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Rationale: Evidence from observational studies and to a lesser extent clinical trials suggest that a healthy diet may improve symptoms and lung function in patients with asthma. We conducted a pilot study to determine the feasibility of conducting a larger scale dietary trial and to provide preliminary evidence on the impact of a healthy diet on asthma outcomes., Methods: In a randomized, two period cross-over trial, participants with asthma received a 4-week dietary intervention followed by a usual diet (or vice versa), separated by a 4-week washout. The dietary intervention was a healthy diet rich in unsaturated fat. During the dietary intervention, participants ate three meals per week on site at the Johns Hopkins ProHealth Research Center. All remaining meals and snacks were provided for participants to consume off-site. During the control diet, participants were instructed to continue their usual dietary intake. Relevant biomarkers and asthma clinical outcomes were assessed at 0, 2, and 4 weeks after starting each arm of the study., Results: Eleven participants were randomized, and seven completed the full study protocol. Among these seven participants, average age was 42 years, six were female, and six were African American. Participant self-report of dietary intake revealed significant increases in fruit, vegetable, and omega-3 fatty acid intake with the dietary intervention compared to usual diet. Serum carotenoids (eg. lutein and beta-cryptoxanthin) increased in the intervention versus control. Total cholesterol decreased in the intervention versus control diet. There was no consistent effect on asthma outcomes., Conclusions: The findings suggest that a feeding trial in participants with asthma is feasible. Larger trials are needed to definitively assess the potential benefits of dietary interventions on pulmonary symptoms and function in patients with asthma.

Polycyclic aromatic hydrocarbons (PAHs), the by-products of incomplete combustion of organic materials, are commonly found on particulate matter (PM) and have been associated with the development of asthma and asthma exacerbation in urban populations. We examined time spent in the home and outdoors as predictors of exposures to airborne PAHs and measured urinary 1-hydroxypyrene-glucuronide (1-OHPG) as internal dose of PAHs in 118 children aged 5-12 years from Baltimore, MD. During weeklong periods (Saturday-Saturday) in each of four seasons: daily activities were assessed using questionnaires, indoor air nicotine and PM concentrations were monitored, and urine specimens were collected on Tuesday (day 3) and Saturday (day 7) for measurement of 1-OHPG. Time spent in non-smoking homes was associated with significantly decreased 1-OHPG concentration in urine (β=-0.045, 95% CI (-0.076, -0.013)), and secondhand smoke (SHS) exposures modified these associations, with higher urinary 1-OHPG concentrations in children spending time in smoking homes than non-smoking homes (P-value for interaction=0.012). Time spent outdoors was associated with increased urinary 1-OHPG concentrations (β=0.097, 95% CI (0.037, 0.157)) in boys only. Our results suggest that SHS and ambient (outdoor) air pollution contribute to internal dose of PAHs in inner city children.

Rationale: There is limited evidence of the effect of exposure to heat on chronic obstructive pulmonary disease (COPD) morbidity, and the interactive effect between indoor heat and air pollution has not been established., Objectives: To determine the effect of indoor and outdoor heat exposure on COPD morbidity and to determine whether air pollution concentrations modify the effect of temperature., Methods: Sixty-nine participants with COPD were enrolled in a longitudinal cohort study, and data from the 601 participant days that occurred during the warm weather season were included in the analysis. Participants completed home environmental monitoring with measurement of temperature, relative humidity, and indoor air pollutants and simultaneous daily assessment of respiratory health with questionnaires and portable spirometry., Measurements and Main Results: Participants had moderate to severe COPD and spent the majority of their time indoors. Increases in maximal indoor temperature were associated with worsening of daily Breathlessness, Cough, and Sputum Scale scores and increases in rescue inhaler use. The effect was detected on the same day and lags of 1 and 2 days. The detrimental effect of temperature on these outcomes increased with higher concentrations of indoor fine particulate matter and nitrogen dioxide (P < 0.05 for interaction terms). On days during which participants went outdoors, increases in maximal daily outdoor temperature were associated with increases in Breathlessness, Cough, and Sputum Scale scores after adjusting for outdoor pollution concentrations., Conclusions: For patients with COPD who spend the majority of their time indoors, indoor heat exposure during the warmer months represents a modifiable environmental exposure that may contribute to respiratory morbidity. In the context of climate change, adaptive strategies that include optimization of indoor environmental conditions are needed to protect this high-risk group from the adverse health effects of heat.

Background: Broccoli sprouts (BS) are the richest source of sulforaphane (SFN), which is a potent inducer of phase II enzymes, which play a critical role in preventing oxidative stress (OS) and inflammation., Objectives: The objective of this study was to determine if ingestion of whole BS improves airway inflammatory and physiologic outcomes, and OS in adults with asthma and allergic sensitization to an indoor allergen., Methods: The study is a double-blind, placebo-controlled, randomized trial to compare the effects of BS with placebo (alfalfa sprouts [AS]) on airway inflammation and markers of OS. Forty adults (aged 18-50 years) were randomized to eat either (a) 100 g of BS daily or (b) 100 g of AS daily for 3 days. Fractional exhaled nitric oxide (FENO), forced expiratory volume 1, nasal epithelial and PBMC gene expression, inflammatory and OS biomarkers, and symptoms were assessed both before and after ingestion of the sprouts. The primary outcome variable was the change in FENO. Secondary outcome measures included rhinitis and asthma symptoms, lung function, and OS and inflammatory biomarkers., Results: BS ingestion for 3 consecutive days did not reduce FENO, despite resulting in a marked increase in serum SFN concentrations (21 vs 22 parts per billion, P = .76). Furthermore, BS consumption did not induce cytoprotective antioxidant genes in either PBMCs or nasal epithelial cells, reduce OS and inflammatory markers, or improve lung function., Conclusions: Ingestion of whole BS for 3 days does not appear to improve eosinophilic pulmonary inflammation, inflammatory and OS biomarkers, or clinical features of asthma among atopic adults with asthma despite resulting in a marked increase in serum SFN levels., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Airborne contaminants produced by industrial agricultural facilities contain chemical and biological compounds that can impact the health of residents living in close proximity. Settled dust can be a reservoir for these contaminants and can influence long-term exposures. In this study, we sampled the indoor- and outdoor-settled dust from 40 homes that varied in proximity to industrial-scale dairies (ISD; industrial-scale dairy, a term used in this paper to describe a large dairy farm and adjacent waste sprayfields, concentrated animal feeding operation or animal feeding operation, that uses industrial processes) in the Yakima Valley, Washington. We analyzed settled dust samples for cow allergen (Bos d2, a cow allergen associated with dander, hair, sweat and urine, it is a member of the lipocalin family of allergens associated with mammals), mouse allergen (Mus m1; major mouse allergen, a mouse urinary allergen, in the lipocalin family), dust mite allergens (Der p1 (Dermatophagoides pteronissinus 1) and Der f1 (Dermatophagoides farinae 1)), and endotoxin (a component of the cell walls of gram negative bacteria, lipopolysaccharide, which can be found in air and dust and can produce a strong inflammatory response). A concentration gradient was observed for Bos d2 and endotoxin measured in outdoor-settled dust samples based on proximity to ISD. Indoor-settled dust concentrations of Bos d2 and endotoxin were also highest in proximal homes. While the associated health effects of exposure to cow allergen in settled dust is unknown, endotoxin at concentrations observed in these proximal homes (100 EU/mg) has been associated with increased negative respiratory health effects. These findings document that biological contaminants emitted from ISDs are elevated in indoor- and outdoor-settled dust samples at homes close to these facilities and extend to as much as three miles (4.8 km) away.

