Person:

Gold, Diane

Both environmental tobacco smoke and indoor allergens can exacerbate already established childhood albeit primarily through quite disparate mechanisms. In infancy and childhood, environmental tobacco smoke (ETS) exposure is associated with measures of decreased flow in the airways, bronchial hyperresponsiveness, and increased respiratory infections, but the relationship between ETS and allergy is poorly understood. Indoor allergens from dust mite, cockroach, and cat can be associated with asthma exacerbation in children sensitized to the specific allergens. The precise role of either ETS or indoor allergens in the development of asthma is less well understood. The strong and consistent association between ETS and asthma development in young children may relate to both prenatal and postnatal influences on airway caliber or bronchial responsiveness. Dust mite allergen levels predict asthma in children sensitized to dust mite. The tendency to develop specific IgE antibodies to allergens (sensitization) is associated with and may be preceded by the development of a T-helper (Th)2 profile of cytokine release. The importance of either ETS or indoor allergens in the differentiation of T cells into a Th2-type profile of cytokine release or in the localization of immediate-type allergic responses to the lung is unknown. This article evaluates the strength of the evidence that ETS or indoor allergens influence asthma exacerbation and asthma development in children. We also selectively review data for the effectiveness of allergen reduction in reducing asthma symptoms and present a potential research agenda regarding these two broad areas of environmental exposure and their relationship to childhood asthma.

Exposure to elevated levels of endotoxin in family-room dust was previously observed to be significantly associated with increased wheeze in the first year of life among a cohort of 404 children in the Boston, Massachusetts, metropolitan area. However, it is likely that family-room dust endotoxin was a surrogate for airborne endotoxin exposure. Therefore, a related substudy characterized the relationship between levels of airborne household endotoxin and the level of endotoxin present in house dust, in addition to identifying other significant predictors of airborne endotoxin in the home. We now reexamine the relationship between endotoxin exposure and wheeze under the assumption that the level of airborne endotoxin in the home is the exposure of interest and that the amount of endotoxin in household dust is a surrogate for this exposure. We applied a measurement error correction technique, using all available data to estimate the effect of endotoxin exposure in terms of airborne concentration and accounting for the measurement error induced by using house-dust endotoxin as a surrogate measure in the portion of the data in which airborne endotoxin could not be directly measured. After adjusting for confounding by lower respiratory infection status and race/ethnicity, endotoxin exposure was found to be significantly associated with a nearly 6-fold increase in prevalence of wheeze for a one interquartile range increase in airborne endotoxin (95% confidence interval, 1.2–26) among the 360 children in households with dust endotoxin levels between the 5th and 95th percentiles.

Background: Human controlled-exposure studies have assessed the impact of ambient fine particulate matter on cardiac autonomic function measured by heart rate variability (HRV), but whether these effects are modified by concomitant ozone exposure remains unknown. Objective: In this study we assessed the impact of O(_3) and particulate matter exposure on HRV in humans. Methods: In a crossover design, 50 subjects (19–48 years of age) were randomized to 2-hr controlled exposures to filtered air (FA), concentrated ambient particles (CAPs), O(_3), or combined CAPs and ozone (CAPs + O(_3)). The primary end point was change in HRV between the start and end of exposure. Secondary analyses included blood pressure (BP) responses, and effect modification by asthmatic status. Results: Achieved mean CAPs and O(_3) exposure concentrations were 121.6 ± 48.0 μg/m(^3) and 113.9 ± 6.6 ppb, respectively. In a categorical analysis, exposure had no consistent effect on HRV indices. However, the dose–response relationship between CAPs mass concentration and HRV indices seemed to vary depending on the presence of O(_3). This heterogeneity was statistically significant for the low-frequency component of HRV (p = 0.02) and approached significance for the high-frequency component and time-domain measures of HRV. Exposure to CAPs + O(_3) increased diastolic BP by 2.0 mmHg (SE, 1.2; p = 0.02). No other statistically significant changes in BP were observed. Asthmatic status did not modify these effects. Conclusion: The potentiation by O(_3) of CAPs effects on diastolic BP and possibly HRV is of small magnitude in young adults. Further studies are needed to assess potential effects in more vulnerable populations.

