Treatment of pulmonary fibrosis and combined pulmonary fibrosis and emphysema syndrome with herbs for promoting blood circulation and removing blood stasis: A review of pharmacological studies.

While human genetics implicate the interleukin-6 (IL6) signaling pathway as a potential therapeutic target in chronic obstructive pulmonary disease (COPD), its functional role in pulmonary macrophages remains paradoxical given its established role in promoting cholesterol efflux. Here, integrating single-cell transcriptomics of human COPD lungs with mechanistic studies, we resolve this paradox by identifying a pathogenic rewiring of the IL6/STAT3 pathway. We discovered a disease-enriched macrophage subpopulation exhibiting co-activation of IL6/STAT3 signaling, cholesterol biosynthesis, and inflammatory pathways. In a murine COPD model, chronic cigarette smoke (CS) exposure recapitulated this immunometabolic phenotype. We defined a linear pathway wherein CS-induced IL6 activates STAT3, which directly transactivates the sterol regulatory element-binding protein 2 (SREBP2) to drive de novo cholesterol synthesis. This SREBP2-dependent cholesterol accumulation was essential for NLRP3 inflammasome activation and pro-inflammatory cytokine release. In vitro, pharmacological inhibition of STAT3 or SREBP2, as well as IL6 silencing, disrupted this cascade, suppressing cholesterol-driven inflammation. Critically, in vivo macrophage-specific Il6 knockdown attenuated pulmonary inflammation, cholesterol accumulation, and emphysema development by disrupting the entire IL6/STAT3/SREBP2 axis. Thus, we define the IL6/STAT3/SREBP2 axis as a core immunometabolic driver of COPD pathogenesis, which directly couples CS exposure to sustained macrophage inflammation via pathological cholesterol synthesis, thereby providing a mechanistic basis for targeting this druggable pathway.

Rheumatoid arthritis (RA) is a prevalent chronic systemic autoimmune inflammatory disease that primarily targets synovial joints and periarticular tissues. In RA, systemic inflammation has been associated with extra-articular manifestations, including pulmonary involvement, which are leading causes of reduced survival. Tobacco smoking is a well-established risk factor for anti-citrullinated protein antibody (ACPA)-positive RA and is also associated with chronic obstructive pulmonary disease, interstitial lung disease (ILD) and lung cancer, the prevalence of which is elevated in people with RA. Pulmonary manifestations such as airway obstructive disease, ILD and bronchiolitis affect a substantial proportion of people with RA. Screening for pulmonary disease, particularly ILD, is gaining emphasis, with high-resolution CT recommended based on risk factors including age, sex, antibody status and smoking. Despite advances in therapies to effectively manage joint inflammation, evidence-based treatments for RA-associated ILD remain limited. Chronic obstructive pulmonary disease and bronchiectasis in RA warrant more recognition owing to their effect on morbidity and mortality, and should be managed in accordance with current international treatment guidelines for these conditions. This Review summarizes the pathophysiology of lung involvement in RA, diagnostic challenges and evolving management strategies aimed at optimizing patient outcomes.

Strain-induced pulmonary interstitial emphysema: Exploring trauma-associated injury mechanisms.

The yak lung functions as a vital adaptive organ in cold, low-oxygen environments. Hypoxia can induce pathological remodeling in yak lung tissue, so we need to understand the molecular mechanisms of this remodeling. For this study, we used cross-omics comparative approaches, including transcriptomics, label-free proteomics, and untargeted metabolomics, to examine both normal and diseased yak lung tissues. From histological observations, the disease phenotype was identified as pulmonary emphysema. Our results showed a significant up-regulation of differentially expressed genes such as MTTP, CXCL8, RETN, and NNAT, while genes like SLC45A1, IL10, SDSL, and COL12A1 were clearly down-regulated. In the differential protein analysis, proteins such as RASSF4, EDC4, CTSC, and FECH were notably up-regulated, whereas CYP27A1, FKBP9, RAD23A, and PLSCR2 were significantly down-regulated. Metabolomic profiling revealed that palmitoyl-L-carnitine, decanoyl-L-carnitine, and o-acetylcarnitine were significantly higher in emphysematous lung tissue, whereas racemethionine and L-methionine S-oxide were significantly much lower. Also, when we compared of bulk RNA-seq, label-free proteomics, and untargeted metabolomics data revealed enrichment in three common pathways: the asthma pathway, the linoleic acid metabolism pathway, and the gastric acid secretion pathway. Of note, histamine levels were higher in both the asthma and gastric acid secretion pathways. While the mRNA expression level of BoLA-DQB was increased in the asthma pathway, its protein expression level was decreased. This study offers some initial cross-omics evidence about what happens. These findings give us a scientific basis for developing effective prevention and control strategies, which in turn can help the protection of yak health and the sustainable development of plateau animal husbandry.

