ABSTRACT
Importance: It is unknown whether adenotonsillectomy causes undesirable weight gain in children with mild obstructive sleep-disordered breathing (oSDB). Objective: To compare changes in anthropometric measures in children with mild oSDB treated with adenotonsillectomy vs watchful waiting. Design, Setting, and Participants: This was an exploratory analysis of the Pediatric Adenotonsillectomy Trial for Snoring (PATS) randomized clinical trial of adenotonsillectomy vs watchful waiting for mild oSDB (snoring with obstructive apnea-hypopnea index of <3 events/hour) that took place at 7 pediatric tertiary care centers across the US and included 458 children aged 3.0 to 12.9 years with mild oSDB. Participants were recruited from June 29, 2016, to February 1, 2021. Anthropomorphic measures taken at baseline and 12 months after randomization were standardized for age and sex, including each participant's percentage of the 95th body mass index percentile (%BMIp95). Data analyses were performed from March 15, 2023, to April 1, 2024. Intervention: Early adenotonsillectomy (eAT) vs watchful waiting with supportive care (WWSC). Main Outcomes and Measures: Twelve-month change in %BMIp95 from baseline and undesirable weight gain (defined as any weight gain in a child who already had overweight or obesity or an increase from baseline normal weight/underweight to overweight/obesity) at follow-up assessment. Results: The study analysis included 375 children (mean [SD] age, 6.1 [2.3] years; 188 [50.2%] females), of whom 143 (38%) had overweight or obesity at baseline. At 12 months, children in the eAT group experienced a 1.25-point increase in %BMIp95 compared with a 0.59-point increase in the WWSC group (mean difference, 0.93; 95% CI, -0.39 to 2.25). Undesirable weight gain was also similar between the eAT (n = 120; 32%) and WWSC (n = 101; 27%) groups (mean difference, 4%; 95% CI, 5% to 14%). Conclusions and Relevance: The findings of this exploratory analysis of the PATS trial indicate that adenotonsillectomy was not independently associated with an increased risk of undesirable weight gain in children with mild oSDB. However, one-third of the children gained undesirable weight during the study, which suggests that there is an opportunity to address healthy weight management during the evaluation and treatment of children with mild oSDB. Trial Registration: ClinicalTrials.gov Identifier: NCT02562040.
Subject(s)
Adenoidectomy , Asthma , Snoring , Tonsillectomy , Humans , Tonsillectomy/methods , Snoring/surgery , Asthma/surgery , Child , Female , Male , Treatment Outcome , Child, Preschool , AdolescentABSTRACT
Background: Severe, uncontrolled asthma and asthma exacerbations in children are associated with abnormal lung function and airway development, and increased risk of chronic obstructive lung disease in adulthood. The rationale for this post hoc analysis was to explore the relationship between changes in asthma exacerbation rates and lung function in children treated with dupilumab. Methods: This post hoc analysis included children aged 6 to 11 years with uncontrolled, moderate-to-severe type 2 asthma (blood eosinophils ≥150 cells/µL or fractional exhaled nitric oxide ≥20 ppb) who received dupilumab or placebo in the phase 3 LIBERTY ASTHMA VOYAGE study (NCT02948959). Endpoints were the proportion of patients achieving clinically meaningful improvements (≥5% or ≥10%) in pre-bronchodilator percent-predicted forced expiratory volume in 1 second (ppFEV1) by Week 12, annualized severe asthma exacerbation rates from Week 12-52, and mean change from baseline in ppFEV1 to Week 12. Results: At Week 12 of VOYAGE, 141/236 (60%) of children treated with dupilumab and 57/114 (50%) of children receiving placebo showed improvements of ≥5% in ppFEV1; 106/236 (45%) children receiving dupilumab and 36/114 (32%) receiving placebo achieved improvements in ppFEV1 ≥10%. During the Week 12-52 treatment period, dupilumab vs placebo significantly reduced severe exacerbation rates in all subgroups by 52-60% (all P<0.05). Dupilumab treatment resulted in rapid and sustained improvements in ppFEV1 (Week 12 least squares mean difference [95% CI] vs placebo: 3.54 [0.30, 6.78] percentage points; P=0.03) in children who achieved improvements of ≥5%. Conclusion: Dupilumab vs placebo significantly improved pre-bronchodilator ppFEV1, with a higher proportion of patients achieving a clinically meaningful response at Week 12. Dupilumab also significantly reduced severe exacerbation rates, independent of pre-bronchodilator ppFEV1 response at Week 12. Trial Registration: NCT02948959.