Objective: This study aimed to describe food and nutrient intake for low-income, urban African American children and adolescents, to highlight the need for further nutrition intervention programs and appropriate tools to address overweight and obesity., Methods: This was a cross-sectional study using interviewer-administered single 24-hour dietary recalls. Participants were low-income African American boys and girls aged 5-16 years or their caregivers in Baltimore City. Frequency of food consumption and dietary intakes were analyzed by gender and age groups., Results: Eighty-one participants were included for analysis. Mean daily energy intakes exceeded Dietary Reference Intakes (DRIs) from 10% to 71% across all gender-age groups: 2304 kcal for children aged 5-8 years; 2429 kcal and 2732 kcal for boys and girls aged 9-13 years, respectively; and 3339 kcal and 2846 kcal for boys and girls aged 14-16 years, respectively. The most frequently reported consumed foods were sweetened drinks, chips, candies, and milk across all age groups. The majority of participants (79-100%) did not meet the DRIs for dietary fiber and vitamin E across all gender-age groups. Milk accounted for 14%, 17%, and 21% of energy, fat, and protein intake, respectively, among children 5-8 years of age, while pizza was the top source of energy, fat, and protein (11%, 13%, and 18%, respectively) among 14-to 16-year-old adolescents. Sweetened drinks and sweetened juices were major sources of sugar, contributing 33% for 5-8 year olds, 29% for 9-13 year olds, and 35% for 14-16 year olds., Conclusions: Mean daily energy intake exceeded dietary recommendations across all gender-age groups. This study has provided previously unavailable information on diet and highlights foods to be targeted in nutrition intervention programs.

Objective: Risk factors beyond tobacco smoking associated with chronic bronchitis are not well understood. We sought to describe the prevalence and risk factors of chronic bronchitis across four distinct settings in Peru with overall low prevalence of tobacco smoking yet varying degrees of urbanization, daily exposure to biomass fuel smoke and living at high altitude., Methods: We analyzed data of 2,947 participants from rural and urban Puno, Lima and Tumbes including spirometry, blood samples, anthropometry and administered questionnaires about respiratory symptoms. We used multivariable Poisson regression to assess biologic, socioeconomic and environmental risk factors associated with chronic bronchitis., Results: Overall prevalence of chronic bronchitis was 5.9% (95%CI 5.1%-6.9%) with variation by setting: prevalence was lower in semi-urban Tumbes (1.3%) vs. highly urbanized Lima (8.9%), urban Puno (7.0%) and rural Puno (7.8%; p < 0.001). Chronic bronchitis was more common among participants with vs. without COPD based on FEV1/FVC< LLN (12.1% vs 5.6%, p < 0.01) and it was associated with increased reporting of dyspnea on exertion (p < 0.001), hospitalization (p = 0.003) and workdays missed due to respiratory symptoms (p < 0.001). Older age (Prevalence ratio [PR] = 1.23 for each 10-years of age, 95%CI 1.09-1.40) past history of asthma (PR = 2.87, 95%CI 1.80-4.56), urbanization (PR = 3.34, 95%CI 2.18-5.11) and daily exposure to biomass fuel smoke (PR = 2.00, 95%CI 1.30-3.07) were all associated with chronic bronchitis., Conclusions: We found important variations in the prevalence of chronic bronchitis across settings. Prevalence increased with both urbanization and with daily exposure to biomass fuel smoke. Having chronic bronchitis was also associated with worse patient-centered outcomes including dyspnea, hospitalization and missed workdays.

Asthma development and pathogenesis are influenced by the interactions of airway epithelial cells and innate and adaptive immune cells in response to allergens. Oxidative stress is an important mediator of asthmatic phenotypes in these cell types. Nuclear erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that is the key regulator of the response to oxidative and environmental stress. We previously demonstrated that Nrf2-deficient mice have heightened susceptibility to asthma, including elevated oxidative stress, inflammation, mucus, and airway hyperresponsiveness (AHR) (Rangasamy T, Guo J, Mitzner WA, Roman J, Singh A, Fryer AD, Yamamoto M, Kensler TW, Tuder RM, Georas SN, Biswal S. J Exp Med 202: 47-59, 2005). Here we dissected the role of Nrf2 in lung epithelial cells and tested whether genetic or pharmacological activation of Nrf2 reduces allergic asthma in mice. Cell-specific activation of Nrf2 in club cells of the airway epithelium significantly reduced allergen-induced AHR, inflammation, mucus, Th2 cytokine secretion, oxidative stress, and airway leakiness and increased airway levels of tight junction proteins zonula occludens-1 and E-cadherin. In isolated airway epithelial cells, Nrf2 enhanced epithelial barrier function and increased localization of zonula occludens-1 to the cell surface. Pharmacological activation of Nrf2 by 2-trifluoromethyl-2'-methoxychalone during the allergen challenge was sufficient to reduce allergic inflammation and AHR. New therapeutic options are needed for asthma, and this study demonstrates that activation of Nrf2 in lung epithelial cells is a novel potential therapeutic target to reduce asthma susceptibility., (Copyright © 2015 the American Physiological Society.)

Our goal was to investigate whether obesity increases susceptibility to the adverse effects of indoor particulate matter on respiratory morbidity among individuals with chronic obstructive pulmonary disease (COPD). Participants with COPD were studied at baseline, 3 and 6 months. Obesity was defined as a body mass index ≥30 kg·m(-2). At each time point, indoor air was sampled for 5-7 days and particulate matter (PM) with an aerodynamic size ≤2.5 μm (PM2.5) and 2.5-10 μm (PM2.5-10) was measured. Respiratory symptoms, health status, rescue medication use, exacerbations, blood biomarkers and exhaled nitric oxide were assessed simultaneously. Of the 84 participants enrolled, 56% were obese and all were former smokers with moderate-to-severe COPD. Obese participants tended to have less severe disease as assessed by Global Initiative for Chronic Obstructive Pulmonary Disease stage and fewer pack-years of smoking. There was evidence that obesity modified the effects of indoor PM on COPD respiratory outcomes. Increases in PM2.5 and PM2.5-10 were associated with greater increases in nocturnal symptoms, dyspnoea and rescue medication use among obese versus non-obese participants. The impact of indoor PM on exacerbations, respiratory status and wheeze also tended to be greater among obese versus non-obese participants, as were differences in airway and systemic inflammatory responses to indoor PM. We found evidence that obesity was associated with exaggerated responses to indoor fine and coarse PM exposure among individuals with COPD., (Copyright ©ERS 2015.)

Background: It is unclear how geographic and social diversity affects the prevalence of chronic obstructive pulmonary disease (COPD). We sought to characterize the prevalence of COPD and identify risk factors across four settings in Peru with varying degrees of urbanization, altitude, and biomass fuel use., Methods: We collected sociodemographics, clinical history, and post-bronchodilator spirometry in a randomly selected, age-, sex- and site-stratified, population-based sample of 2,957 adults aged ≥35 years (median age was 54.8 years and 49.3% were men) from four resource-poor settings: Lima, Tumbes, urban and rural Puno. We defined COPD as a post-bronchodilator FEV1/FVC < 70%., Results: Overall prevalence of COPD was 6.0% (95% CI 5.1%-6.8%) but with marked variation across sites: 3.6% in semi-urban Tumbes, 6.1% in urban Puno, 6.2% in Lima, and 9.9% in rural Puno (p < 0.001). Population attributable risks (PARs) of COPD due to smoking ≥10 pack-years were less than 10% for all sites, consistent with a low prevalence of daily smoking (3.3%). Rather, we found that PARs of COPD varied by setting. In Lima, for example, the highest PARs were attributed to post-treatment tuberculosis (16% and 22% for men and women, respectively). In rural Puno, daily biomass fuel for cooking among women was associated with COPD (prevalence ratio 2.22, 95% CI 1.02-4.81) and the PAR of COPD due to daily exposure to biomass fuel smoke was 55%., Conclusions: The burden of COPD in Peru was not uniform and, unlike other settings, was not predominantly explained by tobacco smoking. This study emphasizes the role of biomass fuel use, and highlights pulmonary tuberculosis as an often neglected risk factor in endemic areas.

Rationale: Links between occupational exposures and morbidity in individuals with established chronic obstructive pulmonary disease (COPD) remain unclear., Objectives: To determine the impact of occupational exposures on COPD morbidity., Methods: A job exposure matrix (JEM) determined occupational exposure likelihood based on longest job in current/former smokers (n = 1,075) recruited as part of the Subpopulations and Intermediate Outcomes in COPD Study, of whom 721 had established COPD. Bivariate and multivariate linear regression models estimated the association of occupational exposure with COPD, and among those with established disease, the occupational exposure associations with 6-minute-walk distance (6MWD), the Modified Medical Research Council Dyspnea Scale (mMRC), the COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), 12-item Short-Form Physical Component (SF-12), and COPD exacerbations requiring health care utilization, adjusting for demographics, current smoking status, and cumulative pack-years., Measurements and Main Results: An intermediate/high risk of occupational exposure by JEM was found in 38% of participants. In multivariate analysis, those with job exposures had higher odds of COPD (odds ratio, 1.44; 95% confidence interval, 1.04-1.97). Among those with COPD, job exposures were associated with shorter 6MWDs (-26.0 m; P = 0.006); worse scores for mMRC (0.23; P = 0.004), CAT (1.8; P = 0.003), SGRQ (4.5; P = 0.003), and SF-12 Physical (-3.3; P < 0.0001); and greater odds of exacerbation requiring health care utilization (odds ratio, 1.55; P = 0.03)., Conclusions: Accounting for smoking, occupational exposure was associated with COPD risk and, for those with established disease, shorter walk distance, greater breathlessness, worse quality of life, and increased exacerbation risk. Clinicians should obtain occupational histories from patients with COPD because work-related exposures may influence disease burden.

