Airway hyperresponsiveness, inflammation, and subepithelial collagen deposition in recently diagnosed versus long-standing mild asthma. Influence of inhaled corticosteroids

Am J Respir Crit Care Med. 2000 Oct;162(4 Pt 1):1308-13. doi: 10.1164/ajrccm.162.4.9910051.


This study aimed at documenting airway inflammation and subepithelial collagen deposition in patients using only inhaled beta(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 microgram/day. Baseline FEV(1) (mean +/- SEM) was normal and similar in both groups (RDA: 98.1 +/- 2.7, LSA: 94.5 +/- 4.6%). Geometric mean methacholine PC(20) 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. PC(20) normalized (>/= 16 mg/ml) in five patients with RDA and two patients with LSA. Baseline mean bronchial cell counts (per mm(2) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adult
  • Androstadienes / administration & dosage*
  • Anti-Asthmatic Agents / administration & dosage*
  • Asthma / drug therapy*
  • Asthma / immunology
  • Basement Membrane / drug effects
  • Basement Membrane / pathology
  • Biopsy
  • Bronchi / drug effects
  • Bronchi / pathology
  • Bronchial Hyperreactivity / drug therapy*
  • Bronchial Hyperreactivity / pathology
  • Bronchial Provocation Tests
  • Bronchitis / drug therapy*
  • Bronchitis / immunology
  • Bronchoscopy
  • Collagen / metabolism*
  • Epithelium / drug effects
  • Epithelium / pathology
  • Female
  • Fluticasone
  • Forced Expiratory Volume / drug effects
  • Humans
  • Immunoenzyme Techniques
  • Male


  • Androstadienes
  • Anti-Asthmatic Agents
  • Collagen
  • Fluticasone