Respiratory Research最新文献

Thunderstorm asthma (TA) refers to a phenomenon characterized by sudden onset, large-scale outbreaks, and potentially fatal acute exacerbations of asthma. Despite accumulating epidemiological evidence, its cellular and molecular mechanisms remain unclear. Recent studies have proposed a core framework involving "environmental triggers-epithelial barrier damage-immune dysregulation." During thunderstorms, high humidity and strong convection can cause pollen to hydrate and rupture into sub-pollen particles (SPPs) smaller than 2.5 μm, which may further combine with other pollutants such as particulate matter ≤ 2.5 μm(PM_2.5) and ozone (O₃) to form bioaerosols capable of penetrating small airways. These factors can lead to damage of the airway epithelial barrier, with sequential cellular and molecular pathophysiological changes including downregulation of various tight junction proteins in the epithelial barrier, imbalance of mucociliary clearance function, and upregulated secretion of epithelial alarmins such as interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP). This results in increased disease severity through activation of innate and adaptive immunity (e.g., type 2 innate lymphoid cells (ILC2)/T helper 2(Th2) axis activation leading to immunoglobulin E(IgE) upregulation, eosinophil activation, and mast cell degranulation; Th17-mediated neutrophilic inflammation; and toll-like receptor(TLR)-mediated innate immune processes and mucosal inflammation) and enhancement of intrinsic susceptibility factors (e.g., TLR gene polymorphisms and abnormal expression, DNA methylation and histone modifications, as well as microbiome-host interactions). According to research in meteorology, exposomics, and molecular immunology, we believe that airway epithelial barrier dysfunction and immune dysregulation play significant roles in TA. Future translational directions primarily involve establishing a population stratification and early warning system through combinations of meteorological factors with allergens/pollutants, thereby enhancing public protection and health management efforts to improve the early warning, prevention, and clinical management of TA.

Background: Inflammation drives COPD development in people living with HIV (PLwHIV), and the HIV virus impairs T regulatory (Treg) cell responses that deter immune-mediated lung injury. This study sought to determine how cigarette smoke exposure alters lung Treg responses to increase COPD susceptibility in PLwHIV.

Methods: Lung lavage levels of the Treg chemoattractant CXCL11 were quantified in a cohort of 26 HIV-infected subjects and 34 age-matched controls. To ascertain how CXCL11 modifies lung Treg responses, analyses were then conducted using a chimeric HIV (EcoHIV) infection smoke exposure mouse model and elastase treatment of Treg depleted (DEREG) mice.

Results: CXCL11 lung lavage levels increased in HIV + subjects compared to controls. However, CXCL11 levels were significantly lower in those HIV + subjects with a reduced diffusing capacity for carbon monoxide compared to HIV + subjects with normal lung function. Cigarette smoke exposure reduced CXCL11 levels in HIV + current smokers and decreased lung Cxcl11 levels and Treg frequency in control and EcoHIV-infected mice. Cigarette smoke increased lung c-Src activity in mice and the c-Src inhibitor AZD0530 restored Cxcl11 expression in smoke exposed mice and alveolar macrophages. Direct administration of CXCL11 protein to the airways of EcoHIV infected or smoke exposed mice significantly enhanced lung Treg responses. Treg deficient DEREG mice exhibited increased airway resistance at baseline and had greater lung tissue destruction post elastase treatment.

Conclusions: These findings indicate that cigarette smoke activates c-Src to suppress CXCL11 levels thereby diminishing lung Treg responses that counter airways disease and lung tissue destruction in HIV-infected individuals.

Background: People with HIV (PWH) are at increased risk for chronic lung disease and may be more susceptible to pulmonary complications following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. It remains unclear whether HIV infection modifies long-term pulmonary outcomes after coronavirus disease 2019 (COVID-19). This study assessed longitudinal changes in pulmonary function and respiratory symptoms among PWH and people without HIV (PWoH) with serologically-confirmed SARS-CoV-2 infection.

Methods: We analyzed data from the Multicenter AIDS Cohort Study (MACS)/Women's Interagency HIV Study (WIHS) Combined Cohort Study (MWCCS), a prospective US cohort of PWH and PWoH. Participants with serologic evidence of past SARS-CoV-2 infection and acceptable pre- and post-SARS-CoV-2 pulmonary function testing (PFT) including spirometry and diffusing capacity for carbon monoxide (DLCO) were included. Annualized changes in post-bronchodilator (BD) forced expiratory volume in 1 second (FEV₁), forced vital capacity (FVC), and DLCO were compared by HIV serostatus, stratified by sex. Respiratory symptoms were assessed using the St. George's Respiratory Questionnaire (SGRQ). Linear regression estimated differences in pulmonary function change by HIV serostatus, stratifying by relevant covariates.

Results: Among 778 participants (204 men; 574 women) exposed to SARS-CoV-2 and who underwent PFTs before and after infection, 66% were PWH. Men with HIV (MWH) had a mean annualized FEV₁ decline of -44.3 mL/year versus -33.8 mL/year in men without HIV (MWoH) (mean difference -10.5 mL/year; 95% CI: -30.7, 9.7). Among women, FEV₁ declined -19.8 mL/year in PWH vs. -14.8 mL/year in PWoH (mean difference -5.0 mL/year; 95% CI: -18.2, 8.2). Changes in FVC and DLCO were similar across HIV serostatus groups. No consistent differences in respiratory symptom changes were observed between PWH and PWoH. Subgroup analyses did not reveal any HIV-associated differential changes.

Conclusions: Among individuals with serologic evidence of SARS-CoV-2 infection, HIV serostatus was not associated with greater declines in pulmonary function or worsening of respiratory symptoms. Our findings suggest that having HIV alone may not increase the risk for pulmonary impairments following a SARS-CoV-2 infection. Further research is needed to understand how uncontrolled HIV infection and severity of SARS-CoV-2 infection may increase risks of adverse pulmonary outcomes following a SARS-CoV-2 infection.