Recent intervention studies targeted at reducing indoor air pollution have demonstrated both the ability to improve respiratory health outcomes and to reduce particulate matter (PM) levels in the home. However, these studies generally do not address whether it is the reduction of PM levels specifically that improves respiratory health. In this paper we apply the method of principal stratification to data from a randomized air cleaner intervention designed to reduce indoor PM in homes of children with asthma. We estimate the health benefit of the intervention amongst study subjects who would experience a substantial reduction in PM in response to the intervention. For those subjects we find an increase in symptom-free days that is almost three times as large as the overall intention-to-treat effect. We also explore the presence of treatment effects amongst those subjects whose PM levels would not respond to the air cleaner. This analysis demonstrates the usefulness of principal stratification for environmental intervention trials and its potential for much broader application in this area.

Previous research has found evidence of an association between indoor air pollution and asthma morbidity in children. Environmental intervention studies have been performed to examine the role of household environmental interventions in altering indoor air pollution concentrations and improving health. Previous environmental intervention studies have found only modest effects on health outcomes and it is unclear if the health benefits provided by environmental modification are comparable with those provided by medication. Traditionally, the statistical analysis of environmental intervention studies has involved performing two intention-to-treat analyses that separately estimate the effect of the environmental intervention on health and the effect of the environmental intervention on indoor air pollution concentrations. We propose a principal stratification approach to examine the extent to which an environmental intervention's effect on health outcomes coincides with its effect on indoor air pollution. We apply this approach to data from a randomized air cleaner intervention trial conducted in a population of asthmatic children living in Baltimore, Maryland, USA. We find that among children for whom the air cleaner reduced indoor particulate matter concentrations, the intervention resulted in a meaningful improvement of asthma symptoms with an effect generally larger than previous studies have shown. A key benefit of using principal stratification in environmental intervention studies is that it allows investigators to estimate causal effects of the intervention for sub-groups defined by changes in the indoor air pollution concentration., (Copyright © 2014 John Wiley & Sons, Ltd.)

Rationale: Pulmonologists frequently encounter indeterminate pulmonary nodules in practice, but it is unclear what clinical factors they rely on to guide the diagnostic evaluation., Objectives: To assess the current approach to the management of indeterminate pulmonary nodules and to determine the extent to which the addition of a hypothetical diagnostic blood test will influence clinical decision making., Methods: Selected pulmonologists practicing in the United States were invited to participate in a conjoint exercise based on 20 randomly generated cases of varying age, smoking history, and nodule size. Some cases included the result of a hypothetical blood test. Each respondent chose from among three diagnostic options for a patient: noninvasive monitoring (i.e., serial CT or positron emission tomography scan), a minor procedure (i.e., biopsy or bronchoscopy), or a major procedure (i.e., video-assisted thorascopic surgery or thoracotomy). Multivariate logistic regression was used to assess the impact of the three risk factors and the diagnostic blood test on decision making., Measurements and Main Results: Four hundred nineteen physicians participated (response rate, 10%). One hundred fifty-three physician surveys met predetermined criteria and were analyzed (4% of all invitees). A diagnostic procedure was recommended for 23% of 6-mm nodules, versus 54, 66, 77, and 84% of nodules 10, 14, 18, and 22 mm, respectively (P < 0.001). Older age limited recommendations for invasive testing: 54% of 80-year-olds versus 61, 64, 63, and 61% of patients 71, 62, 53, and 44 years of age, respectively (P < 0.001). In multivariate analyses, nodule size, smoking history, age, and the blood test each influenced decision making (P < 0.001)., Conclusions: The pulmonologists who participated in this survey were more likely to proceed with invasive testing, instead of observation or additional imaging, as the size of the nodule increased. The use of a hypothetical blood test resulted in significant alterations in the decision to pursue invasive testing.

Background: Genome-wide association studies have yet to identify the majority of genetic variants involved in asthma. We hypothesized that expression quantitative trait locus (eQTL) mapping can identify novel asthma genes by enabling prioritization of putative functional variants for association testing., Objective: We evaluated 6706 cis-acting expression-associated variants (eSNPs) identified through a genome-wide eQTL survey of CD4(+) lymphocytes for association with asthma., Methods: eSNPs were tested for association with asthma in 359 asthmatic patients and 846 control subjects from the Childhood Asthma Management Program, with verification by using family-based testing. Significant associations were tested for replication in 579 parent-child trios with asthma from Costa Rica. Further functional validation was performed by using formaldehyde-assisted isolation of regulatory elements (FAIRE) quantitative PCR and chromatin immunoprecipitation PCR in lung-derived epithelial cell lines (Beas-2B and A549) and Jurkat cells, a leukemia cell line derived from T lymphocytes., Results: Cis-acting eSNPs demonstrated associations with asthma in both cohorts. We confirmed the previously reported association of ORMDL3/GSDMB variants with asthma (combined P = 2.9 × 10(-8)). Reproducible associations were also observed for eSNPs in 3 additional genes: fatty acid desaturase 2 (FADS2; P = .002), N-acetyl-α-D-galactosaminidase (NAGA; P = .0002), and Factor XIII, A1 (F13A1; P = .0001). Subsequently, we demonstrated that FADS2 mRNA is increased in CD4(+) lymphocytes in asthmatic patients and that the associated eSNPs reside within DNA segments with histone modifications that denote open chromatin status and confer enhancer activity., Conclusions: Our results demonstrate the utility of eQTL mapping in the identification of novel asthma genes and provide evidence for the importance of FADS2, NAGA, and F13A1 in the pathogenesis of asthma., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: Indoor particulate matter (PM) has been linked to respiratory symptoms in former smokers with COPD. While subjects with COPD and atopy have also been shown to have more frequent respiratory symptoms, whether they exhibit increased susceptibility to PM as compared to their non-atopic counterparts remains unclear. The aim of this study was to determine whether atopic individuals with COPD have greater susceptibility to PM compared to non-atopic individuals with COPD., Methods: Former smokers with moderate to severe COPD were enrolled (n = 77). PM2.5, PM with diameter <2.5 micrometers, was measured in the main living area over three one-week monitoring periods at baseline, 3, and 6 months. Quality of life, respiratory symptoms and medication use were assessed by questionnaires. Serum was analyzed for specific IgE for mouse, cockroach, cat, dog and dust mite allergens. Atopy was established if at least one test was positive. Interaction terms between PM and atopy were tested and generalized estimating equation analysis determined the effect of PM concentrations on health outcomes. Multivariate models were adjusted for age, sex, education, race, season, and baseline lung function and stratified by atopic status., Results: Among atopic individuals, each 10 μg/m(3) increase in PM was associated with higher risk of nocturnal symptoms (OR, 1.95; P = 0.02), frequent wheezing (OR, 2.49; P = 0.02), increased rescue medication use (β = 0.14; P = 0.02), dyspnea (β = 0.23; P < 0.001), higher St. George's Respiratory Quality of Life score (β = 2.55; P = 0.01), and higher breathlessness, cough, and sputum score (BCSS) (β = 0.44; P = 0.01). There was no association between PM and health outcomes among the non-atopic individuals. Interaction terms between PM2.5 and atopy were statistically significant for nocturnal symptoms, frequency of rescue medication use, and BCSS (all P < 0.1)., Conclusions: Individuals with COPD and atopy appear to be at higher risk of adverse respiratory health effects of PM exposure compared to non-atopic individuals with COPD.

