American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Dec 2019
Overlap of Genetic Risk Between Interstitial Lung Abnormalities and Idiopathic Pulmonary Fibrosis.
Rationale: Interstitial lung abnormalities (ILAs) are associated with the highest genetic risk locus for idiopathic pulmonary fibrosis (IPF); however, the extent to which there are unique associations among individuals with ILAs or additional overlap with IPF is not known. Objectives: To perform a genome-wide association study (GWAS) of ILAs. Methods: ILAs and a subpleural-predominant subtype were assessed on chest computed tomography (CT) scans in the AGES (Age Gene/Environment Susceptibility), COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]), Framingham Heart, ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points), MESA (Multi-Ethnic Study of Atherosclerosis), and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) studies. ⋯ Among 12 previously reported IPF GWAS loci, five (DPP9, DSP, FAM13A, IVD, and MUC5B) were significantly associated (P < 0.05/12) with ILAs. Conclusions: In a GWAS of ILAs in six studies, we confirmed the association with a MUC5B promoter variant and found strong evidence for an effect of previously described IPF loci; however, novel ILA associations were not associated with IPF. These findings highlight common genetically driven biologic pathways between ILAs and IPF, and also suggest distinct ones.
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Am. J. Respir. Crit. Care Med. · Dec 2019
Elevated Levels of Type 2 Respiratory Innate Lymphoid Cells in Human Infants with Severe RSV Bronchiolitis.
Rationale: Studies of the immune responses at the site of respiratory syncytial virus (RSV) infection are sparse despite nearly five decades of research into understanding RSV disease. Objectives: To investigate the role of mucosal innate immune responses to RSV and respiratory viral load in infants hospitalized with the natural disease. Methods: Cytokines, viral load, and type 2 innate lymphoid cell (ILC2) levels in nasal aspirates, collected within 24 hours of enrollment, from infants hospitalized with RSV infection were quantified. ⋯ Factors associated with disease severity were gestational age (odds ratio, 0.49; 95% confidence interval, 0.29-0.82; P = 0.007) and IL-4 (odds ratio, 9.67; 95% confidence interval, 2.45-38.15; P = 0.001). Conclusions: This study shows, for the first time, that elevated levels of ILC2s is associated with infant RSV severity. The findings highlight the dominance of type-2 responses to RSV infection in infants and suggest an important role of ILC2 in shaping the immune response early during RSV infection.
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Am. J. Respir. Crit. Care Med. · Dec 2019
Chronic E-Cigarette Use Increases Neutrophil Elastase and Matrix Metalloprotease Levels in the Lung.
Rationale: Proteolysis is a key aspect of the lung's innate immune system. Proteases, including neutrophil elastase and MMPs (matrix metalloproteases), modulate cell signaling, inflammation, tissue remodeling, and leukocyte recruitment via cleavage of their target proteins. Excessive proteolysis occurs with chronic tobacco use and is causative for bronchiectasis and emphysema. ⋯ Conclusions: We conclude that vaping induces nicotine-dependent protease release from resident pulmonary immune cells. Thus, chronic vaping disrupts the protease-antiprotease balance by increasing proteolysis in lung, which may place vapers at risk of developing chronic lung disease. These data indicate that vaping may not be safer than tobacco smoking.