Inflammation of small airways in asthma,☆☆,,★★

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Abstract

This study was designed to examine the inflammatory process in the central and peripheral airways of surgically resected lungs from asthmatic and nonasthmatic subjects. Lung specimens were inflated with cryoprotective, rapidly frozen, and systematically sampled. Cryosections prepared from frozen tissue blocks were fixed in acetone/methanol and immunostained with monoclonal antibodies by using the alkaline phosphatase–anti-alkaline phosphatase technique to detect CD3 (T cells), major basic protein (total eosinophils), EG2 (activated eosinophils), anti-tryptase (mast cells), anti-elastase (neutrophils), and CD68 (macrophages). All airways from patients with asthma demonstrated a significant increase in the numbers of T cells and total and activated eosinophils compared with airways from nonasthmatic subjects (p < 0.001). In the patients with asthma, the numbers of activated eosinophils but not T cells were significantly greater in airways with an internal perimeter less than 2 mm compared with those with an internal perimeter greater than 2 mm (p < 0.05). There were also significantly higher numbers of major basic protein–positive eosinophils, when expressed as a fraction of the alveolar wall tissue, in patients with asthma compared with control subjects (p < 0.05). In asthmatic airways with an internal perimeter of more than 2 mm, there was a greater number of activated eosinophils in the tissue between the epithelium and the smooth muscle compared with the tissue between the smooth muscle layer and lung parenchyma (p < 0.05). In contrast, there was a greater number of total eosinophils in the outer airway layer compared with the inner airway layer (p < 0.05). These results show that there is a similar but more severe inflammatory process present in the peripheral compared with the central airways of patients with asthma, which is consistent with the fact that the smaller airways are a major site of obstruction in asthma. (J Allergy Clin Immunol 1997;100:44-51.)

Section snippets

Subjects

Lung tissue was obtained from 16 subjects selected from a group of 108 patients who entered the St. Paul's Hospital Lung Study between 1991 and 1995, for which ethical approval was obtained. This ongoing study of lung structure and function is based on a prospective study of pulmonary function in patients requiring lung resection for treatment of carcinoma. Lung function was measured in the immediate preoperative period. A clinical diagnosis of asthma was made in six of these 108 patients in

Results

Table I provides the pulmonary function data for all of the patients, showing that both the asthmatic and control groups had approximate 40 pack-year histories of smoking and were well matched for age, sex, and lung function.

. Pulmonary function data in patients with asthma and nonasthmatic control subjects

Empty CellPatients with asthma (n = 6)Nonasthmatic subjects (n = 10)
Age (yr)55.0 ± 15.557.9 ± 14.4
Sex (M:F)4:26:4
Cigarettes (pack-years)40.8 ± 31.941.9 ± 26.8
TLC (% predicted)103.9 ± 1.9107.0 ± 10.2
FVC

Discussion

This study demonstrates an increase in the number of T lymphocytes and eosinophils in the airways of patients with asthma compared with nonasthmatic control subjects matched for age, sex, smoking history, lung function, and airway size. The presence of these inflammatory cells in larger airways is consistent with the increased numbers of T lymphocytes and eosinophils reported from bronchoscopic biopsy specimens of asthmatic airways.8, 9, 14, 16 The observed differences in inflammatory cells

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    From athe Meakins-Christie Laboratories, McGill University, Montreal; and bPulmonary Research Laboratory, University of British Columbia, St. Paul's Hospital, Vancouver.

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    Supported by Respiratory Health Network Centre of Excellence and MRC Grant 7246.

    Reprint requests: Qutayba Hamid, Meakins-Christie Laboratories, McGill University, 3626 St. Urbain St., Montreal, QC H2X 2P2, Canada.

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