Key members of the CALC, led by the American Lung Association, recently sent a letter to representatives and senators on Capitol Hill requesting an increase in funding for CDC’s National Asthma Control Program, bringing funding to $34.0 million for FY 2020. Click here to read the letter.
Members of the Childhood Asthma Leadership Coalition recently provided comments on the Department of Health and Human Services’ proposed Healthy People 2030 objectives.
Every decade, HHS updates the Healthy People initiative and develops a new set of 10-year national objectives with the goal of improving the health of all Americans. The CALC comments provide recommendations to improve the administration’s proposed objectives related to asthma, which are insufficient to capture the magnitude of the public health burden of asthma, or the impact of approaches to address it.
Earlier this year, the administration published a proposed rule in the Federal Register that would make it much harder for immigrants to obtain visas (including visas to study or work in the U.S.), extend their visas, or adjust their status to become lawful permanent residents. It would hold an immigrant’s receipt of crucial public non-cash benefits, including Medicaid, Section 8, and other social programs, as part of the public charge determination process. This rule is likely to worsen health outcomes for children with asthma and increase healthcare spending. Over the two month comment period, over 200,000 comments were submitted to the federal government, the vast majority of which opposed this harmful proposed rule.
Members of the Childhood Asthma Leadership Coalition submitted joint comments drafted from a childhood asthma stakeholder perspective, expressing deep concerns about the potential effects of this rule on children with asthma. Linking public benefits to immigration status deters legitimate uses of needed services and could create a chilling effect on families forgoing care and benefits to which they are legally entitled. By threatening access to health care for noncitizen children, and potentially reducing access to comprehensive asthma management services, the demonstrated health and economic benefits of having comprehensive health insurance that we have seen could decline. We anticipate that the proposed changes would not only worsen health outcomes for children with asthma, but increase health care spending.
Advancing City-Level Healthy Housing - Policies, Programs and Practices in Asthma and Lead, is a new report prepared for the National League of Cities by the George Washington University School of Public Health.
Cities across the country face housing stock riddled with lead and asthma hazards. One in three US homes has lead paint; nearly half of all US homes have elevated levels of at least three asthma-related allergens. These unhealthy housing conditions in rental units are making residents sick. This report reviews nine cities that have implemented programs, policies and practices aimed at addressing asthma and lead triggers in private rental housing in their jurisdictions.
Read the full report: https://www.nlc.org/sites/default/files/users/user93/YEF_Healthy_Housing%20WEB.pdf
Gaps in Asthma Knowledge and Lack of Care Plan Create Barrier to Control
Phalates Exposure Not Found To Be Associated with Increased Risk of Asthma
Different Nasal Bacteria Associated with Different Asthma Phenotypes
Pollution Prevention a Major Opportunity To Improve Childhood Asthma
ARIA Study Proposes 4th Phase
C-Section May Increase Asthma Risk More for Girls than Boys
Adolescents with Asthma Have Increased Risk of Subclinical Arterial Injury
Daily Inhaled Corticosteroids Treatment Improves Two of Four Asthma Classes
Fish Oil Supplementation in Pregnancy Improves Child Wheeze but Not Asthma
Parikh, K., et al. Barriers and Facilitators to Asthma Care After Hospitalization as Reported by Caregivers, Health Providers, and School Nurses. Hospital Pediatrics. Oct 4, 2018. doi: 10.1542/hpeds.2017-0182. [e-pub ahead of print; abstract only]
OBJECTIVES: To develop a comprehensive understanding of the barriers and/or facilitators for asthma management for the health professionals and caregivers of children with >1 hospitalization.
METHODS: Individual interviews were conducted with family caregivers and health professionals. Focus groups were conducted with school nurses. The interview and focus group guide were used to probe for barriers and facilitators of asthma management. Interviews were recorded, transcribed, and coded by using qualitative software. Themes were identified by using content analysis in the interviews and descriptive qualitative analysis in the focus groups.
RESULTS: Caregivers (n = 10), asthma educators (n = 4), physicians (n = 4), and a payer (n = 1) were individually interviewed. School nurses were interviewed via a focus group (n = 10). Children had a median age of 7 years, mean length of stay of 1.9 days, and 56% had a previous hospitalization in the previous 12 months. The "gaps in asthma knowledge" theme (which includes an inadequate understanding of asthma chronicity, activity restrictions, and management with controller medications) emerged as a theme for both caregivers and health professionals but with different health beliefs. School nurses reinforced the difficulty they have in managing children who have asthma in schools, and they identified using the asthma action plan as a facilitator.
CONCLUSIONS: Caregivers and health professionals have different health beliefs about asthma knowledge, which raises challenges in the care of a child who has asthma. In addition, school nurses highlight specific barriers that are focused on medication use in schools. A comprehensive understanding of the barriers and facilitators of asthma management that families experience after hospital discharge is crucial to design better efforts to support families.
Associations between prenatal maternal urinary concentrations of personal care product chemical biomarkers and childhood respiratory and allergic outcomes in the CHAMACOS study. Environmental International. Oct 4, 2018; 121(1): 538-549. doi: 10.1016/j.envint.2018.09.027. [e-pub ahead of print]
BACKGROUND: Personal care product chemicals may be contributing to risk for asthma and other atopic illnesses. The existing literature is conflicting, and many studies do not control for multiple chemical exposures.
METHODS: We quantified concentrations of three phthalate metabolites, three parabens, and four other phenols in urine collected twice during pregnancy from 392 women. We measured T helper 1 (Th1) and T helper 2 (Th2) cells in their children's blood at ages two, five, and seven, and assessed probable asthma, aeroallergies, eczema, and lung function at age seven. We conducted linear and logistic regressions, controlling for additional biomarkers measured in this population as selected by Bayesian Model Averaging.
RESULTS: The majority of comparisons showed null associations. Mono-n-butyl phthalate (MnBP) was associated with higher Th2% (RR: 10.40, 95% CI: 3.37, 17.92), and methyl paraben was associated with lower Th1% (RR: -3.35, 95% CI: -6.58, -0.02) and Th2% at borderline significance (RR: -4.45, 95% CI: -8.77, 0.08). Monoethyl phthalate was associated with lower forced expiratory flow from 25 to 75% of forced vital capacity (FEF25-75%) (RR: -3.22 L/s, 95% CI: -6.02, -0.34). Propyl paraben (OR: 0.86, 95% CI: 0.74, 0.99) was associated with decreased odds of probable asthma.
CONCLUSIONS: While some biomarkers, particularly those from low molecular weight phthalates, were associated with an atopic cytokine profile and poorer lung function, no biomarkers were associated with a corresponding increase in atopic disease.
Pérez-Losada, Marcos, et al. Pediatric asthma comprises different phenotypic clusters with unique nasal microbiotas. Microbiome. Oct 4, 2018; 6(1): 179. doi: 10.1186/s40168-018-0564-7.
BACKGROUND: Pediatric asthma is the most common chronic childhood disease in the USA, currently affecting ~ 7 million children. This heterogeneous syndrome is thought to encompass various disease phenotypes of clinically observable characteristics, which can be statistically identified by applying clustering approaches to patient clinical information. Extensive evidence has shown that the airway microbiome impacts both clinical heterogeneity and pathogenesis in pediatric asthma. Yet, so far, airway microbiotas have been consistently neglected in the study of asthma phenotypes. Here, we couple extensive clinical information with 16S rRNA high-throughput sequencing to characterize the microbiota of the nasal cavity in 163 children and adolescents clustered into different asthma phenotypes.
RESULTS: Our clustering analyses identified three statistically distinct phenotypes of pediatric asthma. Four core OTUs of the pathogenic genera Moraxella, Staphylococcus, Streptococcus, and Haemophilus were present in at least 95% of the studied nasal microbiotas. Phyla (Proteobacteria, Actinobacteria, and Bacteroidetes) and genera (Moraxella, Corynebacterium, Dolosigranulum, and Prevotella) abundances, community composition, and structure varied significantly (0.05 < P ≤ 0.0001) across asthma phenotypes and one of the clinical variables (preterm birth). Similarly, microbial networks of co-occurrence of bacterial genera revealed different bacterial associations across asthma phenotypes.
CONCLUSIONS: This study shows that children and adolescents with different clinical characteristics of asthma also show different nasal bacterial profiles, which is indicative of different phenotypes of the disease. Our work also shows how clinical and microbial information could be integrated to validate and refine asthma classification systems and develop biomarkers of disease.
