Anders Näslund, Melker Ottosson, Marija Karadzovska-Kotevska, Karl Teurneau-Hermansson, Jaroslaw Kosieradzki, Stefan Barath, Hamid Akbarshahi
{"title":"Sensitivity for Malignancy with Navigation Bronchoscopy in Small Lung Nodules.","authors":"Anders Näslund, Melker Ottosson, Marija Karadzovska-Kotevska, Karl Teurneau-Hermansson, Jaroslaw Kosieradzki, Stefan Barath, Hamid Akbarshahi","doi":"10.3390/arm94050067","DOIUrl":"10.3390/arm94050067","url":null,"abstract":"<p><p>Electromagnetic navigation bronchoscopy (ENB) is used for minimally invasive assessment of peripheral pulmonary nodules, but data on lesions ≤10 mm are limited. When ENB is performed for suspected lung cancer, the key clinical question is whether malignancy is detected rather than whether any diagnosis is obtained. For this reason, sensitivity for malignancy was selected over diagnostic yield as the primary outcome. We retrospectively analyzed 541 consecutive ENB procedures performed at Skåne University Hospital during 2018-2019 and followed patients for at least two years to determine final diagnosis. Overall, 323 lesions (59.7%) were malignant and median lesion diameter was 13 mm. Sensitivity for malignancy was 44.0% overall but was markedly lower in lesions ≤10 mm than in larger lesions (23.3% vs. 50.0%, <i>p</i> < 0.001). Larger lesion size and the presence of a bronchus sign were independently associated with higher sensitivity, whereas lower lobe location was associated with reduced sensitivity. In very small nodules, the low probability of obtaining a malignant diagnosis with ENB should be considered when selecting patients and weighing ENB against surveillance, surgery, or alternative diagnostic approaches.</p>","PeriodicalId":7391,"journal":{"name":"Advances in respiratory medicine","volume":"94 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gastroesophageal Reflux Burden Before and After Exercise Challenge in Children with Poorly Controlled Asthma: A 48-Hour MII-pH Study.","authors":"Urszula Jedynak-Wąsowicz, Izabela Jastrzębska, Małgorzata Sładek, Liliana Klim, Ewa Cichocka-Jarosz, Grzegorz Lis","doi":"10.3390/arm94050066","DOIUrl":"10.3390/arm94050066","url":null,"abstract":"<p><p><b>Background</b>: Gastroesophageal reflux and exercise-induced bronchoconstriction (EIB) commonly coexist with asthma, but the effect of exercise on reflux remains unclear. We aimed to assess the prevalence of abnormal impedance-detected acid exposure in children with partially controlled or uncontrolled asthma, its association with EIB, and changes in reflux parameters after an exercise challenge test (ECT). <b>Methods</b>: Thirty patients aged 7-18 years underwent spirometry, treadmill ECT, and 48 h multichannel intraluminal impedance-pH monitoring. EIB was defined as a ≥10% fall in FEV<sub>1</sub>, and abnormal acid exposure as impedance-detected acid reflux lasting ≥1.2% of recording time. <b>Results</b>: Abnormal acid exposure was identified in 14/30 patients (46.7%), whereas EIB occurred in 6/30 (20.0%), with no significant association between them. The absolute number of reflux episodes was higher after ECT in the count-based analysis (43.0 [35.2-69.8] vs. 33.5 [21.2-54.5], <i>p</i> = 0.006); however, this finding was not confirmed after normalization to analyzable recording time in a sensitivity analysis. Overweight or obesity was present in 9 patients (30.0%) and correlated positively with acid exposure. BMI-for-age z-score correlated positively with acid exposure (ρ = 0.41, <i>p</i> = 0.025), but these findings did not remain significant after correction for multiple testing. <b>Conclusions</b>: Using the prespecified acid-exposure criterion, abnormal acid exposure was frequently identified in this cohort. No statistically significant association with EIB was demonstrated; however, the small number of EIB events limits definitive conclusions. The higher absolute post-ECT reflux episode count was not confirmed in a rate-based sensitivity analysis, and a causal effect of exercise on reflux cannot be established.