Atopy, cytokine production, and airway reactivity as predictors of pre-school asthma and airway responsiveness

Abstract

Summary Background Childhood asthma is often characterized by recurrent wheezing, airway hyper-reactivity, atopy, and altered immune characteristics; however, our understanding of the development of these relationships from early in life remains unclear. The aim of our study was to evaluate whether atopy, cytokine production by peripheral blood mononuclear cells (PBMCs), and airway responsiveness, assessed in infants and toddlers, are associated with asthma and airway responsiveness at 4-years of age. Methods Infants with eczema (N = 116), enrolled prior to wheezing, were assessed at entry (mean age of 10.7 months), at 1-year follow-up (N = 112), and at 4-years of age (N = 94). Total serum IgE, specific IgE to allergens, and cytokines produced by stimulated PBMCs, were assessed at entry and 1-year follow-up. Spirometry was obtained at all 3-visits, while airway reactivity to methacholine was assessed at entry and 1-year follow-up, and bronchodilator (BD) responsiveness, as well as current asthma was assessed at 4-years of age. Results We found that pre-school children with asthma had lower spirometry and a greater BD-response. Serum IgE, particularly to egg and/or milk, and altered cytokine production by PBMCs at entry to the study were associated with asthma, lower spirometry, and greater airway responsiveness at 4-years of age. In addition, we found that airway responsiveness, as well as spirometry, tracked from infancy to 4-years of age. Conclusions While spirometry and airway responsiveness track longitudinally from early in life, atopy and cytokine production by PBMCs are associated not only with an increased risk of pre-school asthma, but also lower spirometry and increased airway responsiveness.

Exhaled nitric oxide during infancy as a risk factor for asthma and airway hyperreactivity

“…We did not find that cytokine production by stimulated PBMCs was associated with asthma at 5 years of age, which contrasts with our previous findings that increasing IL-4 and IL-10 as an infant was associated with an increased risk of asthma at 4 years of age [4]. However, we did find that increasing IL-17 production at entry to the study was associated with lower lung function and higher eNO at 5 years of age.…”

“…These findings are consistent with our previous report that food sensitisation during infancy was associated with asthma and lung function at 4 years of age [4], and consistent with other cohort studies demonstrating the importance of food allergies early in life, while aeroallergen sensitisation does not become important until several years of age [30-33]. …”

“…As neither study evaluated post-bronchodilator spirometry during infancy and at follow-up, it remains unclear whether the lower flows early in life, as well as the worsening with time, are related to fixed, non-reversible airway dysfunction or increased airway tone. At 4-year follow-up of our cohort, the lower spirometry in subjects with asthma was no longer present following a bronchodilator [4]. We also found that lower spirometry during infancy was associated with a greater bronchodilator response at 4 years of age, which suggested an increase in airway tone, rather than fixed airway obstruction or abnormal lung growth.…”

“…Airway inflammation and lung function measurements in infants can improve our understanding of the onset and progression of airway disease and may be useful in assessing the risk for developing asthma. While there have been relatively few longitudinal studies assessing airway physiology in infants prior to the onset of episodes of wheezing, the use of forced expiratory flows (FEF) has enabled a similar methodology to be applied longitudinally from infancy into adulthood and has provided the most important insights into the development of airway disease associated with childhood asthma [4-8]. …”

The development and in vivo function of T helper 9 cells

“…Furthermore, targeting IL-9 in other allergic diseases has not been reported. Because increases of IL-9 are seen early in life in an atopic population of infants and increases are associated with early changes in airway responsiveness 24, 105 , an acceptable safety profile might provide a basis for early intervention in high-risk infants to limit the development of atopic diseases. The recent descriptions of T H 9 cells in IBD suggest that targeting IL-9 might be a potential treatment in this disease.…”