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Published ahead of print on November 24, 2004, doi:10.1164/rccm.200407-949OC

Am. J. Respir. Crit. Care Med., Volume 171, Number 5, March 2005, 431-439

A more recent version of this article appeared on March 1, 2005
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Submitted on July 21, 2004
Accepted on November 18, 2004

Relationship of Small Airway Chymase-Positive Mast Cells and Lung Function in Severe Asthma

Silvana Balzar1*, Hong Wei Chu1, Matthew Strand2, and Sally Wenzel1

1 Department of Medicine, National Jewish Medical and Research Center, Denver, CO, USA; Department of Medicine, University of Colorado Health Sciences Center, Denver, CO, USA, 2 Department of Medicine, National Jewish Medical and Research Center, Denver, CO, USA; Division of Biostatistics, University of Colorado Health Sciences Center, Denver, CO, USA

* To whom correspondence should be addressed. E-mail: balzars{at}njc.org.

Distal lung inflammation may be important in asthma pathophysiology. The goal of this study was to measure cellular inflammation in the large airway and four distal lung regions (small airway inner and outer wall, alveolar attachments and peripheral alveolar tissue) and to correlate the specific inflammatory cells with several lung function parameters. Sections of concurrently-obtained endobronchial and transbronchial/surgical biopsy tissue from twenty severe asthmatics were immunostained for T-lymphocyte, eosinophil, monocyte/macrophage, neutrophil and two mast cell markers (tryptase and chymase). Specific cell distributions were determined and correlated with lung function measures. The number of inflammatory cells generally increased toward the periphery, but the percentage of T-lymphocytes, eosinophils, monocytes/macrophages and neutrophils remained similar or decreased from large to small airways. In contrast, mast cell number, percentage, as well as the chymase-positive phenotype increased in small airway regions. After the analysis was adjusted for multiple comparisons, only chymase-positive mast cells significantly and positively correlated with lung function. Such a relationship was seen only in the small airway/alveolar attachments lung region (rs=0.61-0.89; p≤0.001 for all correlations).These data suggest that induction of chymase-positive mast cells particularly in the small airway outer wall/alveolar attachments region may be protective for lung function in severe asthma.
Key words: Bronchial asthma, Inflammation, Mast cells




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