ABSTRACT
Rationale: Neighborhood disadvantage (ND) has been associated with sleep-disordered breathing (SDB) in children. However, the association between ND and SDB symptom burden and quality of life (QOL) has not yet been studied.Objectives: To evaluate associations between ND with SDB symptom burden and QOL.Methods: Cross-sectional analyses were performed on 453 children, ages 3-12.9 years, with mild SDB (habitual snoring and apnea-hypopnea index < 3/h) enrolled in the PATS (Pediatric Adenotonsillectomy Trial for Snoring) multicenter study. The primary exposure, neighborhood disadvantage, was characterized by the Child Opportunity Index (COI) (range, 0-100), in which lower values (specifically COI ⩽ 40) signify less advantageous neighborhoods. The primary outcomes were QOL assessed by the obstructive sleep apnea (OSA)-18 questionnaire (range, 18-126) and SDB symptom burden assessed by the Pediatric Sleep Questionnaire-Sleep-related Breathing Disorder (PSQ-SRBD) scale (range, 0-1). The primary model was adjusted for age, sex, race, ethnicity, maternal education, recruitment site, and season. In addition, we explored the role of body mass index (BMI) percentile, environmental tobacco smoke (ETS), and asthma in these associations.Results: The sample included 453 children (16% Hispanic, 26% Black or African American, 52% White, and 6% other). COI mean (standard deviation [SD]) was 50.3 (29.4), and 37% (n = 169) of participants lived in disadvantaged neighborhoods. Poor SDB-related QOL (OSA-18 ⩾ 60) and high symptom burden (PSQ-SRBD ⩾ 0.33) were found in 30% (n = 134) and 75% (n = 341) of participants, respectively. In adjusted models, a COI increase by 1 SD (i.e., more advantageous neighborhood) was associated with an improvement in OSA-18 score by 2.5 points (95% confidence interval [CI], -4.34 to -0.62) and in PSQ-SRBD score by 0.03 points (95% CI, -0.05 to -0.01). These associations remained significant after adjusting for BMI percentile, ETS, or asthma; however, associations between COI and SDB-related QOL attenuated by 23% and 10% after adjusting for ETS or asthma, respectively.Conclusions: Neighborhood disadvantage was associated with poorer SDB-related QOL and greater SDB symptoms. Associations were partially attenuated after considering the effects of ETS or asthma. The findings support efforts to reduce ETS and neighborhood-level asthma-related risk factors and identify other neighborhood-level factors that contribute to SDB symptom burden as strategies to address sleep-health disparities.Clinical trial registered with www.clinicaltrials.gov (NCT02562040).
Subject(s)
Asthma , Sleep Apnea Syndromes , Sleep Apnea, Obstructive , Child , Humans , Snoring/epidemiology , Snoring/complications , Quality of Life , Symptom Burden , Cross-Sectional Studies , Sleep Apnea, Obstructive/complications , Neighborhood Characteristics , Asthma/epidemiology , Asthma/complications , Surveys and QuestionnairesABSTRACT
Schools are in a unique position to address social determinants of health (SDOHs) in pediatric asthma management because of their potential to provide resources and facilitate collaboration with health care providers and services for children at risk within their community. SDOHs include economic factors, educational attainment and health literacy, neighborhood factors and the built environment, social and community aspects including discrimination and racism, and health care access and quality. These factors have a significant impact on asthma health in children, and certain populations such as minoritzed populations and those living in high-poverty environments have been shown to be at greater risk for adverse effects of SDOHs on asthma outcomes. School-based asthma programs address several SDOHs including health literacy, the built environment, and health care quality and access and have been shown to improve asthma outcomes. Key components include connection between the school and the health care team, self-management education, and directly observed therapy. School nurses play a key role in directing and managing effective programs because they can evaluate and support a student's health while considering the effect of SDOHs at interpersonal, institutional, community, and policy levels.