Jang, Hoon, et al. Factors Associated With First Medication Time for Children Treated in the Emergency Department for Asthma. Pediatric Emergency Care. Oct 2, 2018; doi: 10.1097/PEC.0000000000001609. [e-pub ahead of print]
OBJECTIVES: Acute asthma exacerbations are among the most common reasons for childhood emergency department (ED) visits and hospitalizations. Although early ED administration of asthma medication has been shown to decrease hospitalizations, studies of factors associated with early ED asthma medication delivery have been limited. The objective of our study was to identify patient- and ED-related factors associated with early medication delivery among children treated in the ED for asthma exacerbations.
METHODS: This retrospective study used electronic health record data from all encounters for a primary diagnosis of asthma in an academic children's hospital ED during the study period 2009 to 2013. Using multivariate logistic regression, we identified the association between patient- and ED-related factors and the time to first medication defined as a binary outcome using a threshold of 1 hour from ED arrival. We then stratified our analysis by triage level (Emergency Severity Index [ESI]).
RESULTS: Of the 4846 encounters during the study period, 62% were male, mean age was 7.30 years, 76% had public insurance, and 57% had an ESI level of 3. Medication was administered within 1 hour of arrival in 2236 encounters (46%). After adjusting for covariates, multivariate logistic regression revealed that patients were less likely to have medications within 1 hour when they had less severe ESI (ESI 2 vs ESI 4: odds ratio [OR], 0.139; confidence interval [CI], 0.114-0.170), arrived via non-emergency medical services (OR, 0.525; CI, 0.413-0.665), or arrived to a crowded ED (OR, 0.574; CI, 0.505-0.652). Age, sex, and insurance type were not associated with timeliness of initial medication administration. Stratified analyses demonstrated that the crowding effect was larger for less severely ill patients.
CONCLUSIONS: Our study found that patient severity (acuity level, arrival mode) and level of ED crowing-but not demographic factors-are associated with the administration of medication in the first hour to pediatric patients with asthma. Our findings may be helpful in redesigning asthma care management strategies.
Landigran, P.J., et al. Pollution and Children’s Health. Science of the Total Environment. Oct 2, 2018; 650(2): 2389-2394. doi: 10.1016/j.scitotenv.2018.09.375. [e-pub ahead of print]
FINDINGS: The Lancet Commission on Pollution and Health found that pollution - air, water, soil, and chemical pollution - was responsible in 2016 for 940,000 deaths in children worldwide, two-thirds of them in children under the age of 5. Pollution is inequitably distributed, and the overwhelming majority of pollution-related deaths in children occurred in low- and middle-income countries (LMICs). Most were due to respiratory and gastrointestinal diseases caused by polluted air and water. Pollution is linked also to multiple non-communicable diseases (NCDs) in children including low birth weight, asthma, cancer and neurodevelopmental disorders, and these diseases are on the rise. The full impact of pollution, especially chemical pollution on the global burden of pediatric disease is not yet known, but almost certainly is undercounted because patterns of chemical exposure are not well charted and the potential toxicity of many chemical pollutants has not been characterized. The list of pediatric NCDs attributed to pollution will likely expand as the health effects of newer chemical pollutants are better defined and additional associations between pollution and disease are discovered.
CONCLUSION: Pollution prevention presents a major, largely unexploited opportunity to improve children's health and prevent NCDs, especially in LMICs. Failure to incorporate pollution prevention into NCD control programs is a major missed opportunity for disease prevention.
ARIA Phase 4 (2018): Change management in allergic rhinitis and asthma multimorbidity using mobile technology. Journal of Asthma and Clinical Immunology. Sept 28, 2018. doi: 10.1016/j.jaci.2018.08.049. [e-pub ahead of print]
Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline using the best approach to integrated care pathways (ICPs) using mobile technology in AR and asthma multimorbidity. The proposed next phase of ARIA is Change Management (CM) with the aim of providing an active and healthy life to rhinitis sufferers and to those with asthma multimorbidity across the life cycle whatever their gender or socio-economic status in order to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the impact of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of IT evidence-based tools (MASK: Mobile Airways Sentinel Network) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
Pennington, Audrey F., et al. Caesarean delivery, childhood asthma, and effect modification by sex: An observational study and meta-analysis. Paediatric Perinatal Epidemiology. Sept 28, 2018. doi: 10.1111/ppe.12510. [e-pub ahead of print]
BACKGROUND: Numerous studies indicate caesarean delivery is associated with childhood asthma. Sex-specific associations were reported in four of these studies, and in all four studies, the estimated association between caesarean delivery and asthma was of greater magnitude among girls, although most report a lack of evidence of multiplicative interaction.
METHODS: We assessed potential effect modification by sex, on the additive and multiplicative scales, of the association between caesarean delivery and asthma by ages 2 through 6 in up to 17 075 racially diverse children from a retrospective birth cohort, the Kaiser Air Pollution and Pediatric Asthma (KAPPA) Study. We also conducted a random-effects meta-analysis, combining our sex-stratified results (using the odds ratio for compatibility with previous studies) with previously published results.
RESULTS: Adjusted risk differences for caesarean delivery and asthma in the KAPPA cohort were higher among girls than boys at every follow-up age. By age 5, caesarean delivery was associated with an absolute 3.8% (95% confidence interval [CI] 0.4%, 7.3%) higher asthma risk among girls and a 1.9% (95% CI -1.7, 5.4) higher risk among boys. The summary odds ratio from the meta-analysis for caesarean delivery and asthma among girls was 1.26 (95% CI 1.14, 1.39) and 1.08 (95% CI 0.98, 1.20) among boys (P = 0.036).
CONCLUSIONS: Higher, but imprecise, estimates for females across five studies should motivate investigators to estimate sex-specific associations for caesarean delivery and asthma and to explore biological mechanisms or sex-dependent biases that could explain this possible heterogeneity. (NOTE: “In four out of five studies that assessed these sex‐specific associations (including ours), statistical tests of interaction were not significant (ie, P < 0.05).”)
Tattersall, Matthew C., et al. Asthma is associated with carotid arterial injury in children: The Childhood Origins of Asthma (COAST) Cohort. PLoS One. Sept 27, 2018; 13(9): e0204708. doi: 10.1371/journal.pone.0204708
BACKGROUND: Asthma is associated with an increased cardiovascular disease (CVD) risk in adults, but the impact of asthma and atopic conditions on CVD risk in children is less well established. We hypothesized that children in the Childhood Origins of Asthma (COAST) Cohort with asthma and atopic conditions would have early carotid arterial injury.
METHODS: The COAST study is a longitudinal birth cohort of children at increased risk of developing asthma. Children underwent ultrasonography measuring far wall right carotid bifurcation (RCB) and common carotid artery (RCCA) intima-media thickness (IMT; a measure of arterial injury). Multivariable linear regression models adjusted for age, gender, race, blood pressure, and body-mass index were used to assess associations of asthma and markers of arterial injury.
RESULTS: The 89 participants were a mean (standard deviation) 15.3 (0.6) years old and 42% were female; 28 asthmatics had atopic disease, 34 asthmatics were without other atopic disease, and 15 non-asthmatics had atopic disease. This study population was compared to 12 controls (participants free of asthma or atopic disease). Compared to controls (589 μm), those with atopic disease (653 μm, p = 0.07), asthma (649 μm, p = 0.05), or both (677 μm, p = 0.005) had progressively higher RCB IMT values (ptrend = 0.011). In adjusted models, asthmatic and/or atopic participants had significantly higher RCB IMT than those without asthma or atopic disease (all p≤0.03). Similar relationships were found for RCCA IMT.
CONCLUSION: Adolescents with asthma and other atopic diseases have an increased risk of subclinical arterial injury compared to children without asthma or other atopic disease.
Fitzpatrick, A.M., et al. Phenotypes of Recurrent Wheezing in Preschool Children: Identification by Latent Class Analysis and Utility in Prediction of Future Exacerbation. Journal of Allergy and Clinical Immunology. Sept 26, 2018. doi: 10.1016/j.jaip.2018.09.016. [e-pub ahead of print; abstract only]
BACKGROUND: Recurrent preschool wheezing is a heterogeneous disorder with significant morbidity, yet little is known about phenotypic determinants and their impact on clinical outcomes. OBJECTIVE: Latent class analysis (LCA) was used to identify latent classes of recurrent preschool wheeze and their association with future exacerbations and inhaled corticosteroid (ICS) treatment response.
