Effects of Treatment on Airway Inflammation and Thickening of Basement Membrane Reticular Collagen in Asthma: A Quantitative Light and Electron Microscopic Study

Abstract

We have obtained airway mucosal biopsies by fiberoptic bronchoscopy for light and electron microscopic analysis of three distinct airway levels of the left lung in three subject groups. Group A: 11 subjects with mild atopic asthma (mean age, 29 yr; %FEV1, 89 to 116%; mean PC20 histamine, 2.42 mg/ml), each biopsied twice, one prior to 4 wk of treatment with either inhaled terbutaline (250 micrograms, two puffs four times daily; n = 5) or inhaled budesonide (200 micrograms, one puff twice daily; n = 6) followed by a second biopsy to allow determination of the effects of treatment. Group B: 10 subjects with severe asthma receiving long-term (average, 3.7 yr) corticosteroid treatment were biopsied once only (mean age, 28 yr; %FEV1, 86 to 129%; mean PC20 histamine, 1.85 mg/ml). Group C: 12 normal healthy control subjects (mean age, 35 yr; %FEV1, 92 to 135%; PC20 histamine greater than 16 mg/ml) biopsied once. By light microscopy of plastic-embedded sections, Group A asthmatics had an increased cellular infiltrate when compared with either the healthy control group or the Group B asthmatics (p less than 0.05). Both asthma groups had a thickening of basement membrane reticular collagen compared with the healthy control group (p less than 0.01). Compared with the control group, there was an increase in the percentage of the total cells that were mast cells (p less than 0.01) and eosinophils (p less than 0.05) in Group A and of eosinophils (p less than 0.01) and histiocytes (p less than 0.01) in Group B. The results of cell counts by electron microscopy largely supported these findings, and, in addition, they demonstrated an increased frequency of foci of free eosinophil granules and decreased numbers of neutrophils (p less than 0.01). By light microscopy, budesonide reduced the percentage of mast cells and eosinophils (p less than 0.05). But for the percentage of lymphocytes, which increased (p less than 0.05), terbutaline was without effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhaled corticosteroids as combination therapy with β-adrenergic agonists in airways disease: present and future

“…Effects on inflammation ICS are effective anti-asthma agents that can reverse the specific chronic airway inflammation present in asthma [16][17][18][19]. ICS reduce the number of mast cells, macrophages, T-lymphocytes and eosinophils in the sputum, bronchoalveolar lavage and bronchial wall [20,21].…”

CD4+ cells are required for chronic eosinophilic lung inflammation but not airway remodeling

“…The relationship between inflammation and remodeling remains unclear, although some studies suggest that the two may be independent. For example, bronchial biopsies from asthmatics have shown similar levels of subepithelial fibrosis after anti-inflammatory therapy with corticosteroids (4,8,19). Aside from remodeling, the degree of CD4 T cell involvement in chronic allergic inflammation is unclear because other mechanisms that could support chronic inflammation may exist that are CD4 independent, including Th2 cytokine production by mast cells and eosinophils, as well as release of chemokines such as eotaxin from airway epithelium.…”

Dose-related effect of inhaled fluticasone on allergen-induced airway changes in rats

“…These changes that include goblet cell hyperplasia (GCH), smooth muscle hypertrophy/hyperplasia, airway wall thickening and increased deposition of extracellular matrix proteins are present even in patients with mild asthma [2] and early in the disease process [3,4]. Most [5][6][7][8][9], but not all [10,11], biopsy studies show a limited effect of ICS on remodelling of asthmatic airways, possibly attributable to an effect on growth factor expression [8] or on the balance between matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 [9]. Comparison of these studies is hampered by differences in the steroids used, dosing regimen or treatment duration.…”