American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Nov 2022
Randomized Controlled TrialA Phase IIb Randomized Study of an Anti-αvβ6 Monoclonal Antibody in Idiopathic Pulmonary Fibrosis.
Rationale: Treatment options for idiopathic pulmonary fibrosis (IPF) are limited. Objectives: To evaluate the efficacy and safety of BG00011, an anti-αvβ6 IgG1 monoclonal antibody, in the treatment of patients with IPF. Methods: In a phase IIb randomized, double-blind, placebo-controlled trial, patients with IPF (FVC ⩾50% predicted, on or off background therapy) were randomized 1:1 to once-weekly subcutaneous BG00011 56 mg or placebo. ⋯ Conclusions: The results do not support the continued clinical development of BG00011. Further research is warranted to identify new treatment strategies that modify inflammatory and fibrotic pathways in IPF. Clinical trial registered with www.clinicaltrials.gov (NCT03573505).
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Am. J. Respir. Crit. Care Med. · Nov 2022
Epidemiology, Management, and Outcomes of Sepsis in Intensive Care Units Among Countries of Differing National Wealth Across Asia.
Rationale: Directly comparative data on sepsis epidemiology and sepsis bundle implementation in countries of differing national wealth remain sparse. Objectives: To evaluate across countries/regions of differing income status in Asia 1) the prevalence, causes, and outcomes of sepsis as a reason for ICU admission and 2) sepsis bundle (antibiotic administration, blood culture, and lactate measurement) compliance and its association with hospital mortality. Methods: A prospective point prevalence study was conducted among 386 adult ICUs from 22 Asian countries/regions. ⋯ Sepsis bundle compliance remains low. Delaying antibiotic administration beyond 3 hours from diagnosis is associated with increased mortality. Clinical trial registered with www.ctri.nic.in (CTRI/2019/01/016898).
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Am. J. Respir. Crit. Care Med. · Nov 2022
Solid Fuel, Second-Hand Smoke, and Lung Cancer Mortality: A Prospective Cohort of 323,794 Chinese Never-Smokers.
Rationale: Household air pollution and secondhand tobacco smoke are known carcinogens for lung cancer, but large-scale estimates of the relationship with lung cancer mortality are lacking. Objectives: Using the large-scale cohort China Kadoorie Biobank, we prospectively investigated associations between these two risk factors and lung cancer death among never-smokers. Methods: The Biobank recruited 512,715 adults aged 30-79 years from 10 regions in China during 2004-2008. ⋯ The association was largely consistent across various subgroups. No significant association was found between secondhand smoke and lung cancer death. Conclusions: This cohort study provides new prospective evidence suggesting that domestic solid fuel use is associated with lung cancer death among never-smokers.
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Am. J. Respir. Crit. Care Med. · Nov 2022
ReviewMechanistic Insights into the Impact of Air Pollution on Pneumococcal Pathogenesis and Transmission.
Streptococcus pneumoniae (the pneumococcus) is the leading cause of pneumonia and bacterial meningitis. A number of recent studies indicate an association between the incidence of pneumococcal disease and exposure to air pollution. Although the epidemiological evidence is substantial, the underlying mechanisms by which the various components of air pollution (particulate matter and gases such as NO2 and SO2) can increase susceptibility to pneumococcal infection are less well understood. ⋯ This increases recruitment of innate immune cells, including macrophages and neutrophils. The inflammatory response that ensues may result in significant tissue damage, thereby increasing susceptibility to invasive disease, because it allows S. pneumoniae access to the underlying tissues and blood. This review provides an in-depth understanding of the interaction between air pollution and the pneumococcus, which has the potential to aid the development of novel treatments or alternative strategies to prevent disease, especially in areas with high concentrations of air pollution.
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Am. J. Respir. Crit. Care Med. · Nov 2022
Mucins MUC5AC and MUC5B Are Variably Packaged in the Same and in Separate Secretory Granules.
Rationale: MUC5AC (mucin 5AC, oligomeric gel-forming) and MUC5B (mucin 5B, oligomeric gel-forming) are the predominant secreted polymeric mucins in mammalian airways. They contribute differently to the pathogenesis of various muco-obstructive and interstitial lung diseases, and their genes are separately regulated, but whether they are packaged together or in separate secretory granules is not known. Objectives: To determine the packaging of MUC5AC and MUC5B within individual secretory granules in mouse and human airways under varying conditions of inflammation and along the proximal-distal axis. ⋯ Conclusions: MUC5AC and MUC5B are variably stored both in the same and in separate secretory granules of both mice and humans. The high fraction of granules containing both mucins under a variety of conditions makes it unlikely that their secretion can be differentially controlled as a therapeutic strategy. This work also advances knowledge of the packaging of mucins within secretory granules to understand mechanisms of epithelial stress in the pathogenesis of chronic lung diseases.