Subject(s)
Asthma , Social Determinants of Health , Humans , Child , Schools , Educational Status , Asthma/epidemiology , Asthma/therapy , Poverty , School Health ServicesABSTRACT
Importance: The utility of adenotonsillectomy in children who have habitual snoring without frequent obstructive breathing events (mild sleep-disordered breathing [SDB]) is unknown. Objectives: To evaluate early adenotonsillectomy compared with watchful waiting and supportive care (watchful waiting) on neurodevelopmental, behavioral, health, and polysomnographic outcomes in children with mild SDB. Design, Setting, and Participants: Randomized clinical trial enrolling 459 children aged 3 to 12.9 years with snoring and an obstructive apnea-hypopnea index (AHI) less than 3 enrolled at 7 US academic sleep centers from June 29, 2016, to February 1, 2021, and followed up for 12 months. Intervention: Participants were randomized 1:1 to either early adenotonsillectomy (n = 231) or watchful waiting (n = 228). Main Outcomes and Measures: The 2 primary outcomes were changes from baseline to 12 months for caregiver-reported Behavior Rating Inventory of Executive Function (BRIEF) Global Executive Composite (GEC) T score, a measure of executive function; and a computerized test of attention, the Go/No-go (GNG) test d-prime signal detection score, reflecting the probability of response to target vs nontarget stimuli. Twenty-two secondary outcomes included 12-month changes in neurodevelopmental, behavioral, quality of life, sleep, and health outcomes. Results: Of the 458 participants in the analyzed sample (231 adenotonsillectomy and 237 watchful waiting; mean age, 6.1 years; 230 female [50%]; 123 Black/African American [26.9%]; 75 Hispanic [16.3%]; median AHI, 0.5 [IQR, 0.2-1.1]), 394 children (86%) completed 12-month follow-up visits. There were no statistically significant differences in change from baseline between the 2 groups in executive function (BRIEF GEC T-scores: -3.1 for adenotonsillectomy vs -1.9 for watchful waiting; difference, -0.96 [95% CI, -2.66 to 0.74]) or attention (GNG d-prime scores: 0.2 for adenotonsillectomy vs 0.1 for watchful waiting; difference, 0.05 [95% CI, -0.18 to 0.27]) at 12 months. Behavioral problems, sleepiness, symptoms, and quality of life each improved more with adenotonsillectomy than with watchful waiting. Adenotonsillectomy was associated with a greater 12-month decline in systolic and diastolic blood pressure percentile levels (difference in changes, -9.02 [97% CI, -15.49 to -2.54] and -6.52 [97% CI, -11.59 to -1.45], respectively) and less progression of the AHI to greater than 3 events/h (1.3% of children in the adenotonsillectomy group compared with 13.2% in the watchful waiting group; difference, -11.2% [97% CI, -17.5% to -4.9%]). Six children (2.7%) experienced a serious adverse event associated with adenotonsillectomy. Conclusions: In children with mild SDB, adenotonsillectomy, compared with watchful waiting, did not significantly improve executive function or attention at 12 months. However, children with adenotonsillectomy had improved secondary outcomes, including behavior, symptoms, and quality of life and decreased blood pressure, at 12-month follow-up. Trial Registration: ClinicalTrials.gov Identifier: NCT02562040.