METHODS: Data from five clinical trials of 1,708 children age 12-71 months with recurrent wheezing were merged. LCA was performed on 10 demographic, exposure and sensitization variables to determine the optimal number of latent classes. The primary outcome was the annualized rate of wheezing exacerbations requiring systemic corticosteroids during the study intervention period; the secondary outcome was the time to first exacerbation. Exploratory analyses examined the effect of daily ICS treatment on exacerbation outcomes.
RESULTS: Four latent classes of recurrent wheezing were identified; these were not distinguished by current symptoms or historical exacerbations but differed with regard to allergen sensitization and/or exposures. Annualized exacerbation rates (mean ± SEM/year) were 0.65 ± 0.06 for class 1 ("minimal sensitization"), 0.93 ± 0.10 for class 2 ("sensitization with indoor pet exposure"), 0.60 ± 0.07 for class 3 ("sensitization with tobacco smoke exposure"), and 0.81 ± 0.10 for class 4 ("multiple sensitization and eczema") (p < 0.001). In a research setting of high adherence, daily ICS treatment improved exacerbation rates in classes 2 and 4 but not the other groups.
CONCLUSION: Sensitization and exposure assessments are useful in the prediction of future exacerbation and may identify children most likely to respond favorably to daily ICS treatment.
Lin, J., et al. Effects of supplementation with omega-3 fatty acids during pregnancy on asthma or wheeze of children: A Systematic Rev and meta-analysis. The Journal of Maternal-fetal and Neonatal Medicine. Set 25, 2018: 1-151. doi: 10.1080/14767058.2018.1529161. [e-pub ahead of print; abstract only]
OBJECTIVE: To evaluate the effects of omega-3 fatty acids during pregnancy on the incidence of wheeze and asthma of children.
METHODS: A search was conducted in PubMed, Embase and CENTRAL until September 2017. Randomized controlled trials (RCTs) assessing the effects of omega-3 fatty acids during pregnancy on wheeze/asthma of children were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. Outcomes of relative risks were pooled. Subgroup analyses were conducted.
RESULTS: Seven RCTs involving 2047 children were included. The pooled data revealed the supplementation during pregnancy reduced the incidence of wheeze/asthma (risk ratio (RR) 0.81; 95% CI 0.66-0.99; p 0.04), but the incidence of childhood asthma was not significantly reduced (RR 0.89; 95%CI 0.67-1.17; p 0.40). Subgroup analyses indicated that the risk of childhood wheeze/asthma was significantly decreased 1) in studies located in Europe (RR 0.67 95% CI 0.51 0.88), 2) in children whose first-degree relatives were diagnosed with allergic disease (RR 0.65 95% CI 0.49 0.85), 3) when a dose of omega - 3 fatty acids ≥ 2000mg/d was applied (RR 0.61 95% CI 0.45 0.81), 4) in wheeze/asthma without sensitivity (RR 0.71 95% CI 0.54 0.94).
CONCLUSION: The available low-quality evidence indicated that omega-3 fatty acids supplementation during pregnancy may reduce the incidence of wheeze/asthma of children, but incidence of asthma was not reduced after omega-3 fatty acids supplementation during pregnancy. More well-designed RCTs with large sample sizes need to be conducted to better understand the effectiveness of omega-3 fatty acids supplementation during pregnancy with asthma in childhood.
For generations, community leaders have seen how valuable community health workers (CHWs), promotores, community health representatives, and the many other variations of community-based peer support workers can be. Nevertheless, decision makers often ask CHW advocates to make the business case for paying for CHW services and integrating them into care teams. To support these efforts, Families USA worked with Katharine London and her team at the Center for Health Law and Economics of the University of Massachusetts Medical School to develop a unique, interactive CHW Impact Estimator Tool.
CALC members the National Center for Healthy Housing (NCHH) and the George Washington University Milken Institute School of Public Health have released two new technical briefs related to funding community health worker services:
Read NCHH’s press release for more information about these resources.
Toups, M.M., Press, V.G., and A. Volerman. National Analysis of State Health Policies on Students' Right to Self-Carry and Self-Administer Asthma Inhalers at School. Journal of School Health. Oct 2018; 88(10): 776-784. doi: 10.1111/josh.12681.
BACKGROUND: Asthma has no known cure, and though manageable, it disrupts the everyday lives of over 6 million US children. Because children spend more than half of their waking hours in school, students must be able to carry and administer their inhaler at school to manage their asthma.
METHODS: This policy paper is a comprehensive review of all 50 states and the District of Columbia's laws and policies for the self-carry and administration of quick-relief asthmainhalers among children in prekindergarten through 12th grade. RESULTS: All states permit students to carry and administer their inhalers at school, although each state differs in their development and implementation of policies for asthma self-management at school. This review examines how states regulate self-carry policies by looking at policy development, regulated school systems, relevant stakeholders, required medical records, and school liability.
CONCLUSIONS: Each state's laws have nuances that create gray areas, increasing the potential of misinterpreted or incorrectly implemented policies for asthma self-management at school. As a result, children may not have immediate access to their inhaler for symptom management or in an emergency. State policymakers should reform current laws to remove barriers for students to carry and use inhalers at school.
Teixeira, Samantha and Anita Zuberi. Neighborhood Social and Environmental Factors and Asthma Among Children Living in Low-Income Neighborhoods: The Importance of Informal Social Control. Family and Community Health. Oct/Dec 2018; 41(4): 214-224. doi: 10.1097/FCH.0000000000000202.
Despite the knowledge that children in low-income neighborhoods are particularly vulnerable to asthma, few studies of child asthma focus on variation among low-income neighborhoods. We examined the relationship between child asthma and features associated with neighborhood poverty including safety, social cohesion, informal social control, collective efficacy, and disorder, across a sample of children from low-income neighborhoods (N = 3010; 2005-2007). Results show that the relationship between asthma and poverty is accounted for by family-level characteristics, but informal social control remains significantly and positively related to asthma after accounting for family-level characteristics. We discuss the importance of neighborhood environmental features for children's asthma.
Reynolds, K.C., et al. Featured Article: Multiple Comorbid Conditions, Sleep Quality and Duration, and Academic Performance in Urban Children With Asthma. Journal of Pediatric Psychology. Oct 2018; 43(9): 943-954. doi: 10.1093/jpepsy/jsy027.
OBJECTIVE: Common comorbid medical conditions including allergic rhinitis (AR), obesity, and sleep disordered breathing (SDB) have been linked with asthma exacerbations; however, these conditions also impact sleep and academic functioning. The current study sought to examine unique and combined associations of these common comorbidities on sleep and academic performance among urban minority children with persistent asthma. We expected additional comorbid diagnoses would be associated with poorer sleep and academic functioning.
METHOD: Urban children 7-9 years old (n = 249) with persistent asthma from African American, Latino, and non-Latino White backgrounds participated in this cross-sectional study. Asthma and AR were assessed using guidelines-based approaches. Overweight/obesity was assessed using body mass index and parents reported on SDB risk. Sleep quality (sleep efficiency) and sleep duration were assessed via 4 weeks of actigraphy. A cumulative risk index (CRI) score of asthma-related comorbidities (i.e., number of comorbidities for which each child met criteria) was calculated.
RESULTS: Comorbid conditions were prevalent (AR, 85%; overweight/obese, 39%; SDB risk, 44%). Lower SDB risk and better AR control were both associated with fewer school absences. A higher CRI score was associated with shorter sleep duration and more absences. For children with 1 comorbid condition, better lung function was associated with better sleep efficiency.
CONCLUSION: Findings suggest increased risk of shorter sleep and more frequent school absences among urban minority children with asthma and more comorbid conditions. Assessment and treatment of this high-risk group must consider how comorbid conditions exacerbate children's asthma and may affect sleep and daytime functioning.
Shaffo, F.C., et al. Mechanisms of organophosphorus pesticide toxicity in the context of airway hyperreactivity and asthma. American Journal of Physiology: Lung Cellular and Molecular Physiology. Oct 2018; 315(4): L485-L501. doi: 10.1152/ajplung.00211.2018.
