Airway hyperresponsiveness, inflammation, and subepithelial collagen deposition in recently diagnosed versus long-standing mild asthma. Influence of inhaled corticosteroids.
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.
Boulet
L P
LP
Institut de Cardiologie et de Pneumologie de L'Université Laval, H opital Laval, Sainte-Foy, Québec, Canada. lpboulet@med.ulaval.ca
Turcotte
H
H
Laviolette
M
M
Naud
F
F
Bernier
M C
MC
Martel
S
S
Chakir
J
J
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001485:Basement Membrane / Q000187:drug effects / Q000473:pathology; D001706:Biopsy; D001980:Bronchi / Q000187:drug effects / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000473:pathology; D001985:Bronchial Provocation Tests; D001991:Bronchitis / Q000188:drug therapy* / Q000276:immunology; D001999:Bronchoscopy; D003094:Collagen / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D003094:Collagen; D000068298:Fluticasone