Subject(s)
Adenoidectomy , Sleep Apnea Syndromes , Snoring , Tonsillectomy , Watchful Waiting , Child , Female , Humans , Polysomnography , Quality of Life , Sleep Apnea Syndromes/diagnosis , Sleep Apnea Syndromes/etiology , Sleep Apnea Syndromes/surgery , Sleep Apnea, Obstructive/diagnosis , Sleep Apnea, Obstructive/etiology , Sleep Apnea, Obstructive/surgery , Snoring/etiology , Snoring/surgery , Tonsillectomy/adverse effects , Tonsillectomy/methods , Male , Adenoidectomy/adverse effects , Adenoidectomy/methods , Child, Preschool , Treatment Outcome , Follow-Up StudiesABSTRACT
INTRODUCTION: Parent caregivers of children who require lifesaving medical technology (e.g., mechanical ventilation, feeding tubes) must constantly maintain vigilance. Poor physical and psychological health can negatively impact their ability to do so. METHOD: A two-arm randomized controlled trial was conducted with 197 parent caregivers of technology-dependent children (aged < 18 years) to test the efficacy of Resourcefulness Training1, a cognitive-behavioral intervention that teaches social (help-seeking) and personal (self-help) resourcefulness skills, in improving key outcomes including mental health-related quality of life (HRQOL), depressive cognitions and symptoms, perceived and physiological chronic stress, burden, and physical HRQOL at five-time points. RESULTS: Mixed-effects models using the intent-to-treat principle indicated statistically significant improvement with intervention participants at six and/or nine months postintervention for depressive cognitions, perceived stress, and physical HRQOL, controlling for covariates. DISCUSSION: Study findings support the efficacy of Resourcefulness Training to significantly decrease perceived stress and improve psychological/physical outcomes with these vulnerable caregivers.
ABSTRACT
BACKGROUND: Frequent asthma exacerbators, defined as those experiencing more than 1 hospitalization in a year for an asthma exacerbation, represent an important subgroup of individuals with asthma. However, this group remains poorly defined and understudied in children. OBJECTIVE: Our aim was to determine the molecular mechanisms underlying asthma pathogenesis and exacerbation frequency. METHODS: We performed RNA sequencing of upper airway cells from both frequent and nonfrequent exacerbators enrolled in the Ohio Pediatric Asthma Repository. RESULTS: Through molecular network analysis, we found that nonfrequent exacerbators display an increase in modules enriched for immune system processes, including type 2 inflammation and response to infection. In contrast, frequent exacerbators showed expression of modules enriched for nervous system processes, such as synaptic formation and axonal outgrowth. CONCLUSION: These data suggest that the upper airway of frequent exacerbators undergoes peripheral nervous system remodeling, representing a novel mechanism underlying pediatric asthma exacerbation.
Subject(s)
Asthma , Pulmonary Disease, Chronic Obstructive , Humans , Child , Transcriptome , Asthma/genetics , Inflammation , Nose , Disease ProgressionABSTRACT
OBJECTIVE: Caregivers frequently report poor quality of life (QOL) in children with sleep-disordered breathing (SDB). Our objective is to assess the correlation between caregiver- and child-reported QOL in children with mild SDB and identify factors associated with differences between caregiver and child report. STUDY DESIGN: Analysis of baseline data from a multi-institutional randomized trial SETTING: Pediatric Adenotonsillectomy Trial for Snoring, where children with mild SDB (obstructive apnea-hypopnea index <3) were randomized to observation or adenotonsillectomy. METHODS: The Pediatric Quality of Life Inventory (PedsQL) assessed baseline global QOL in participating children 5 to 12 years old and their caregivers. Caregiver and child scores were compared. Multivariable regression assessed whether clinical factors were associated with differences between caregiver and child report. RESULTS: PedsQL scores were available for 309 families (mean child age, 7.0 years). The mean caregiver-reported PedsQL score was higher at 75.2 (indicating better QOL) than the mean child-reported score of 67.9 (P < .001). The agreement between caregiver and child total PedsQL scores was poor, with intraclass correlation coefficients of 0.03 (95% CI, -0.09 to 0.15) for children 5 to 7 years old and 0.21 (95% CI, 0.03-0.38) for children 8 to 12 years old. Higher child age and health literacy were associated with closer agreement between caregiver and child report. CONCLUSION: Caregiver- and child-reported global QOL in children with SDB was weakly correlated, more so for young children. In pediatric SDB, child-perceived QOL may be poorer than that reported by caregivers. Further research is needed to assess whether similar trends exist for disease-specific QOL metrics.