ABSTRACTParaneoplastic pemphigus (PNP) is a life‐threatening autoimmune blistering disease with a mortality rate of 70%–90%, driven largely by respiratory complications such as bronchiolitis obliterans. Managing respiratory failure in these patients remains exceptionally difficult. We report a 33‐year‐old male with follicular dendritic cell sarcoma who developed severe PNP complicated by type II respiratory failure and obstructive bronchiolitis requiring veno‐venous extracorporeal membrane oxygenation (ECMO) support. The patient's PNP skin lesions improved during a treatment course that included ECMO support, intravenous immunoglobulin (IVIG), immunosuppressants, hemodialysis, and plasma exchange. Serial immune cell subset monitoring showed a rising CD4/CD8 ratio (+94.8%) and Helper T cells (+33.8%), alongside declining NK cells (−48.2%), T lymphocytes (−17.7%), and Suppressor T cells (−31.6%). This case illustrates successful short‐term management of severe PNP with respiratory failure through multidisciplinary care, including ECMO. Because multiple interventions were administered concurrently, improvement cannot be attributed to any single therapy. Serial immune‐cell monitoring may help track treatment response in this setting.

Respiratory disorders, ranging from acute viral infections such as influenza and bronchitis to chronic inflammatory conditions including chronic obstructive pulmonary disease, asthma, emphysema, and pneumonia, represent a major global health burden, affecting millions annually. Traditional Anatolian folk medicine has long relied on plant-based remedies to manage these conditions, offering a valuable reservoir of therapeutic knowledge. Ethnobotanical data on Anatolian medicinal plants are integrated to evaluate their therapeutic relevance through a mechanistic perspective. A meta-analysis of 187 ethnobotanical studies published since 1991 was conducted, with 110 meeting strict inclusion criteria. The dataset includes 508 plant taxa, with prominent families such as Rosaceae, Lamiaceae, Asteraceae, and Malvaceae. Key species include Cydonia oblonga, Glycyrrhiza glabra, Juniperus oxycedrus, Matricaria chamomilla, Pinus spp., Plantago spp., Rubus spp., Sambucus nigra, and Urtica dioica. A clear divergence in treatment strategies is evident. Essential oil- and anthocyanin-rich taxa are associated with acute conditions via antimicrobial activity and γδ T-cell modulation. In contrast, mucilage- and iridoid-rich species are linked to chronic conditions, where mucosal protection and regulation of NF-κB and COX-2 pathways represent central mechanisms. A coherent framework for evidence-based respiratory therapeutics emerges from ethnobotanical evidence integrated with mechanistic insights and updated toxicological evaluation. This review defines the mechanistic and ethnopharmacological landscape of plant-based interventions targeting respiratory disorders.

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder that generally predisposes to pulmonary emphysema with or without chronic obstructive pulmonary disease (COPD). Despite the lack of spirometric obstruction, early Small Airways Dysfunction (SAD) may occur in AATD patients preceding lung damage. We conducted a retrospective, single-center study on 60 AATD patients without airflow obstruction (FEV₁/FVC ≥ 0.70). SAD was defined as: reduced spirometric flows (≥2 of FEF25-75, FEF50, FEF75 <65% predicted) and/or IOS R5-R20 value greater than 0.07 kPa•s•L⁻¹. Correlation and agreement between spirometry and IOS were assessed, as well as associations with Modified Medical Research Council (mMRC) dyspnea scores. SAD was detected in 23% of patients by spirometry, 10% by IOS, and 13% by both methods. A slight agreement was found between spirometric and IOS criteria (κ = 0.22). Only IOS-defined SAD was significantly associated with dyspnea (mMRC ≥2; p = 0.05), and R5-R20 values correlated with mMRC scores (r = 0.38, p = 0.003). No association was observed between spirometry-defined SAD and symptoms. These findings support IOS as a partially complementary tool for the early detection of peripheral airway impairment in AATD. Moreover, IOS but not spirometry criteria were related to breathlessness perception in AATD patients without airflow obstruction, with IOS proving to be a clinically more sensitive measure.

