Advances in Respiratory Medicine

19 pages, 2538 KB

Open AccessArticle

Reticular Basement Membrane Remodelling Regulates Bronchial Epithelial Attachment, Barrier Integrity and Inflammatory Signalling in Asthma

by Aileen Hsieh, Jenna Barker-Mulleder, Chen Xi Yang, May Fouadi and Tillie-Louise Hackett

Adv. Respir. Med. 2026, 94(3), 38; https://doi.org/10.3390/arm94030038 - 10 Jun 2026

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Abstract

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 [...] Read more.

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. Full article

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20 pages, 900 KB

Open AccessReview

Characteristics of Respiratory Microbiome in COPD—A Literature Review

by Iga Ciesielska-Markowska, Katarzyna Mycroft-Rzeszotarska, Piotr Korczyński, Kaja Pulik and Katarzyna Górska

Adv. Respir. Med. 2026, 94(3), 37; https://doi.org/10.3390/arm94030037 - 8 Jun 2026

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Abstract

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 [...] Read more.

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. Full article

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12 pages, 1287 KB

Open AccessArticle

Impact of Highly Effective CFTR Modulator Therapy on Physical Activity, Sleep, and Sinonasal Symptoms in Preschool Children with Cystic Fibrosis: A Prospective Single-Center Pilot Study

by Stella Schellhorn, Hanna Schmidt, Ales Janda, Doris Gülke, Monika Toth, Dorit Fabricius and Sebastian F. N. Bode

Adv. Respir. Med. 2026, 94(3), 36; https://doi.org/10.3390/arm94030036 - 5 Jun 2026

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Abstract

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, [...] Read more.

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. Full article

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16 pages, 4450 KB

Open AccessArticle

Role of Innate Lymphoid Cells in Chronic Rhinosinusitis: Insights from Tissue and Peripheral Blood Flow Cytometric Analysis

by Rina Hoffmann, Franziska Rombach, Jens Grimm, Agmal Scherzad, Stephan Hackenberg and Pascal Ickrath

Adv. Respir. Med. 2026, 94(3), 35; https://doi.org/10.3390/arm94030035 - 3 Jun 2026

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Abstract

(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 [...] Read more.

(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 CD56^dimCD16⁺ and CD56^brightCD16⁻ 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 CD56^dimCD16⁺ 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. Full article

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12 pages, 1490 KB

Open AccessArticle

Epidemiological Analysis of Hospitalized Children with Acute Asthma Exacerbation over 30 Years

by Xuee Zhuang, Mengyuan Liu, Kunhong Lin, Yangxin Xiao, Xuyan Zhao, Zifan Gai and Yan Xing

Adv. Respir. Med. 2026, 94(3), 34; https://doi.org/10.3390/arm94030034 - 29 May 2026

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Abstract

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 [...] Read more.

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. Full article

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15 pages, 1100 KB

Open AccessArticle

Pulmonary Actinomycosis: A Hidden Threat with Clinical Impact

by 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 and Laura V. Klotz

Adv. Respir. Med. 2026, 94(3), 33; https://doi.org/10.3390/arm94030033 - 18 May 2026

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Abstract

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 [...] Read more.

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. Full article

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

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21 pages, 824 KB

Open AccessReview

Psychosocial Interventions for Improving Treatment Adherence in Tuberculosis Patients: A Scoping Review of Evidence-Based Approaches

by Rana Abdullah Bin Qamar, Henrique Pereira and Felipe Alckmin-Carvalho

Adv. Respir. Med. 2026, 94(3), 32; https://doi.org/10.3390/arm94030032 - 15 May 2026

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Abstract

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 [...] Read more.

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. Full article

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9 pages, 388 KB

Open AccessReview

Association Between Air Pollution and Childhood Asthma: A Systematic Review of Recent Evidence

by Maria Kyrmanidou, Ioannis Smaraidos and Asterios Kampouras

Adv. Respir. Med. 2026, 94(3), 31; https://doi.org/10.3390/arm94030031 - 12 May 2026

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Abstract

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 [...] Read more.

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 PM_2.5, 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 PM_2.5, 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 PM_2.5 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. Full article

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15 pages, 2933 KB

Open AccessBrief Report

Antifibrotic Drugs Regulate the Expression of Epithelial Sodium Channels in the Lungs

by 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 and Tetsu Kobayashi

Adv. Respir. Med. 2026, 94(3), 30; https://doi.org/10.3390/arm94030030 - 29 Apr 2026

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Abstract

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 [...] Read more.

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. Full article

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12 pages, 1398 KB

Open AccessArticle

Inflammatory Biomarkers and Outcome Heterogeneity in Anti-MDA5 Antibody-Associated Interstitial Lung Disease: A Single-Center Consecutive Cohort Study

by Akina Nigi, Keisuke Iwamoto, Hidetoshi Itani, Shigeto Kondou, Yuki Okunishi and Takahiro Ohnishi

Adv. Respir. Med. 2026, 94(3), 29; https://doi.org/10.3390/arm94030029 - 28 Apr 2026

Cited by 1 | Viewed by 394

Abstract

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 [...] Read more.

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. Full article

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12 pages, 540 KB

Open AccessArticle

Validation of SpO₂/FiO₂ as a Non-Invasive Surrogate of PaO₂/FiO₂ in Mechanically Ventilated COVID-19 Patients at High Altitude

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

Adv. Respir. Med. 2026, 94(3), 28; https://doi.org/10.3390/arm94030028 - 28 Apr 2026

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Abstract

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 [...] Read more.

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. Full article

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14 pages, 2488 KB

Open AccessArticle

Exploratory Changes in Surfactant Protein D During Intermittent Hypoxia and Modulation by Galectin-3 Inhibition

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

Adv. Respir. Med. 2026, 94(3), 27; https://doi.org/10.3390/arm94030027 - 24 Apr 2026

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Abstract

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 [...] Read more.

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. Full article

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