</p>","PeriodicalId":7391,"journal":{"name":"Advances in respiratory medicine","volume":"94 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Extracorporeal Life Support in ARDS: Lessons from Maternal-Fetal Physiology.","authors":"Raffaele Merola, Denise Battaglini, Sung-Min Cho","doi":"10.3390/arm94050065","DOIUrl":"10.3390/arm94050065","url":null,"abstract":"<p><p>Despite decades of clinical experience, the physiological rationale for extracorporeal life support (ECLS) in acute respiratory distress syndrome (ARDS) remains incompletely defined. Existing trials have primarily evaluated ECLS as a rescue intervention, with limited attention to the physiological adaptations required to sustain extracorporeal gas exchange. We propose that the maternal-fetal circulation, the only naturally occurring example of prolonged extracorporeal gas exchange, provides a hypothesis-generating physiological analogy. In this paradigm, gas exchange is externalized through a low-resistance, high-flow circuit while systemic physiology reorganizes to unload the native lung. Translating this concept to severe ARDS suggests that ECLS should be viewed not simply as an adjunct to conventional support, but as a transition to an alternative physiological state centered on extracorporeal gas exchange. This perspective may inform physiology-based patient selection, management strategies, and the design of future clinical trials.</p>","PeriodicalId":7391,"journal":{"name":"Advances in respiratory medicine","volume":"94 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cristina Aljama, Robson Aparecido Prudente, Ane Lopez-Gonzalez, María Sáez, Suzana E Tanni, Júlia Sampol, Núria Rodés, Yesly Esthepannie Carlos, Mercedes Pallero, Sergi Martí, Gerard Orriols, Marian Ramon, Galo Granados, Cristina Esquinas, Marc Miravitlles, Miriam Barrecheguren
{"title":"COPD Assessment Test Variability as a Predictor of Exacerbations in Patients with COPD: A Prospective Study Using Virtual Assistant Monitoring.","authors":"Cristina Aljama, Robson Aparecido Prudente, Ane Lopez-Gonzalez, María Sáez, Suzana E Tanni, Júlia Sampol, Núria Rodés, Yesly Esthepannie Carlos, Mercedes Pallero, Sergi Martí, Gerard Orriols, Marian Ramon, Galo Granados, Cristina Esquinas, Marc Miravitlles, Miriam Barrecheguren","doi":"10.3390/arm94050064","DOIUrl":"10.3390/arm94050064","url":null,"abstract":"<p><p>Although short-term CAT score variability has been associated with COPD exacerbations, evidence supporting its integration into virtual assistant-based monitoring remains limited. The aim of this study was to assess the short-term variability in CAT scores using a virtual management tool in patients with COPD and to examine its relationship with the prediction of exacerbations. A prospective observational single-center study was conducted in patients aged >35 with COPD and an exacerbator phenotype (≥2 outpatient exacerbations or ≥1 hospitalization in the previous year). Follow-up was performed weekly, including the CAT questionnaire, through calls were conducted by the virtual assistant Tucuvi Health Manager<sup>®</sup> during a period of one year. A total of 106 patients were included; 64.2% were male, with a mean (SD) age of 66.8 (7.9) years and a median FEV<sub>1</sub>(%) of 38.8 (30.1-45.0). The mean follow-up was 25 weeks [IQR 20-35], during which 73 (69%) patients experienced ≥1 exacerbation, accounting for 192 episodes (26% of which required hospitalization). A total of 2550 CAT scores were collected. The mean baseline CAT score was 17.9 (7.6), and scores increased significantly during exacerbations compared with non-exacerbation periods and according to exacerbation severity. Each one-point increase in absolute CAT score was associated with an 11.1% increase in the odds of exacerbation (OR: 1.11; 95% CI: 1.08-1.13), while a weekly variation of ≥2 points (MCID) was associated with more than sixfold higher odds (OR: 6.30; 95% CI: 4.28-9.27). The optimal cut-off for CAT change in the prediction of exacerbation risk was 3 points with a ROC curve of 0.773. Weekly deterioration in CAT scores was associated with increased exacerbation risk in patients with COPD. Short-term increases in CAT may serve as clinically useful warning signals for exacerbation.</p>","PeriodicalId":7391,"journal":{"name":"Advances in respiratory medicine","volume":"94 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Precision Medicine in Overlap Syndrome (COPD-Obstructive Sleep Apnea): From Phenotypes and Endotypes to Treatable Traits.","authors":"Carina Adina Afloarei, Andreea Zabara Antal, David Toma, Adriana Loredana Pintilie, Georgiana Pitusac, Raluca Tiron, Tudor Birladeanu, Teodor Zaharia, Radu Crisan Dabija","doi":"10.3390/arm94050063","DOIUrl":"10.3390/arm94050063","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 PaCO<sub>2</sub>, BMI, and T90, allows for a practical approach to identifying the dominant endotype.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":7391,"journal":{"name":"Advances in respiratory medicine","volume":"94 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrzej Obojski, Krzysztof Kuziemski, Marek Barczyk, Rafał Krenke, Ewa Wycinka, Adam Barczyk
