Effect of ambient air quality on exacerbation of COPD in patients and its potential mechanism

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a disease of continuous progress and environmental factors may affect the progress. COPD patients' activity tolerance and quality of life are associated with air quality. COPD exacerbation from the perspective of geographical air quality has not been reported.

Objectives: To explore environmental effect of two different geographical places on COPD exacerbation and the effect of cigarette smoke extract and carbon particles on bronchial epithelial cell viability.

Methods: Total 139 COPD patients, who lived in Beijing during summer and temporarily migrated to Sanya city in winter, have been enrolled. Respiratory symptoms and lung function data were collected when they were living in Beijing or Sanya, respectively. Effect of cigarette smoke extract plus ultrafine carbon particles on airway epithelial cells were studied.

Measurements and main results: Air pollution as measured by air quality index (AQI) in Beijing summer (113.1±14.2) was significantly worse than that in Sanya winter (49.4±8.9, p<0.001). The COPD Assessment Test (CAT) score was significantly higher in Beijing (26.4±7.1) than that in Sanya (20.0±8.0, p=0.019). Modified Medical Research Council dyspnea scale was also significantly higher in Beijing (2.9±0.9) than that in Sanya (1.9±0.8, p<0.001). FEV₁ was significantly improved when the patients were in Sanya (48.88±24.78%) compared to that in Beijing (41.79±20.06%, p<0.01). Compared with Beijing and Sanya, the relative risk (RR) of hospitalization and acute exacerbation were 1.64 and 3.36, respectively. In vitro study demonstrated that apoptosis of BEAS2B cells in response to cigarette smoke extract plus ultrafine carbon particles (25.50±2.10%) was significantly higher than that of control culture (2.30±1.05%, p<0.01).

Conclusion: These findings suggested that ambient air pollution cause COPD exacerbation, and that air pollutants particle matters induce apoptosis of airway epithelial cells.

Keywords: air pollution; apoptosis of airway epithelial cells; chronic obstructive pulmonary disease; lung function; temporary migration.

Figure 1

Comparison of temperature, humidity and ambient air quality between Beijing and Sanya. Monthly average temperature, humidity and air quality data were obtained from the Meteorological Department of Beijing City and Sanya City. (A) Monthly average of temperature. (B) Monthly average of humidity. (C) Monthly average of air quality in Beijing and Sanya.

Figure 2

Comparison of COPD Assessment Test (CAT) score in patients when they were in Beijing or Sanya. (A) CAT score of common symptoms. (B) Average CAT score of the patients in Beijing or Sanya.

Figure 3

Comparison of Modified Medical Research Council (MMRC) dyspnea scale.

Figure 4

Comparison of pulmonary function test. Patients’ pulmonary function was tested when they were in Beijing or Sanya. (A) FVE₁ or FEV₁/FVC. (B) FVC. (C) MEF₇₅. (D) MEF₅₀. (E) MEF₂₅. Abbreviations: MEF, maximum expiratory flow; L, liter.

Figure 5

Effect of CSE and UFCP on BEAS2B cell viability. BEAS2B cells were exposed to 10% cigarette smoke extract (CSE) and/or ultrafine carbon particles (UFCP) for 24 hrs. TUNEL assay was performed as described in the methods. (A) Representative image of TUNEL staining. Green: TUNEL positive staining; Blue: nuclei. (B) Quantitative graph of TUNEL positivity. Horizontal axis: treatment of the cells; vertical axis: TUNEL positivity in 5 high power field. *p<0.05.

Figure 6

Immunoblotting of caspase-3, caspase-9 and Bcl-2. BEAS2B cells were exposed to 10% cigarette smoke extract (CSE) and/or ultrafine carbon particle (UFCP) for 24 hrs. Cells were harvested with cell lysis buffer and subjected for immunoblotting as described in the methods. (A) Representative image of the immunoblotting. (B) Semi-quantification of caspase-3. *p<0.05 compared to control. (C) Semi-quantification of caspase-9. (D) Semi-quantification of Bcl-2. *p<0.05.

Figure 7

Effect of CSE and UFCP on production of inflammatory cytokines and growth factors. BEAS2B cells were treated with 10% cigarette smoke extract (CSE) and/or ultrafine carbon particle (UFCP) for 24 hrs. Medium was harvested and used for quantification of cytokines and growth factors as described in the methods. (A) IL-1ß; (B) IL-6; (C) IL-8; (D) TGF-ß1. Vertical axis: concentration of cytokines or growth factor (pg/mL); horizontal axis: treatment of the cells. *p<0.05; **p<0.01.