Unlabelled: Nitrogen dioxide (NO2 ), a by-product of combustion produced by indoor gas appliances such as cooking stoves, is associated with respiratory symptoms in those with obstructive airways disease. We conducted a three-armed randomized trial to evaluate the efficacy of interventions aimed at reducing indoor NO2 concentrations in homes with unvented gas stoves: (i) replacement of existing gas stove with electric stove; (ii) installation of ventilation hood over existing gas stove; and (iii) placement of air purifiers with high-efficiency particulate air (HEPA) and carbon filters. Home inspection and NO2 monitoring were conducted at 1 week pre-intervention and at 1 week and 3 months post-intervention. Stove replacement resulted in a 51% and 42% decrease in median NO2 concentration at 3 months of follow-up in the kitchen and bedroom, respectively (P = 0.01, P = 0.01); air purifier placement resulted in an immediate decrease in median NO2 concentration in the kitchen (27%, P < 0.01) and bedroom (22%, P = 0.02), but at 3 months, a significant reduction was seen only in the kitchen (20%, P = 0.05). NO2 concentrations in the kitchen and bedroom did not significantly change following ventilation hood installation. Replacing unvented gas stoves with electric stoves or placement of air purifiers with HEPA and carbon filters can decrease indoor NO2 concentrations in urban homes., Practical Implications: Several combustion sources unique to the residential indoor environment, including gas stoves, produce nitrogen dioxide (NO2), and higher NO2 concentrations, are associated with worse respiratory morbidity in people with obstructive lung disease. A handful of studies have modified the indoor environment by replacing unvented gas heaters; this study, to our knowledge, is the first randomized study to target unvented gas stoves. The results of this study show that simple home interventions, including replacement of an unvented gas stove with an electric stove or placement of HEPA air purifiers with carbon filters, can significantly decrease indoor NO2 concentrations., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Despite a growing interest, few pediatric asthma questionnaires assess multiple dimensions of asthma morbidity, as recommended by national asthma guidelines, or use patient-reported outcomes., Objective: To evaluate a questionnaire that measures multiple dimensions of parent-reported asthma morbidity (Direction, Bother, and Risk)., Methods: We administered the Pediatric Asthma Control and Communication Instrument (PACCI) and assessed asthma control (PACCI Control), quality of life, and lung function among children who presented for routine asthma care. The PACCI was evaluated for discriminative validity., Results: A total of 317 children participated (mean age, 8.2 years; 58% boys; 44% African American). As parent-reported PACCI Direction changed from "better" to "worse," we observed poorer asthma control (P < .001), mean Pediatric Asthma Caregiver Quality of Life Questionnaire (PACQLQ) scores (P < .001), and FEV1% (P = .025). Linear regression showed that, for each change in PACCI Direction, the mean PACQLQ score decreased by -0.6 (95% CI, -0.8 to -0.4). As parent-reported PACCI Bother changed from "not bothered" to "very bothered," we observed poorer asthma control (P < .001) and lower mean PACQLQ scores (P < .001). Linear regression showed that, for each change in PACCI Bother category, the mean PACQLQ score decreased by -1.1 (95% CI, -1.3 to -0.9). Any reported PACCI Risk event (emergency department visit, hospitalization, or use of an oral corticosteroid) was associated with poorer asthma control (P < .05) and PACQLQ scores (P < .01)., Conclusions: PACCI Direction, Bother, and Risk are valid measures of parent-reported outcomes and show good discriminative validity. The PACCI is a simple clinical tool to assess multiple dimensions of parent-reported asthma morbidity, in addition to risk and control., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: We sought to understand if pediatrician characteristics and asthma assessment and treatment varied in association with the proportion of African-American and Latino children in the pediatrician's practice., Methods: We conducted a cross-sectional survey of 500 American Academy of Pediatrics members between November 2005 and May 2006. Standardized vignettes were used to test how different indicators of a patient's asthma status affect pediatrician asthma assessments and recommendations. Linear and logistic regression models were used to examine the association of pediatrician assessments and treatment recommendations for these vignettes, respectively, with the proportion of reported African-American and Latino children seen in their practice., Results: There were 270 respondents (response rate = 54%). Based on pediatrician-reported percentage of minority patients, there were no differences in board certification status, recognition of poorly controlled asthma nor in the likelihood of appropriately increasing long-term controller medications to treat poorly controlled asthma (p > 0.05 for all analyses)., Conclusions: Caring primarily for minority children by AAP pediatricians appears unrelated to training qualifications or in their reported knowledge of how to appropriately assess and treat asthma. Therefore, studies of asthma care disparities should focus on understanding the knowledge-base of non-AAP pediatric providers who care for minority populations and exploring other potential contributory provider-level factors (e.g. communication skills).

Rationale: The effect of endotoxin on asthma morbidity in urban populations is unclear., Objectives: To determine if indoor pollutant exposure modifies the relationships between indoor airborne endotoxin and asthma health and morbidity., Methods: One hundred forty-six children and adolescents with persistent asthma underwent repeated clinical assessments at 0, 3, 6, 9, and 12 months. Home visits were conducted at the same time points for assessment of airborne nicotine, endotoxin, and nitrogen dioxide (NO2) concentrations. The effect of concomitant pollutant exposure on relationships between endotoxin and asthma outcomes were examined in stratified analyses and statistical models with interaction terms., Measurements and Main Results: Both air nicotine and NO2 concentrations modified the relationships between airborne endotoxin and asthma outcomes. Among children living in homes with no detectable air nicotine, higher endotoxin was inversely associated with acute visits and oral corticosteroid bursts, whereas among those in homes with detectable air nicotine, endotoxin was positively associated with these outcomes (interaction P value = 0.004 and 0.07, respectively). Among children living in homes with lower NO2 concentrations (<20 ppb), higher endotoxin was positively associated with acute visits, whereas among those living in homes with higher NO2 concentrations, endotoxin was negatively associated with acute visit (interaction P value = 0.05). NO2 also modified the effect of endotoxin on asthma symptom outcomes in a similar manner., Conclusions: The effects of household airborne endotoxin exposure on asthma are modified by coexposure to air nicotine and NO2, and these pollutants have opposite effects on the relationships between endotoxin and asthma-related outcomes.

Background: Cockroach and mouse allergens have both been implicated as causes in inner-city asthma morbidity in multicenter studies, but whether both allergens are clinically relevant within specific inner-city communities is unclear., Objective: Our study aimed to identify relevant allergens in Baltimore City., Methods: One hundred forty-four children (5-17 years old) with asthma underwent skin prick tests at baseline and had clinical data collected at baseline and 3, 6, 9, and 12 months. Home settled dust samples were collected at the same time points for quantification of indoor allergens. Participants were grouped based on their sensitization and exposure status to each allergen. All analyses were adjusted for age, sex, and serum total IgE level., Results: Forty-one percent were mouse sensitized/exposed, and 41% were cockroach sensitized/exposed based on bedroom floor exposure data. Mouse sensitization/exposure was associated with acute care visits, decreased FEV1/forced vital capacity percentage values, fraction of exhaled nitric oxide levels, and bronchodilator reversibility. Cockroach sensitization/exposure was only associated with acute care visits and bronchodilator reversibility when exposure was defined by using bedroom floor allergen levels. Mouse-specific IgE levels were associated with poor asthma health across a range of outcomes, whereas cockroach-specific IgE levels were not. The relationships between asthma outcomes and mouse allergen were independent of cockroach allergen. Although sensitization/exposure to both mouse and cockroach was generally associated with worse asthma, mouse sensitization/exposure was the primary contributor to these relationships., Conclusions: In a community with high levels of both mouse and cockroach allergens, mouse allergen appears to be more strongly and consistently associated with poor asthma outcomes than cockroach allergen. Community-level asthma interventions in Baltimore should prioritize reducing mouse allergen exposure., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background and Objective: Health care provider adherence to asthma guidelines is poor. The objective of this study was to assess the effect of interventions to improve health care providers' adherence to asthma guidelines on health care process and clinical outcomes., Methods: Data sources included Medline, Embase, Cochrane CENTRAL Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Educational Resources Information Center, PsycINFO, and Research and Development Resource Base in Continuing Medical Education up to July 2012. Paired investigators independently assessed study eligibility. Investigators abstracted data sequentially and independently graded the evidence., Results: Sixty-eight eligible studies were classified by intervention: decision support, organizational change, feedback and audit, clinical pharmacy support, education only, quality improvement/pay-for-performance, multicomponent, and information only. Half were randomized trials (n = 35). There was moderate evidence for increased prescriptions of controller medications for decision support, feedback and audit, and clinical pharmacy support and low-grade evidence for organizational change and multicomponent interventions. Moderate evidence supports the use of decision support and clinical pharmacy interventions to increase provision of patient self-education/asthma action plans. Moderate evidence supports use of decision support tools to reduce emergency department visits, and low-grade evidence suggests there is no benefit for this outcome with organizational change, education only, and quality improvement/pay-for-performance., Conclusions: Decision support tools, feedback and audit, and clinical pharmacy support were most likely to improve provider adherence to asthma guidelines, as measured through health care process outcomes. There is a need to evaluate health care provider-targeted interventions with standardized outcomes.