Subject(s)
Caregivers , Sleep Apnea Syndromes , Humans , Child , Child, Preschool , Quality of Life , Sleep Apnea Syndromes/surgery , Snoring , AdenoidectomyABSTRACT
BACKGROUND: Children with asthma are at risk for low lung function extending into adulthood, but understanding of clinical predictors is incomplete. OBJECTIVE: We sought to determine phenotypic factors associated with FEV1 throughout childhood in the Severe Asthma Research Program 3 pediatric cohort. METHODS: Lung function was measured at baseline and annually. Multivariate linear mixed-effects models were constructed to assess the effect of baseline and time-varying predictors of prebronchodilator FEV1 at each assessment for up to 6 years. All models were adjusted for age, predicted FEV1 by Global Lung Function Initiative reference equations, race, sex, and height. Secondary outcomes included postbronchodilator FEV1 and prebronchodilator FEV1/forced vital capacity. RESULTS: A total of 862 spirometry assessments were performed for 188 participants. Factors associated with FEV1 include baseline Feno (B, -49 mL/log2 PPB; 95% CI, -92 to -6), response to a characterizing dose of triamcinolone acetonide (B, -8.4 mL/1% change FEV1 posttriamcinolone; 95% CI, -12.3 to -4.5), and maximal bronchodilator reversibility (B, -27 mL/1% change postbronchodilator FEV1; 95% CI, -37 to -16). Annually assessed time-varying factors of age, obesity, and exacerbation frequency predicted FEV1 over time. Notably, there was a significant age and sex interaction. Among girls, there was no exacerbation effect. For boys, however, moderate (1-2) exacerbation frequency in the previous 12 months was associated with -20 mL (95% CI, -39 to -2) FEV1 at each successive year. High exacerbation frequency (≥3) 12 to 24 months before assessment was associated with -34 mL (95% CI, -61 to -7) FEV1 at each successive year. CONCLUSIONS: In children with severe and nonsevere asthma, several clinically relevant factors predict FEV1 over time. Boys with recurrent exacerbations are at high risk of lower FEV1 through childhood.
Subject(s)
Asthma , Male , Female , Child , Humans , Adult , Forced Expiratory Volume , Asthma/drug therapy , Bronchodilator Agents/therapeutic use , Bronchodilator Agents/pharmacology , Respiratory Function Tests , Spirometry , LungSubject(s)
Fellowships and Scholarships , Pulmonary Medicine , Child , Humans , United States , Workforce , Education, Medical, GraduateABSTRACT
At the start of the Coronavirus Disease of 2019 (COVID-19) pandemic, the risk of cases in childcare programs was unknown. Thus, a rapid-response research approach was launched in Ohio childcare settings. Passive surveillance data from a state-operated incident reporting system were evaluated to estimate the number of COVID-19 cases from 15 August 2020 to 1 January 2021. Additionally, active surveillance with self-administered reverse transcriptase-polymerase chain reaction (RT-PCR) tests were conducted among staff at 46 childcare programs. Finally, six zoom-based focus groups with program administrators were used to gain feedback. Staff and children in childcare settings contributed 0.38% and 0.15% of the COVID-19 cases in Ohio during this timeframe, respectively. RT-PCR testing identified 3 unrecognized cases (0.88% of tests), and all occurred when the statewide positivity rate was >5%. Focus groups revealed that access to affordable cleaning supplies, masks, and reliable staffing were critical. Perhaps most importantly, we conclude that expanding the incident reporting system to include a childcare census would allow for the tracking of future health problems with highly valuable incidence rate estimations.