Chronic obstructive pulmonary disease (COPD) is the fifth leading cause of death in Canada. The Efficacy and Safety of Triple Therapy in Obstructive Lung Disease (NCT02465567) and Informing the Pathway of COPD Treatment (NCT02164513) randomized controlled trials demonstrated reduced exacerbations and all-cause mortality for patients with COPD on single-inhaler triple therapy (SITT). The 2023 Canadian Thoracic Society (CTS) COPD pharmacotherapy guidelines recommend triple therapy, and preferably SITT use, in patients with moderate to severe symptom burden and high future risk of exacerbations. The clinical impact of broader SITT use in Canada has not yet been studied. We aimed to estimate the benefit of appropriate SITT use according to CTS COPD guidelines on mortality, exacerbations, and their corresponding costs in Canada. We used a stochastic model using literature-derived characteristics (e.g., incidence, changes in COPD severity, treatment, mortality, and exacerbations) that simulated the Canadian COPD population. Patients were assigned percentage of forced expiratory volume in 1 second predicted levels, and their annual characteristics were modeled for 2025–2034 under 2 scenarios: “status quo” (current practice) and “increased SITT” (following CTS guidelines). Based on our simulated results for the flagged population, “Increased SITT” use over 10 years compared to current treatment reduced moderate and severe exacerbation rates by 23% and 12%, respectively, for a reduction of 159,000 severe and 2.81 million moderate exacerbations and reduced the all-cause mortality rate by 22%. In the flagged population alone, this reduction in exacerbations would equate to a savings of CA$3.9 billion over 10 years. Appropriate use of SITT, informed by the 2023 CTS COPD guidelines, could lower mortality, exacerbation frequency, and their corresponding costs in patients with COPD.

Attenuated FTO induces necroptosis of alveolar epithelium via the m6A/CYP1B1/ROS/MLKL axis to promote the aggravation of pulmonary emphysema

Tolerability and effectiveness of definitive chemoradiotherapy in locally advanced lung cancer patients with combined pulmonary fibrosis and emphysema.

Although mechanical pleurectomy effectively prevents recurrent pneumothorax in elderly patients with diffuse emphysematous bullae, it entails substantial surgical trauma and postoperative pain. This study evaluates an enhanced pleurodesis technique-combining intraoperative hypertonic glucose spraying with three-day postoperative intrapleural perfusion-as a minimally invasive alternative. A retrospective analysis included 155 patients who underwent thoracoscopic bullectomy: 72 in the glucose protocol group and 83 in the parietal pleurectomy control group. Following 1:1 propensity score matching, 72 well-balanced matched pairs were obtained. The glucose protocol group exhibited significantly improved perioperative outcomes compared with the parietal pleurectomy control group, including shorter operative duration (65.33 ± 2.43 vs. 84.92 ± 2.35min), reduced intraoperative blood loss (50.00 ± 3.82 vs. 71.89 ± 4.62 mL), lower postoperative chest tube drainage volume (551.39 ± 27.76 vs. 785.42 ± 57.83 mL), shorter chest tube dwell time (4.42 ± 0.17 vs. 5.32 ± 0.21 days), lower pain scores on postoperative day 3 (0.93 ± 0.07 vs. 1.28 ± 0.06), and shorter length of hospital stay (5.04 ± 0.16 vs. 6.31 ± 0.24 days) (all P < 0.05). No significant differences were observed in postoperative complication rates (18.1% vs. 15.3%) or one-year pneumothorax recurrence rates (4.2% vs. 2.8%) between the two groups (both P > 0.05). In this retrospective, propensity-score matched cohort study involving elderly high-risk patients with recurrent diffuse pulmonary bullae, an enhanced pleurodesis protocol-comprising intraoperative hypertonic glucose spray followed by three-day postoperative intrapleural perfusion-was associated with significantly improved perioperative outcomes compared with parietal pleurectomy. No statistically significant difference was detected in 1-year recurrence; however, this finding should not be interpreted as evidence of equivalence or non-inferiority because the recurrence analysis was underpowered and no non-inferiority margin was prespecified. These results indicate that the glucose-based protocol may serve as a viable, less invasive alternative to mechanical pleurectomy in this vulnerable population; however, validation through prospective, randomized controlled trials remains essential to establish causality and generalizability.

