Fine particulate matter aggravates smoking induced lung injury via NLRP3/caspase-1 pathway in COPD

Exposure to noxious particles, including cigarette smoke and fine particulate matter (PM_2.5), is a risk factor for chronic obstructive pulmonary disease (COPD) and promotes inflammation and cell death in the lungs. We investigated the combined effects of cigarette smoking and PM_2.5 exposure in patients with COPD, mice, and human bronchial epithelial cells.

The relationship between PM_2.5 exposure and clinical parameters was investigated in patients with COPD based on smoking status. Alveolar destruction, inflammatory cell infiltration, and pro-inflammatory cytokines were monitored in the smoking-exposed emphysema mouse model. To investigate the mechanisms, cell viability and death and pyroptosis-related changes in BEAS-2B cells were assessed following the exposure to cigarette smoke extract (CSE) and PM_2.5.

High levels of ambient PM_2.5 were more strongly associated with high Saint George's respiratory questionnaire specific for COPD (SGRQ-C) scores in currently smoking patients with COPD. Combined exposure to cigarette smoke and PM_2.5 increased mean linear intercept and TUNEL-positive cells in lung tissue, which was associated with increased inflammatory cell infiltration and inflammatory cytokine release in mice. Exposure to a combination of CSE and PM_2.5 reduced cell viability and upregulated NLRP3, caspase-1, IL-1β, and IL-18 transcription in BEAS-2B cells. NLRP3 silencing with siRNA reduced pyroptosis and restored cell viability.

PM_2.5 aggravates smoking-induced airway inflammation and cell death via pyroptosis. Clinically, PM_2.5 deteriorates quality of life and may worsen prognosis in currently smoking patients with COPD.