Date Published: October 8, 2012
Publisher: BioMed Central
Author(s): Susan Waserman, Parameswaran Nair, Denis Snider, Mary Conway, Lata Jayaram, Lynn M McCleary, Jerry Dolovich, Frederick E Hargreave, Jean S Marshall.
The immunological and clinical parameters that are associated with asthma remission are poorly understood. The cytokine and local mediator changes associated with the resolution of asthma symptoms were examined in three groups of subjects 12–18 years of age (n = 15 in each group): (a) continuing asthma group (CA) who had persistent symptoms since early childhood, (b) an age, sex and atopic status-matched group who had persistent symptoms in early childhood but in whom these had resolved (RA), and (c) a non-atopic, non-asthmatic control group. Clinical parameters, sputum cell counts, peripheral blood mononuclear cell (PBMC) cytokine production and activation marker expression were determined. All of the CA had methacholine airway hyperresponsiveness compared with only half of the RA subjects. The CA showed elevated numbers of eosinophils and increased ECP and IL-5 in sputum, which were not observed in the RA. PBMC cytokine studies revealed increased production of the type 1 cytokines IL-12, IFN-γ and TNF-α in the CA group compared with the RA group, under a range of activation conditions, however, the production of IL-4 and IL-5 were unchanged. These findings suggest that decreased type 1 cytokine expression as well as decreased eosinophilic inflammation is associated with the resolution of asthma symptoms.
Asthma is characterized by episodic symptoms of wheeze, breathlessness or chest tightness due to variable airflow obstruction and increased airway responsiveness that may or may not be associated with bronchitis. The prevalence has been estimated at 10-20% in children
[1,2]. Wheezing is more likely to persist and develop into asthma in children with atopy, a positive family history, (especially maternal) of asthma or atopy, airway hyperresponsiveness, and exposure to indoor allergens or cigarette smoke
[3-11]. Wheezing associated with the development of asthma tends to begin at age 3 or persists beyond this age
The studies we describe here provide novel insights into the differences between children whose asthma has resolved spontaneously and those in which it remains symptomatic. Increased levels of sputum eosinophils and sputum IL-5, increased peripheral blood mononuclear cell-derived TNF-α, IL-12, and decreased IFN-γ levels were associated with on-going asthma symptoms and airway hyperresponsiveness. We did not demonstrate any clear differences in T or B cell subsets, memory cells or activation markers between children with ongoing asthma symptoms and those in whom symptoms had completely resolved. However, where subtle differences were noted between the CA and RA groups, the RA group reflected values closer to those of the control subjects.
Dr. Nair is listed on a patent for a sputum filtration device and provides scientific advice to Cellometrics Inc, a university spin off company.
This study was supported by an unrestricted educational grant from AstraZeneca Canada. Dr Nair was supported by a Clinician Scientist Award from the Canadian Institutes of Health Research.