Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) resulting from an immune-mediated response in susceptible and sensitized individuals to a large variety of inhaled antigens. Chronic HP with a fibrotic phenotype is characterized by disease progression and a dismal prognosis. The aim of this study was to identify predictors of progression and mortality in patients with chronic HP in real clinical practice. Materials and methods: This retrospective, multicenter, observational study used data from a registry of 1355 patients with fibrosing ILDs. The study included 292 patients diagnosed with chronic HP based on the conclusion of a multidisciplinary discussion (MDD). Results: The patients were divided into groups with progressive (92 (30.3%) patients) and nonprogressive pulmonary fibrosis (200 (69.7%) patients). The most significant predictors of adverse outcomes were a DLco < 50% predicted, an SpO2 at the end of a six-minute walk test (6-MWT) < 85%, and a GAP score ≥ 4 points. Conclusion: Pulmonary fibrosis and a progressive fibrotic phenotype are common in patients with chronic HP. Early detection of the predictors of an adverse prognosis of chronic HP is necessary for the timely initiation of antifibrotic therapy.

Cystic fibrosis (CF) is a hereditary disease characterized by the progression of respiratory disorders, especially in adult patients. The purpose of the study was to identify volatile organic compounds (VOCs) as predictors of respiratory dysfunction, chronic respiratory infections of Staphylococcus aureus, Pseudomonas aeruginosa, Burkholderia cepacia, and VOCs associated with severe genotype and highly effective modulator treatment (HEMT). Exhaled breath samples from 102 adults with CF were analyzed using PTR-TOF-MS, obtained during a forced expiratory maneuver and normal quiet breathing. Using cross-validation and building gradient boosting classifiers (XGBoost), the importance of VOCs for functional and clinical outcomes was determined. The presence of the previously identified VOCs indole, phenol, and dimethyl sulfide were metabolic outcomes associated with impaired respiratory function. New VOCs associated with respiratory disorders were methyl acetate, carbamic acid, 1,3-Pentadiene, and 2,3-dimethyl-2-butene; VOCs associated with the above mentioned respiratory pathogens were non-differentiable nitrogen-containing organic compounds m/z = 47.041 (CH5NO)+ and m/z = 44.044 (C2H5NH+), hydrocarbons (cyclopropane, propene) and methanethiol; and VOCs associated with severe CFTR genotype were non-differentiable VOC m/z = 281.053. No significant features associated with the use of HEMT were identified. Early non-invasive determination of VOCs as biomarkers of the severity of CF and specific pathogenic respiratory flora could make it possible to prescribe adequate therapy and assess the prognosis of the disease. However, further larger standardized studies are needed for clinical use.

Background: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) that occurs in susceptible individuals in response to various inhaled antigens. The fibrotic phenotype of HP is characterized by disease progression and can lead to pulmonary hypertension (PH). The aim of this study was to estimate the prevalence of PH and to identify predictors of PH in patients with chronic HP. Methods: We conducted an observational longitudinal study that included 85 patients with an established diagnosis of HP. Clinical examination, quality of life questionnaires, high-resolution computed tomography (HRCT) of the chest, arterial blood gases analyses, six-minute walking test (6-MWT), pulmonary function tests, and echocardiography were performed. Results: Patients were divided into groups with fibrotic (71.8%) and nonfibrotic phenotype (28.2%). PH was detected in 41 (48.2%) patients. Patients with PH had the predominant fibrotic phenotype of HP, were older, more symptomatic, and had a higher FVC/DLco ratio. The most significant predictors of PH were CT signs of fibrosis, finger clubbing, FVC/DLco, decreased distance, and SpO₂ at the end of 6-MWT, as well as the presence of cardiovascular diseases. Conclusions: PH is a common condition in patients with chronic HP, especially with the fibrotic phenotype. Early detection of the PH predictors is necessary for the timely diagnosis of this complication of HP.

Background: Asthma and chronic obstructive pulmonary disease (COPD) are prevalent obstructive lung diseases with distinct inflammatory pathways but overlapping clinical features. Bronchodilator responsiveness (BDR) is a key diagnostic criterion, yet its metabolic determinants are poorly understood. Objective: This cross-sectional study investigated whether integrated profiling of exhaled volatile organic compounds (VOCs) and clinical biomarkers can differentiate BA, COPD, and health, and predict BDR. Methods: Exhaled breath from 160 BA patients, 128 COPD patients, and 254 healthy controls was analyzed in real-time using proton-transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS) during tidal and forced expiration. Clinical assessment included spirometry, fractional exhaled nitric oxide (FeNO), blood eosinophil count, and total IgE. Machine-learning (XGBoost) was employed for feature selection and model development. Results: Distinct VOC signatures effectively discriminated disease groups from controls and from each other. The model for distinguishing asthma from healthy controls achieved an AUC of 0.747 during normal quiet breathing and 0.710 during forced exhale. For discriminating COPD from healthy controls, the model performance was higher, with an AUC of 0.821 for normal quiet breathing and 0.856 for forced exhale. A model integrating VOC profiles with clinical biomarkers (FeNO, eosinophils, IgE) demonstrated very high accuracy in internal validation in predicting BDR (AUC = 1.000 for tidal breathing; AUC = 0.970 for forced expiration). Specific mass spectral features (m/z 79, m/z 101) were significantly associated with a positive BDR test. Conclusions: This study delineates disease-specific VOC signatures and underscores the profound synergy between exhaled metabolomics and clinical immunology for identifying associations treatment response, advocating for the integration of real-time breath analysis into personalized management strategies for obstructive lung diseases.

Background: Chronic cough is a common symptom in patients with interstitial lung diseases (ILDs), which significantly affects health-related quality of life (HRQoL). The prevalence of chronic cough varies from 30% to almost 90% in different ILDs, with the highest rate in patients with idiopathic pulmonary fibrosis. However, the pathophysiology of cough in ILDs remains poorly understood, with multiple proposed mechanisms contributing to its development. This knowledge gap complicates both clinical assessment and treatment, as current therapeutic strategies target general cough mechanisms rather than ILD-specific pathways. This review synthesizes existing data to clarify distinct cough mechanisms across ILD subtypes and identify opportunities for more targeted therapeutic strategies in this challenging patient population. Moreover, cough can be a clinical marker of disease severity and a predictor of ILD progression and transplant-free survival. Effective cough-specific therapeutic options that consider potential mechanisms, comorbidities, and individual effects on HRQoL are needed for cough associated with ILD. Therefore, the aim of this review was to analyze the prevalence, the impact on HRQoL, the pathophysiology, and the management of chronic cough in ILDs. Methods: We performed a comprehensive search in PubMed, MEDLINE, Embase, and the Cochrane Library. This review included randomized clinical trials, observational studies, systematic reviews, and meta-analyses in adults with chronic cough comparing ILD types. The following were excluded: commentaries, letters, case reports and case series, conference abstracts, and studies and publications lacking cough-specific outcomes. Results: Several approaches to reduce cough frequency and severity were described: antifibrotic agents, neuromodulators, opiates, inhaled local anesthetics, oxygen, speech therapy, and anti-reflux therapy. Some therapeutic approaches, such as oral corticosteroids and thalidomide, can cause significant side effects. Novel agents, such as P2X3 receptor antagonists, which are in phase III trials (COUGH-1/2), show promising results for refractory cough and may benefit ILD-related cough. Conclusions: Thus, a comprehensive assessment of cough is required for effective cough treatment in patients with ILDs considering possible mechanisms and individual impact on QoL.