Background: American Thoracic Society guidelines support using fractional exhaled nitric oxide (FENO) measurements in patients with asthma and highlight gaps in the evidence base. Little is known about the use of FENO levels to predict asthma exacerbations among high-risk, urban, minority populations receiving usual care., Methods: Children with persistent asthma (n = 138) were enrolled in a prospective, observational cohort study and skin tested at baseline (a wheal ≥ 3 mm indicated a positive skin-prick test). FENO levels, lung function, and asthma-related health-care use were assessed at baseline and every 3 months thereafter for 1 year. Relationships between FENO levels and health-care use in the subsequent 3 months were examined. Final models accounted for repeated outcome measures and were adjusted for age, sex, and lung function., Results: The mean age of the children was 11 years (range, 5-17 years), and most were male (57%), black (91%), and atopic (90%). At baseline, the median FENO level was 31.5 parts per billion (interquartile range, 16-61 ppb) and mean FEV1/FVC was 80.7% (SD, ± 9.6%). There were 237 acute asthma-related health-care visits, 105 unscheduled doctor visits, 125 ED visits, and seven hospitalizations during the follow-up period. FENO level was not a significant predictor of acute visits, ED visits, unscheduled doctor visits, or hospitalization in either unadjusted or adjusted analyses. Use of recommended cut points did not improve the predictive value of the FENO level (positive predictive value, 0.6%-32.8%) nor did application of the guideline-based algorithm to assess change over time., Conclusions: FENO level may not be a clinically useful predictor of health-care use for asthma exacerbations in urban minority children with asthma.

Background: Applied environmental strategies for asthma control are often expensive, but may save longer-term healthcare costs. Whether these savings outweigh additional costs of implementing these strategies is uncertain., Methods: We conducted a systematic review to estimate the expenditures and savings of environmental interventions for asthma in the state of Maryland. Direct costs included hospitalizations, emergency room, and clinic visits. Indirect expenditures included costs of lost work productivity and travel incurred during the usage of healthcare services. We used decision analysis, assuming a hypothetical cohort of the approximated 49,290 pediatric individuals in Maryland with persistent asthma, to compare costs and benefits of environmental asthma interventions against the standard of care (no intervention) from the societal perspective., Results: Three interventions among nine articles met the inclusion criteria for the systematic review: 1) environmental education using medical professionals; 2) education using non-medical personnel; and 3) multi-component strategy involving education with non-medical personnel, allergen-impermeable covers, and pest management. All interventions were found to be cost-saving relative to the standard of care. Home environmental education using non-medical professionals yielded the highest net savings of $14.1 million (95% simulation interval (SI): $-.283 million, $19.4 million), while the multi-component intervention resulted in the lowest net savings of $8.1 million (95% SI: $-4.9 million, $15.9 million). All strategies were most sensitive to the baseline number of hospitalizations in those not receiving targeted interventions for asthma., Conclusions: Limited environmental reduction strategies for asthma are likely to be cost-saving to the healthcare system in Maryland and should be considered for broader scale-up in other economically similar settings.

Home mouse allergen exposure is associated with asthma morbidity, but little is known about the shape of the dose-response relationship or the relevance of location of exposure within the home. Asthma outcome and allergen exposure data were collected every 3 months for 1 year in 150 urban children with asthma. Participants were stratified by mouse sensitization, and relationships between continuous measures of mouse allergen exposure and outcomes of interest were analyzed. Every tenfold increase in the bed mouse allergen level was associated with an 87% increase in the odds of any asthma-related health care use among mouse-sensitized [Odds Ratio (95% CI): 1.87 (1.21-2.88)], but not non-mouse-sensitized participants. Similar relationships were observed for emergency department visit and unscheduled doctor visit among mouse-sensitized participants. Kitchen floor and bedroom air mouse allergen concentrations were also associated with greater odds of asthma-related healthcare utilization; however, the magnitude of the association was less than that observed for bed mouse allergen concentrations. In this population of urban children with asthma, there is a linear dose-response relationship between mouse allergen concentrations and asthma morbidity among mouse-sensitized asthmatics. Bed and bedroom air mouse allergen exposure compartments may have a greater impact on asthma morbidity than other compartments., (© 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Rationale: Chronic obstructive pulmonary disease (COPD) guidelines make no recommendations for allergy diagnosis or treatment., Objectives: To determine whether an allergic phenotype contributes to respiratory symptoms and exacerbations in patients with COPD., Methods: Two separate cohorts were analyzed: National Health and Nutrition Survey III (NHANES III) and the COPD and domestic endotoxin (CODE) cohort. Subjects from NHANES III with COPD (n = 1,381) defined as age > 40 years, history of smoking, FEV1/FVC < 0.70, and no diagnosis of asthma were identified. The presence of an allergic phenotype (n = 296) was defined as self-reported doctor diagnosed hay fever or allergic upper respiratory symptoms. In CODE, former smokers with COPD (n = 77) were evaluated for allergic sensitization defined as a detectable specific IgE to perennial allergens. Bivariate and multivariate models were used to determine whether an allergic phenotype was associated with respiratory symptoms and exacerbations., Measurements and Main Results: In NHANES III, multivariate analysis revealed that individuals with allergic phenotype were more likely to wheeze (odds ratio [OR], 2.1; P < 0.01), to have chronic cough (OR, 1.9; P = 0.01) and chronic phlegm (OR, 1.5; P < 0.05), and to have increased risk of COPD exacerbation requiring an acute doctor visit (OR, 1.7; P = 0.04). In the CODE cohort, multivariate analysis revealed that sensitized subjects reported more wheeze (OR, 5.91; P < 0.01), more nighttime awakening due to cough (OR, 4.20; P = 0.03), increased risk of COPD exacerbations requiring treatment with antibiotics (OR, 3.79; P = 0.02), and acute health visits (OR, 11.05; P < 0.01). An increasing number of sensitizations was associated with a higher risk for adverse health outcomes., Conclusions: Among individuals with COPD, evidence of an allergic phenotype is associated with increased respiratory symptoms and risk of COPD exacerbations.

Background: National Institutes of Health asthma guidelines recommend questionnaires to assess asthma control, but these questionnaires are not useable across the entire pediatric age spectrum and have not been validated among significant numbers of minority or Spanish-speaking children., Objective: We sought to evaluate a questionnaire designed to assess asthma control across a broad age range of minority and Spanish-speaking children cared for in an outpatient setting., Methods: Between July 1, 2007, and September 30, 2010, we collected information using the Pediatric Asthma Control and Communication Instrument (PACCI), the Asthma Control Test (ACT; or the childhood ACT for children 4-11 years old), the Pediatric Asthma Caregiver Quality of Life Questionnaire, and lung function and clinicians' ratings of asthma status among a population of children presenting for routine asthma specialist care. The PACCI measure of asthma control was validated by evaluating accuracy, internal reliability, and concurrent, discriminative, and known-groups validity., Results: We collected information on 265 English- and 52 Spanish-speaking children (mean age, 8.2 years; 58% male; 44% African American). Across all age groups and in both languages, PACCI control showed good internal reliability and strong concurrent, discriminative, and known-groups validity with ACT and Pediatric Asthma Caregiver Quality of Life Questionnaire scores and clinicians' ratings of asthma control. The accuracy of the PACCI in classifying children with uncontrolled asthma was good (area under the curve, 0.83; 95% CI, 0.79-0.88)., Conclusions: The PACCI accurately measures asthma control in English- and Spanish-speaking children. The PACCI should be useful to clinicians to assess and classify asthma according to National Institutes of Health asthma guidelines., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: The inner-city pediatric population in the United States has a disproportionate burden of asthma. Recent attention has focused on the immunomodulatory role of vitamin D, which may be protective against disease morbidity. As the primary determinant of vitamin D status in humans is exposure to sunlight, we aimed to determine if 25-OH vitamin D levels in urban preschool children with asthma were low, influenced by time spent outdoors, and associated with asthma morbidity., Methods: Serum 25-OH vitamin D levels were measured at baseline in a cohort of 121 inner-city children ages 2-6 years with asthma in Baltimore, MD. Participants were followed longitudinally at 3 and 6 months to assess time spent outdoors, asthma symptoms through questionnaires and daily diaries, and allergic markers., Results: In a predominantly black population of preschool children, the median 25-OH vitamin D level was 28 ng/mL (IQR 21.2-36.9), with 54% of the children below the traditionally sufficient level of 30 ng/mL and 7.4% in the range associated with risk of rickets (< 15 ng/mL). The median time spent outdoors was 3 hours/day (IQR 2-4), and greater time spent outdoors was not associated with higher vitamin D levels. 25-OH vitamin D did not show seasonal variation in our cohort (p = 0.66). Lower 25-OH levels were correlated with higher IgE levels., Conclusions: Urban African-American preschool children with asthma have high rates of vitamin D insufficiency, and increased outdoor exposure is unlikely to correct these low 25-OH vitamin D levels. Repletion in this population may require dietary supplementation.

