Chest
Volume 111, Issue 4, April 1997, Pages 852-857
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Clinical Investigations: Asthma
Airways Remodeling Is a Distinctive Feature of Asthma and Is Related to Severity of Disease

https://doi.org/10.1378/chest.111.4.852Get rights and content

Purpose

Airways remodeling, evaluated as the subepithelial layer thickness, was compared in asthmatic patients with that of healthy subjects, and was related to clinical grading of disease, presence of atopy, and length of asthmatic history.

Subjects and methods

Thirty-four patients with stable asthma (mean age±SD: 26.5±9.2 years; 10 female) treated with only inhaled β2-agonists and eight healthy volunteers (mean age±SD: 24.6±2.5 years; four female) were recruited for the study. Twenty-seven of 34 asthmatics had atopy. Eleven patients had newly diagnosed conditions (duration of disease ≤1 year), nine patients had long asthmatic history (>1 year and ≤10 years), and 14 had prolonged asthmatic history (>10 years). Bronchial responsiveness to methacholine (M) was expressed as provocative concentration of M causing a 20% fall in FEV1 (PC20) (mg/mL). Degree of asthma severity was assessed using a 0- to 12-point score based on symptoms, bronchodilator use, and daily peak expiratory flow variability over a 3-week period. Bronchoscopy and bronchial biopsy were performed successfully for all subjects; the subepithelial layer thickness, in biopsy samples, was measured from the base of bronchial epithelium to the outer limit of reticular lamina.

Results

In asthmatics, baseline FEV1 values (percent of predicted) ranged from 75.7 to 137.0%, and PC20 M ranged from 0.15 to 14.4 mg/mL. According to the asthma severity score, 14 asthmatics were classified as having mild disease, 14 as having moderate disease, and six as having severe disease. The mean values of subepithelial layer thickness were 12.4±3.3 µm (range, 6.8 to 22.1 µm) in asthmatics, and 4.4±0.5 µm (range, 3.8 to 5.2 µm) in healthy subjects (p<0.001). Subepithelial layer thickness of those with severe asthma differed significantly from that of patients with moderate and mild asthma (16.7±3.1 µm vs 12.1 ±2.7 µm and 10.8±2.4 µm, p<0.01 and p<0.003, respectively). Moreover, in asthmatics, degree of thickening was positively correlated to asthma severity score (Spearman rank correlation coefficient [rs]=0.581; p<0.001), and negatively correlated with baseline FEV1 (rs=—0.553; p<0.001) and PC20 M (rs=—0.510; p<0.01). No difference was found between degree of thickening observed in atopic asthmatics, compared with that of nonatopic asthmatics, or between degree of thickening in patients with different lengths of asthmatic history. Lastly, multiple regression analysis revealed that asthma severity score was the significant predictive factor for thickness of subepithelial layer.

Conclusions

We confirmed that airways remodeling is a very distinctive and characteristic pathologic finding of asthma. We also demonstrated that it is related to the clinical and functional severity of asthma, but not to atopy or length of asthmatic history.

Section snippets

Subjects

We studied a group of 34 patients (age range, 18 to 55 years) with bronchial asthma as defined by the American Thoracic Society11 in our outpatient clinic (Table 1). We included lifetime nonsmoking patients with no respiratory infection or spontaneous asthmatic relapses in the 4 weeks prior to study. Respiratory symptoms were controlled with inhaled β2-agonists on a daily basis or as required. Patients requiring theophylline, steroids, or sodium cromoglycate were excluded. Baseline FEV1 had to

Results

In asthmatic subjects, baseline FEV1 values ranged from 75.7 to 137.0% (mean±SD: 101.2± 16.5%). Moreover, bronchial responsiveness of asthmatics to M ranged from severe to very mild: PC20 M values ranged from 0.15 to 14.4 mg/mL (mean±geometric SEM: 1.69±1.25 mg/mL). In healthy subjects, FEV1 baseline values ranged between 93.0 and 117.0% (mean±SD: 108.1±8.4%) and bronchial responsiveness to M was not measurable.

According to the asthma severity score, 14 asthmatics (female/male [F/M]: 4/10) were

Conclusions

We found a clear cutoff between the thickness of the subepithelial layer of asthmatics compared with that of healthy subjects. Thus, we confirmed that airway remodeling is a very distinctive and characteristic pathologic finding of bronchial asthma. Moreover, we demonstrated that in a large group of asthmatic patients treated with only inhaled β2-agonists on demand or on a regular basis, the degree of subepithelial layer thickness is highly related to clinical severity of asthma. However, we

ACKNOWLEDGMENTS

The authors gratefully acknowledge Drs. Gian Franco Consigli, Angelo Casalini, and Maria Vittoria Tonna of the Bronchoscopy Unit of the Rasori Hospital, Parma, for performing bronchoscopy procedures; Ms. Elena Neri, Department of Respiratory Disease, University of Parma, for performing pulmonary function testing; and Ms. Elizabeth de Young, Language Center, University of Parma, for reviewing the text.

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