American journal of respiratory and critical care medicine
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Rationale: The respiratory tract constitutes an elaborate line of defense that is based on a unique cellular ecosystem. Objectives: We aimed to investigate cell population distributions and transcriptional changes along the airways by using single-cell RNA profiling. Methods: We have explored the cellular heterogeneity of the human airway epithelium in 10 healthy living volunteers by single-cell RNA profiling. ⋯ We also report the association of KRT13 with dividing cells that are reminiscent of previously described mouse "hillock" cells and with squamous cells expressing SCEL and SPRR1A/B. Conclusions: Robust characterization of a single-cell cohort in healthy airways establishes a valuable resource for future investigations. The precise description of the continuum existing from the nasal epithelium to successive divisions of the airways and the stable gene expression profile of these regions better defines conditions under which relevant tracheobronchial proxies of human respiratory diseases can be developed.
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Am. J. Respir. Crit. Care Med. · Dec 2020
Development and Initial Validation Analyses of the Living with Idiopathic Pulmonary Fibrosis (L-IPF) Questionnaire.
Rationale: Several new drugs for idiopathic pulmonary fibrosis (IPF) are in development. Tools are needed to assess whether these drugs benefit patients on outcomes that matter most to them. Health-related quality of life (HRQL) is one such outcome. ⋯ After factor and item analyses, 35 items were retained, and these comprise the two modules (symptoms and impacts) of the Living with IPF (L-IPF) questionnaire. The L-IPF yields five scales demonstrating good psychometric properties, including correlation with concurrently collected FVC% predicted and the ability to discriminate between patients with differing levels of IPF severity. Conclusions: The L-IPF is a new questionnaire that assesses symptoms, disease impacts, and HRQL in patients with IPF.
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Am. J. Respir. Crit. Care Med. · Dec 2020
Evidence for Environmental-human Microbiota Transfer at a Manufacturing Facility with Novel Work-related Respiratory Disease.
Rationale: Workers' exposure to metalworking fluid (MWF) has been associated with respiratory disease. Objectives: As part of a public health investigation of a manufacturing facility, we performed a cross-sectional study using paired environmental and human sampling to evaluate the cross-pollination of microbes between the environment and the host and possible effects on lung pathology present among workers. Methods: Workplace environmental microbiota were evaluated in air and MWF samples. ⋯ Lung samples from four index cases and skin and nasal samples from workers in the machine shop area were enriched with Pseudomonas, the dominant taxa in MWF. Exposure to used MWF stimulated murine B-cell proliferation in vitro, a hallmark cell subtype found in the pathology of index cases. Conclusions: Evaluation of a manufacturing facility with a cluster of workers with respiratory disease supports cross-pollination of microbes from MWF to humans and suggests the potential for exposure to these microbes to be a health hazard.
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Am. J. Respir. Crit. Care Med. · Dec 2020
Multicenter StudyOutcome of Hospitalization for COVID-19 in Patients with Interstitial Lung Disease: An International Multicenter Study.
Rationale: The impact of coronavirus disease (COVID-19) on patients with interstitial lung disease (ILD) has not been established. Objectives: To assess outcomes in patients with ILD hospitalized for COVID-19 versus those without ILD in a contemporaneous age-, sex-, and comorbidity-matched population. Methods: An international multicenter audit of patients with a prior diagnosis of ILD admitted to the hospital with COVID-19 between March 1 and May 1, 2020, was undertaken and compared with patients without ILD, obtained from the ISARIC4C (International Severe Acute Respiratory and Emerging Infection Consortium Coronavirus Clinical Characterisation Consortium) cohort, admitted with COVID-19 over the same period. ⋯ Furthermore, obese patients with ILD had an elevated risk of death (HR, 2.27; 1.39-3.71). Conclusions: Patients with ILD are at increased risk of death from COVID-19, particularly those with poor lung function and obesity. Stringent precautions should be taken to avoid COVID-19 in patients with ILD.