed using the Arksey and O’Malley framework, with methodological refinements from the Joanna Briggs Institute. Following PRISMA-ScR guidelines, we searched PubMed, Scopus, and gray literature for publications from 2014 to 2024. After screening 1761 records and full-text review, nine studies were included in the final synthesis, comprising two systematic reviews, two narrative literature reviews, and five observational studies. Results: Key risk factors identified included prolonged exposure to silica and coal dust, tobacco use, and genetic susceptibility. Diagnostic delays were attributed to the underuse of high-resolution CT and exhaled nitric oxide analysis. Several studies highlighted the diagnostic value of oxidative stress and inflammatory markers (e.g., IL-6, TNF-α). Nutritional rehabilitation and polyphenol-enriched herbal therapies were associated with improved respiratory function and quality of life. However, these strategies remain underutilized, particularly in low-resource settings. Conclusions: A coordinated, biomarker-driven approach integrating early diagnosis, dust exposure control, and tailored rehabilitation is urgently needed. Multidisciplinary models may reduce the clinical and socioeconomic burden of OBPDs.

Advances in Respiratory Medicine doi: 10.3390/arm93040029

Authors: Majed Odeh Yana Kogan Edmond Sabo

Background and Objectives: Discrimination between various causes of exudative pleural effusion (PE) remains a major clinical challenge, and to date, definitive biochemical markers for this discrimination remain lacking. An increasing number of studies have reported that serum C-reactive protein (CRPs), pleural fluid CRP (CRPpf), and CRPpf/CRPs ratio (CRPr) are useful for the differential diagnosis of exudative PE; however, their efficacy rate is not similar in these studies. The majority of these studies were conducted on small groups of subjects, and the efficacy of the gradient between CRPs and CRPpf (CRPg—calculated as CRPs—CRPpf) in this differentiation has not been previously investigated. This study aims to evaluate the efficacy rate of CRPs, CRPpf, CRPg, and CRPr in the differential diagnoses of various causes of exudative PE in a relatively large cohort of patients. Materials and Methods: The research group included 282 subjects with exudative PE—146 had parapneumonic effusion (PPE), 126 had malignant pleural effusion (MPE), and 10 had tuberculous pleural effusion (TPE). The values are presented as mean ± SD. Results: The mean CRPs level was significantly higher in the PPE group compared to the MPE group (p < 0.0001) and the TPE group (p < 0.001), and also significantly higher in the TPE group than in the MPE group (p = 0.0009). Similarly, the mean CRPpf level was significantly higher in the PPE group than in the MPE group (p < 0.0001) and the TPE group (p = 0.04), and also significantly higher in the TPE group than in the MPE group (p < 0.0001). The mean CRPg level was significantly higher in the PPE group than in both the MPE group (p < 0.0001) and the TPE group (p < 0.002). The mean CRPr level did not differ significantly among these groups of exudate. Conclusions: CRPs, CRPpf, and CRPg are effective in the differential diagnosis of exudative PE, while CRPr was not effective in this regard. The main limitation of this study is that the sample size of the TPE group is very small.

Advances in Respiratory Medicine doi: 10.3390/arm93040028

Authors: Chidubem Egboluche Rifath Ara Alam Barsha Shervin Assari Michelle Mercure Marc Laveau Oluwatosin Olateju Payam Sheikhattari

Background: School-based tobacco control policies are critical for preventing youth tobacco use. While many districts adopt formal policies to create smoke- and vape-free environments, the degree to which these policies are enforced at the school level may vary, influencing their effectiveness. Little is known about how consistently such policies are implemented across schools within urban school districts. Objectives: This study aimed to examine the existence and enforcement of school-level tobacco control policies in an urban public school system, using Baltimore City schools as a case example. Methods: We conducted a survey of school personnel from 20 high schools in Baltimore City in 2024. The survey instrument assessed the presence and enforcement of policies related to tobacco use prevention, communication, signage, disciplinary actions, and institutional support. Descriptive statistics (frequencies and percentages) were used to summarize responses. Spearman correlations were also used for bivariate correlations. Additional school-level and neighborhood-level contextual data were collected from the internet (neighborhood socioeconomic status and school performance). Results: While many policies existed across the 20 participating schools, their enforcement was widely inconsistent. Most schools reported the existence of policies prohibiting tobacco use in school buildings (60%) and vehicles (55%). However, few schools had visible tobacco-free signage (35%) or offered cessation programs (15%). Communication of policies to students (70%) and staff (65%) was the most commonly enforced aspect of tobacco control policies. Conclusions: Findings suggest that while tobacco control policies may be adopted across urban school systems, their enforcement at the school level remains uneven. Greater attention may be needed to support policy implementation and to reduce variability in school-level practices. Baltimore City serves as a useful case study to understand these challenges and identify opportunities for strengthening school-based tobacco prevention efforts.