Subject(s)
COVID-19 , Child , Humans , COVID-19/epidemiology , Child Care , Ohio/epidemiology , COVID-19 Testing , PandemicsABSTRACT
A systematic review of interventions in community environments found significant reductions in childhood asthma exacerbations leading to emergency department visits and hospitalizations. BACKGROUND AND OBJECTIVES: Structural and social determinants of childhood asthma inequities manifest within geographic communities that are often segregated. Childhood asthma disproportionately affects Black, Hispanic, and low-income populations. Community interventions have the potential to improve inequities in emergency healthcare. This systematic review was conducted to assess the effectiveness of childhood asthma community interventions and provide a conceptual model to inform implementation of future community interventions. METHODS: Publications from PubMed, ScienceDirect, CINAHL, Cochrane Library, Web of Science, and hand searched references were examined from 2010 to 2021. Community intervention studies among children with asthma were included. Main outcomes were emergency department visits and hospitalizations. Community interventions exclusively focusing on schools or hospitals were excluded. Two reviewers independently assessed eligibility for final inclusion. Emergency healthcare findings were extracted in addition to co-benefits (eg, fewer missed school days and caregiver workdays). RESULTS: Out of 1856 records, 26 publications met the inclusion criteria. Community interventions were categorized by care coordination (n = 8), policy and environmental changes (eg, smoke-free legislature, traffic reduction models, and green housing) (n = 8), home-based (n = 6), and community-based health services (n = 4). Selected studies indicated that community interventions significantly reduced childhood asthma emergency department visits and hospitalizations through increased caregiver self-efficacy, home environmental trigger reduction, and increased access to healthcare. Because of heterogeneity among studies, we were unable to conduct a meta-analysis. CONCLUSIONS: Findings show significant associations between community interventions and the reduction of emergency healthcare, suggesting a protective effect for severe cases of childhood asthma.
Subject(s)
Asthma , Asthma/therapy , Caregivers , Child , Hospitalization , Housing , Humans , SchoolsABSTRACT
OBJECTIVES: To determine the association between human milk exposure at 3 months corrected gestational age and recurrent wheeze in preterm Black infants. METHODS: This is a secondary analysis of data from the D-Wheeze trial (ClinicalTrials.gov identifier NCT01601847). Associations between human milk feeding at 3 months corrected age and wheezing outcomes were examined by generalized linear models. RESULTS: Exclusively human milk fed infants (n = 13) had significantly fewer wheezing episodes than formula fed infants (n = 230) (IRR (95% CI) = 0.25 (0.07, 0.89), p = 0.03). There were no hospitalizations in infants receiving exclusive human milk. Receiving any human milk was associated with decreased odds of hospitalization by 12 months corrected age (OR (95% CI) = 0.12 (0.02, 0.79), p = 0.03). CONCLUSIONS: Exclusive human milk feeding at three months corrected gestational age is associated with decreased number of wheezing episodes in the first year of life in preterm Black infants.
Subject(s)
Milk, Human , Respiratory Sounds , Female , Humans , Infant , Infant, Newborn , Black People , Breast Feeding , Hospitalization , Infant Formula , Infant, PrematureABSTRACT
STUDY OBJECTIVES: Obstructive sleep apnea is associated with neurobehavioral dysfunction, but the relationship between disease severity as measured by the apnea-hypopnea index and neurobehavioral morbidity is unclear. The objective of our study is to compare the neurobehavioral morbidity of mild sleep-disordered breathing versus obstructive sleep apnea. METHODS: Children 3-12 years old recruited for mild sleep-disordered breathing (snoring with obstructive apnea-hypopnea index < 3) into the Pediatric Adenotonsillectomy Trial for Snoring were compared to children 5-9 years old recruited for obstructive sleep apnea (obstructive apnea-hypopnea 2-30) into the Childhood Adenotonsillectomy Trial. Baseline demographic, polysomnographic, and neurobehavioral outcomes were compared using univariable and multivariable analysis. RESULTS: The sample included 453 participants with obstructive sleep apnea (median obstructive apnea-hypopnea index 5.7) and 459 participants with mild sleep-disordered breathing (median obstructive apnea-hypopnea index 0.5). By polysomnography, participants with obstructive sleep apnea had poorer sleep efficiency and more arousals. Children with mild sleep-disordered breathing had more abnormal executive function scores (adjusted odds ratio 1.96, 95% CI 1.30-2.94) compared to children with obstructive sleep apnea. There were also elevated Conners scores for inattention (adjusted odds ratio 3.16, CI 1.98-5.02) and hyperactivity (adjusted odds ratio 2.82, CI 1.83-4.34) in children recruited for mild sleep-disordered breathing. CONCLUSIONS: Abnormal executive function, inattention, and hyperactivity were more common in symptomatic children recruited into a trial for mild sleep-disordered breathing compared to children recruited into a trial for obstructive sleep apnea. Young, snoring children with only minimally elevated apnea-hypopnea levels may still be at risk for deficits in executive function and attention. TRIAL REGISTRATION: Pediatric Adenotonsillectomy for Snoring (PATS), NCT02562040; Childhood Adenotonsillectomy Trial (CHAT), NCT00560859.