Vaccination against lumpy skin disease was carried out in Croatia during 2016 and 2017 to prevent this emerging viral disease from causing significant damage to the cattle population. Two unauthorised live vaccines were used for immunoprophylaxis, and adverse reactions in cattle were expected. Adverse events were monitored and 14 selected reported cases of deaths were analysed using the available necropsy results. The cases analysed were classified as probable, possible, inconclusive, or unlikely to be caused by vaccination, primarily based on results of post-mortem examination, taking into consideration factors that contributed to or resulted in death or euthanasia. Most cases were classified as possibly caused by vaccination due to subcutaneous oedema of varying consistency (at the injection site) and intramuscular haemorrhage, in some cases leading to purulent and necrotic processes. These processes eventually led to fatal purulent bronchopneumonia, pulmonary emphysema, septic conditions, or euthanasia. In the remaining cases, necropsy results were unable to be linked to vaccination or the findings were inconclusive due to the presence of other factors, such as Klebsiella infection. It can be assumed that neither vaccine had a direct connection with animal deaths, but they may have contributed to the fatal outcomes due to the complications of severe local reactions and general impact on the immune system.

The implementation of photon-counting (PCD) CT has led to substantial technologic improvements over conventional energy-integrated detector (EID) CT. These advances include better spatial and contrast resolution, intrinsic spectral information, and potential for reductions in radiation doses and contrast media volumes. Since the clinical introduction of PCD CT, numerous studies have been performed to investigate the advantages and potential impact brought by this new technology for various clinical scenarios with respect to cardiothoracic imaging. For example, PCD CT offers improved visualization of pulmonary and cardiac anatomy and allows dose reduction in the assessment of pulmonary vasculature, nodules, emphysema, and interstitial lung diseases. PCD CT also improves visualization of coronary plaque and stents, provides more accurate assessment of coronary stenoses, and facilitates myocardial tissue characterization. The faster data acquisition enabled by PCD CT additionally aids cardiothoracic evaluation in pediatric and/or dyspneic patients. This AJR Expert Panel Narrative Review explores these state-of-the art cardiothoracic applications of PCD CT considering supporting evidence, technical features, protocols, and areas of greatest potential clinical benefit. Ongoing implementation challenges and remaining research priorities that warrant attention to support the integration of PCD CT into standard cardiothoracic imaging practice are highlighted.

To better understand the gap in literature by comparing umbilical hernia repair techniques for < 2cm umbilical hernias in patients with class I and class II obesity Methods: A retrospective review of data from the ACHQC was performed to include adult patients with a BMI of 30.0-39.9kg/m2 who underwent elective UHR for a hernia defect of < 2cm. Patients within each obesity underwent propensity score matching analysis for diabetes mellitus, hypertension, chronic obstructive pulmonary disorder, and smoking status. Outcomes of interest included: compare surgical site infection, surgical site occurrence, 30-day reoperation, recurrence, and re-admission. 1896 patients were included in the analysis after matching. There was no difference in 30-day recurrence, re-admission, or reoperation. There was a statistically greater number of SSO in the class II obesity group (4.6% vs 2.8%, p = 0.04), but no difference in SSI. When comparing suture-based repair between the obesity classes, there was a higher rate of SSO in patients with class II obesity (18 vs 6, p = 0.002). When comparing open repair with mesh and minimally invasive repair with mesh across the entire cohort, we found a higher readmission rate (7 vs 1, p = 0.038) and SSO rate (12 vs 3, p = 0.019) in patients with class II obesity undergoing open repair with mesh. There was no difference in SSI or SSO between the classes when undergoing MIS repair with mesh. Minimally invasive repair for umbilical hernias < 2cm is favored over open repair in patients with class I or class II obesity in regards to wound morbidity and early postoperative hernia recurrence .

Prognostic impact of emphysema extent on mortality and lung function decline in combined pulmonary fibrosis and emphysema: An observational cohort study.