Advances in Respiratory Medicine doi: 10.3390/arm93040027

Authors: Gabriel Román-Ríos Gabriel Rosario-Ortiz Marcos J. Ramos-Benitez Ricardo A. Mosquera Wilfredo De Jesús-Rojas

Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous disorder that impairs mucociliary clearance and leads to progressive lung disease. This study aimed to characterize lung function decline in a genetically homogeneous cohort of Puerto Rican patients with RSPH4A-associated PCD and to develop a clinical tool to predict lung function decline and support transplant referral decisions. We conducted a retrospective chart review of patients (n = 25) with a confirmed RSPH4A [c.921+3_6delAAGT] genetic variant, collecting longitudinal spirometry data and applying linear regressions to calculate each patient’s individual FEV1 decline. The median FEV1 at diagnosis was 55%, with a median annual decline of −0.75% predicted. Adults exhibited significantly lower lung function compared to pediatric patients, while no difference was seen between males and females. Based on this observed decline, we developed the Predicted Capacity Decline Index (PCDx), an index that estimates the age and time until a patient reaches the 30% FEV1 threshold, the point at which lung transplant referral is typically considered. Our findings underscore the need for early intervention and suggest that genotype-specific tools like the PCDx may enhance clinical decision-making in managing progressive lung disease in PCD.

Advances in Respiratory Medicine doi: 10.3390/arm93040026

Authors: Emi Yuda Tomoki Ando Yukihiro Ishida Hiroyuki Sakano Yutaka Yoshida

Measurement of nitric oxide (NO) concentration in exhaled breath (FeNO) is a quantitative, non-invasive, simple, and safe method for assessing airway inflammation. It serves as a complementary tool to other methods for evaluating airway diseases. However, little is known about the typical NO levels in healthy individuals, including individual differences and the influence of measurement timing. Therefore, this study classified measurement times into four periods and statistically analyzed NO levels in healthy individuals. The mean values among groups were compared using repeated measures ANOVA on six participants. The analysis showed large individual variations in NO levels, resulting in no significant difference (p = 0.29). Notably, greater fluctuations were observed in the morning. These findings align with previous studies suggesting the influence of circadian rhythms and the redundancy of repeated measurements. This study highlights the need to consider timing and individual variability when using FeNO as a physiological marker in healthy populations.

Advances in Respiratory Medicine doi: 10.3390/arm93040025

Authors: Chalerm Liwsrisakun Chaicharn Pothirat Athavudh Deesomchok Pilaiporn Duangjit Warawut Chaiwong

Background: The role of impulse oscillometry (IOS) in evaluating asthma control remains a challenge because the interpretation varies by many factors, including ethnicity. We aimed to assess the diagnostic contribution of spirometry and IOS, established from reference equations, in the detection of uncontrolled asthma. Methods: This retrospective study was conducted in adult asthma subjects with normal spirometry. Uncontrolled asthma was defined as an Asthma Control Test (ACT) score ≤ 19. Receiver operating characteristic (ROC) curves were plotted to compare the diagnostic abilities of the %-predicted of heterogeneity of resistance at 5 Hz and 20 Hz (R5-R20) and the %-predicted of forced expiratory volume in the first second (FEV1) in detecting uncontrolled asthma. Multivariable risk regressions were performed to identify the %-predicted of R5-R20 as a predictor for uncontrolled asthma. Results: The %-predicted of R5-R20 demonstrated a superior diagnostic ability for detecting uncontrolled asthma compared to the %-predicted FEV1, with the area under the ROC curves (AuROC) = 0.939 vs. 0.712, respectively, p < 0.001. The %-predicted R5R20 of ≥200 showed the highest AuROC for detecting uncontrolled asthma with an adjusted risk ratio of 10.86 (95%CI; 3.77, 31.29; p < 0.001). Conclusions: IOS demonstrated better diagnostic ability for detecting uncontrolled asthma than spirometry.

Advances in Respiratory Medicine doi: 10.3390/arm93040024

Authors: Hugo Mendieta-Zerón Esteban Cruz-Arenas Salvador Díaz-Meza Alejandro Cabrera-Wrooman Edna Ayerim Mandujano-Tinoco Rosa M. Salgado Hugo Tovar Daniel Muñiz-García Laura Julieta Orozco-Castañeda Sonia Hernández-Enríquez Miriam Deyanira Rodríguez-Piña Ana Sarahí Mulia-Soto José Meneses-Calderón Paul Mondragón-Terán Edgar Krötzsch