Subject(s)
Sleep Apnea Syndromes , Sleep Apnea, Obstructive , Tonsillectomy , Adenoidectomy , Child , Child, Preschool , Clinical Trials as Topic , Humans , Morbidity , Sleep Apnea Syndromes/complications , Sleep Apnea Syndromes/surgery , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/surgery , Snoring/complications , Snoring/surgeryABSTRACT
BACKGROUND: Observational studies have yielded inconsistent findings for the relation between vitamin D level and total IgE or allergic sensitization. OBJECTIVE: To determine whether vitamin D supplementation reduces levels of total IgE and IgE to each of 2 common indoor allergens in children with asthma and low vitamin D levels. METHODS: Total IgE, IgE to Dermatophagoides pteronyssinus, and IgE to Blattella germanica were measured at the randomization and exit visits for 174 participants in the Vitamin D Kids Asthma Study, a multicenter, double-blind, randomized placebo-controlled trial of vitamin D3 supplementation (4000 IU/d) to prevent severe exacerbations in children with persistent asthma and vitamin D levels less than 30 ng/mL. Multivariable linear regression was used for the analysis of the effect of vitamin D supplementation on change in each IgE measure. RESULTS: Participants were followed for an average of 316 days. At the exit visit, more subjects in the vitamin D arm achieved a vitamin D level equal to or more than 30 ng/mL compared with those in the placebo arm (87% vs 30%; P < .001). In a multivariable analysis, vitamin D3 supplementation had no significant effect on change in total IgE, IgE to Dermatophagoides pteronyssinus, or IgE to Blattella germanica between the exit and randomization visits (eg, for log10 total IgE, ß = 0.007; 95% CI, -0.061 to 0.074; P = .85). CONCLUSIONS: Vitamin D supplementation, compared with placebo, has no significant effect on serum levels of total IgE, IgE to dust mite, or IgE to cockroach in children with asthma and low vitamin D levels.
Subject(s)
Allergens/immunology , Antigens, Dermatophagoides/immunology , Arthropod Proteins/immunology , Asthma/drug therapy , Cysteine Endopeptidases/immunology , Immunoglobulin E/blood , Vitamin D/therapeutic use , Vitamins/therapeutic use , Animals , Asthma/blood , Asthma/immunology , Child , Dietary Supplements , Double-Blind Method , Female , Humans , MaleABSTRACT
BACKGROUND: Exposure to violence has been associated with lower lung function in cross-sectional studies. METHODS: We examined whether increasing violence-related distress over time is associated with worse lung function and worse asthma control or quality of life in a secondary analysis of a 48-week randomised clinical trial in 98 youth with asthma (aged 9-16â years) treated with low-dose inhaled corticosteroids (Vitamin D Kids Asthma Study (VDKA)). We then replicated our findings for lung function in a prospective study of 232 Puerto Rican youth followed for an average of 5.4â years. Violence-related distress was assessed using the Checklist of Children's Distress Symptoms (CCDS) scale. Our outcomes of interest were percent predicted lung function measures and (in VDKA only) asthma control (assessed using the Asthma Control Test) and asthma-related quality of life (assessed using the Pediatric Asthma Quality of Life Questionnaire (PAQLQ)). RESULTS: In a multivariable analysis in VDKA, each 1-point increment in CCDS score was associated with decrements of 3.27% in forced expiratory volume in 1â s (FEV1) % pred (95% CI -6.44-â-0.22%; p=0.04), 2.65% in forced vital capacity (FVC) % pred (95% CI -4.86-â-0.45%; p=0.02) and 0.30 points in the overall PAQLQ score (95% CI -0.50-â-0.10 points; p<0.01). Similar findings for FEV1 and FVC were obtained in the prospective study of Puerto Rican youth. CONCLUSIONS: Our findings suggest that violence-related distress may worsen lung function and quality of life in youth with asthma (even those treated with low-dose inhaled corticosteroids), and further support policies to reduce exposure to violence among children in the USA and Puerto Rico.
