BACKGROUND:Increased airway smooth muscle is observed in large and small airways in asthma. Semi-quantitative estimates suggest that cells containing alpha smooth muscle actin (α-SMA) are also increased in the lung parenchyma. This study quantified and characterized α-SMA positive cells (α-SMA+) in the lung parenchyma of non-asthmatic and asthmatic individuals.METHODS:Post-mortem sections of peripheral lung from cases of fatal asthma (FA), persons with asthma dying of non-respiratory causes (NFA) and non-asthma control subjects (NAC) were stained for α-SMA, quantified using point-counting and normalised to alveolar basement membrane length and interstitial area.RESULTS:α-SMA+ fractional area was increased in alveolar parenchyma in both FA (14.7 ± 2.8% of tissue area) and NFA (13.0 ± 1.2%), compared with NAC (7.4 ± 2.4%), p < 0.05 The difference was greater in upper lobes compared with lower lobes (p < 0.01) in both asthma groups. Similar changes were observed in alveolar ducts and alveolar walls. The electron microscopic features of the α-SMA+ cells were characteristic of myofibroblasts.CONCLUSIONS:We conclude that in asthma there is a marked increase in α-SMA+ myofibroblasts in the lung parenchyma. The physiologic consequences of this increase are unknown.

STUDY OBJECTIVES:The bronchial arteries supply systemic blood to the airways, tracheobronchial lymph nodes, and nerves. Their structure has not been studied in patients with asthma.DESIGN:Case-control study of pathologic changes of bronchial arteries in asthma.PARTICIPANTS AND METHODS:Postmortem lungs were examined from three case groups: (1) fatal asthma (n = 12), death due to asthma; (2) nonfatal asthma (n = 12), asthmatic and death due to nonrespiratory causes; and (3) nonasthmatic control subjects (n = 12), no history of asthma and death due to nonrespiratory causes. In bronchial arteries with outer diameters of 0.1 to 1.0 mm, the areas of lumen, intima, and media were measured and compared between case groups.RESULTS:There were no significant differences in artery size (outer diameter) or in medial area between the three groups. In the two asthma groups, the intimal area was increased (p < 0.05), with a corresponding decrease in luminal area compared with the control group. There was a significant effect of gender, age, and smoking on intimal area. In the asthma cases, the area of bronchial artery intima was related to duration of asthma (p < 0.05), and this increase was associated with smooth muscle proliferation, reduplication, and calcification of the elastica, but not with inflammatory cell infiltration.CONCLUSIONS:While the pathophysiologic significance of these changes is uncertain, the relation to duration of asthma, age, and smoking suggests a secondary response to chronic airway disease.

A submucosal network of elastic fibers in a collagen and myofibroblast matrix form discrete longitudinal bundles (LB) in the bronchial tree. The LB may affect airway function by altering the mechanical properties of the airway wall or by changing the folding behavior of the airway mucosa. The area and number of LB were quantified from 12 cases each of fatal asthma (FA), nonfatal asthma (NF), and nonasthmatic (NA) control cases on elastic-trichrome stained airways. The effects of group, sex, age, and smoking were examined using multiple linear regression. The area fraction of LB increased (p < 0.05) approximately twofold in cases of FA compared with NA control cases in both large and small airways. The areas of LB were increased in smokers, older subjects, and men (p < 0.05). The number of mucosal folds was related to the number of longitudinal bundles in asthmatics and nonasthmatics and was not different between groups. Collagen and myofibroblasts were increased (p < 0.05) in LB of FA and NF cases compared with NA control cases. The increased size and altered composition of LB in asthma may influence airway function; however, excessive airway narrowing in asthma is not due to altered numbers of mucosal folds.

Sera were obtained postmortem from 55 subjects classified into three groups; death due to asthma (FA, n = 21), asthmatic but death not due to asthma (NFA, n = 24) and a nonasthmatic control group (NAC, n = 10). A full autopsy was performed on all cases and a medical history, including details of allergies, was obtained by questionnaire from the next of kin. Grading of asthma severity by either questionnaire or autopsy was comparable (tP = 0.435, p > 0.05) and the mean pathology-grade was significantly higher for the FA group (3.375) compared to the NFA group (2.375), p < 0.05. Tryptase was elevated (> 2.0 micrograms/L) in 21/55 sera (38%) and there was no significant difference between the groups. ROC plots showed that tryptase levels did not discriminate between the FA and NFA groups, even if specimens were collected within 24 hours after death. Total IgE was significantly elevated in the FA group (geometric mean 140.3 kU/L) compared to the other two groups (NFA 30.2 kU/L, NAC 9.4 kU/L), p = 0.05. Fatal asthmatics also had a greater positivity (67%) to a screen for common inhalant allergens than did the other groups (NFA 30%, NAC 20%). Sera with a positive screen were tested against a panel of 10 common aero-allergens. Each sample was then assigned a number (N) and a score (S), dependent on either the number of allergens positive (N) or the total sum of pluses for all allergens (S). Both the N and S values were higher for the FA group (N = 98, S = 264) than the NFA group (N = 52, S = 151) and NAC group (N = 4, S = 8). The ratio (S/N) which gives an index (I) was 2.69, 2.90, and 2.00, respectively. Tryptase was poorly correlated to the total IgE level (r = 0.036); however, mean values for N and S were significantly different (N 6.81, S 4.50, and N 19.25, S 11.5, p < 0.05) for sera with tryptase levels < 2.0 or > or = 2.0 micrograms/L, respectively. We conclude that total and specific IgE may be useful predictors of asthma severity but that postmortem tryptase is not useful in the diagnosis of a fatal asthmatic attack.