TMEM16A regulates MUC5AC production in airway diseases: A comprehensive review.

From the archives of MD Anderson Cancer Center: Paraneoplastic autoimmune multiorgan syndrome (PAMS) associated with stroma-rich Castleman disease.

Association of MTOR gene polymorphisms with asthma and poor response to treatment in a Latin American population.

Occupational contact urticaria (OCU) and protein contact dermatitis (PCD) may co-exist with occupational asthma (OA) and occupational rhinitis (OR) and be caused by the same allergen. These diseases are commonly caused by immediate (immunoglobulin E (IgE)-mediated) allergic sensitisation. Limited data exist on the prevalence and causes of concomitant occupational skin and airway diseases (CSAD). To analyse data from the Finnish Register of Occupational Diseases (FROD) for prevalence, main causes, and at-risk occupations for concomitant occupational skin and airway diseases. Data on recognised cases of OCU, PCD, OA and OR in the years 2005-2020 (n = 2413) were retrieved from FROD and analysed. Among OCU/PCD cases, 27% had OA, OR, or both. Conversely, 10% of OA cases and 14% of OR cases had OCU/PCD. Concomitant diseases were most common in farming, animal care, and food-related jobs. Shared causative exposures were identified in 89% of cases, with cow dander, wheat flour, and chemicals being the most frequent. Concomitant occupational skin and airway diseases caused by shared work-related allergens are relatively common. When evaluating patients with occupational immediate allergy, both skin and airway symptoms should be considered.

In 2025, interventional pulmonology continues to progress rapidly through technological innovation and multidisciplinary integration, playing an increasingly prominent role in the diagnosis and management of respiratory diseases. Significant developments are primarily reflected in the maturation of navigational and robotic bronchoscopy technologies, the emergence of transbronchial interventional ablation as a key therapeutic modality for peripheral lung cancer, the expanding repertoire of interventional techniques offering more treatment options for patients with airway diseases, and the transformative potential introduced by artificial intelligence and regenerative medicine. Together, these advances are steering interventional pulmonology toward greater efficiency, precision, intelligence, and personalization.

The molecular mechanisms responsible for the "atopic march" of allergic skin disease to allergic airway disease are incompletely understood. Secreted phospholipase A2 group X (sPLA2-X) is implicated in human asthma and modulates airway hyperresponsiveness (AHR) and inflammation in murine models of allergic asthma. We developed a complete proteolytic allergen model of dermal sensitization followed by airway challenge to mimic the "atopic march" and examined the role of sPLA2-X in regulating peripheral allergen sensitization, AHR, and airway inflammation. Pla2g10-/- mice receiving both house dust mite (HDM) peripheral sensitization and airway challenge had attenuated AHR relative to WT mice and lower airway eosinophils. Transgenic C57BL/6 PLA2G10 mice (only expressing the human sPLA2-X gene) receiving treatment with a small molecule inhibitor of sPLA2-X (ROC0929) during the dermal sensitization phase demonstrated attenuated AHR and a reduction in lung tissue dust mite-specific tissue resident memory CD4+ T cells. Thus, sPLA2-X acts as an endogenous adjuvant to facilitate allergic sensitization in the periphery, which leads to AHR and airway inflammation following inhalation of the allergen. These results provide proof of concept that inhibition of sensitization in the periphery with a sPLA2-X inhibitor modulates subsequent allergen-induced airway dysfunction.

Occupational exposure to polypropylene flock may increase the risk of respiratory symptoms and disease. A cross-sectional study evaluated respiratory effects of polypropylene flock among workers at a large manufacturing facility. Participants completed a questionnaire and spirometry testing; those with abnormal findings received a physical examination. Exposure was based on work history in polypropylene production rooms. Fifty-five workers (39 exposed; 16 unexposed) participated. Exposed workers (59%) more frequently reported phlegm in the past 12 mo compared with unexposed workers (25%) (P = 0.04); other respiratory symptoms did not differ significantly. There were no differences in FEV1% predicted, FVC% predicted, and FEV1/FVC% results between the groups. Nasal cavity erythema (7 exposed; 0 unexposed) was the most prevalent finding on examination. Overall, results showed limited evidence of upper airway irritation from polypropylene flock exposure and no evidence of lower airway disease, including interstitial lung disease. Due to the small sample and the potential for healthy-worker effect bias, results should be interpreted with caution. A longitudinal medical surveillance program to monitor workers with polypropylene fiber exposure above the working occupational exposure limit was recommended.

