The origin of collagen-producing cells in lung fibrosis is unclear. The involvement of embryonic signaling pathways has been acknowledged and trans-differentiation of epithelial cells is discussed critically. The work presented here investigates the role of TGFB in cytoskeleton remodeling and the expression of Epithelial-Mesenchymal-Transition markers by Alveolar Epithelial Cells Type II and tests the hypothesis if human alveolar epithelial cells are capable of trans-differentiation and production of pro-fibrotic collagen. Primary human alveolar epithelial cells type II were extracted from donor tissues and stimulated with TGFβ and a TGFβ-inhibitor. Transcriptome and pathway analyses as well as validation of results on protein level were conducted. A TGFβ-responsive fingerprint was found and investigated for mutual interactions. Interaction modules exhibited enrichment of genes that favor actin cytoskeleton remodeling, differentiation processes and collagen metabolism. Cross-validation of the TGFβ-responsive fingerprint in an independent IPF dataset revealed overlap of genes and supported the direction of regulated genes and TGFβ-specificity. Primary human alveolar epithelial cells type II seem undergo a TGFβ-dependent phenotypic change, exhibit differential expression of EMT markers in vitro and acquire the potential to produce collagen.

Human airways are continuously colonized by microaspiration of microbiota. Less is known about the presence, origin and composition of microbiota in the lung parenchyma. In a study of 13 patients undergoing surgery for peripheral lung cancer microbiota composition was comparatively evaluated in upper airway, lower airway and lung tissue samples using 16S rDNA analysis. Bacterial density decreased stepwise from upper to lower airways and tissue. On a taxonomic level upper and lower airway microbiota were similar whereas lung tissue showed marked dissimilarities compared to lower airways that may reflect different environmental conditions shaping local microbiota and host immunity.

Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SAR2-COV-2), and was first identified in Wuhan, China in December of 2019, but quickly spread to the rest of the world, causing a pandemic. While some studies have found no link between smoking status and severe COVID-19, others demonstrated a significant one. The present study aimed to determine the relationship between smoking and clinical COVID-19 severity via a systematic meta-analysis approach. Methods: We searched the Google Scholar, PubMed, Scopus, Web of Science, and Embase databases to identify clinical studies suitable for inclusion in this meta-analysis. Studies reporting smoking status and comparing non-severe and severe patients were included. Non-severe cases were described as mild, common type, non-intensive care unit (ICU) treatment, survivors, and severe cases as critical, need for ICU, refractory, and non-survivors. Results: A total of 16 articles detailing 11322 COVID-19 patients were included. Our meta-analysis revealed a relationship between a history of smoking and severe COVID-19 cases (OR=2.17; 95% CI: 1.37–3.46; P <.001). Additionally, we found an association between the current smoking status and severe COVID-19 (OR=1.51; 95% CI: 1.12–2.05; P <.008). In 10.7% (978/9067) of non-smokers, COVID-19 was severe, while in active smokers, severe COVID-19 occurred in 21.2% (65/305) of cases. Conclusion: Active smoking and a history of smoking are clearly associated with severe COVID-19. The SARS-COV-2 epidemic should serve as an impetus for patients and those at risk to maintain good health practices and discontinue smoking.

Background: Pulmonary arterial hypertension restricts the ability of patients to perform routine physical activities. As part of pulmonary arterial hypertension treatment, inhaled iloprost can be administered via a nebulizer that tracks inhalation behavior. Pulmonary arterial hypertension treatment is guided by intermittent clinical measurements, such as 6-minute walk distance, assessed during regular physician visits. Continuous digital monitoring of physical activity may facilitate more complete assessment of the impact of pulmonary arterial hypertension on daily life. Physical activity tracking with a wearable has not yet been assessed with simultaneous tracking of pulmonary arterial hypertension medication intake. Objective: We aimed to digitally track the physical parameters of patients with pulmonary arterial hypertension who were starting treatment with iloprost using a Breelib nebulizer. The primary objective was to investigate correlations between changes in digital physical activity measures and changes in traditional clinical measures and health-related quality of life over 3 months. Secondary objectives were to evaluate inhalation behavior, adverse events, and changes in heart rate and sleep quality. Methods: We conducted a prospective, multicenter observational study of adults with pulmonary arterial hypertension in World Health Organization functional class III who were adding inhaled iloprost to existing pulmonary arterial hypertension therapy. Daily distance walked, step count, number of standing-up events, heart rate, and 6-minute walk distance were digitally captured using smartwatch (Apple Watch Series 2) and smartphone (iPhone 6S) apps during a 3-month observation period (which began when iloprost treatment began). Before and at the end of the observation period (within 2 weeks), we also evaluated 6-minute walk distance, Borg dyspnea, functional class, B-type natriuretic peptide (or N-terminal pro–B-type natriuretic peptide) levels, health-related quality of life (EQ-5D questionnaire), and sleep quality (Pittsburgh Sleep Quality Index). Results: Of 31 patients, 18 were included in the full analysis (observation period: median 91.5 days, IQR 88.0 to 92.0). Changes from baseline in traditional and digital 6-minute walk distance were moderately correlated (r=0.57). Physical activity (daily distance walked: median 0.4 km, IQR –0.2 to 1.9; daily step count: median 591, IQR −509 to 2413) and clinical measures (traditional 6-minute walk distance: median 26 m, IQR 0 to 40) changed concordantly from baseline to the end of the observation period. Health-related quality of life showed little change. Total sleep score and resting heart rate slightly decreased. Distance walked and step count showed short-term increases after each iloprost inhalation. No new safety signals were identified (safety analysis set: n=30). Conclusions: Our results suggest that despite challenges, parallel monitoring of physical activity, heart rate, and iloprost inhalation is feasible in patients with pulmonary arterial hypertension and may complement traditional measures in guiding treatment; however, the sample size of this study limits generalizability. Trial Registration: ClinicalTrials.gov NCT03293407; https://clinicaltrials.gov/ct2/show/NCT03293407 International Registered Report Identifier (IRRID): RR2-10.2196/12144

Several substitute products are discussed as a healthier alternative to smoking, thereunder e-cigarettes and smokeless tobacco products, e.g., chewing bags, which are increasingly used in this context. We investigated the acute effects of chewing bags compared to combustible cigarettes and e-cigarettes with and without nicotine on small airways and arterial stiffness in a head-to-head design. This single-center, four-arm cross-overstudy included 20 healthy occasional smokers (25 ± 0.6 years). On four test days, participants consumed one product per day. Before, during, and after consumption, peripheral and central hemodynamic as well as arterial stiffness parameters were measured by Mobil-O-Graph™ (I.E.M., Germany). Resistance and small airway function were assessed by tremoFlo® c-100 (THORASYS Thoracic Medical Systems Inc.). The combustible cigarette and the e-cigarettes with and without nicotine significantly increased the resistance of the small airways (p < 0.05), while chewing bags had no effect. All nicotine containing products (e-cigarette with nicotine, combustible cigarette, chewing bag) as well as the e-cigarette without nicotine significantly increased parameters of hemodynamic and arterial stiffness. Changes in blood pressure and arterial stiffness were similar after smoking, vaping, and using chewing bags. We conclude that e-cigarettes and combustible cigarettes have similar acute harmful effects on small airway dysfunction. All nicotine containing products are associated with an increased cardiovascular risk compared with no product use.