Acromioclavicular (AC) joint injuries represent approximately 11% of all shoulder injuries and are managed surgically in severe cases via techniques such as hook-plating, button fixation, and graft-based reconstruction. While much of the existing literature on AC joint surgery points to relatively high rates of long-term complications and reoperations, short-term outcomes are not fully understood. Therefore, this study investigates short-term outcomes following AC joint surgery using a large database to provide comprehensive complication data and elucidate risk factors. The American College of Surgeons National Surgical Quality Improvement Program database was queried from 2010 to 2023. Patients undergoing surgical intervention for AC joint injuries were identified using Current Procedural Terminology 23550, 23552, and 21320, and their 30-day postoperative outcomes were retrieved. Patients with unknown or null values for demographic or complication metrics were excluded. Statistical analyses included multivariate odds-ratio (OR) logistic regression. Operative time threshold analysis was performed to identify the optimal time cut-point associated with increased complication risk. A total of 13,117 patients underwent AC joint surgery (average age 49.6 ± 15.2 years; average body mass index 30.1 ± 6.44 kg/m2; 70.5% male). The overall adverse event rate was 2.7%: surgical site infection (1.2%) and return to operating room (1%) were among the most common. An average operating time of 85 ± 56 minutes was determined, and threshold analysis revealed a significant increase (P < .001) in complications for operations lasting longer than 148 minutes. Operative time (OR = 1.01), history of chronic obstructive pulmonary disease (OR = 2.47), steroids (OR = 3.16), dialysis (OR = 5.57), bleeding disorders (OR = 2.67), and type 1 diabetes (OR = 1.61) were all significant risk factors for complications. AC joint surgery demonstrated relatively low short-term complication rates; however, comorbidities such as type 1 diabetes and chronic obstructive pulmonary disease are linked to a higher risk of experiencing adverse events. Preoperative counseling is recommended for at-risk patients, and future studies should explore surgery-specific operative time and patient management to provide further insights and enhance surgical decision-making.

Abstract Rational Individuals with chronic obstructive pulmonary disease (COPD) and emphysema have a higher risk of developing non-small cell lung cancer (NSCLC), even after accounting for smoking exposure. Chronic airway and parenchymal injury create a chronic pro-inflammatory microenvironment that facilitates carcinogenesis. Despite this, only about 10% of individuals with COPD develop lung cancer during their lifetime. In this study, we analyzed the COPDGene Phase 1 to identify pulmonary nodules and determine which clinical and imaging characteristics are associated with the presence of nodules 6 mm in diameter. Method A residual encoder Unet was trained for nodule detection and segmentation on publicly available datasets including COVID-19 CT Lung, Lung Image Database Consortium (LIDC), Medical Segmentation Decathlon Lung, and NSCLC-Radiomics. The model was trained for 1000 epochs, using a batch size of 2, and patch-size of (112,256,256). After training, the model was applied to CT scans from COPDGene Phase 1 dataset (n = 9419) to automatically extract pulmonary nodules. The largest AI detected nodule was recorded, and participants were stratified into three groups based on nodule diameter: 6 mm, 6 mm, and no nodules. Univariate analysis was performed non-parametric statistics. Results Among 9419 COPDGene Phase 1 participants, 1710 (18.15%) had no pulmonary nodules, 1455 (15.44%) had nodules &amp;lt;6 mm, and 6254 (65.39%) had nodules ≥ 6 mm, seen in table 1. Participants with nodules ≥ 6 mm were significantly older (median 60.5 years) and had a greater smoking exposure (40.5 pack-years) compared with those without nodules (55.8 years; 36.3 pack-years; p &amp;lt; 0.001). Emphysema and gas trapping were more pronounced in participants with nodules ≥ 6 mm (median %emphysema 2.4; %gas-trapping 15.5) than in those without nodules (1.5 and 11.5, respectively; p &amp;lt; 0.001). These individuals had higher mMRC dyspnea scores (≥2 in 42.33% vs. 37.26%) and elevated SGRQ total scores (median 23.1 vs. 18.5; p &amp;lt; 0.001), exhibiting worse functional limitation. Increasing GOLD stage and BODE index severity were both associated with higher prevalence of nodules ≥ 6 mm (trend p &amp;lt; 0.001). Conclusion This study represents the first characterization of AI detected pulmonary nodules in the COPDGene cohort. The prevalence of CT-detected nodules ≥6 mm was associated with older age, greater smoking exposure, and higher emphysema burden. These findings highlight potential risk factors for nodule development and may inform future risk stratification strategies for lung cancer. Funding NCI K00CA27471, and NHLBI grants 1R01HL149877, U01HL089897, U01HL089856, and NIH contract 75N92023D00011. This abstract is funded by: This work was supported by NCI K00CA27471, NHLBI grants 1R01HL149877, U01 HL089897, and U01 HL089856 and by NIH contract 75N92023D00011”