Numerous epidemiologic studies have identified an association between occupational exposures to organophosphorus pesticides (OPs) and asthma or asthmatic symptoms in adults. Emerging epidemiologic data suggest that environmentally relevant levels of OPs may also be linked to respiratory dysfunction in the general population and that in utero and/or early life exposures to environmental OPs may increase risk for childhood asthma. In support of a causal link between OPs and asthma, experimental evidence demonstrates that occupationally and environmentally relevant OP exposures induce bronchospasm and airway hyperreactivity in preclinical models. Mechanistic studies have identified blockade of autoinhibitory M2 muscarinic receptors on parasympathetic nerves that innervate airway smooth muscle as one mechanism by which OPs induce airway hyperreactivity, but significant questions remain regarding the mechanism(s) by which OPs cause neuronal M2 receptor dysfunction and, more generally, how OPs cause persistent asthma, especially after developmental exposures. The goals of this review are to 1) summarize current understanding of OPs in asthma; 2) discuss mechanisms of OP neurotoxicity and immunotoxicity that warrant consideration in the context of OP-induced airway hyperreactivity and asthma, specifically, inflammatory responses, oxidative stress, neural plasticity, and neurogenic inflammation; and 3) identify critical data gaps that need to be addressed in order to better protect adults and children against the harmful respiratory effects of low-level OP exposures.
Di Cicco, M., et al. Does lung microbiome play a causal or casual role in asthma? Pediatric Pulmonolgy. Oct 2018; 53(1): 1340-1345. doi: 10.1002/ppul.24086.
Asthma is the most common chronic disease in childhood. The pathogenesis of asthma is multifactorial and is thought to include environmental factors interacting with genetics during pregnancy and in the first years of life. In the last decades, a possible role of gut microbiota in allergic disease pathogenesis has been demonstrated. Next generation sequencing techniques have allowed the identification of a distinct microbiome in the healthy lungs. The lung microbiome is characterized by the prevalence of bacteria belonging to the phylum Bacteroidetes (mostly Prevotella and Veilonella spp) in healthy subjects and to the phylum Proteobacteria in asthmatics (mostly Haemophilus, Moraxella, and Neisseria spp). In asthma, as well as in other diseases, the lung microbiome composition changes due to a disruption of the delicate balance between immigration and elimination of bacteria. The lung microbiome can interact with the immune system, thus influencing inflammation. Early infections with viruses, such as respiratory syncytial virus, may alter lung microbiome composition favoring the emergence of Proteobacteria, a phylum which is also linked to severity of asthma and bronchial hyperreactivity. Lastly, antibiotics may alter the gut and lung microbiota and potentially disturb the relationship between microbiota and host. Therefore, antibiotics should be prescribed with increasing awareness of their potential harmful effect on the microbiota in young children with and without asthma. The potential effects of probiotics and prebiotics on lung microbiome are unknown.
Han, Y.Y., et al. Exposure to polycyclic aromatic hydrocarbons, vitamin D, and lung function in children with asthma. Pediatric Pulmonolgy. Oct 2018; 53(10): 1362-1368. doi: 10.1002/ppul.24084.
BACKGROUND: It is unclear whether exposure to polycyclic aromatic hydrocarbons (PAH) affects lung function in children with asthma. Whether vitamin D insufficiency enhances any detrimental effects of PAH on lung function in asthmatic children is also unknown.
METHODS: Cross-sectional study of 1,821 children (6-17 years) who participated in the 2007-2012 National Health and Nutrition Examination Survey. Multivariable linear regression was used to analyze the relation between molar mass of urinary PAH metabolites (sum of all PAH (ΣmolPAH), sum of PAH with 2 benzene rings (Σmol2-PAH), or sum of PAH with 3 or 4 benzene rings (Σmol3,4-PAH)) and lung function or exhaled fraction of nitric oxide (FeNO) in children with and without asthma. In this multivariable analysis, we tested whether vitamin D insufficiency (a serum 25(OH)D level <30 ng/mL) interacts with PAH exposure on lung function in children with asthma.
RESULTS: Children in the highest quartiles of urinary Σmol3,4-PAH had 2.3 times increased odds of asthma than those in the lowest quartile of Σmol3,4-PAH. Urinary PAH were not associated with lung function in children with or without asthma. Given a significant interaction between vitamin D insufficiency and PAH metabolites on lung function in asthmatic children, we stratified the analysis by vitamin D status. In this analysis, urinary PAH metabolites were significantly associated with 2.7-3.9% reduced %predicted FEV1 and %predicted FEV1/FVC in children with asthma and vitamin D insufficiency, but not in those with asthma and vitamin D sufficiency.
CONCLUSIONS: Vitamin D insufficiency and PAH exposure may have synergistic detrimental effects on lung function in asthmatic children.
Fazlollahi, Mina, et al. The nasal microbiome in asthma. Journal of Allergy and Clinical Immunology. Sept 2108; 142(3): 834-843.e2. https://doi.org/10.1016/j.jaci.2018.02.020
BACKGROUND: Nasal microbiota may influence asthma pathobiology.
OBJECTIVE: We sought to characterize the nasal microbiome of subjects with exacerbated asthma, nonexacerbated asthma, and healthy controls to identify nasal microbiota associated with asthma activity.
METHODS: We performed 16S ribosomal RNA sequencing on nasal swabs obtained from 72 primarily adult subjects with exacerbated asthma (n = 20), nonexacerbated asthma (n = 31), and healthy controls (n = 21). Analyses were performed using Quantitative Insights into Microbial (QIIME); linear discriminant analysis effect size (LEfSe); Phylogenetic Investigation of Communities by Reconstruction of Unobserved States; and Statistical Analysis of Metagenomic Profiles (PICRUSt); and Statistical Analysis of Metagenomic Profiles (STAMP). Species found to be associated with asthma activity were validated using quantitative PCR. Metabolic pathways associated with differentially abundant nasal taxa were inferred through metagenomic functional prediction.
RESULTS: Nasal bacterial composition significantly differed among subjects with exacerbated asthma, nonexacerbated asthma, and healthy controls (permutational multivariate ANOVA, P = 2.2 × 10 −2 ). Relative to controls, the nasal microbiota of subjects with asthma were enriched with taxa from Bacteroidetes (Wilcoxon-Mann-Whitney, r = 0.33, P = 5.1 × 10 −3 ) and Proteobacteria ( r = 0.29, P = 1.4 × 10 −2 ). Four species were differentially abundant based on asthma status after correction for multiple comparisons: Prevotella buccalis , P adj = 1.0 × 10 −2 ; Dialister invisus , P adj = 9.1 × 10 −3 ; Gardnerella vaginalis , P adj = 2.8 × 10 −3 ; Alkanindiges hongkongensis , P adj = 2.6 × 10 −3 . These phyla and species were also differentially abundant based on asthma activity (exacerbated asthma vs nonexacerbated asthma vs controls). Quantitative PCR confirmed species overrepresentation in asthma relative to controls for Prevotella buccalis (fold change = 130, P = 2.1 × 10 −4 ) and Gardnerella vaginalis (fold change = 160, P = 6.8 × 10 −4 ). Metagenomic inference revealed differential glycerolipid metabolism (Kruskal-Wallis, P = 1.9 × 10 −4 ) based on asthma activity. CONCLUSIONS: Nasal microbiome composition differs in subjects with exacerbated asthma, nonexacerbated asthma, and healthy controls. The identified nasal taxa could be further investigated for potential mechanistic roles in asthma and as possible biomarkers of asthma activity.
Holt, Patrick G., et al. Developmental regulation of type 1 and type 3 IFN production and risk for infant infections and asthma development. Journal of Allergy and Clinical Immunology. Sept 2018. doi: 10.1016/j.jaci.2018.08.035 [e-pub ahead of print].
Virus-associated febrile lower respiratory tract infections (fLRI) during infancy have been identified as risk factors for persistent wheeze development. We hypothesized that variations in innate immune defence capacity during this period, exemplified by production of types 1 and 3 interferons (T1/3IFNs), may be an underlying determinant of risk. To investigate relationships between postnatal development of innate interferon response capacity and susceptibility to early infections and persistent wheeze. We studied a subset of subjects from a birth cohort at high risk for asthma/allergy, and determined capacity of cord blood cells (n=151) to produce any of a panel of 17 T1/3IFNs in response to the viral mimic poly(I:C), employing a sensitive PCR assay. We investigated relationships between neonatal interferon responses and lower respiratory infection history during infancy, wheezing history to 5Yrs, and ensuing maturation of innate immune capacity by 4Yrs (n=160) and 10Yrs (n=125). While cohort subjects produced on average 2.6±0.3 of the 17 innate IFNs tested at birth, 24% showed no T1/3IFN production. This non-producer subgroup showed increased risk for infant fLRI (OR 2.62[1.14-6.06]p=0.024) and persistent wheeze (OR 4.24[1.60-11.24]p=0.004) at age 5Yrs relative to those producing ≥1 T1/3IFNs, whereas risk for infant wheezy LRI or "transient early wheeze" was unaffected. Moreover, infants who experienced fLRI subsequently demonstrated accelerated development of T1/3IFN response capacity between 1Yr and 4Yrs. T1/3IFN response capacity appears strongly developmentally constrained at birth. Infants in whom this negative regulation is strongest manifest increased risk for severe respiratory infections during infancy and subsequent persistent wheeze.