Chronic airway diseases, including asthma, chronic obstructive pulmonary disease (COPD), and bronchiectasis, impose a significant global health burden. A central unifying feature of these diseases is redox imbalance, which is characterized by an excess of reactive oxygen and nitrogen species (ROS/RNS) that overwhelms the body’s antioxidant defenses, causing cellular dysfunction, inflammation, and tissue damage. Physiological ROS/RNS are essential for immune regulation and transcriptional control, but chronic oxidative stress disrupts these processes, driving disease progression. In asthma, eosinophil- and epithelial-derived ROS worsen airway hyperresponsiveness, induce mucus overproduction, and reduce steroid effects. COPD involves neutrophil-dominated inflammation, mitochondrial dysfunction, protease- and oxidant-mediated extracellular matrix degradation, and accelerated senescence. Bronchiectasis features persistent neutrophilic oxidative injury, microbial colonization, impaired mucociliary clearance, and progressive airway destruction. Exogenous oxidants, cigarette smoke, biomass fuels, pollutants, and pathogens further burden antioxidant systems, including superoxide dismutases, catalase, glutathione peroxidase, and Nrf2-regulated pathways. Redox dysregulation also contributes to post-COVID sequelae, promoting ongoing airway inflammation, fibrosis, and systemic complications. Therapeutic strategies targeting redox imbalance, mainly thiol-based antioxidants, Nrf2 activators, NADPH oxidase inhibitors, and mitochondria-targeted antioxidants, show mechanistic promise but face challenges in specificity, bioavailability, and clinical translation. Advancing precision redox medicine requires biomarker-guided patient stratification, high-resolution redox proteomics, single-cell and organoid models, and spatial imaging to identify disease-specific redox endotypes. Modulating pathological oxidative stress while preserving physiological signaling offers a novel avenue to improve outcomes. Understanding redox biology in airway disease highlights the potential of precision antioxidant strategies as adjuncts to conventional therapies, representing a paradigm shift in managing chronic airway disorders.

Moderate hyperoxia (30-60% O₂) in premature infants promotes bronchial airway hyperresponsiveness (AHR) via airway smooth muscle (ASM), a key regulator of bronchoconstriction, bronchodilation, and remodeling. Understanding how O2 exposure drives long-term bronchial changes in prematurity is critical for developing therapies for airway disease across the lifespan. Premature lungs have immature antioxidant defenses, potentially due to disrupted mitochondrial dynamics, increasing susceptibility to O2-induced oxidative stress. Thus, mitochondrial homeostasis is highly relevant to ASM dysfunction and airway disease. We propose that hyperoxia in prematurity promotes mitochondrial dysfunction, and that the gasotransmitter hydrogen sulfide (H₂S) mitigates O2-induced mitochondrial damage in developing ASM. Human fetal ASM (fASM) were exposed to moderate hyperoxia to investigate the effects of exogenous H₂S donors (GYY4137, AP39) and stabilization of cystathionine β-synthase (CBS), an H₂S biosynthetic enzyme, on mitochondrial structure and function. Hyperoxia impaired fASM mitochondrial integrity, while H₂S donors in particular, or CBS stabilization attenuated adverse O2 effects on mitochondrial morphology, reactive oxygen species, respiration, calcium regulation, and contractility. These findings highlight the therapeutic potential of H₂S in the premature lung exposed to moderate hyperoxia.

Interpretable machine learning based decision tree model for predicting obstructive airway disease in a large non-smoking health screening population.

