Payne DN, Rogers AV, Ädelroth E, et al. Am J Respir Crit Care Med. 2003;167:78–83
Purpose of the Study.
To determine whether reticular basement membrane (RBM) thickening is present among children with difficult-to-control asthma and to compare the findings with those for adults with asthma.
Subjects were 19 children (6–16 years of age) with difficult-to-control asthma. Control subjects were 10 children (7–16 years of age) without asthma, 10 adults with mild asthma, 6 adults with severe asthma, and 8 healthy adults.
The 19 asthmatic children underwent bronchoscopy and endobronchial biopsy as part of an asthma evaluation. Patients were treated with oral prednisolone therapy (40 mg/day) for 2 weeks before the biopsy. Exhaled nitric oxide levels were measured before and after the course of corticosteroids. Endobronchial samples were obtained from third-order or higher bronchi on either side of the lung. The control subjects were pediatric patients undergoing bronchoscopy because of other indications. The adults with mild asthma were corticosteroid-naïfive. Adults with severe asthma underwent biopsy while intubated because of a severe asthma attack. The 8 adult control subjects were nonsmokers. Three biopsy specimens for each patient were fixed immediately and stained for light-microscopic evaluation.
Children with asthma had an average RBM thickness of 8.2 μm (range: 5.4–11.2 μm). Adults with mild asthma had a mean RBM thickness of 8.1 μm (range: 5.8–10.0 μm); adults with severe asthma had a mean RBM thickness of 7.2 μm (range: 2.8–10.0). Adult control subjects had an average RBM thickness of 4.4 μm (range: 3.2–6.3 μm; P < .01); pediatric control subjects had an average RBM thickness of 4.9 μm (range: 3.7–8.3 μm; P < .01). There was no correlation of RBM thickness with duration of asthma or age. The exhaled nitric oxide concentrations before and after prednisolone treatment were 16.9 ppb (range: 1.2–33.4 ppb) and 8.1 ppb (range: 1.3–24.5 ppb), respectively (normal values at the study center: <12.5 ppb). There was no correlation between RBM thickness and exhaled nitric oxide levels.
The authors concluded that RBM thickening is a feature of childhood asthma that is not present among normal control subjects. RBM thickening is a common feature of asthma among adults and children but is not correlated with age, severity, or duration.
This study demonstrated that histologic changes in the airways of children with severe asthma, as evidenced by RBM thickening, are similar to those seen among adults. This is one of the few such studies among children and is novel for the inclusion of child and adult control subjects. The authors were unable to show a link between RBM thickness and severity of asthma or a marker of inflammation (exhaled nitric oxide). This information raises questions regarding the timing and appropriateness of antiinflammatory treatment delivered with the hope of preventing airway remodeling among children with asthma. Clinical trials are needed to establish whether it is possible to prevent these changes and whether such prevention is important.