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Published ahead of print on May 19, 2004, doi:10.1164/rccm.200403-305OC

Am. J. Respir. Crit. Care Med., Volume 170, Number 8, October 2004, 857-862

A more recent version of this article appeared on October 15, 2004
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Submitted on March 9, 2004
Accepted on May 13, 2004

Abnormal Alveolar Attachments with Decreased Elastic Fiber Content in Distal Lung in Fatal Asthma

Thais Mauad1*, Luis F.F. Silva1, Mario A Santos1, Lea Grinberg1, Fabiola D.C. Bernardi1, Milton de Arruda Martins1, Paulo H.N. Saldiva1, and Marisa Dolhnikoff1

1 Department of Pathology, Medical School, Sao Paulo University, Sao Paulo, SP, Brazil

* To whom correspondence should be addressed. E-mail: tmauad{at}usp.br.

Small airway disease is thought to contribute significantly to asthma functional impairment. Functional evidence of airway-parenchyma uncoupling in asthma, such as loss of deep breath bronchodilator effect in bronchoconstrictive episodes and enhanced airway closure have been previously demonstrated. Elastic fibers are essential to maintain the adequate elastic recoil of the lungs. In this study, we hypothesized that alveolar attachments could be abnormal and that elastic fibers could be damaged in the distal lung of fatal asthma patients. For this purpose, we measured the numbers of abnormal alveolar attachments and quantified the content of elastic fibers in the adventitial layer of small airways and in peribronchial and distal alveolar septa in 15 patients who died of asthma (FA) and 9 controls (CTRL). Our data (geometric mean/ranges) showed an increased proportion of abnormal alveolar attachments/cm of basement membrane perimeter in fatal asthma [FA= 0.18 (0.03-4.00); CTRL=0.00 (0.00-0.12), p<0.001], decreased elastic fiber content in the small airways adventitial layer [FA=4.08µm (2.22-11.46µm, CTRL=6.79µm (5.62-10.0 µm, p=0.01] and in the peribronchial alveoli [FA=1.08µm (0.46-1.91µm), CTRL=1.81µm (1.22-1.74µm) p= 0.003] but not in the distal alveoli. We propose that structural alterations at peribronchiolar level might contribute to the pathogenesis of some functional abnormalities observed in severe asthmatics.
Key words: airway-parenchyma uncoupling, autopsy, remodeling, small airways




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