Persisting Remodeling and Less Airway Wall Eosinophil Activation in Complete Remission of Asthma

Rationale Individuals with asthma may outgrow symptoms despite not using treatment, whereas others reach complete remission (CoR) with absence of airway obstruction and bronchial hyper-responsiveness. It is uncertain whether this associates with remission of all inflammatory and remodeling asthma features. Objectives: To compare the pathologic phenotype of individuals with asthma with CoR and clinical remission (ClinR) and those with active asthma, with and without the use of inhaled corticosteroids (ICS). Methods: We investigated 165 individuals known with active asthma, on reexamination having CoR (n = 18), ClinR (n = 44), and current asthma (CuA, n = 103, 64 with and 39 without ICS). Measurements Main Results: Inflammatory cells were measured in blood, induced sputum, and bronchial biopsies; histamine and ECP in sputum; and eosinophilic peroxidase (EPX) immunopositivity and remodeling (epithelial changes, E-cadherin expression, basement membrane [BM] thickening, collagen deposition) in bronchial biopsies. Median (range) blood eosinophils from CoR were significantly lower than those from CuA (0.10 [0.04-0.24] vs. 0.18 [0.02-1.16] x 10(9)/L). Bronchial EPX immunopositivity was lower in CoR than in both ClinR and CuA (67 [0.5-462] vs. 95 [8-5329] and 172 [6-5313] pixels). Other inflammatory findings were comparable. BM thickness was lowest in CuA, caused by lower BM thickness in those using ICS (CoR, 6.3 [4.7-8.4]; ClinR, 6.5 [3.8-11.7]; CuA, 5.7 [2.8-12.6]; and ICS using CuA, 5.3 [2.8-8.2] mu m). Conclusions: CoR is still accompanied by airway abnormalities because BM thickness is similar in individuals with asthma with CoR, ClinR, and CuA without ICS. Airway eosinophilic activation best differentiates these three groups, signifying their importance in the clinical expression and severity of bronchial hyper-responsiveness in asthma.