Background: Although ambient air pollution has been linked to reduced lung function in healthy children, longitudinal analyses of pollution effects in asthma are lacking. Objective: To investigate pollution effects in a longitudinal asthma study and effect modification by controller medications. Methods: We examined associations of lung function and methacholine responsiveness (PC20) with ozone, carbon monoxide (CO), nitrogen dioxide (NO2) and sulfur dioxide (SO2) levels in 1,003 asthmatic children participating in a 4-year clinical trial. We further investigated whether budesonide and nedocromil modified pollution effects. Daily pollutant concentrations were linked to zip/postal code of residence. Linear mixed models tested associations of within-subject pollutant concentrations with FEV1 and FVC %predicted, FEV1/FVC and PC20, adjusting for seasonality and confounders. Results: Same-day and 1-week average CO levels were negatively associated with post-bronchodilator %predicted FEV1 (change(95%CI) per IQR: −0.33(−0.49, −0.16), −0.41(−0.62, −0.21), respectively) and FVC (−0.19(−0.25, −0.07), −0.25(−0.43, −0.07)). Longer-term four-month averages of CO were negatively associated with prebronchodilator %predicted FEV1 and FVC (−0.36(−0.62, −0.10), −0.21(−0.42, −0.01)). Four-month averaged CO and ozone levels were negatively associated with FEV1/FVC (p<0.05). Increased four-month average NO2 levels were associated with reduced post-bronchodilator FEV1 and FVC %predicted. Long-term exposures to SO2 were associated with reduced PC20 (%change(95%CI) per IQR:-6(-11,-1.5)). Treatment augmented the negative short-term CO effect on PC20. Conclusions: Air pollution adversely influences lung function and PC20 in asthmatic children. Treatment with controller medications may not protect but worsens the CO effects on PC20. This clinical trial design evaluates modification of pollution effects by treatment without confounding by indication.

Population-based birth cohorts on asthma and allergies increasingly provide new insights into the development and natural history of the diseases. Over 130 birth cohorts focusing on asthma and allergy have been initiated in the last 30 years. A NIAID (National Institute of Allergy and Infectious Diseases), NHLBI (National Heart Lung and Blood Institute), MeDALL (Mechanisms of the Development of Allergy, Framework Programme 7 of the European Commission) joint workshop was held in Bethesda, MD, USA September 11–12, 2012 with 3 objectives (1) documenting the knowledge that asthma/allergy birth cohorts have provided, (2) identifying the knowledge gaps and inconsistencies and (3) developing strategies for moving forward, including potential new study designs and the harmonization of existing asthma birth cohort data. The meeting was organized around the presentations of 5 distinct workgroups: (1) clinical phenotypes, (2) risk factors, (3) immune development of asthma and allergy, (4) pulmonary development and (5) harmonization of existing birth cohorts. This manuscript presents the workgroup reports and provides web links (AsthmaBirthCohorts.niaid.nih.gov or www.medall-fp7.eu) where the reader will find tables describing the characteristics of the birth cohorts included in this report, type of data collected at differing ages, and a selected bibliography provided by the participating birth cohorts.

Background: The bronchodilator response (BDR) reflects the reversibility of airflow obstruction and is recommended as an adjunctive test to diagnose asthma. The validity of the commonly used definition of BDR, a 12% or greater change in FEV1 from baseline, has been questioned in childhood.

Objectives: We sought to examine the diagnostic accuracy of the BDR test by using 3 large pediatric cohorts.

Methods: Cases include 1041 children with mild-to-moderate asthma from the Childhood Asthma Management Program. Control subjects (nonasthmatic and nonwheezing) were chosen from Project Viva and Home Allergens, 2 population-based pediatric cohorts. Receiver operating characteristic curves were constructed, and areas under the curve were calculated for different BDR cutoffs.

Results: A total of 1041 cases (59.7% male; mean age, 8.9 ± 2.1 years) and 250 control subjects (46.8% male; mean age, 8.7 ± 1.7 years) were analyzed, with mean BDRs of 10.7% ± 10.2% and 2.7% ± 8.4%, respectively. The BDR test differentiated asthmatic patients from nonasthmatic patients with a moderate accuracy (area under the curve, 73.3%). Despite good specificity, a cutoff of 12% was associated with poor sensitivity (35.6%). A cutoff of less than 8% performed significantly better than a cutoff of 12% (P = .03, 8% vs 12%).

Conclusions: Our findings highlight the poor sensitivity associated with the commonly used 12% cutoff for BDR. Although our data show that a threshold of less than 8% performs better than 12%, given the variability of this test in children, we conclude that it might be not be appropriate to choose a specific BDR cutoff as a criterion for the diagnosis of asthma.