Greater ozone-induced inflammatory responses in subjects with asthma.
In order to test the hypothesis that ozone (O3)-induced changes in lung function and respiratory tract injury/inflammation are greater in subjects with asthma than in normal subjects, we exposed 18 asthmatic subjects, on separate days, to O3 (0.2 ppm) and filtered air for 4 h during exercise. Symptom questionnaires were administered before and after exposure, and pulmonary function tests (FEV1, FVC, and specific airway resistance [SRaw]) were performed before, during, and immediately after each exposure. Fiberoptic bronchoscopy, with proximal airway lavage (PAL) of the isolated left main bronchus and bronchoalveolar lavage (BAL; bronchial fraction, the first 10 ml of fluid recovered) of the right middle lobe, was performed 18 h after each exposure. The PAL, bronchial fraction, and BAL fluids were analyzed for the following endpoints: total and differential cell counts; total protein, lactate dehydrogenase (LDH), fibronectin, interleukin-8 (IL-8), granulocyte-macrophage colony-stimulating factor (GM-CSF), myeloperoxidase (MPO), and transforming growth factor-beta (TGF beta 2) concentrations. We found a significant O3 effect on FEV1, FVC, SRaw (p < 0.04) and lower respiratory symptoms (p < 0.001) for the asthmatic subjects. Ozone exposure also significantly increased the percent neutrophils in PAL (p < 0.01); percent neutrophils, total protein, and IL-8 in the bronchial fraction (p < 0.001, p < 0.05, and p < 0.01, respectively); and the percent neutrophils, total protein, LDH, fibronectin, IL-8, GM-CSF, and MPO in BAL (p < 0.001, p < 0.01, p < 0.01, p < 0.001, p < 0.05, p < 0.01, and p < 0.001, respectively) for the asthmatic subjects. There were no significant differences in the lung function responses of the asthmatic subjects in comparison with a group of normal subjects (n = 81) previously studied using an identical protocol, although there was a trend toward a greater O3-induced increase in SRaw in the asthmatic subjects (p < 0.13). In contrast, the asthmatic subjects showed significantly greater (p < 0.05) O3-induced increases in several inflammatory endpoints (percent neutrophils and total protein concentration) in BAL as compared with normal subjects who underwent bronchoscopy (n = 20). Our results indicate that asthmatic persons may be at risk of developing more severe O3-induced respiratory tract injury/inflammation than normal persons, and may help explain the increased asthma morbidity associated with O3 pollution episodes observed in epidemiologic studies.
Scannell
C
C
Lung Biology Center, San Francisco General Hospital, University of California 94143-0854, USA.
Chen
L
L
Aris
R M
RM
Tager
I
I
Christian
D
D
Ferrando
R
R
Welch
B
B
Kelly
T
T
Balmes
J R
JR
D000293:Adolescent; D000328:Adult; D000393:Air Pollutants / Q000009:adverse effects*; D000403:Airway Resistance / Q000187:drug effects; D001249:Asthma / Q000473:pathology* / Q000503:physiopathology; D001707:Biopsy, Needle; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D001999:Bronchoscopy; D002452:Cell Count; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D010126:Ozone / Q000009:adverse effects*; D014797:Vital Capacity / Q000187:drug effects
D000393:Air Pollutants; D010126:Ozone