Advances in Respiratory Medicine

21 pages, 7267 KB

Open AccessArticle

Effects of Inhaled Amitriptyline on Airway Function and Immune Responses in Experimental Asthma

by Anna Michely, Svenja Böll, Lida Yao, Regina Ben Hamza, Irina Rachimow, Klaus Tenbrock, Christian Martin and Eva Verjans

Adv. Respir. Med. 2026, 94(4), 58; https://doi.org/10.3390/arm94040058 - 6 Aug 2026

Abstract

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 [...] Read more.

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 T_H2 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. Full article

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12 pages, 1324 KB

Open AccessArticle

Left Ventricular Diastolic Dysfunction in Patients with Interstitial Lung Disease—A Potential Treatable Trait

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

Adv. Respir. Med. 2026, 94(4), 57; https://doi.org/10.3390/arm94040057 - 4 Aug 2026

Abstract

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 [...] Read more.

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. Full article

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14 pages, 1353 KB

Open AccessArticle

Timothy Grass Pollen-Specific Immunoglobulin E in Nasal Secretions During Natural Allergen Exposure and After a Nasal Provocation Test in Patients with Suspected Local Allergic Rhinitis

by 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 and Marcin Kurowski

Adv. Respir. Med. 2026, 94(4), 56; https://doi.org/10.3390/arm94040056 - 3 Aug 2026

Abstract

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 [...] Read more.

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. Full article

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17 pages, 1179 KB

Open AccessArticle

Who Really Benefits from CPAP? Disease Severity, Response Quality, and Long-Term Survival in Obstructive Sleep Apnea

by Wojciech Kuczyński, Karol Pierzchała, Weronika Bielska, Zuzanna Boczar, Aleksandra Kudrycka and Piotr Białasiewicz

Adv. Respir. Med. 2026, 94(4), 55; https://doi.org/10.3390/arm94040055 - 28 Jul 2026

Abstract

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 [...] Read more.

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. Full article

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21 pages, 6332 KB

Open AccessArticle

Microglia-Mediated Ependymal Injury in Bacille Calmette-Guérin-Induced Meningitis Is Attenuated by Sodium Butyrate with Restoration of Hmgcs2 Expression

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

Adv. Respir. Med. 2026, 94(4), 54; https://doi.org/10.3390/arm94040054 - 27 Jul 2026

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Infectious Diseases in Respiratory Medicine)

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20 pages, 3512 KB

Open AccessReview

Awake Prone Positioning in Non-Intubated Non-COVID-19 ARDS: A Comprehensive Review

by Mairi Ziaka and Aristomenis Exadaktylos

Adv. Respir. Med. 2026, 94(4), 53; https://doi.org/10.3390/arm94040053 - 27 Jul 2026

Cited by 1

Abstract

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 [...] Read more.

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. Full article

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14 pages, 2345 KB

Open AccessArticle

Association Between Physical Function, Pulmonary Function, and Social Determinants of Health in Individuals with Post-Tuberculosis Lung Disease

by 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 and Agnaldo José Lopes

Adv. Respir. Med. 2026, 94(4), 52; https://doi.org/10.3390/arm94040052 - 27 Jul 2026

Abstract

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), [...] Read more.

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. Full article

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9 pages, 822 KB

Open AccessArticle

Interstitial Lung Disease in the United States: CDC Mortality Trends (1999–2024)

by Palak Grover, Rahul Jain, Gurleen Kaur and Bipneet Singh

Adv. Respir. Med. 2026, 94(4), 51; https://doi.org/10.3390/arm94040051 - 24 Jul 2026

Abstract

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 [...] Read more.

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. Full article

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15 pages, 587 KB

Open AccessReview

Nanocarrier-Based Drug Delivery Systems for Lung Cancer: A Systematic Review and Meta-Analysis of Preclinical Studies

by Pranvera Breznica Selmani, Arlinda Daka Grapci, Blerina Koshi, Zana Sllamniku Dalipi and Rozafa Koliqi

Adv. Respir. Med. 2026, 94(4), 50; https://doi.org/10.3390/arm94040050 - 24 Jul 2026

Abstract

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. [...] Read more.

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. Full article

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Graphical abstract

11 pages, 553 KB

Open AccessArticle

Association of ICD-10-Coded Pneumonia Events with Interstitial Lung Disease Outcomes in Patients with Rheumatoid Arthritis: A Large Database Retrospective Cohort

by 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 and Shahrzad Abdollahi

Adv. Respir. Med. 2026, 94(4), 49; https://doi.org/10.3390/arm94040049 - 22 Jul 2026

Abstract

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 [...] Read more.