Although spirometry is a standard diagnostic tool for obstructive lung diseases, it is rarely performed, and the quality of basic spirometry is low in many countries. The impulse oscillometry system (IOS) is a non-invasive method that requires minimal patient cooperation and, therefore, can be performed even in the pediatric population. It has been also suggested that IOS may help to clarify the relationship between small airway disease and the underlying mechanisms of chronic obstructive pulmonary disease (COPD). The primary objective of the study was to compare IOS parameters in COPD patients with those in healthy individuals. Our secondary objective was to determine the relationship between IOS parameters and standard pulmonary function tests (PFTs). Our hypothesis was that airway resistance detected by IOS would be higher in COPD patients than in controls. Hence, IOS would provide findings comparable to and correlated with those of standardized PFTs for small airway obstruction. A total of 104 subjects (62 patients with COPD and 42 healthy non-smoking individuals) were included in the study. All subjects underwent spirometry, diffusing capacity for carbon monoxide (DLCO), lung-volume measurements, and IOS. COPD patients showed significant decreases in forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC, FEF 25-75, and DLCOadj, and significant increases in residual volume (RV) and total lung capacity (TLC) compared with the control group. In terms of IOS parameters, R5%, Z5%, Fres, and R5-R20/R5% values were significantly higher in the COPD group (P = 0.029, P = 0.022, P = 0.009, P = 0.004, respectively). The reactance area (AX) value, defined as the AX, was also significantly increased in the COPD group (P = 0.004). The correlation between FEF 25-75% (L/s) and R5-R20 was moderate and negative (r = -0.491, P < 0.001). A weak correlation (r = 0.240, P = 0.017) was also found between the RV/TLC ratio and R5-R20. This study showed that airway resistance was increased in the COPD group and that IOS parameters were associated with measures of small-airway function in standard PFTs. IOS can be used as a non-invasive, patient-friendly method that complements PFTs by providing a comprehensive assessment of COPD pathology and pathophysiological changes and detecting changes in symptomatic patients.

Impact of Pesticide Exposure on Asthma and Allergic Airway Disease.

The Italian National Congress of Imaging in Pulmonology, held in Milan on November 21st, provided a unique educational platform exploring the evolving role of thoracic imaging in respiratory medicine. Organized by the Italian Respiratory Society (SIP-IRS) Imaging Study Group, the congress brought together over 160 participants, including pulmonologists, radiologists, interventional specialists, and early-career professionals, reflecting the essential role of multidisciplinary collaboration in modern respiratory care. Topics included functional imaging approaches to small airway disease in COPD and asthma, multimodal imaging in lung transplantation, the role of CT angiography for haemoptysis management, and radiomics applications for quantifying emphysema patterns and fibrotic changes. The role of imaging in guiding inhaled and biological therapies was explored, alongside a lively debate on thoracic ultrasound for interstitial lung disease screening. Advanced sessions covered medical thoracoscopy techniques, quantitative ultrasound and artificial intelligence in pleural diseases, shape-sensing robotic-assisted bronchoscopy for peripheral nodules, expanding cryobiopsy applications, and imaging's role in monitoring progressive pulmonary fibrosis therapeutics. A distinctive feature was the first "Images in Pulmonology" contest, won by a remarkable case simultaneously depicting lung cancer and new life. This meeting report summarizes key congress highlights and underscores the importance of fostering multidisciplinary collaboration and structured imaging education to bridge the gap between technological capabilities and clinical expertise in respiratory medicine.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a disorder characterized by neuroendocrine cell hyperplasia, tumorlets and tumors, manifesting as lung nodules, chronic cough, and airflow obstruction. Often misdiagnosed as asthma, DIPNECH lies at the cross-section of oncology, obstructive airway disease and interstitial lung disease. With the increasing use of CT scans leading to higher rates of lung nodule detection, it is important for clinicians to be familiar with DIPNECH. The evidence base in DIPNECH is sparse and limited to retrospective case series. In the last 5 years, clinical experiences in large academic centers have been published describing variability in clinical presentation and pulmonary function, use of DOTATATE scans, efficacy of somatostatin analogs, and principles of surveillance imaging. More awareness of DIPNECH is needed among pulmonary clinicians. Apart from the usual presentation of cough with lung nodules and spirometric obstruction in women, patients also present with dyspnea and/or restrictive patterns on PFTs. Variability in diagnosis and management is widespread. Multidisciplinary assessment is helpful in guiding management. Multicenter and multispecialty collaboration is needed to establish best practices and improve clinical management.

