Am. J. Respir. Crit. Care Med., Volume 162, Number 4, October 2000, 1308-1313

Airway Hyperresponsiveness, Inflammation, and Subepithelial Collagen Deposition in Recently Diagnosed versus Long-standing Mild Asthma
Influence of Inhaled Corticosteroids

LOUIS-PHILIPPE BOULET, HÉLÈNE TURCOTTE, MICHEL LAVIOLETTE, FRANÇOISE NAUD, MARIE-CLAUDE BERNIER, SIMON MARTEL, and JAMILA CHAKIR

Institut de Cardiologie et de Pneumologie de L'Université Laval, Hôpital Laval, Sainte-Foy, Québec, Canada

This study aimed at documenting airway inflammation and subepithelial collagen deposition in patients using only inhaled ₂-agonists with either recently diagnosed asthma (RDA:  2 yr, n = 16) or long-standing asthma (LSA:  13 yr, n = 16) and at the influence of an intense inhaled corticosteroid (ICS) treatment on these parameters, in relation to changes in airway responsiveness. Patients had a methacholine inhalation test and a bronchoscopy with bronchial biopsies before and after an 8-wk treatment with inhaled fluticasone propionate (FP), 1,000 µg/day. Baseline FEV₁ (mean ± SEM) was normal and similar in both groups (RDA: 98.1 ± 2.7, LSA: 94.5 ± 4.6%). Geometric mean methacholine PC₂₀ was lower in LSA than in RDA (0.44 versus 3.37 mg/ml) at baseline and improved similarly by 1.85 and 1.86 double concentrations with FP treatment. PC₂₀ normalized ( 16 mg/ml) in five patients with RDA and two patients with LSA. Baseline mean bronchial cell counts (per mm² connective tissue surface) for CD3⁺, CD4⁺, CD8⁺, CD25⁺, EG1⁺, CD45ro⁺, and AA1⁺ cells were similar in both groups. With FP, EG1⁺ (p < 0.001), EG2⁺ (p = 0.018), and AA1⁺ counts (p = 0.009) decreased significantly in both groups while CD45ro⁺ (p = 0.02) counts decreased only in LSA. Baseline type 1 and type 3 collagen deposition underneath the basement membrane was similar in RDA and LSA and did not change significantly after FP. This study shows that recent compared to long-standing mild asthma is associated with a similar degree of airway inflammation and subepithelial fibrosis, and a similar improvement in airway hyperresponsiveness after 8 wk on high-dose ICS. It also indicates that once asthma becomes symptomatic, airway responsiveness cannot normalize in most subjects over such a time period, even with a high dose of ICS.

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