The therapeutic target of COVID-19 is focused on controlling inflammation and preventing fibrosis. Collagen–polyvinylpyrrolidone (collagen-PVP) and pirfenidone both have the ability to control the cytokine storm observed in rheumatic and fibrotic disorders. In this work, our aim was to understand the benefits of treatment with each of these drugs in patients with severe COVID-19. In total, 36 patients were treated with dexamethasone and enoxaparin, but 26 were allocated collagen-PVP or pirfenidone (n = 15 and 11, respectively); the clinical and metabolic effects were compared among them. Since pirfenidone works via transcriptional mechanisms, we performed a human genome microarray assay using RNA isolated from fibroblast and monocyte cultures treated with the biodrug, with the aim of hypothesising a possible mechanism of action for collagen-PVP. Our results showed that hospital stay duration, quick COVID-19 severity index (qCSI), and admission to the intensive care unit were statistically significantly lower (p < 0.02) in patients treated with collagen-PVP or pirfenidone when compared with the control group, and that only collagen-PVP normalised serum glucose at discharge. Ingenuity Pathway Analysis showed that the cell cycle, inflammation, and cell surface–extracellular matrix interactions could be regulated with collagen-PVP via the downmodulation of proinflammatory cytokines, while Th2 anti-inflammatory response signalling could be upregulated. Furthermore, the downregulation of some of the genes involved in nitric oxide production showed a possible control for JAK in the IFN-γ pathway, allowing for the possibility of controlling inflammation through the JAK/STAT pathway, as has been observed for pirfenidone and other immunomodulators, such as ruxolitinib.

Advances in Respiratory Medicine doi: 10.3390/arm93040023

Authors: Jose Luis Estela-Zape Valeria Sanclemente-Cardoza Maria Alejandra Espinosa-Cifuentes Leidy Tatiana Ordoñez-Mora

The lung microbiota is integral to maintaining microenvironmental homeostasis, influencing immune regulation, host defense against pathogens, and overall respiratory health. The dynamic interplay among the lung microbiota emphasizes their significance in shaping the respiratory milieu and potential impact on diverse pulmonary affections. This investigation aimed to identify the effects of invasive mechanical ventilation on the lung microbiome. Materials and Methods: A systematic review was conducted with registration number CRD42023461618, based on a search of PubMed, SCOPUS, and Web of Science databases, in line with the PRISMA guidelines. To achieve this, “(mechanical ventilation) AND (microbiota)” was used as the search term, replicable across all databases. The closing date of the search was 12 March 2025, and the evidence was scored using the MINORS scale. Results: A total of 16 studies were included, with patients aged 13.6 months to 76 years, predominantly male (64.2%). Common ICU admission diagnoses requiring invasive mechanical ventilation (IMV) included pneumonia, acute respiratory failure, and COVID-19. IMV was associated with reduced lung microbiota diversity and an increased prevalence of pathogenic bacteria, including Prevotella, Streptococcus, Staphylococcus, Pseudomonas, and Acinetobacter. The most frequently used antibiotics were cephalosporins, aminoglycosides, and penicillins. IMV-induced pulmonary dysbiosis correlated with higher infection risk and mortality, particularly in pneumonia and COVID-19 cases. Factors such as antimicrobial therapy, enteral nutrition, and systemic inflammation contributed to these alterations. Conclusions: Invasive mechanical ventilation has been associated with the development of alterations in the respiratory microbiome, resulting in reduced diversity of lung microorganisms.

Advances in Respiratory Medicine doi: 10.3390/arm93040022

Authors: Ewelina Tobiczyk Hanna Maria Winiarska Daria Springer Aleksandra Ludziejewska Ewa Wysocka Szymon Skoczyński Szczepan Cofta

Background: COVID-19 most often affects the respiratory system and may manifest as acute respiratory failure requiring the use of non-invasive respiratory support (NIRS). The aim of this study was to find predictors based on laboratory results and chest computed tomography (CT) scans performed on admission to the hospital indicating the need for NIRS and predicting mortality after hospital discharge. Methods: We retrospectively analysed data from consecutive patients hospitalised in the Pulmonology Department of the Temporary COVID Hospital in Poznan from 1 February 2021 to 31 March 2022. Upon admission to the department, the patients underwent a series of laboratory blood tests and high-resolution chest CT scan. Results: The study group included 282 patients, with an average age of 60.0 ± 15.0 years. In total, 54 (53%) patients of 101 requiring NIRS died from various causes or required intubation. Patients who required NIRS were significantly older and had more severe changes in the lung parenchyma. They had higher white blood cell and neutrophil counts and lower lymphocyte counts, as well as higher concentrations of D-dimer, CRP, PCT, and IL-6 and greater activities of LDH and AST. Conclusions: Laboratory tests and chest CT performed on hospital admission may be useful to rapidly identify patients at higher risk for severe disease.