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Rationale: Epidemiologic studies on patients with asthma and in vitro data suggest a protective role of type 2 (T2) inflammation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objectives: Using a large, multisite cohort, we studied clinical outcomes after SARS-CoV-2 infection in multiple asthma endotypes and examined the effects of T2-directed biologics in infected patients with asthma. Methods: The National COVID Cohort Collaborative Data Enclave was used to identify and stratify patients with asthma by endotype to include those with non-T2 and T2 asthma, as well as exposure to T2-directed biologic therapy. We evaluated the risk of hospitalization, invasive mechanical ventilation, and 90-day mortality by endotype and exposure to biologics. Results: For this study, 402,376 patients met the inclusion criteria, of whom 138,142 (34%) were characterized as having non-T2 asthma and 264,234 (66%) as having T2 asthma, a group further divided into 104,823 (26%) atopic, 84,440 (21%) eosinophilic, and 74,971 (19%) T2-high asthmatic endotypes. Compared with patients with non-T2 asthma, those with atopic and T2-high asthma experienced decreased odds of hospitalization and 90-day mortality. Conversely, patients with eosinophilic asthma experienced higher odds of hospitalization, intubation, and 90-day mortality. Exposure to T2-directed biologic therapies did not alter outcomes after propensity score matching. In contrast, maximum eosinophil count and recent systemic corticosteroid use were directly correlated with increased odds of all outcomes. Conclusions: Coronavirus disease (COVID-19) outcomes differ depending on asthma endotype, with patients with atopic asthma experiencing lower odds and those with eosinophilic asthma experiencing higher odds of deleterious outcomes. T2-directed biologic treatment did not alter these outcomes, but recent systemic corticosteroid use predisposes all patients with asthma to adverse outcomes. [ABSTRACT FROM AUTHOR]

The article offers information about the history of the human primary bronchial epithelial (HBE) in respiratory research. It mentions the impacts of the Covid-19 pandemic on the shortages of clinical supplies including masks and hand sanitizers. It discusses that how HBE cells exposed to inflammatory mediators exhibit changes in epithelial structure/function.

Question: Cystic fibrosis (CF) is characterised by the accumulation of viscous adherent mucus in the lungs. While several hypotheses invoke a direct relationship with cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction ( i.e. acidic airway surface liquid (ASL) pH, low bicarbonate (HCO 3 - ) concentration, airway dehydration), the dominant biochemical alteration of CF mucus remains unknown., Materials/methods: We characterised a novel cell line (CFTR-KO Calu3 cells) and the responses of human bronchial epithelial (HBE) cells from subjects with G551D or F508del mutations to ivacaftor and elexacaftor-tezacaftor-ivacaftor. A spectrum of assays such as short-circuit currents, quantitative PCR, ASL pH, Western blotting, light scattering/refractometry (size-exclusion chromatography with inline multi-angle light scattering), scanning electron microscopy, percentage solids and particle tracking were performed to determine the impact of CFTR function on mucus properties., Results: Loss of CFTR function in Calu3 cells resulted in ASL pH acidification and mucus hyperconcentration (dehydration). Modulation of CFTR in CF HBE cells did not affect ASL pH or mucin mRNA expression, but decreased mucus concentration, relaxed mucus network ultrastructure and improved mucus transport. In contrast with modulator-treated cells, a large fraction of airway mucins remained attached to naïve CF cells following short apical washes, as revealed by the use of reducing agents to remove residual mucus from the cell surfaces. Extended hydration, but not buffers alkalised with sodium hydroxide or HCO 3 - , normalised mucus recovery to modulator-treated cell levels., Conclusion: These results indicate that airway dehydration, not acidic pH and/or low [HCO 3 - ], is responsible for abnormal mucus properties in CF airways and CFTR modulation predominantly restores normal mucin entanglement., Competing Interests: Conflict of interest: C.B. Morrison has nothing to disclose. Conflict of interest: K.M. Shaffer has nothing to disclose. Conflict of interest: K.C. Araba has nothing to disclose. Conflict of interest: M.R. Markovetz has nothing to disclose. Conflict of interest: J.A. Wykoff has nothing to disclose. Conflict of interest: N.L. Quinney has nothing to disclose. Conflict of interest: S. Hao has nothing to disclose. Conflict of interest: M.F. Delion has nothing to disclose. Conflict of interest: A.L. Flen has nothing to disclose. Conflict of interest: L.C. Morton has nothing to disclose. Conflict of interest: J. Liao has nothing to disclose. Conflict of interest: D.B. Hill has nothing to disclose. Conflict of interest: M.L. Drumm has nothing to disclose. Conflict of interest: W.K. O'Neal has nothing to disclose. Conflict of interest: M. Kesimer has nothing to disclose. Conflict of interest: M. Gentzsch has nothing to disclose. Conflict of interest: C. Ehre has nothing to disclose., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)