The distribution of eosinophils and lymphocytes in the large and small airways of asthmatics

Abstract

Airway inflammation in asthma consists of variably increased numbers of mononuclear and polymorphonuclear cells, and there is a growing body of evidence to suggest a primary role for lymphocytes and eosinophils in the pathogenesis of asthma. The aim of this study was to examine the distribution of lymphocytes and eosinophils in the bronchial tree of cases of mild and severe asthma.In cases of fatal asthma (n=10), nonfatal asthma (sudden nonrespiratory death with a history of asthma n=10), and control cases (sudden death with no history of respiratory illness, n=10), lymphocytes and eosinophils were counted in transverse sections of large and small airways stained with haematoxylin and eosin.Cases of fatal asthma had longstanding severe asthma and nonfatal cases generally had mild asthma. Lymphocytes were increased in all airway size groups both in fatal and nonfatal cases of asthma compared to control cases (p<0.001). Eosinophils were increased (p<0.001) in all airway size groups in the cases of fatal asthma compared to the nonfatal asthma and control groups, which were similar. These differences between case groups were of similar magnitude, when only a random single airway section from each case in each size group was examined. The numbers of lymphocytes correlated with the number of eosinophils in the fatal asthma group (r=0.60; p<0.0001), and to a lesser extent in the nonfatal (r=0.34; p=0.001) and control groups (r=0.32; p=0.001).These findings suggest that increased numbers of lymphocytes are uniformly distributed in the large and small airways in cases of asthma, independently of asthma severity, and that eosinophil recruitment may be related to asthma severity. Hence, biopsy specimens of the proximal airways are likely to be representative of the cellular infiltrate in large and small airways in mild and severe asthma.

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

“…For example, the density of neutrophils and activated eosinophils in the submucosa is not only much less than that of mast cells [6,8], but their density relative to that of mast cells appears to vary according to sub-compartments, such as mucous glands [34] and airway smooth muscle [50]. Lymphocyte numbers are much higher in the airway wall [6,24] and their density is subject to much greater variability [51]. Furthermore, the mast cell appears to be by far the predominant inflammatory cell within the layer of smooth muscle [52].…”

“…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.…”

“…Finally, the density and distribution of inflammatory cells in the small peripheral airways may differ from that observed in the larger proximal airways [23,24]. Therefore, the relationship between inflammatory cell density in endobronchial biopsies and that in the remainder of the bronchial tree and throughout the lung requires further study.…”

Assessing and accessing the small airways; implications for asthma management

“…Asthma is a chronic inflammatory disease of the airways including the most peripheral ones. There is abundant evidence that inflammatory and functional abnormalities of the lung periphery occur in all stages of the disease from the mildest [10,11] to the most severe form [12,13]. Interestingly, a correlation between disease severity and the magnitude of small airway impairment has been documented [14].…”

Remodelamento das vias aéreas inferiores e superiores

“…Patients with fatal asthma have an increased number of blood vessels; in these cases, however, the extension of neovascularization and angiogenesis remain uncertain. 14,15 …”