Jatropha curcas (J. curcas), a member of the Euphorbiaceae family, is a tropical medicinal plant that has been used in African Traditional Medicine for the treatment of asthma and related allergic airway diseases. This study investigated the ameliorative effects of Jatropha curcas leaf extract on ovalbumin-induced allergic airway inflammation in Wistar rats. Preliminary phytochemical screening of the extract was carried out using standard procedures, and oral median lethal dose (LD50) was determined using Lorke’s method. Allergic airway inflammation was induced in Wistar rats via ovalbumin sensitization and challenge over 28 days. Rats were divided into six groups: normal control, ovalbumin control, three groups treated with J. curcas extract at 35, 70, and 140 mg/kg, and a positive control receiving prednisolone (10 mg/kg). Post-treatment, bronchoalveolar lavage fluid (BALF) was analyzed for leukocytes and cytokines, and lung tissues were examined histologically. Phytochemical analysis identified flavonoids, alkaloids, terpenes, saponins, glycosides, steroids, and anthraquinones. Acute oral toxicity test revealed an LD50 exceeding 5000 mg/kg, indicating that the extract is relatively safe. Anti-inflammatory activity evaluation showed that J. curcas at 140 mg/kg dose significantly (p ≤ 0.05) reduced eosinophil counts and IL-13 levels, which was comparable to that of prednisolone group. the extract also showed a dose-dependent reduction in IL-4 and IL-5 levels. Histopathological examination revealed protection against alveolar necrosis and tracheal hyperplasia at higher doses. Overall, the extract demonstrated notable anti-inflammatory and airway-protective effects, suggesting its potential as a complementary therapy for allergic airway diseases. Further clinical studies are warranted to confirm these findings.

Air pollution has long been recognized as a threat to human health. There is growing evidence that exposure to air pollution increases the risk of upper airway inflammatory disease including allergic and non-allergic rhinitis, and chronic rhinosinusitis. Recent improvement in air pollution measurement, including wearable pollution monitors, may improve our understanding of patient exposures. In this piece, we summarize salient literature and interventions.

Profiles of circulating T follicular helper (cTfh) cell subpopulations in patients with asthma, COPD and asthma-COPD overlap (ACO).

Genetically predicted associations between blood cell perturbation responses and bronchiectasis through immune mediation: A Mendelian Randomization study.

Electronic cigarettes (e-cigarettes) are often perceived to be a less harmful alternative to tobacco cigarettes. Potentially due to this perception, they are used by people with pre-existing respiratory conditions, such as asthma, who otherwise would not smoke. Despite this, there are few studies exploring the health effects of e-cigarette use on pre-existing asthma. In this study, a house dust mite-induced allergic-airways disease phenotype was generated in adult BALB/c mice over 7weeks. For the last 2weeks of this period, mice were also exposed to either medical air, or tobacco smoke or e-cigarette aerosol (with or without nicotine) for 2h/day. Twenty-four hours later, respiratory parameters including lung volume/function and responsiveness to methacholine were assessed. Biological samples were taken for analysis of pulmonary cellular inflammation and mediator levels, serum IgE and lung/airway structure. There were complex effects of exposure on respiratory outcomes. For example, tobacco smoke-exposed mice of both sexes were the most responsive to methacholine but had suppressed total cellular and eosinophilic inflammation. Female e-cigarette aerosol-exposed mice had impaired parenchymal mechanics at functional residual capacity compared with tobacco smoke-exposed mice, irrespective of nicotine. Interferon γ levels were suppressed in both e-cigarette-exposed groups. There was no effect of any exposure on IgE or lung structural parameters. E-cigarette aerosol exposure exacerbated aspects of an allergic airways disease phenotype in mice. This suggests that asthmatics should exercise increased caution if thinking of using e-cigarettes.

A functional lyoprotectant platform enables storage-stable, mucus-penetrating siRNA delivery to the lung.