Martenies, Sheen E. and Stuart A. Batterman. Effectiveness of Using Enhanced Filters in Schools and Homes to Reduce Indoor Exposures to PM2.5 from Outdoor Sources and Subsequent Health Benefits for Children with Asthma. Environmental Science & Technology. Sept 2018; 52(18): 10767-10776. doi: 10.1021/acs.est.8b02053
Filters can reduce indoor concentrations of particulate matter (PM2.5), but their benefits have not been well-characterized. This study investigates exposure, health, and cost impacts of high efficiency filters in homes and schools, focusing on the asthma-related outcomes. Reductions in indoor exposures to PM2.5 from outdoor sources with enhanced filters (e.g., MERV 12) are estimated using probabilistic indoor air quality models, and avoided health impacts are quantified using health impact assessment. These methods are applied using data from Detroit, Michigan, an urban region with elevated asthma rates. Replacing inefficient filters with enhanced filters in schools would reduce the PM2.5-attributable asthma burden by 13% annually, with higher benefits for more efficient filters. Marginal costs average $63 per classroom or $32 per child with asthma per year. In homes, using efficient furnace filters or air cleaners yields 11 to 16% reductions in the asthma burden with an annualized marginal costs of $151-494 per household. Additional benefits include reductions in health risk for adults and lower exposures to other contaminants such as PM from indoor sources. On the basis of the included health outcomes, efficient filters in schools in particular is a potentially cost-efficient way to reduce the asthma-related health burden for children.
Bernstein, J.A. and L. Mansfield. Step-up and step-down treatments for optimal asthma control in children and adolescents. Journal of Asthma. Sept 2018: 1-13. doi: 10.1080/02770903.2018.1490752. [Epub ahead of print]
OBJECTIVE: To review therapeutic options for stepwise management of pediatric asthma in the context of this population's unique needs such as potential effects of asthma, treatments, or both on growth and psychosocial development, and caregiver involvement.
DATA SOURCES AND STUDY SELECTION: We conducted PubMed searches to identify relevant articles then reviewed resultant articles, guidelines for asthma management in children, and articles from personal files.
RESULTS: Stepwise management of asthma, similar to adults, is recommended for children in current global and US guidelines. Treatment may be stepped up or stepped down temporarily or long-term based on response over time. Inhaled corticosteroids remain the recommended treatment for persistent childhood asthma and any potential small effects on growth are considered relatively minor compared with their benefit. Controller medication options for patients <18 years old are limited, especially for Global Initiative for Asthma Steps 2-5. The long-acting antimuscarinic antagonist tiotropium (Steps 4/5, patients aged ≥12 years) and in certain circumstances (Step 5), anti-immunoglobulin E (aged ≥6 years) and interleukin-5 antibodies (aged ≥12 years) are newer treatment options. Tiotropium is indicated in the United States and Europe for patients ≥6 years old. Stepping down treatment, which is recommended but infrequently practiced, can maintain symptom control and minimize adverse events while substantially reducing costs. Patient education and better monitoring remain important for self-management and optimum outcomes.
CONCLUSION: A need exists to target individual treatment goals for children with asthma by using step-up and step-down approaches to maximize treatment benefits and minimize potential adverse effects.
Sonney, Jennifer, et al. Applying Human-Centered Design to the Development of an Asthma Essentials Kit for School-Aged Children and Their Parents. Journal of Pediatric Health Care. Sept 2018; pii: S0891-5245(18)30346-8. doi: 10.1016/j.pedhc.2018.07.008. [e-pub ahead of print]
This study aimed to design and test an asthma essentials kit to support parent-child shared asthma management. Fourteen children (age range = 7-11 years) with asthma and their parents participated in this study. Development of the asthma essentials kit involved a generative phase, focused on understanding and designing to meet user needs, and an evaluative phase, which entailed narrowing, evaluating, and refining the asthma essentials kit. As is typical in human-centered design, analysis was iterative throughout the design process such that findings informed each subsequent phase. The final asthma essentials kit concepts collectively addressed the three user-identified priorities: roles and responsibilities, desire for normalcy, and shared asthma management. Concept prototypes included a to-go bag, cue card, wearable device, and mobile health application. Usability and acceptability testing showed that the asthma essentials kit prototypes were highly useful, acceptable, and easy to navigate. Human-centered design holds promise in developing interventions to meet user needs.
Mensah, George A., Kiley, James P, and Gary H. Gibbons. Generating evidence to inform an update of asthma clinical practice guidelines: Perspectives from the National Heart, Lung, and Blood Institute. Journal of Asthma and Clinical Immunology. Sept 2018; 142(3): 744-748. https://doi.org/10.1016/j.jaci.2018.07.004
Asthma is the most prevalent chronic respiratory disease worldwide. Its increasing prevalence and evidence of suboptimal control require renewed efforts in the development and widespread implementation of clinical practice guidelines for prevention, treatment, and control. Given the rapidly changing landscape and evolving best practices for guideline development, the National Heart, Lung, and Blood Institute made a commitment to support rigorous systematic evidence reviews that frontline health care providers and stakeholders could use to create new or update existing guidelines. This article describes the protocols, key questions, methodology, and analytic framework to support the update of the 2007 National Asthma Education and Prevention Program Expert Panel Report 3 (EPR-3) on the diagnosis and management of asthma in adults and children. It also describes the expert panel's practical experience in managing asthmatic patients across the age and severity spectrum. The article explains the process for ensuring that the expert panel's deliberations are conducted in accordance with the Institute of Medicine's standards and recommendations for guideline development. The outcome of this ambitious effort will be an update of the EPR-3 asthma guidelines and publication of the key recommendations in the Journal of Allergy and Clinical Immunology. Importantly, several novel approaches will be explored and incorporated as appropriate to accelerate adoption and sustained implementation of the guidelines.
Stein, Michelle M., et al. A decade of research on the 17q12-21 asthma locus: Piecing together the puzzle. Journal of Allery and Clinical Immunology. Sept 2018; 142(3): 749-764.e3. https://doi.org/10.1016/j.jaci.2017.12.974
Chromosome 17q12-21 remains the most highly replicated and significant asthma locus. Genotypes in the core region defined by the first genome-wide association study correlate with expression of 2 genes, ORM1-like 3 (ORMDL3) and gasdermin B (GSDMB) , making these prime candidate asthma genes, although recent studies have implicated gasdermin A (GSDMA) distal to and post-GPI attachment to proteins 3 (PGAP3) proximal to the core region as independent loci. We review 10 years of studies on the 17q12-21 locus and suggest that genotype-specific risks for asthma at the proximal and distal loci are not specific to early-onset asthma and mediated by PGAP3 , ORMDL3 , and/or GSDMA expression. We propose that the weak and inconsistent associations of 17q single nucleotide polymorphisms with asthma in African Americans is due to the high frequency of some 17q alleles, the breakdown of linkage disequilibrium on African-derived chromosomes, and possibly different early-life asthma endotypes in these children. Finally, the inconsistent association between asthma and gene expression levels in blood or lung cells from older children and adults suggests that genotype effects may mediate asthma risk or protection during critical developmental windows and/or in response to relevant exposures in early life. Thus studies of young children and ethnically diverse populations are required to fully understand the relationship between genotype and asthma phenotype and the gene regulatory architecture at this locus.
Verma, Mukesh, et al. Experimental asthma persists in IL-33 receptor knockout mice because of the emergence of thymic stromal lymphopoietin–driven IL-9 + and IL-13 + type 2 innate lymphoid cell subpopulations. Journal of Allergy and Clinical Immunology. Sept 2018; 142(3): 793-803.e8.
BACKGROUND: IL-33 plays an important role in the development of experimental asthma. OBJECTIVE: We sought to study the role of the IL-33 receptor suppressor of tumorigenicity 2 (ST2) in the persistence of asthma in a mouse model.
METHODS: We studied allergen-induced experimental asthma in ST2 knockout (KO) and wild-type control mice. We measured airway hyperresponsiveness by using flexiVent; inflammatory indices by using ELISA, histology, and real-time PCR; and type 2 innate lymphoid cells (ILC2s) in lung single-cell preparations by using flow cytometry.