Introduction The Raynaud’s phenomenon (RP) is often an initial symptom of mixed connective tissue disease (MCTD), and its progression to skin necrosis and gangrene remains rare and life-threatening. This report presents a case of severe microvascular angiopathy in MCTD leading to phalangeal necrosis requiring vasodilator therapy and surgical intervention. Case description A 53-year-old patient with MCTD was admitted to the Rheumatology Department in Lodz for disease activity assessment and treatment modification. Diagnosed in 2020, the patient initially presented with mild skin fibrosis and severe RP without necrosis. Treatment included methylprednisolone (16 mg, tapering), methotrexate (25 mg s.c.), and pentoxifylline (600 mg). In August 2025, the patient experienced a significant worsening of skin ulcers on both hands, with dry necrosis of the distal phalanges. On admission, inflammatory markers were moderately elevated, along with anaemia of chronic disease, thrombocytosis, and cyanotic, indurated skin on the hands, feet, and face. The patient exhibited features typical of systemic sclerosis and massive, hard oedema in the lower limbs, as well as stable pulmonary emphysema and dysphagia due to esophagitis. No other organ manifestations were noted. Prostaglandin E1 infusions were initiated for five days, improving blood supply to the distal limbs. A calcium channel blocker was added, and targeted intravenous antibiotics were administered for infected ulcers on the right hand. The patient was discharged in satisfactory condition. Four weeks later, the patient returned for another prostaglandin cycle. Significant improvement in the skin on the face and feet was observed, along with healing of the left hand ulcers. However, the right hand’s necrosis deepened, a bacterial infection reactivated, and an abscess developed. Prostaglandin infusions continued, and surgical debridement of the right hand was performed, resulting in finger amputations. The patient’s general condition improved, inflammatory markers decreased, and a follow-up a month later showed significant skin improvement, no swelling, enhanced well-being, and normal healing of amputation wounds. Prostaglandin treatment will continue for another three months, with close monitoring of wound healing. Conclusions This case shows that angiopathy in MCTD may progress from RP to gangrene, and that critical digital ischemia requires multidisciplinary management.

Chronic lung allograft dysfunction significantly limits survival after lung transplantation. The obstructive phenotype bronchiolitis obliterans syndrome (BOS) is characterized by the abnormal activation of airways epithelium, fibrotic changes with excessive extracellular matrix deposition, and airway obliteration. Mast cells, through mediators such as tryptase and chymase, play a role in lung fibrosis. The proteins osteoprotegerin (OPG) and SERPIN family member A 3 (SERPINA3) have been associated with lung fibrosis progression. Tryptase-mast cells can produce OPG, while chymase interacts with SERPINA3. This study aimed to investigate if and how SERPINA3, OPG, and tryptase/chymase-positive mast cells are related to fibrotic airway obliteration and potentially show an association with BOS severity. Serum SERPINA3 levels in BOS and non-BOS were examined using ELISA. In BOS lung tissue, non-cartilaginous airways were classified into normal, partially obstructed, and completely obstructed airways. Immunohistochemistry detected SERPINA3, OPG, chymase, and tryptase. Colocalization of and interactions between SERPINA3, OPG, and tryptase were assessed by immunofluorescence, proximity ligation assay, and AlphaFold modeling. SERPINA3 serum levels in BOS patients were higher compared to non-BOS patients. A low percentage of SERPINA3 and OPG was detected in partially and completely obstructed airways. Cells positive for OPG and SERPINA3 colocalized with tryptase-mast cells in airways. OPG colocalized with SERPINA3, and they positively correlated in partially obstructed airways. In completely obstructed airways, OPG, SERPINA3, and tryptase all positively correlated with each other. These findings suggest mast cells express SERPINA3 and OPG, and these proteins potentially form a complex in lung tissue, possibly contributing to airway remodeling in BOS.