Characteristics of the Inflammation in Biopsies from Large Airways of Subjects with Asthma and Subjects with Chronic Airflow Limitation

Abstract

Although the characteristics of the histopathologic changes present in subjects who die with status asthmaticus are well documented, the structural changes present in subjects with mild to moderately severe asthma are not well described and the inflammatory changes in the large airways of subjects with chronic airflow limitation (CAL) and asthma have not been compared. Ten subjects with asthma, five taking inhaled corticosteroids and five taking beta 2-agonist aerosols, five subjects with CAL, and four subjects with no respiratory illness had four biopsies taken from airways 10 mm in diameter. The length of intact epithelium, thickness of basement membrane, and number of lymphocytes, neutrophils, eosinophils, plasma cells, monocytes, and mast cells in the lamina propria, bronchial smooth muscle, and submucosa were measured. Intact epithelium was present along 56% of the basement membrane in the asthmatic subjects, along 54% in the subjects with CAL, and along 84% in the control subjects. In the asthmatic subjects there was no direct relationship between the severity of asthma and the amount of epithelial cell loss or the number of inflammatory cells. The basement membrane was thickened in all asthmatic subjects but not in normal subjects or subjects with CAL. There was a significant increase in the number of lymphocytes, eosinophils, and mast cells in the asthmatic airways, particularly in the lamina propria, compared with the CAL subjects. There were no eosinophils or mast cells in any of the control subjects. The airways of subjects with CAL contained significantly more inflammatory cells than the control subjects. Subjects with asthma on inhaled corticosteroids had significantly fewer lymphocytes, eosinophils, and mast cells compared with subjects taking only beta 2-agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Do bronchial biopsies represent mast cell density in airways? A stereological study

“…Endobronchial biopsy has been widely used as a research tool to assess airway inflammation in asthma [3,4,[6][7][8][9][10][11][12][13][14][15][16]22]. Its use as a tool in clinical research has recently become the subject of review [20].…”

“…Biopsy studies of airway inflammation have generally used only two or three biopsies per case to enumerate a particular cell type [3,4,[6][7][8][9][10][12][13][14][15][16], and have often relied on 2D cell profile methods, expressing density as cells per area [4,[8][9][10][11][12][14][15][16].…”

“…If it had been possible to use lung tissue from much larger numbers of subjects, it is more likely that case means based on fewer than four biopsies would have been correlated significantly with case means over the WAi in all transverse sections, adding weight to the argument that two or three biopsies could be sufficiently representative of the WAi generally in such circumstances. However, in biopsy studies of airway inflammation in asthma, the size of case groups representing disease states is typically of the order of 10 subjects [3,4,7,8,11,12,15,16,19], rarely much more [6], and in the case of control subjects, often much less [4, 7-9, 11, 12]. Furthermore, increasing the number of subjects is unlikely to substantially alter r values, so that while four or more biopsies will probably reflect .50% of the variance over the WAi generally, fewer than four biopsies will probably reflect much less.…”

“…Since most biopsy studies reporting the density of inflammatory cells have been in mild cases of asthma [3,4,[6][7][8][9][10][11][12][13][14][15][16]22], comparisons with post mortem studies are effectively limited to the small number of such studies that have compared transverse sections from cases of less severe, nonfatal asthma and controls [23,24]. Results of biopsy studies in mild asthma have not been entirely consistent with either results of the post mortem studies using cases of nonfatal asthma, or with each other.…”

Regulation of stem cell factor expression in inflammation and asthma

“…In vitro it increases the antigen-induced degranulation of human pulmonary mast cells (Bischoff & Dahinden 1992, Okayama et al 1994) and it-self induces mast cell degranulation both in vitro (Columbo et al 1992, Takaishi et al 1994, Taylor et al 1996a) and in vivo (Wershil et al 1992, Costa et al 1996. Mast cell number and activation are locally increased in chronic inflammatory diseases such as asthma (Lozewicz et al 1988, Beasley et al 1989, Djukanovic et al 1990, Bradley et al 1991, Ollerenshaw & Woolcock 1992, Saetta et al 1992, Pesci et al 1993, Laitinen et al 1993, Bradding et al 1994, Koshino et al 1996. Since SCF is the principal growth factor for mast cells, it might be expressed in human bronchi and regulated in airway structural cells in pro-and anti-inflammatory conditions.…”