American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Jan 2024
Meta AnalysisOccupational Benzene Exposure and Lung Cancer Risk: A Pooled Analysis of 14 Case-Control Studies.
Rationale: Benzene has been classified as carcinogenic to humans, but there is limited evidence linking benzene exposure to lung cancer. Objectives: We aimed to examine the relationship between occupational benzene exposure and lung cancer. Methods: Subjects from 14 case-control studies across Europe and Canada were pooled. ⋯ These associations were observed across different subgroups, including nonsmokers. Our findings support the hypothesis that occupational benzene exposure increases the risk of developing lung cancer. Consequently, there is a need to revisit published epidemiological and molecular data on the pulmonary carcinogenicity of benzene.
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Am. J. Respir. Crit. Care Med. · Jan 2024
Loss of p73 Expression Contributes to Chronic Obstructive Pulmonary Disease.
Rationale: Multiciliated cell (MCC) loss and/or dysfunction is common in the small airways of patients with chronic obstructive pulmonary disease (COPD), but it is unclear if this contributes to COPD lung pathology. Objectives: To determine if loss of p73 causes a COPD-like phenotype in mice and explore whether smoking or COPD impact p73 expression. Methods: p73floxE7-E9 mice were crossed with Shh-Cre mice to generate mice lacking MCCs in the airway epithelium. ⋯ Furthermore, tumor protein 73 mRNA expression was reduced in the airways of current smokers (n = 82) compared with former smokers (n = 69), and p73-expressing MCCs were reduced in the small airways of patients with COPD (n = 11) compared with control subjects without COPD (n = 12). Conclusions: Loss of functional p73 in murine airway epithelium results in the absence of MCCs and promotes COPD-like lung pathology. In smokers and patients with COPD, loss of p73 may contribute to MCC loss or dysfunction.
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Am. J. Respir. Crit. Care Med. · Jan 2024
Single-Cell Imaging Maps Inflammatory Cell Subsets to Pulmonary Arterial Hypertension Vasculopathy.
Rationale: Unraveling immune-driven vascular pathology in pulmonary arterial hypertension (PAH) requires a comprehensive understanding of the immune cell landscape. Although patients with hereditary (H)PAH and bone morphogenetic protein receptor type 2 (BMPR2) mutations have more severe pulmonary vascular pathology, it is not known whether this is related to specific immune cell subsets. Objectives: This study aims to elucidate immune-driven vascular pathology by identifying immune cell subtypes linked to severity of pulmonary arterial lesions in PAH. ⋯ This correlated with an expanded DC subset expressing indoleamine 2,3-dioxygenase 1, TIM-3, and SAM and HD domain-containing deoxynucleoside triphosphate triphosphohydrolase 1, alongside increased neutrophils, SMCs, and alpha-smooth muscle actin (ACTA2)+ endothelial cells, reinforcing the heightened severity of pulmonary vascular lesions. Conclusions: This study presents the first architectural map of PAH lungs, connecting immune subsets not only with specific PA lesions but also with heightened severity in HPAH compared with IPAH. Our findings emphasize the therapeutic potential of targeting monocyte-derived dendritic cells, neutrophils, cellular interactions, and immune responses to alleviate severe vascular pathology in IPAH and HPAH.
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Am. J. Respir. Crit. Care Med. · Jan 2024
HEPA Air Filters for Preventing Wildfire-related Asthma Complications, a Cost-Effectiveness Study.
Rationale: Air pollution caused by wildfire smoke is linked to adverse health outcomes, especially for people living with asthma. Objectives: To evaluate whether government rebates for high-efficiency particulate air (HEPA) filters, which reduce concentrations of smoke particles indoors, are cost effective in managing asthma and preventing exacerbations in British Columbia (BC), Canada. Methods: We used a Markov model to analyze health states for asthma control, exacerbation severity, and death over a retrospective time horizon of 5 years (2018-2022). ⋯ A $100 rebate was cost effective in most HSDAs. Conclusions: The cost-effectiveness of HEPA filters in managing wildfire smoke-related asthma issues in BC varies by region. Government rebates up to two-thirds of the filter cost are generally cost effective, with a full rebate being cost effective only in Kootenay Boundary.