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. Full article

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13 pages, 831 KB

Open AccessArticle

Artificial Intelligence-Induced Deskilling in Interventional Pulmonology: An International Cross-Sectional Survey on Risk Perception and Mitigation Strategies

by Guido Marchi and Lorenzo Corbetta

Adv. Respir. Med. 2026, 94(4), 48; https://doi.org/10.3390/arm94040048 - 20 Jul 2026

Abstract

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 [...] Read more.

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. Full article

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13 pages, 705 KB

Open AccessArticle

Cystic Fibrosis Mortality Trends 1999–2024—A CDC Wonder Study

by Palak Grover, Rahul Jain, Gurleen Kaur, Niroshan Ranjan and Bipneet Singh

Adv. Respir. Med. 2026, 94(4), 47; https://doi.org/10.3390/arm94040047 - 14 Jul 2026

Abstract

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 [...] Read more.

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. Full article

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14 pages, 1448 KB

Open AccessSystematic Review

Prevalence and Impact of Pulmonary Hypertension Associated with Arteriovenous Fistulas and Grafts in End-Stage Renal Disease: A Systematic Review and Meta-Analysis

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

Adv. Respir. Med. 2026, 94(4), 46; https://doi.org/10.3390/arm94040046 - 6 Jul 2026

Abstract

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 [...] Read more.

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. Full article

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15 pages, 757 KB

Open AccessArticle

Clinical Impact of RSV Vaccination in Hemodialysis Patients: Real-World Evidence on Hospitalization Risk and the Role of Chronic Lung Disease

by Francesca K. Martino, Francesca Fioretti, Lucia Federica Stefanelli, Gianni Carraro, Miriam Capuano, Giuseppe Scaparrotta and Federico Nalesso

Adv. Respir. Med. 2026, 94(4), 45; https://doi.org/10.3390/arm94040045 - 2 Jul 2026

Abstract

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. [...] Read more.

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. Full article

(This article belongs to the Special Issue Infectious Diseases in Respiratory Medicine)

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29 pages, 1208 KB

Open AccessEditor’s ChoiceGuidelines

Guidelines for Minimizing Bleeding Risk During Bronchoscopic Procedures

by 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 and Filip Mejza

Adv. Respir. Med. 2026, 94(4), 44; https://doi.org/10.3390/arm94040044 - 30 Jun 2026

Abstract

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, [...] Read more.

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. Full article

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13 pages, 897 KB

Open AccessOpinion

Utilization Patterns of Nebulized Glycopyrronium in Patients Hospitalized for Acute Exacerbations of Obstructive Airway Disease (AEOAD)—Indian Expert Perspectives

by Arjun Khanna, Pradyut Waghray, Ashok Kr Singh, Jinay Mehta, Rithik, Sagar Bhagat, Saiprasad Patil and Hanmant Barkate

Adv. Respir. Med. 2026, 94(4), 43; https://doi.org/10.3390/arm94040043 - 29 Jun 2026

Abstract

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 [...] Read more.

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. Full article

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24 pages, 3026 KB

Open AccessEditor’s ChoiceReview

Acute Exacerbation of Interstitial Lung Disease: A Case Series and a Narrative Literature Review

by Bartłomiej Czyżak, Adam Lasota and Sebastian Majewski

Adv. Respir. Med. 2026, 94(3), 42; https://doi.org/10.3390/arm94030042 - 22 Jun 2026

Abstract

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 [...] Read more.

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. Full article

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17 pages, 490 KB

Open AccessReview

Advances in Therapeutic Options for Pulmonary and Sleep Disorders in Mucopolysaccharidosis (MPS) Patients: A Narrative Review

by Bimaje Akpa

Adv. Respir. Med. 2026, 94(3), 41; https://doi.org/10.3390/arm94030041 - 22 Jun 2026

Abstract

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 [...] Read more.

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. Full article

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15 pages, 4761 KB

Open AccessArticle

Vertical Displacement Index and Early Treatment-Related Physiological Improvement in Acute Respiratory Failure: An Exploratory Ultrasound-Based Study

by Bedriye Müge Sönmez, İlker Şirin, Gülşen Akçay, Murat Özdemir and Necip Gökhan Güner

Adv. Respir. Med. 2026, 94(3), 40; https://doi.org/10.3390/arm94030040 - 22 Jun 2026

Abstract

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 [...] Read more.

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. Full article

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