Subject(s)
Asthma , Quality of Life , Adolescent , Adrenal Cortex Hormones/therapeutic use , Asthma/drug therapy , Child , Cross-Sectional Studies , Forced Expiratory Volume , Humans , Longitudinal Studies , Lung , Prospective Studies , Violence , Vitamin DABSTRACT
Background: The fractional exhaled nitric oxide (FENO) test is a point-of-care test that is used in the assessment of asthma. Objective: To provide evidence-based clinical guidance on whether FENO testing is indicated to optimize asthma treatment in patients with asthma in whom treatment is being considered. Methods: An international, multidisciplinary panel of experts was convened to form a consensus document regarding a single question relevant to the use of FENO. The question was selected from three potential questions based on the greatest perceived impact on clinical practice and the unmet need for evidence-based answers related to this question. The panel performed systematic reviews of published randomized controlled trials between 2004 and 2019 and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence-to-decision framework to develop recommendations. All panel members evaluated and approved the recommendations. Main Results: After considering the overall low quality of the evidence, the panel made a conditional recommendation for FENO-based care. In patients with asthma in whom treatment is being considered, we suggest that FENO is beneficial and should be used in addition to usual care. This judgment is based on a balance of effects that probably favors the intervention; the moderate costs and availability of resources, which probably favors the intervention; and the perceived acceptability and feasibility of the intervention in daily practice. Conclusions: Clinicians should consider this recommendation to measure FENO in patients with asthma in whom treatment is being considered based on current best available evidence.
Subject(s)
Adrenal Cortex Hormones/standards , Adrenal Cortex Hormones/therapeutic use , Anti-Asthmatic Agents/standards , Anti-Asthmatic Agents/therapeutic use , Asthma/diagnosis , Asthma/drug therapy , Nitric Oxide/analysis , Practice Guidelines as Topic , Humans , United StatesABSTRACT
Thiol-NO adducts such as S-nitrosoglutathione (GSNO) are endogenous bronchodilators in human airways. Decreased airway S-nitrosothiol concentrations are associated with asthma. Nitric oxide (NO), a breakdown product of GSNO, is measured in exhaled breath as a biomarker in asthma; an elevated fraction of expired NO (FENO) is associated with asthmatic airway inflammation. We hypothesized that FENO could reflect airway S-nitrosothiol concentrations. To test this hypothesis, we first studied the relationship between mixed expired NO and airway S-nitrosothiols in patients endotracheally intubated for respiratory failure. The inverse (Lineweaver-Burke type) relationship suggested that expired NO could reflect the rate of pulmonary S-nitrosothiol breakdown. We thus studied NO evolution from the lungs of mice (GSNO reductase -/-) unable reductively to catabolize GSNO. More NO was produced from GSNO in the -/- compared to wild type lungs. Finally, we formally tested the hypothesis that airway GSNO increases FENO using an inhalational challenge model in normal human subjects. FENO increased in all subjects tested, with a median t1/2 of 32.0 min. Taken together, these data demonstrate that FENO reports, at least in part, GSNO breakdown in the lungs. Unlike GSNO, NO is not present in the lungs in physiologically relevant concentrations. However, FENO following a GSNO challenge could be a non-invasive test for airway GSNO catabolism.