Relationship Of Atopy, Airway Function, Exhaled Nitric Oxide And Cytokine Production Early In Life To Airway Function And Current Asthma At 5-Years Of Age

Abstract

Childhood asthma is characterized by atopy, airway hyper-reactivity, and airway inflammation; however, it remains unclear how Rationale these relationships develop from very early in life. We previously described that infants mean age 11 months with eczema (atopic or non-atopic) have lower forced expiratory flows, heightened airway reactivity, and elevated exhaled nitric oxide (eNO) prior to any episodes of wheezing (JACI 2008 Oct;122(4):760-5).: At 5-years of age, we have so far obtained longitudinal follow-up measurements in 65 of the 116 subjects. At entry to the study, Methods blood was obtained to assess specific IgE to a panel of 10 allergens, and peripheral blood mononuclear cells (PBMC) were isolated and stimulated to assess cytokine production. Spirometry, airway reactivity to inhaled methacholine, and exhaled nitric oxide (eNO) were measured during infancy and at 5-year follow-up. We evaluated the relationship between these measurements and Current asthma at 5-years of age, which was defined by 1) any episode of wheezing during the past year and asthma diagnosis by a physician, or 2) use of asthma medication within the past year.: Subjects with Current Asthma (N = 43) compared to those without Current Asthma (N = 22) had more frequent sensitization to Results egg and/or milk (37.84% vs 5.26%, p = 0.009), lower spirometry (ZFEF25-25, -0.66 vs 0.16, p = 0.014), a greater percent decrease in FEV1 with methacholine challenge (33.0% vs. 20.11%, p = 0.012), and higher eNO (p = 0.012). At entry to the study, prior to wheezing, predictors of Current Asthma at 5-years of age included: eNO (OR: 4.867, p = 0.048), any positive allergen-specific IgE (OR: 3.520, p = 0.036), and greater IL-5 production from stimulated PBMCs (OR: 6.725, p = 0.028). In addition, sensitization to egg and/or milk (p = 0.034) and higher SCORAD (p = 0.010) upon entry to the study were associated with lower spirometry (FEF25-75) in 5-year olds. Lastly, lower spirometry (FEF25-75; p = 0.015) and higher eNO (p = 0.016) upon entry to the study were associated with greater airway reactivity at 5-years of age.: Our findings suggest that atopy, increased cytokine production, airway inflammation, and low lung function early in life, prior Conclusion to the onset of wheezing, may be early biomarkers in the natural history of childhood asthma. This abstract is funded by: NIH grants #HL080071, AI070448 and AI057459 Am J Respir Crit Care Med 185;2012:A2339 Internet address: www.atsjournals.org Online Abstracts Issue

Exhaled nitric oxide predicts persistence of wheezing, exacerbations, and decline in lung function in wheezy infants and toddlers

“…Finally, SB-FE NO, but not tidal-FE NO , measured prior to age 3 years was associated with BDR. Our SB-FE NO results are consistent with a recent report from a prospective cohort of infants with atopic dermatitis, but without prior wheezing wherein SB-FE NO measured at enrolment (mean age 10.7 months) was predictive of asthma as well as airway reactivity at age 5 years [33]. However, to our knowledge, our study is the first to perform SB-FE NO measurements and obtain longitudinal lung function measurements in a cohort of infants and toddlers with recurrent physician-diagnosed wheezing.…”

<p>Exhaled Nitric Oxide in Wheezy Infants Predicts Persistent Atopic Asthma and Exacerbations at School Age</p>

“…Chang et al reported that in their prospective cohort of infants with atopic dermatitis but without prior wheezing, SB-FE NO measured at enrollment (mean age 10.7 months) was predictive of asthma as well as airway reactivity at age 5 years. 30 However, we believe that our study is the first to perform SB-FE NO measurements in a cohort of infants and toddlers with recurrent physician-diagnosed wheezing that were then prospectively followed into the school-age years to determine the predictive value of SB-FE NO for school-age asthma, exacerbations, and lung function. Furthermore, we found that an elevated SB-FE NO (concentration ≥31.5 ppb) in wheezy infants and toddlers predicted active asthma at age 6 years with a high degree of accuracy (AUC of 0.92, sensitivity of 93%, specificity of 86%, positive predictive value of 81%, negative predictive value of 95% and a relative risk of 16).…”