Chest
Volume 124, Issue 1, July 2003, Pages 32-41
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Clinical Investigations
Asthma
Histopathology of Severe Childhood Asthma: A Case Series

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Background

To date, little has been published describing the pathology of severe childhood asthma. The currently accepted model of asthma holds that persistent airway inflammation leads to various symptoms of asthma, airway hyperresponsiveness, and airway remodeling that ultimately results in permanent loss of lung function.

Methods

Evaluation of six children referred to the National Jewish Medical and Research Center with difficult-to-control asthma, despite aggressive anti-inflammatory therapy, who underwent bronchoscopy with endobronchial biopsy to better characterize their disease.

Results

In every case, endobronchial biopsies revealed changes consistent with airway remodeling characterized by thickening of the basement membrane, smooth-muscle hypertrophy, with varying degrees of goblet-cell and submucous gland hyperplasia. The degree of subbasement membrane thickening did not appear to correlate with baseline FEV1, ultimate FEV1 following aggressive therapy, or lability in lung function. In five of six cases, there was minimal to no histologic evidence for airway inflammation with mild and patchy submucosal lymphocytic infiltration noted; eosinophils and neutrophils were not present. Further, the majority of the patients achieved normal FEV1 values despite significant subbasement membrane thickening, counter to the current beliefs regarding airway remodeling and irreversible loss of lung function.

Conclusions

This case report highlights some of the shortcomings of the current inflammatory paradigm for severe asthma. Despite little evidence of ongoing airway inflammation, many of the subjects displayed significant lung function lability. The lack of inflammation argues against steroid resistance at a cellular level, although it could be argued that inflammation may have been distal to the site sampled. Additionally, normal to nearly normal lung function was achieved despite the presence of significant remodeling. These findings suggest the need to look beyond inflammation to fully treat severe asthma and ultimately alter its progression.

Section snippets

Bronchoscopy and Biopsy Sample Processing

Flexible bronchoscopy was carried out using standard pediatric techniques.5 The safety of this procedure in severe asthmatics has been documented.6 For children < 12 years of age (depending on body size), the Olympus BF-3C20 (Melville, NY) [outer diameter, 3.7 mm] or the BF-3C40 (outer diameter, 3.6 mm) fiberoptic bronchoscopes were used; for adolescents, the Olympus BF-40 (outer diameter, 5.9 mm, suction channel 2.2 mm) was used. Patients underwent conscious sedation using IV narcotics

Historical and Clinical Data

The cohort studied included six children (three whites and three African Americans) evaluated at National Jewish Medical and Research Center (NJMRC) from 1993 to 1998 for evaluation of severe, persistent, steroid-dependent asthma and who underwent a clinically indicated bronchoscopy with endobronchial biopsy. The decision to perform bronchoscopy was at the discretion of the attending physician. The bronchoscopies were performed in every case to rule out other respiratory conditions and/or to

Discussion

Airway remodeling is a distinctive pathologic feature of asthma,1 and is thought to be the result of an aberrant reparative process associated with ongoing allergic inflammation. The histopathologic changes that occur within the airways of asthmatics include epithelial desquamation and regeneration, goblet-cell hyperplasia, submucosal gland hypertrophy, subepithelial fibrosis or thickening of the basement membrane, inflammatory cell infiltration, hyperplasia and hypertrophy of the bronchial

ACKNOWLEDGMENT

The authors thank Jan Henson for preparing the biopsy specimens, and all of the children with severe asthma and their parents who have been evaluated at National Jewish Medical and Research Center.

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