RESULTS: Airway hyperresponsiveness was increased in allergen-treated ST2 KO mice and comparable with that in allergen-treated wild-type control mice. Peribronchial and perivascular inflammation and mucus production were largely similar in both groups. Persistence of experimental asthma in ST2 KO mice was associated with an increase in levels of thymic stromal lymphopoietin (TSLP), IL-9, and IL-13, but not IL-5, in bronchoalveolar lavage fluid. Expectedly, ST2 deletion caused a reduction in IL-13 + CD4 T cells, forkhead box P3–positive regulatory T cells, and IL-5 + ILC2s. Unexpectedly, ST2 deletion led to an overall increase in innate lymphoid cells (CD45 + lin − CD25 + cells) and IL-13 + ILC2s, emergence of a TSLP receptor–positive IL-9 + ILC2 population, and an increase in intraepithelial mast cell numbers in the lung. An anti-TSLP antibody abrogated airway hyperresponsiveness, inflammation, and mucus production in allergen-treated ST2 KO mice. It also caused a reduction in innate lymphoid cell, ILC2, and IL-9 + and IL-13 + ILC2 numbers in the lung.
CONCLUSIONS: Genetic deletion of the IL-33 receptor paradoxically increases TSLP production, which stimulates the emergence of IL-9 + and IL-13 + ILC2s and mast cells and leads to development of chronic experimental asthma. An anti-TSLP antibody abrogates all pathologic features of asthma in this model.
Skevaki, Chysanthi, et al. Influenza-derived peptides cross-react with allergens and provide asthma protection. Journal of Allergy and Clinical Immunology. Sept 2018; 142(3): 804-814.
BACKGROUND: The hygiene hypothesis is the leading concept to explain the current asthma epidemic, which is built on the observation that a lack of bacterial contact early in life induces allergic T H 2 immune responses.
OBJECTIVE: Because little is known about the contribution of respiratory tract viruses in this context, we evaluated the effect of prior influenza infection on the development of allergic asthma.
METHODS: Mice were infected with influenza and, once recovered, subjected to an ovalbumin- or house dust mite–induced experimental asthma protocol. Influenza-polarized effector memory T (Tem) cells were transferred adoptively to allergen-sensitized animals before allergen challenge. A comprehensive in silico analysis assessed homologies between virus- and allergen-derived proteins. Influenza-polarized Tem cells were stimulated ex vivo with candidate peptides. Mice were immunized with a pool of virus-derived T-cell epitopes.
RESULTS: In 2 murine models we found a long-lasting preventive effect against experimental asthma features. Protection could be attributed about equally to CD4 + and CD8 + Tem cells from influenza-infected mice. An in silico bioinformatic analysis identified 4 influenza- and 3 allergen-derived MHC class I and MHC class II candidate T-cell epitopes with potential antigen-specific cross-reactivity between influenza and allergens. Lymphocytes from influenza-infected mice produced IFN-γ and IL-2 but not IL-5 on stimulation with the aforementioned peptides. Immunization with a mixture of the influenza peptides conferred asthma protection, and peptide-immunized mice transferred protection through CD4 + and CD8 + Tem cells.
CONCLUSION: For the first time, our results illustrate heterologous immunity of virus-infected animals toward allergens. This finding extends the original hygiene hypothesis.
Andre-Gregoire, Gwennan, et al. Targeting of Rac1 prevents bronchoconstriction and airway hyperresponsiveness. Journal of Allergy and Clinical Immunology. Sept 2018; 142(3): 824-833.e3. https://doi.org/10.1016/j.jaci.2017.09.049
BACKGROUND: The molecular mechanisms responsible for airway smooth muscle cells' (aSMCs) contraction and proliferation in airway hyperresponsiveness (AHR) associated with asthma are still largely unknown. The small GTPases of the Rho family (RhoA, Rac1, and Cdc42) play a central role in SMC functions including migration, proliferation, and contraction.
OBJECTIVE: The objective of this study was to identify the role of Rac1 in aSMC contraction and to investigate its involvement in AHR associated with allergic asthma.
METHODS: To define the role of Rac1 in aSMC, ex and in vitro analyses of bronchial reactivity were performed on bronchi from smooth muscle (SM)-specific Rac1 knockout mice and human individuals. In addition, this murine model was exposed to allergens (ovalbumin or house dust mite extract) to decipher in vivo the implication of Rac1 in AHR. RESULTS: The specific SMC deletion or pharmacological inhibition of Rac1 in mice prevented the bronchoconstrictor response to methacholine. In human bronchi, a similar role of Rac1 was observed during bronchoconstriction. We further demonstrated that Rac1 activation is responsible for bronchoconstrictor-induced increase in intracellular Ca2+ concentration and contraction both in murine and in human bronchial aSMCs, through its association with phospholipase C β2 and the stimulation of inositol 1,4,5-trisphosphate production. In vivo, Rac1 deletion in SMCs or pharmacological Rac1 inhibition by nebulization of NSC23766 prevented AHR in murine models of allergic asthma. Moreover, nebulization of NSC23766 decreased eosinophil and neutrophil populations in bronchoalveolar lavages from mice with asthma.
CONCLUSIONS: Our data reveal an unexpected and essential role of Rac1 in the regulation of intracellular Ca2+ and contraction of aSMCs, and the development of AHR. Rac1 thus appears as an attractive therapeutic target in asthma, with a combined beneficial action on both bronchoconstriction and pulmonary inflammation.
Lam, Phoebe H., et al. Family obligations and asthma in youth: The moderating role of socioeconomic status. Health Psychology. Sept 2018; 37(10): 968-978. http://dx.doi.org/10.1037/hea0000655
OBJECTIVE: Fulfilling family obligations—providing instrumental help to and spending time with family—is a common aspect of family relationships. However, whether fulfilling these obligations links with physical health remains unclear. In this study, we investigated whether fulfilling family obligations was associated with asthma outcomes among youth, and whether these associations differed depending on family socioeconomic status (SES).
METHOD: Participants were 172 youth, 8 to 17 years of age (Mage = 12.1; 54% boys) who had been physician-diagnosed with asthma and reported on family-obligation frequency; completed the Asthma Control Test (ACT; Nathan et al., 2004), a clinical measure of asthma control; and completed a measure of airway inflammation (i.e., fractional exhaled nitric oxide). Parents also completed the ACT in reference to their asthmatic children and reported on family income.
RESULTS: Fulfilling family obligations was not associated with asthma outcomes (βs< .14, ps >.075). However, SES (family income) interacted with family obligations, such that fulfilling family obligations was associated with greater airway inflammation (interaction term β = −.17, p = .023) and poorer parent-reported asthma control (interaction term β = .15, p = .039), only among youth from lower SES backgrounds. Exploratory analyses suggest that these interactions were robust against covariates and were largely consistent across age and the two dimensions of family-obligation behaviors.
CONCLUSION: Findings from this study suggest that among youth from lower SES backgrounds, engaging in more frequent family-obligation behaviors may have negative repercussions in terms of their asthma.
Dumas, Orianne, et al. Severe Bronchiolitis Profiles and Risk of Developing Recurrent Wheezing by Age 3 Years. Journal of Allergy and Clinical Immunology. Sept 2018; pii: S0091-6749(18)31296-X. doi: 10.1016/j.jaci.2018.08.043. [e-pub ahead of print]
BACKGROUND: A better understanding of bronchiolitis heterogeneity may help clarify its relationship with the development of recurrent wheezing and asthma.
OBJECTIVES: To identify severe bronchiolitis profiles by a clustering approach, and to investigate for the first time their association with allergy/inflammatory biomarkers; nasopharyngeal microbiota; and development of recurrent wheezing by age 3 years.
METHODS: We analyzed data from a prospective, 17-center U.S. cohort study of 921 infants (age <1 year) hospitalized with bronchiolitis (2011-2014 winters) with post-hospitalization follow-up. Severe bronchiolitis profiles at baseline (hospitalization) were determined by latent class analysis, based on clinical factors and viral etiology. Blood biomarkers and nasopharyngeal microbiota profiles were determined using samples collected within 24h of hospitalization. Recurrent wheezing by age 3 years was defined based on parental report of breathing problem episodes post-discharge. RESULTS: Three severe bronchiolitis profiles were identified: profile A (15%), characterized by history of breathing problems/eczema during infancy and non-RSV (mostly rhinovirus) infection; profile B (49%) with the largest probability of RSV infection and which resembled classic RSV-bronchiolitis; and profile C (36%), the most severely ill group. Profile A infants had higher eosinophil counts, higher cathelicidin levels, and elevated proportions of Haemophilus-dominant or Moraxella-dominant microbiota profile. Compared to profile B, we observed significantly increased risk of developing recurrent wheezing in children with profile A (hazard ratio 2.64; 95% CI 1.90-3.68), and, to a lesser extent, with profile C (1.51; 1.14-2.01).