Rationale: The effect of indoor air pollutants on respiratory morbidity among patients with chronic obstructive pulmonary disease (COPD) in developed countries is uncertain., Objectives: The first longitudinal study to investigate the independent effects of indoor particulate matter (PM) and nitrogen dioxide (NO(2)) concentrations on COPD morbidity in a periurban community., Methods: Former smokers with COPD were recruited and indoor air was monitored over a 1-week period in the participant's bedroom and main living area at baseline, 3 months, and 6 months. At each visit, participants completed spirometry and questionnaires assessing respiratory symptoms. Exacerbations were assessed by questionnaires administered at clinic visits and monthly telephone calls., Measurements and Main Results: Participants (n = 84) had moderate or severe COPD with a mean FEV1 of 48.6% predicted. The mean (± SD) indoor PM(2.5) and NO(2) concentrations were 11.4 ± 13.3 µg/m(3) and 10.8 ± 10.6 ppb in the bedroom, and 12.2 ± 12.2 µg/m(3) and 12.2 ± 11.8 ppb in the main living area. Increases in PM(2.5) concentrations in the main living area were associated with increases in respiratory symptoms, rescue medication use, and risk of severe COPD exacerbations. Increases in NO(2) concentrations in the main living area were independently associated with worse dyspnea. Increases in bedroom NO(2) concentrations were associated with increases in nocturnal symptoms and risk of severe COPD exacerbations., Conclusions: Indoor pollutant exposure, including PM(2.5) and NO(2), was associated with increased respiratory symptoms and risk of COPD exacerbation. Future investigations should include intervention studies that optimize indoor air quality as a novel therapeutic approach to improving COPD health outcomes.

Background: Both being overweight and exposure to indoor pollutants, which have been associated with worse health of asthmatic patients, are common in urban minority populations. Whether being overweight is a risk factor for the effects of indoor pollutant exposure on asthma health is unknown., Objectives: We sought to examine the effect of weight on the relationship between indoor pollutant exposure and asthma health in urban minority children., Methods: One hundred forty-eight children (age, 5-17 years) with persistent asthma were followed for 1 year. Asthma symptoms, health care use, lung function, pulmonary inflammation, and indoor pollutants were assessed every 3 months. Weight category was based on body mass index percentile., Results: Participants were predominantly African American (91%) and had public health insurance (85%). Four percent were underweight, 52% were normal weight, 16% were overweight, and 28% were obese. Overweight or obese participants had more symptoms associated with exposure to fine particulate matter measuring less than 2.5 μm in diameter (PM2.5) than normal-weight participants across a range of asthma symptoms. Overweight or obese participants also had more asthma symptoms associated with nitrogen dioxide (NO2) exposure than normal-weight participants, although this was not observed across all types of asthma symptoms. Weight did not affect the relationship between exposure to coarse particulate matter measuring between 2.5 and 10 μm in diameter and asthma symptoms. Relationships between indoor pollutant exposure and health care use, lung function, or pulmonary inflammation did not differ by weight., Conclusion: Being overweight or obese can increase susceptibility to indoor PM2.5 and NO2 in urban children with asthma. Interventions aimed at weight loss might reduce asthma symptom responses to PM2.5 and NO2, and interventions aimed at reducing indoor pollutant levels might be particularly beneficial in overweight children., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Introduction: High-frequency chest wall oscillation (HFCWO) has been traditionally implemented for airway secretion clearance in conditions such as cystic fibrosis (CF) and bronchiectasis. There have been few reports of its use in refractory asthma., Case Report: A 36-year-old, non-smoker male presented with a lifelong history of poorly controlled asthma. Despite multiple controller medications, he reported daily chest congestion, copious phlegm, and frequent exacerbations. Imaging, blood work, and bronchoscopy ruled out atypical infections, immunodeficiency, CF, and other chronic conditions. Pulmonary function tests supported a diagnosis of asthma., Results: We initiated HFCWO therapy twice daily in addition to standard inhaled pharmacological therapy. After 2 months, the patient noted resolution of respiratory symptoms as well as improvement in lung function. He remained symptom-free at his 2-year follow-up., Conclusion: High-frequency chest oscillation may be useful in phenotypes of asthma characterized by prominent mucus hypersecretion.

Though the high prevalence of biomass fuel use in the developing world is widely known, the use of burning biomass for cooking and heating in the developed world is under-recognized. Combustion materials including coal and wood are also used for heating in some areas of the United States. We conducted a pilot study to assess the feasibility of conducting indoor environmental monitoring in rural Appalachia. We sought to explore the type of biomass being used for home heating and its impact upon indoor air quality in non-heating and heating seasons. Residential indoor air monitoring for particulate matter (PM) and nitrogen dioxide (NO 2 ) was conducted in Lee County, Virginia. Homes had evidence of poor indoor air quality with high concentrations of indoor PM and a large burden of cigarette smoking. Further characterization of indoor combustion material use in this region to determine the health impacts associated with such exposures is warranted.

It is estimated that up to half of the world's population burns biomass fuel (wood, crop residues, animal dung and coal) for indoor uses such as cooking, lighting and heating. As a result, a large proportion of women and children are exposed to high levels of household air pollution (HAP). The short and long term effects of these exposures on the respiratory health of this population are not clearly understood. On May 9-11, 2011 NIH held an international workshop on the "Health Burden of Indoor Air Pollution on Women and Children," in Arlington, VA. To gather information on the knowledge base on this topic and identify research gaps, ahead of the meeting we conducted a literature search using PubMed to identify publications that related to HAP, asthma, and chronic obstructive pulmonary disease (COPD). Abstracts were all analyzed and we report on those considered by the respiratory sub study group at the meeting to be most relevant to the field. Many of the studies published are symptom-based studies (as opposed to objective measures of lung function or clinical examination etc.) and measurement of HAP was not done. Many found some association between indoor exposures to biomass smoke as assessed by stove type (e.g., open fire vs. liquid propane gas) and respiratory symptoms such as wheeze and cough. Among the studies that examined objective measures (e.g. spirometry) as a health outcome, the data supporting an association between biomass smoke exposure and COPD in adult women are fairly robust, but the findings for asthma are mixed. If an association was observed between the exposures and lung function, most data seemed to demonstrate mild to moderate reductions in lung function, the pathophysiological mechanisms of which need to be investigated. In the end, the group identified a series of scientific gaps and opportunities for research that need to be addressed to better understand the respiratory effects of exposure to indoor burning of the different forms of biomass fuels.

Staphylococcus aureus in home environments may serve as a reservoir for human colonization, making sampling of indoor surfaces relevant to exposure assessment. Using laboratory experiments and application to homes of asthmatic children in Barbados, we characterize microbiological methods adapted for settings with transportation delays between sampling and initiation of culture.

