Changes in airway inflammation, remodelling and PD20 following inhaled corticosteroid treatment are not temporally concordant

C. Ward, R. Bish, D. Reid, S. Gollant, M. Pais, G. Westall, E. H. Walters

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Abstract

Introduction. There have been direct calls for studies evaluating "the relationship of airway inflammation to airway remodelling, lung function and BHR" (Pedersen S. AJRCCM. 2000; 161 : pp S182-185). Current asthma guidelines rely on lung function and symptoms in management decisions. Methods. In a prospective, double blind study 33 steroid naïve, symptomatic asthmatics were randomised to receive FP 750μg bd or identical placebo. We obtained airway biopsies and 3x60 mL BAL at time zero, 3 and 12 months. 2μm glycol methacrylate embedded sections were stained for collagen I for assessment of reticular basement membrane thickness (rbm) using image analysis (Image Pro Plus). In addition BAL differential cell counts and PD20 FEV1.0 to methacholine (BHR) were assessed at each time point. Results. Mean (s.d) rbm was increased in asthmatics vs normals (9.1±2.2 vs 7.7±1.μm,p=0.003), as were % BAL eosinophils (2.9±4.1 vs 1.0±1.62, p=0.011) and mast cells (0.13±0.13 vs 0.03±0.04, p<0.0001). Log rbm thickness, % eosinophils and % mast cells were negatively correlated with log PD20; r=-0.46 p=0.006, r=-0.34 p=0.05, r=-0.37 p=0.03, respectively. There were no significant changes in rbm following placebo or 3 months FP treatment. 12 month FP treatment was associated with decreased rbm compared to baseline and the 3 month time point and placebo changes. In contrast, spirometry, geometric mean PD20 and BAL inflammation improved following 3 months FP, but only BHR continued to improve further with 12 months of treatment as rbm thickness decreased: FP rbm(μm) FP BHR mg FP%Eos FP%Mast BASELINE 9.7±2.4 0.032(.002-1.57) 3.6±5.3 0.14±.11 3 MONTHS 9.5±2.1 0.30(.086-1.07)** 1.4±1.1 **,# 0.07±.07** 12 MONTHS 8.2±2.0*,**,# 5.4(1.1->6.4)**,∧ 1.3±1.7**,# 0.06±.06**# **p<0.01 vsbaseline, *p<0.05 vs3 months, ∧p<0.001 vs3 months, #p<0.05vsplacebo. Summary. Increased rbm thickness is related both to airway inflammation and BHR. ICS can modulate airway wall remodelling but this begins later than changes in spirometry, PD20 and airway inflammation. PD20 continues to improve as modulation of airway remodelling occurs. Conclusions: Changes in airway inflammation, spirometry, PD20 and airway remodelling are not temporally concordant. Maximal benefit of ICS on spirometry and inflammation are manifest before changes in airway remodelling or maximal benefits in BHR. Prolonged ICS treatment is necessary if maximal improvement in PD20 and airway remodelling are desired. Current asthma guidelines, based on lung function and symptoms, do not provide an index of disease progression reflecting these long-term effects of ICS.

Original languageEnglish
Pages (from-to)A1
Number of pages1
JournalThorax
Volume55
Issue numberSuppl. 3
Publication statusPublished - Dec 2000
EventBritish Thorax Society Winter Meeting 2000 - The Queen Elizabeth II Conference Centre; Broad Sanctuary; Westminster; London SW1P 3EE, London, United Kingdom
Duration: 13 Dec 200015 Dec 2000

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Ward, C., Bish, R., Reid, D., Gollant, S., Pais, M., Westall, G., & Walters, E. H. (2000). Changes in airway inflammation, remodelling and PD20 following inhaled corticosteroid treatment are not temporally concordant. Thorax, 55(Suppl. 3), A1.