Airway structure and inflammatory cells in fatal attacks of asthma

Abstract

Fatal attacks of asthma usually occur against a background of chronic persistent symptoms, presumably due to chronic airway inflammation and changes in airway wall structure. Death from asthma is usually attributed to excessive airway narrowing due to a combination of muscle spasm and mucous plugging. To test the hypothesis that airway wall structure and/or the inflammatory cell profile are related to the duration of a fatal attack of asthma, inflammatory cell profiles and airway structure were examined in cases of fatal asthma and related to the duration of the fatal attack.In transverse sections of large and small airways from subjects dying from asthma, the numbers of eosinophils, neutrophils and lymphomononuclear cells were counted. The amount of smooth muscle shortening, the areas of airway wall, smooth muscle, mucous gland and cartilage were measured. Cell counts, airway dimensions and muscle shortening were compared in cases dying within 2 h of the fatal attack (short duration) and those dying more than 5 h after the onset of the fatal attack (long duration).In cases with fatal attacks of short duration, the numbers of neutrophils and the mucous gland area were increased and the numbers of eosinophils were reduced compared to cases with fatal attacks of long duration. Lymphocyte numbers, airway wall thickness, the areas of smooth muscle and cartilage and the amount of smooth muscle shortening were similar in the two groups.These findings suggest fatal attacks of asthma may be triggered by an inflammatory stimulus and suggest that increased production of mucous may contribute to sudden death in such cases.

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

“…It is possible that the increased numbers of eosinophils in the cases of fatal asthma is due to factors related not only to severity but also to a final episode of asthma. SUR et al [20] have shown that cell profiles in the airway wall may be temporally related to a fatal attack of asthma, and we have recently confirmed these findings [39]. In both studies, neutrophils were observed in much smaller numbers than lymphocytes and eosinophils in cases of fatal asthma, and may be important in the pathogenesis of a fatal attack of asthma.…”

“…The relationship between airway inflammation and structural change is of interest in asthma. Longstanding asthma is related to fixed airway narrowing [41], and the rapidity of death from an attack of asthma is related not only to inflammatory cell profiles but also to the size of mucous glands [39]. It is assumed that chronic airway inflammation results in structural change.…”

Airway smooth muscle in health and disease; methods of measurement and relation to function

“…In chronic obstructive pulmonary disease this consists predominantly of lymphocytes and neutrophils [61] and in asthma predominantly of lymphocytes and eosinophils [34,62], although the relative numbers of neutrophils and eosinophils may vary in both conditions [62,63]. However, these inflammatory cells may be less important than mast cells in determining airway smooth muscle function.…”

Stimulation of Airway Mucin Gene Expression by Interleukin (IL)-17 through IL-6 Paracrine/Autocrine Loop

“…These results suggest that changes in MUC gene expression, especially MUC5B, are associated with airway diseases. The source of increased mucus production in diseases such as asthma and COPD is due at least partially to an increased number of goblet cells in the airway epithelium (11)(12)(13). Studies have linked goblet cell metaplasia to the increase of mucin gene expression in airway epithelial cells (10,14).…”

“…In the lung, synthesis and secretion of mucins are restricted largely to the airway with little to no expression in alveolar airspaces (1). Although at least eight mucin genes (MUC 1, 2, 4, 5AC, 5B, 7,8,13) have been found to be expressed in adult human lung (4), MUC5AC and MUC5B appear to be the predominant genes expressed, and their glycoprotein products are the most abundant in mucus secretions (4, 6 -9). MUC5AC appears to be produced mainly in the airway epithelium by goblet cells (8,10), while MUC5B is mostly produced in the underlying submucosal glands (10).…”