BACKGROUND: According to National Institutes of Health (NIH) guidelines, asthma control and severity are unique constructs. Little is known about how asthma control and severity are distinguished by pediatricians and if they influence treatment recommendations. METHODS: We conducted a random-sample survey of 500 pediatricians using patient vignettes with different asthma status indicators (recent hospitalization, parental report of bother from asthma, frequent symptoms, parental report of worsening asthma, and wheeze during physical exam) and a visual analog scale (VAS) to rate control and severity. Regression models assessed the independent effects of these indicators on asthma control and severity ratings, and the effects of these ratings on treatment recommendations. RESULTS: A total of 270 respondents provided usable data. Compared to patients with well-controlled asthma: (1) medication intensity influenced only severity ratings; (2) frequent symptoms and recent hospitalization influenced control and severity ratings; (3) wheeze and bother influenced control ratings only (p<0.001 for all comparisons); (4) a report of worse asthma did not significantly affect any ratings (p>0.2). Poorer VAS control ratings were associated with recommendations to step-up treatment (odds ratio [OR] 2.61, 95% confidence interval [CI], 2.2-3.1, p<0.001), but more severe VAS ratings were not (OR 1.02, 95% CI, 0.9-1.2, p=0.8). Recommendations to step-down treatment were associated with poorer VAS control ratings (OR 0.70, 95% CI, 0.6-0.8, p<0.001) and more severe VAS ratings (OR 0.82, 95% CI, 0.7-0.9, p<0.001). CONCLUSIONS: Pediatricians who step-up asthma treatment base their assessments on asthma control, while assessments of both control and severity factor into their decision to step-down asthma therapy.

Background and Aims: Children living in the inner city are particularly vulnerable to asthma. While we know much about factors that affect near-term outcomes in inner-city children, there is little evidence to guide clinicians on what to expect in the coming years, especially in preschool children. The purpose of our study was to determine which clinical and environmental factors are predictive of poor long-term asthma control in preschool inner-city children., Materials and Methods: Baseline characteristics determined to be potential predictors of asthma severity were examined: demographics, asthma symptoms, medication use, healthcare utilization, early life medical history, family history, allergen exposure and allergic disease, and pollutant exposure. Bivariate and multivariate analyses were performed using logistic regression to examine the association of predictors of asthma severity with healthcare utilization at 2 years., Results: Of the 150 children at baseline, the follow-up rate was 83% at 2 years; therefore, 124 children were included in final analyses. At baseline, the mean age was 4.4 years and participants were predominantly African-American (90%). Most of the children were atopic and 32.5% reported using inhaled corticosteroids. Nighttime awakening from asthma and a history of pneumonia were predictive of future poor control., Conclusion: Preschool children with nighttime awakening from asthma and a history of pneumonia may deserve closer monitoring to prevent future asthma morbidity.

Background: High frequency chest wall oscillation (HFCWO) is used for airway mucus clearance. The objective of this study was to evaluate the use of HFCWO early in the treatment of adults hospitalized for acute asthma or chronic obstructive pulmonary disease (COPD)., Methods: Randomized, multi-center, double-masked phase II clinical trial of active or sham treatment initiated within 24 hours of hospital admission for acute asthma or COPD at four academic medical centers. Patients received active or sham treatment for 15 minutes three times a day for four treatments. Medical management was standardized across groups. The primary outcomes were patient adherence to therapy after four treatments (minutes used/60 minutes prescribed) and satisfaction. Secondary outcomes included change in Borg dyspnea score (≥ 1 unit indicates a clinically significant change), spontaneously expectorated sputum volume, and forced expired volume in 1 second., Results: Fifty-two participants were randomized to active (n = 25) or sham (n = 27) treatment. Patient adherence was similarly high in both groups (91% vs. 93%; p = 0.70). Patient satisfaction was also similarly high in both groups. After four treatments, a higher proportion of patients in the active treatment group had a clinically significant improvement in dyspnea (70.8% vs. 42.3%, p = 0.04). There were no significant differences in other secondary outcomes., Conclusions: HFCWO is well tolerated in adults hospitalized for acute asthma or COPD and significantly improves dyspnea. The high levels of patient satisfaction in both treatment groups justify the need for sham controls when evaluating the use of HFCWO on patient-reported outcomes. Additional studies are needed to more fully evaluate the role of HFCWO in improving in-hospital and post-discharge outcomes in this population., Trial Registration: ClinicalTrials.gov: NCT00181285.

Background: Community exposures to environmental contaminants from industrial scale dairy operations are poorly understood. The purpose of this study was to evaluate the impact of dairy operations on nearby communities by assessing airborne contaminants (particulate matter, ammonia, and cow allergen, Bos d 2) associated with dairy operations inside and outside homes., Methods: The study was conducted in 40 homes in the Yakima Valley, Washington State where over 61 dairies operate., Results: A concentration gradient was observed showing that airborne contaminants are significantly greater at homes within one-quarter mile (0.4 km) of dairy facilities, outdoor Bos d 2, ammonia, and TD were 60, eight, and two times higher as compared to homes greater than three miles (4.8 km) away. In addition median indoor airborne Bos d 2 and ammonia concentrations were approximately 10 and two times higher in homes within one-quarter mile (0.4 km) compared to homes greater than three miles (4.8 km) away., Conclusions: These findings demonstrate that dairy operations increase community exposures to agents with known human health effects. This study also provides evidence that airborne biological contaminants (i.e. cow allergen) associated with airborne particulate matter are statistically elevated at distances up to three miles (4.8 km) from dairy operations.

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma.

The goal of the study was to examine the association between biomarkers and environmental measures of second hand smoke (SHS) with caregiver, i.e. parent or legal guardian, report of household smoking behavior and morbidity measures among children with asthma. Baseline data were drawn from a longitudinal intervention for 126 inner city children with asthma, residing with a smoker. Most children met criteria for moderate to severe persistent asthma (63%) versus mild intermittent (20%) or mild persistent (17%). Household smoking behavior and asthma morbidity were compared with child urine cotinine and indoor measures of air quality including fine particulate matter (PM(2.5)) and air nicotine (AN). Kruskal-Wallis, Wilcoxon rank-sum and Spearman rho correlation tests were used to determine the level of association between biomarkers of SHS exposure and household smoking behavior and asthma morbidity. Most children had uncontrolled asthma (62%). The primary household smoker was the child's caregiver (86/126, 68%) of which 66 (77%) were the child's mother. Significantly higher mean PM(2.5), AN and cotinine concentrations were detected in households where the caregiver was the smoker (caregiver smoker: PM(2.5) μg/m(3): 44.16, AN: 1.79 μg/m(3), cotinine: 27.39 ng/ml; caregiver non-smoker: PM(2.5): 28.88 μg/m(3), AN: 0.71 μg/m(3), cotinine:10.78 ng/ml, all P ≤ 0.01). Urine cotinine concentrations trended higher in children who reported 5 or more symptom days within the past 2 weeks (>5 days/past 2 weeks, cotinine: 28.1 ng/ml vs. <5 days/past 2 weeks, cotinine: 16.2 ng/ml; P = 0.08). However, environmental measures of SHS exposures were not associated with asthma symptoms. Urban children with persistent asthma, residing with a smoker are exposed to high levels of SHS predominantly from their primary caregiver. Because cotinine was more strongly associated with asthma symptoms than environmental measures of SHS exposure and is independent of the site of exposure, it remains the gold standard for SHS exposure assessment in children with asthma.

Few studies have assessed in home factors which contribute to airborne endotoxin concentrations. In 85 inner city Baltimore homes, we found no significant correlation between settled dust and airborne endotoxin concentrations. Certain household activities and characteristics, including frequency of dusting, air conditioner use and type of flooring, explained 36-42% of the variability of airborne concentrations. Measurements of both airborne and settled dust endotoxin concentrations may be needed to fully characterize domestic exposure in epidemiologic investigations., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Asthma treatment guidelines recommend medications based on the level of asthma control., Objective: To evaluate differences in asthma control between patients who initiated asthma controller monotherapy versus combination therapy., Patients and Methods: Children (5-16 years; n = 488) and adults (17-80 years; n = 530) with asthma and no controller therapy in the prior 6 months were included. Telephone surveys were conducted within 5 days of filling a new asthma controller prescription with either the caregiver of children or the adult patient. Demographics, asthma control before therapy, and asthma-related resource use were assessed for patients initiating monotherapy (filling one asthma controller prescription) and combination therapy (filling more than one controller medication or a fixed-dose combination)., Results: Mean pediatric age was 10 years; 53% were male. Mean adult age was 47 years; 25% were male. There were no significant differences in asthma control score between patients receiving monotherapy and combination therapy. Children on combination therapy did not have more nighttime awakening or short-acting β-agonist use but were more likely to have been hospitalized due to asthma attack (p = .05) and have more unscheduled (p = .0374) and scheduled (p = .009) physician visits. Adults on combination therapy were more likely to have been hospitalized due to asthma attack (p < .05) and have regular doctor visits for asthma (p < .01)., Conclusions: Assessment of asthma control scores in the 4 weeks before index medication suggests that asthma severity during a treatment-free period did not differ significantly for patients initiating controller monotherapy versus combination therapy. From these findings, it appears that although physicians may not focus on asthma control when choosing the intensity of initial controller therapy, the intensity of health-care encounters may be an influence.

