Asthma diagnosis and treatment
Specificity of basement membrane thickening in severe asthma

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Background

Reticular basement membrane (RBM) thickness is considered a hallmark for airway remodeling in airway diseases such as asthma. It is still unclear whether this measurement could be associated with disease severity or apply to chronic obstructive pulmonary disease (COPD). A wide range of results, at baseline or after therapeutic intervention, have been reported using different measurement methods.

Objective

To determine whether increased RBM thickness could be associated specifically with severe asthma and in COPD in large samples.

Methods

We blindly measured RBM thickness in endobronchial biopsies from 50 patients with severe asthma (mean age, 53 years; FEV1 66% predicted, inhaled steroids ≥1500 μg and 20 mg daily dose of oral corticosteroids, lifelong nonsmokers), 50 untreated patients with mild asthma (mean age, 33 years; FEV1 93%pred, lifelong nonsmokers), 50 patients with COPD (mean age, 57 years; FEV1 53%pred, all current smokers), and 18 control subjects using 2 different validated quantitative and computer-assisted methods (repeated multiple point-to-point vs area by length ratio).

Results

Reticular basement membrane thickness was higher in severe asthma compared with mild asthma and COPD (P = .0053). On the basis of receiver operating characteristic curves, RBM thickness was effective in differentiating severe asthma from other groups (sensitivity and specificity, 98% and 95%, respectively, above a threshold of 5 μm vs control, 70% and 75% at 7 μm vs mild, 83% and 68% at 6 μm vs COPD).

Conclusion

Increased RBM thickness was specifically associated with severe asthma, whereas surprisingly, COPD and mild asthma had similar remodeling features.

Clinical implications

Reticular basement membrane thickness can be considered a hallmark of severe asthma.

Section snippets

Patients

From 1996 to 2000, endobronchial biopsies (EBBs) were performed in 6 different clinical studies, approved by ethics committees, involving more than 300 patients. We selected the first 50 well characterized patients with mild-to-moderate untreated asthma, 50 current smokers with untreated COPD, and 50 patients with severe oral steroid–treated asthma. The diagnoses were made according to current guidelines.11, 12 The first 2 groups of patients were naive for anti-inflammatory treatment at the

Patient characteristics

Patients with mild and severe asthma and COPD presented markedly different phenotypes, as reported in Table I. Seventy percent of patients with mild asthma and 60% with severe asthma were atopic, and 3 of them were exsmokers (<5 pack-years, ceased for at least 1 year; Table I). Patients with COPD had a lower reversibility than patients with asthma (P = .0001). They were all current heavy smokers. Severe asthma and COPD groups presented with similar lung function at rest but significantly

Discussion

This study demonstrated that RBM thickness could differentiate patients with chronic airway disease when measured by 2 different validated methods. Remodeling in severe asthma was clearly different from remodeling in mild asthma and COPD, both of which differed from the situation observed in control subjects.

We chose the methods for RBM assessment by Wilson and Li8 and Sullivan et al9 because of their wide use and validation compared with methods as effective as TEM.8 Stereologic approaches

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    Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

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