{"title":"Patterns of Comorbidity in Asthma-COPD Overlap Cohort According to Various ACO Definitions.","authors":"Andrzej Obojski, Krzysztof Kuziemski, Marek Barczyk, Rafał Krenke, Ewa Wycinka, Adam Barczyk","doi":"10.3390/arm94050062","DOIUrl":"10.3390/arm94050062","url":null,"abstract":"<p><p><b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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.</p>","PeriodicalId":7391,"journal":{"name":"Advances in respiratory medicine","volume":"94 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
{"title":"Morphological Analysis of the Flow-Volume Curve for Identifying Fixed Airflow Obstruction: A Scoping Review.","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","doi":"10.3390/arm94050061","DOIUrl":"10.3390/arm94050061","url":null,"abstract":"<p><p><b>Background/Objective:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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.</p>","PeriodicalId":7391,"journal":{"name":"Advances in respiratory medicine","volume":"94 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
{"title":"Chlorogenic Acid Attenuates Bleomycin-Induced Pulmonary Fibrosis in a Murine Model by Modulating TGF-β1 Expression.","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","doi":"10.3390/arm94050060","DOIUrl":"10.3390/arm94050060","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":7391,"journal":{"name":"Advances in respiratory medicine","volume":"94 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jyoti Bajpai, Akshyaya Pradhan, Mohammed Kaleem Ahmad, Surya Kant, Ajay Kumar Verma, Darshan Kumar Bajaj, Rishi Sethi, Mario Cazzola
{"title":"Serum Angiopoietin-1 and Angiopoietin-2 as Biomarkers of Pulmonary Hemodynamic Burden in COPD-Associated Pulmonary Hypertension: A Cross-Sectional Study.","authors":"Jyoti Bajpai, Akshyaya Pradhan, Mohammed Kaleem Ahmad, Surya Kant, Ajay Kumar Verma, Darshan Kumar Bajaj, Rishi Sethi, Mario Cazzola","doi":"10.3390/arm94040059","DOIUrl":"10.3390/arm94040059","url":null,"abstract":"<p><p><b>Purpose:</b> 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. <b>Methods:</b> 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; <i>n</i> = 46) and the COPD without PH (mPAP < 20 mmHg; <i>n</i> = 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. <b>Results:</b> 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); <i>p</i> < 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; <i>p</i> < 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 <i>p</i> < 0.001). In multivariable models, e-mPAP and RAP were independently associated with ANGP-1, whereas RAP was independently associated with ANGP-2. <b>Conclusions:</b> 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.</p>","PeriodicalId":7391,"journal":{"name":"Advances in respiratory medicine","volume":"94 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13509259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Michely, Svenja Böll, Lida Yao, Regina Ben Hamza, Irina Rachimow, Klaus Tenbrock, Christian Martin, Eva Verjans
{"title":"Effects of Inhaled Amitriptyline on Airway Function and Immune Responses in Experimental Asthma.","authors":"Anna Michely, Svenja Böll, Lida Yao, Regina Ben Hamza, Irina Rachimow, Klaus Tenbrock, Christian Martin, Eva Verjans","doi":"10.3390/arm94040058","DOIUrl":"10.3390/arm94040058","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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<sup>®</sup>, 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<sup>+</sup> T cells.</p><p><strong>Results: </strong>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<sub>H</sub>2 cells, no significant changes in cytokine production or gene expression were observed. Ex vivo, amitriptyline dose-dependently inhibited allergen-induced bronchoconstriction in PCLSs.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":7391,"journal":{"name":"Advances in respiratory medicine","volume":"94 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13509968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}