Although population differences in gene expression have been established, the impact on differential gene expression studies in large populations is not well understood. We describe the effect of self-reported race on a gene expression study of lung function in asthma. We generated gene expression profiles for 254 young adults (205 non-Hispanic whites and 49 African Americans) with asthma on whom concurrent total RNA derived from peripheral blood CD4(+) lymphocytes and lung function measurements were obtained. We identified four principal components that explained 62% of the variance in gene expression. The dominant principal component, which explained 29% of the total variance in gene expression, was strongly associated with self-identified race (P<10(-16)). The impact of these racial differences was observed when we performed differential gene expression analysis of lung function. Using multivariate linear models, we tested whether gene expression was associated with a quantitative measure of lung function: pre-bronchodilator forced expiratory volume in one second (FEV(1)). Though unadjusted linear models of FEV(1) identified several genes strongly correlated with lung function, these correlations were due to racial differences in the distribution of both FEV(1) and gene expression, and were no longer statistically significant following adjustment for self-identified race. These results suggest that self-identified race is a critical confounding covariate in epidemiologic studies of gene expression and that, similar to genetic studies, careful consideration of self-identified race in gene expression profiling studies is needed to avoid spurious association., (© 2011 Wiley-Liss, Inc.)

Genome-wide association studies of human gene expression promise to identify functional regulatory genetic variation that contributes to phenotypic diversity. However, it is unclear how useful this approach will be for the identification of disease-susceptibility variants. We generated gene expression profiles for 22 184 mRNA transcripts using RNA derived from peripheral blood CD4+ lymphocytes, and genome-wide genotype data for 516 512 autosomal markers in 200 subjects. We screened for cis-acting variants by testing variants mapping within 50 kb of expressed transcripts for association with transcript abundance using generalized linear models. Significant associations were identified for 1585 genes at a false discovery rate of 0.05 (corresponding to P-values ranging from 1 × 10(-91) to 7 × 10(-4)). Importantly, we identified evidence of regulatory variation for 119 previously mapped disease genes, including 24 examples where the variant with the strongest evidence of disease-association demonstrates strong association with specific transcript abundance. The prevalence of cis-acting variants among disease-associated genes was 63% higher than the genome-wide rate in our data set (P = 6.41 × 10(-6)), and although many of the implicated loci were associated with immune-related diseases (including asthma, connective tissue disorders and inflammatory bowel disease), associations with genes implicated in non-immune-related diseases including lipid profiles, anthropomorphic measurements, cancer and neurologic disease were also observed. Genetic variants that confer inter-individual differences in gene expression represent an important subset of variants that contribute to disease susceptibility. Population-based integrative genetic approaches can help identify such variation and enhance our understanding of the genetic basis of complex traits.

Objectives: Bone marrow aspiration and biopsy (BMAB) is painful when performed with only local anesthetic. Our objective was to determine whether viewing nature scenes and listening to nature sounds can reduce pain during BMAB., Design: This was a randomized, controlled clinical trial. Adult patients undergoing outpatient BMAB with only local anesthetic were assigned to use either a nature scene with accompanying nature sounds, city scene with city sounds, or standard care. The primary outcome was a visual analog scale (0-10) of pain. Prespecified secondary analyses included categorizing pain as mild and moderate to severe and using multiple logistic regression to adjust for potential confounding variables., Results: One hundred and twenty (120) subjects were enrolled: 44 in the Nature arm, 39 in the City arm, and 37 in the Standard Care arm. The mean pain scores, which were the primary outcome, were not significantly different between the three arms. A higher proportion in the Standard Care arm had moderate-to-severe pain (pain rating ≥4) than in the Nature arm (78.4% versus 60.5%), though this was not statistically significant (p = 0.097). This difference was statistically significant after adjusting for differences in the operators who performed the procedures (odds ratio = 3.71, p = 0.02)., Conclusions: We confirmed earlier findings showing that BMAB is poorly tolerated. While mean pain scores were not significantly different between the study arms, secondary analyses suggest that viewing a nature scene while listening to nature sounds is a safe, inexpensive method that may reduce pain during BMAB. This approach should be considered to alleviate pain during invasive procedures.

Background: Allergic rhinitis (AR), also known as hay fever, is caused by an overreaction of the immune system to airborne allergens. AR is a substantial cause of widespread morbidity, medical treatment costs, and reduced productivity at work and school., Objective: The goal of this research was to describe patient characteristics and prescription fill patterns for patients with AR and to determine those factors associated with the use of montelukast in a large population of commercially insured patients who sought medical treatment for AR., Methods: This was a retrospective cohort study using administrative claims data from a commercially available database. Patients, aged 4 to 64 years, with >or=3 years' continuous enrollment and >or=1 medical claim for AR between January 1, 2004, and December 31, 2006, were included. Patients with a concomitant asthma diagnosis were excluded. Patients' demographic and clinical characteristics, comorbidities, health care resource utilization, AR-related medication use, and AR-related physician office visits were assessed for 12 months before the first AR medication fill (index) in 2006. Stepwise logistic regression was used to identify factors predicting the initiation of montelukast therapy for the treatment of AR in 2006., Results: The study population consisted of 75,140 children (mean [SD] age, 10.6 [4.0] years) and 226,236 adults (mean age, 43.8 [11.8] years). Slightly more than half (52.4%) of the pediatric population was male compared with 44.7% of the adult population. Fifty percent of patients had no pharmacy fills for an AR medication in 2006. Among patients with AR pharmacy fills (n = 150,751), 78.1% had a single index medication fill (montelukast represented 4.5%) and 21.9% were prescribed multiple index medications. Children with AR were more likely to fill a prescription for montelukast (n = 7513) if they were 4 to 11 years of age; male; diagnosed with cough/wheeze; and had 1 or 2 oral corticosteroid fills, >or=3 antibiotic fills, and AR-related physician office visits in the prior 12 months (all, P < 0.001). Prescription fills for montelukast among adult patients with AR were significantly (P < 0.001) associated with other respiratory/atopic conditions; prior fills for antihistamines, oral corticosteroids, or intranasal corticosteroids; and AR-related physician office visits in the prior 12 months. Children and adults with health plans based in the midwestern or southern region of the United States had greater odds of initiating montelukast than those with plans based in the western region (P < 0.001)., Conclusions: Half of the patients identified with AR did not fill a prescription for an AR medication. Among those patients with AR-related prescription drug fills, most were prescribed a single index pharmacotherapy and did not receive additional AR medications within 30 days of the index date. The use of montelukast was limited and was more commonly prescribed to children and adults with AR whose condition was not controlled with other AR medications.

The purpose of this article is to review indoor air pollution factors that can modify asthma severity, particularly in inner-city environments. While there is a large literature linking ambient air pollution and asthma morbidity, less is known about the impact of indoor air pollution on asthma. Concentrating on the indoor environments is particularly important for children, since they can spend as much as 90% of their time indoors. This review focuses on studies conducted by the Johns Hopkins Center for Childhood Asthma in the Urban Environment as well as other relevant epidemiologic studies. Analysis of exposure outcome relationships in the published literature demonstrates the importance of evaluating indoor home environmental air pollution sources as risk factors for asthma morbidity. Important indoor air pollution determinants of asthma morbidity in urban environments include particulate matter (particularly the coarse fraction), nitrogen dioxide, and airborne mouse allergen exposure. Avoidance of harmful environmental exposures is a key component of national and international guideline recommendations for management of asthma. This literature suggests that modifying the indoor environment to reduce particulate matter, NO(2), and mouse allergen may be an important asthma management strategy. More research documenting effectiveness of interventions to reduce those exposures and improve asthma outcomes is needed.