CONCLUSION: Although longer follow-up is needed, our results may help identify, among childrenhospitalized for bronchiolitis, subgroups with particularly elevated risk of developing asthma.
Rhinitis in Children and Adolescents with Asthma: Ubiquitous, Difficult to Control, and Associated with Asthma Outcomes. Journal of Asthma and Clinical Immunology. Sept 2018; ii: S0091-6749(18)31282-X. doi: 10.1016/j.jaci.2018.07.041. [Epub ahead of print]
BACKGROUND: Rhinitis and asthma are linked, but substantial knowledge gaps in this relationship exist.
OBJECTIVE: To determine the prevalence of rhinitis and its phenotypes in children and adolescents with asthma, assess symptom severity and medication requirements for rhinitis control, and investigate associations between rhinitis and asthma.
METHODS: 749 children with asthma participating in the Asthma Phenotypes in the Inner-City study received baseline evaluations and were managed for 1 year with algorithm-based treatments for rhinitis and asthma. Rhinitis was diagnosed by questionnaire focusing on individual symptoms, and pre-defined phenotypes were determined by combining symptom patterns with skin testing and serum specific IgE. RESULTS: Analyses were done on 619 children with asthma who completed at least 4 of 6 visits. Rhinitis was present in 93.5%, and phenotypes identified at baseline were confirmed during the observation/management year. Perennial allergic rhinitis with seasonal exacerbations (PARSE) was most common (34.2%) and severe. Nonallergic rhinitis was least common (11.2%) and least severe. The majority of children remained symptomatic despite the use of nasal corticosteroids ± oral antihistamines. Rhinitis was worse in difficult-to-control vs. easy-to-control asthma and its seasonal patterns partially corresponded to those of difficult-to-control asthma.
CONCLUSION: Rhinitis is almost ubiquitous in urban children with asthma, and its activity tracks that of lower airway disease. PARSE is the most severe phenotype and most likely to be associated with difficult-to-control asthma. This study offers strong support to the concept that rhinitis and asthma represent the manifestations of one disease in two parts of the airways.
Kuzeniewicz, M.W., et al. Hyperbilirubinemia, Phototherapy, and Childhood Asthma. Pediatrics. Sept 2018; pii: e20180662. doi: 10.1542/peds.2018-0662. [Epub ahead of print]
OBJECTIVES: Our aim was to quantify the associations of both hyperbilirubinemia and phototherapy with childhood asthma using a population-based cohort with total serum bilirubin (TSB) levels.
METHODS: Retrospective cohort study of infants born at ≥35 weeks' gestation in the Kaiser Permanente Northern California health system (n = 109 212) from 2010 to 2014. Cox models were used to estimate hazard ratios (HRs) for a diagnosis of asthma.
RESULTS: In the study, 16.7% of infants had a maximum TSB level of ≥15 mg/dL, 4.5% of infants had a maximum TSB level of ≥18 mg/dL, and 11.5% of infants received phototherapy. Compared with children with a maximum TSB level of 3 to 5.9 mg/L, children with a TSB level of 9 to 11.9 mg/dL, 12 to 14.9 mg/dL, and 15 to 17.9 mg/dL were at an increased risk for asthma (HR: 1.22 [95% confidence interval (CI): 1.11-1.3], HR: 1.18 [95% CI: 1.08-1.29], and HR: 1.30 [95% CI: 1.18-1.43], respectively). Children with a TSB level of ≥18 mg/dL were not at an increased risk for asthma (HR: 1.04; 95% CI: 0.90-1.20). In propensity-adjusted analyses, phototherapy was not associated with asthma (HR: 1.07; 95% CI: 0.96-1.20).
CONCLUSIONS: Modest levels of hyperbilirubinemia were associated with an increased risk of asthma, but an association was not seen at higher levels. No dose-response relationship was seen. Using phototherapy to prevent infants from reaching these modest TSB levels is unlikely to be protective against asthma.
Spear, M.L., et al. A genome-wide association and admixture mapping study of bronchodilator drug response in African Americans with asthma. Pharmacogenomics Journal. Sept 2018. doi: 10.1038/s41397-018-0042-4. [Epub ahead of print]
Short-acting β2-adrenergic receptor agonists (SABAs) are the most commonly prescribed asthma medications worldwide. Response to SABAs is measured as bronchodilator drug response (BDR), which varies among racial/ethnic groups in the United States. However, the genetic variation that contributes to BDR is largely undefined in African Americans with asthma. To identify genetic variants that may contribute to differences in BDR in African Americans with asthma, we performed a genome-wide association study (GWAS) of BDR in 949 African American children with asthma, genotyped with the Axiom World Array 4 (Affymetrix, Santa Clara, CA) followed by imputation using 1000 Genomes phase III genotypes. We used linear regression models adjusting for age, sex, body mass index (BMI) and genetic ancestry to test for an association between BDR and genotype at single-nucleotide polymorphisms (SNPs). To increase power and distinguish between shared vs. population-specific associations with BDR in children with asthma, we performed a meta-analysis across 949 African Americans and 1830 Latinos (total = 2779). Finally, we performed genome-wide admixture mapping to identify regions whereby local African or European ancestry is associated with BDR in African Americans. We identified a population-specific association with an intergenic SNP on chromosome 9q21 that was significantly associated with BDR (rs73650726, p = 7.69 × 10-9). A trans-ethnic meta-analysis across African Americans and Latinos identified three additional SNPs within the intron of PRKG1 that were significantly associated with BDR (rs7903366, rs7070958 and rs7081864, p ≤ 5 × 10-8). Our results failed to replicate in three additional populations of 416 Latinos and 1615 African Americans. Our findings indicate that both population-specific and shared genetic variation contributes to differences in BDR in minority children with asthma, and that the genetic underpinnings of BDR may differ between racial/ethnic groups.
Ochoa, K., Richman, J., an V. J. Wang. LA phonospirometry technique compared to pediatric respiratory assessment measure and peak expiratory flow measurement as a novel technique to assess the severity of an asthma exacerbation. 12:1-5. doi: 10.1080/02770903.2018.1514046. [Epub ahead of print]
OBJECTIVE: Asthma is a common chronic disease treated in emergency departments. The measurements of Peak Expiratory Flow (PEF) and Pediatric Respiratory Assessment Measure (PRAM) scores have been recommended as objective techniques in the assessment of acute asthma exacerbations, but have multiple barriers limiting their use. The Los Angeles phonospirometry technique is an easier, trans-cultural technique. The technique assesses dyspnea by measuring how many seconds a child is able to chant "LA LA LA" in a single breath. The objective of this study is to determine the correlation of this technique with PEF measurements and PRAM scores in children with acute asthma exacerbations, both before and after nebulized bronchodilator treatment.
METHODS: A convenient sample of children aged 5-17 years being treated for asthma in the ED was enrolled. Phonospirometry, PRAM, and PEF measurements were obtained through pre and post inhaled bronchodilator treatments. The highest values from each measurement were correlated using Spearman's correlation coefficient.
RESULTS: A total of 91 children were enrolled. The correlations at pre-treatment, after first, second, and third treatments between phonospirometry and PEF were 0.38 (p < 0.001), 0.60 (p < 0.001), 0.54 (p < 0.001), 0.52 (p < 0.01), respectively; between phonospirometry and PRAM were -0.37 (p < 0.001), -0.42 (p < 0.001), -0.26 (p < 0.05), and -0.06 (p > 0.05), respectively; and between PEF and PRAM were -0.6 (p < 0.01), -0.54 (p < 0.001), -0.38 (p < 0.01), and -0.36 (p - 0.05), respectively.
CONCLUSIONS: This novel technique correlates mild to moderately with PEF, and shows promising aide in the assessment of children with acute asthma exacerbations.
More than 6 million children in the United States have asthma, making it the most common childhood chronic condition in the country. Asthma particularly impacts low-income children and children of color due to many factors including exposure to environmental triggers and toxic stress. When managed, children with asthma lead healthy, active lives. However, uncontrolled asthma leads to increased emergency room visits and hospitalizations. Improving asthma management and reducing exposure to triggers among vulnerable populations have been proven to not only reduce the onset of asthma symptoms these interventions also result in significant savings in terms of health care costs.
One proven intervention to help control childhood asthma and reduce asthma disparities is the use of Community Health Workers (CHWs), frontline public health workers who are trusted members of, and deeply rooted in, the communities they serve. Families USA recently published a new report, Community Health Workers: Key Partners in Improving Children's Health and Eliminating Inequities, that offers specific examples of state-based initiatives that are promising or have demonstrated impact in improving health care and health outcomes for children of color.
The brief highlights two examples of the successful deployment of CHWs to address childhood asthma, one model in northern Manhattan and one in Washington State. These successful programs demonstrate how home-based interventions that utilize CHWs can be valuable in helping families manage their child’s asthma. In both examples, the CHWs work with families in respectful, culturally centered ways to educate caregivers on asthma prevention strategies and treatment options, including medication management. CHWs also have training to identify environmental triggers. These examples show how CHWs can help children and their families improve their long term health outcomes, and their overall quality of life and productivity.
As policymakers and advocates at the state and federal levels look for opportunities to accelerate prevention and improve the diagnosis, treatment, and long-term management of childhood asthma, CHWs should continue to be integrated into these efforts to help address serious childhood asthma disparities.
Bose, Sonali, et al. Prenatal nitrate air pollution exposure and reduced child lung function: Timing and fetal sex effects. Environmental Research. Nov 2018; 167: 591-597. https://doi.org/10.1016/j.envres.2018.08.019
Naar, Sylvie, et al. Comprehensive Community-Based Intervention and Asthma Outcomes in African American Adolescents. Pediatrics. Oct 2018; 142(4): e20173737. http://pediatrics.aappublications.org/content/pediatrics/early/2018/09/04/peds.2017-3737.full.pdf
Toftlund, L.H., et al. Improved lung function at age 6 in children born very preterm and fed extra protein post discharge. Pediatric Allergy and Immunology. Sept 2018; 29(6). [e-pub ahead of print]
Buelo, Audrey, et al. At-risk children with asthma (ARC): a systematic review. Thorax. Sept 2018; 72(9): 813-824. http://dx.doi.org/10.1136/thoraxjnl-2017-210939
Rogers, Valerie E., et al. Inflammation and asthma control in children with comorbid obstructive sleep apnea. Pediatric Pulmonology. Sept 2018; 53(9): 1200-1207. https://doi.org/10.1002/ppul.24074
Orfanos, Sarah, et al. Obesity increases airway smooth muscle responses to contractile agonists. American Journal of Physiology. August 2018. https://doi.org/10.1152/ajplung.00459.2017
Gerald, J.K., et al. School-Supervised Use of a Once-Daily Inhaled Corticosteroid Regimen: A Cluster Randomized Trial. Allergy and Clinical Immunology. Aug 2018. [e-pub ahead of print].
Vereen, Shanda, et al. Association Between Maternal 2nd Trimester Plasma Folate Levels and Infant Bronchiolitis. Maternal and Child Health Journal. 2018. https://doi.org/10.1007/s10995-018-2610-2 [e-pub ahead of print]
Teixiera, Samantha and Anita Zuberi. Neighborhood Social and Environmental Factors and Asthma Among Children Living in Low-Income Neighborhoods: The Importance of Informal Social Control. Family & Community Health. October/December 2018; 41(4): 214-224. DOI: 10.1097/FCH.0000000000000202
Mirzakhani, H, et al. Impact of Preeclampsia on the Relationship of Maternal Asthma with Offspring Asthma: An Observation from the VDAART Clinical Trial. American Journal of Respiratory Critical Care Medicine. August 28, 2018. DOI: 10.1164/rccm.201804-0770OC. [Epub ahead of print]
Martenies, Sheena E. and Stuart A. Batterman. Effectiveness of Using Enhanced Filters in Schools and Homes to Reduce Indoor Exposures to PM2.5 from Outdoor Sources and Subsequent Health Benefits for Children with Asthma. Environmental Science & Technology. Aug 24, 2018. DOI: 10.1021/acs.est.8b02053
Boek, A, et al. Ca2+ and innate immune pathways are activated and differentially expressed in childhood asthma phenotypes. Pediatric Allergy and Immunology. Aug 13 2018. DOI: 10.1111/pai.12971 [e-pub ahead of print]
Banasiak, N.C. Implementation of the Asthma Control Test in Primary Care to Improve Patient Outcomes. Journal of Pediatric Health Care. August 10, 2018. DOI: 10.1016/j.pedhc.2018.05.004. [e-pub ahead of print]
Ferraro, Valentina, et al. Exhaled biomarkers in childhood asthma: old and new approaches. Asthma Research and Practice. August 7, 2018; 4(9). DOI: 10.1186/s40733-018-0045-6
Hennessy, Aine, et al. Antenatal vitamin D exposure and childhood eczema, food allergy, asthma and allergic rhinitis at 2 and 5 years of age in the atopic disease-specific Cork BASELINE Birth Cohort Study. Allergy. Aug 7, 2018. DOI: 10.1111/all.13590 [e-pub ahead of print]
Bacharier, Leonard, et al. Longitudinal Phenotypes of Respiratory Health in a High-Risk Urban Birth Cohort. American Journal of Respiratory and Critical Care Medicine. August 4, 2018. DOI: 10.1164/rccm.201801-0190OC. [e-pub ahead of print].
Levy, Zamora M., et al. Maternal exposure to PM2.5 in south Texas, a pilot study. The Science of the Total Environment. July 2018; 628-629: 1497-1507. DOI: 10.1016/j.scitotenv.2018.02.138
Gao, Lu, et al. Self-reported prenatal tobacco smoke exposure, AXL gene-body methylation, and childhood asthma phenotypes. Clinical Epigenetics. July 2018; 10(1): 98. DOI: 10.1186/s13148-018-0532-x
Tsai, Hui-Ju, et al. Early Life Weight Gain and Development of Childhood Asthma in a Prospective Birth Cohort. Annals of the American Thoracic Society. July 2018. DOI: 10.1513/AnnalsATS.201712-921OC
May is Asthma and Allergy Awareness Month, an important opportunity for Childhood Asthma Leadership Coalition member organizations and their partners to raise awareness of the important role public policy plays in helping children with asthma stay healthy.
We can help parents and policymakers around the country see that decisions in Washington and state capitals have an important impact on the health of local children. We encourage you to use this toolkit to observe Asthma Awareness Month and to customize it to fit the needs of your organization.
This toolkit offers ideas and examples you can use in your community. Feel free to use any or all of these resources:
- A sample op-ed describing the importance of Medicaid for children with asthma, with a call to action to Congress urging Members to reject Medicaid cuts, block grants, and per capita caps
- A tipsheet on pitching newspaper opinion editors
- A tipsheet for messaging and framing your argument
- Sample Facebook and Twitter posts designed to gradually move your online networks, over the course of the month from awareness of Medicaid’s important role for children with asthma to engagement with policymakers
- A social media tipsheet
- Twitter Cover Image: Download Image
- Facebook cover image: Download Image 1 | Download Image 2 | Download Image 3
- Facebook Post: Download Image 1 | Download Image 2 | Download Image 3 | Download Image 4 | Download Image 5 | Download Image 6
- Twitter Post: Download Image 1 | Download Image 2
The toolkit was developed by First Focus for Coalition members. If you have questions or need extra help, please feel free to contact the First Focus communications team. If you use the toolkit in your Asthma Awareness Month outreach efforts, please share examples of your work to make it even easier for other Coalition members to get involved.
This document serves as a resource to show funding levels of federal programs relating to child asthma over the last few budget cycles as well as the requested amounts by President Obama and the House and Senate for FY 17.
CALC partners signed on to a letter urging Congress to level-fund the CDC’s National Asthma Control Program at $29million.
At present, 24 states and Puerto Rico receive critical funding from the National Asthma Control Program. Our request for level funding for the National Asthma Control Program at $29.0 million would ensure these much needed resources would continue to assist states with combatting the terrible human and economic burden caused by asthma.
CALC members sent a letter to U.S. Secretary of Health and Human Services Tom Price urging support of CHIP and Medicaid, as these programs are essential for populations with asthma, including low-income and minority children.
CALC members submitted a letter to Congress expressing their concern over the welfare of children in upcoming discussions about Medicaid, CHIP and the ACA.