Megan E. Jensen

Obesity and childhood asthma - mechanisms and manifestations.

Purpose of reviewObesity is a chronic condition affecting children worldwide. However, the prevalence is higher in asthmatic children. Obese children most likely become obese adults. Understanding the clinical presentation of this subgroup is essential to their clinical management, now and in the future. This review highlights the most recent findings over the past 18 months in understanding the presentation and potential mechanisms of obesity in childhood asthma. Recent findingsRecent research suggests that inhaled corticosteroid efficacy is reduced in obese asthmatic children whereas ventilatory function and bronchoreactivity appear to be marginally affected. A paucity of studies describing airway inflammation and lung volume measurements in this subgroup limits their clinical characterization. Recent studies indicate metabolic abnormalities that typically manifest with excess adiposity may be associated with asthma, providing an interesting factor in the asthma–obesity link. The inception, persistence and composition of obesity prove important considerations for future studies. SummaryHighlighted is the need for more descriptive airway inflammation studies, lung volume assessments and longitudinal studies to better characterize the obese asthma phenotype in children and understand the pathogenesis from childhood to adulthood. Understanding the manifestations and mechanisms of obese asthma in childhood will help direct clinical management and targeted therapeutic interventions.

Diet-induced weight loss in obese children with asthma: a randomized controlled trial

Obesity is highly prevalent in asthmatic children and associated with worse clinical outcomes. Energy restriction to induce weight loss in asthmatic children has not been investigated in a randomized controlled trial (RCT).

Airway and systemic inflammation in obese children with asthma

Obese asthma presents via altered airway and systemic inflammation in adults. This has not been comprehensively described in children. The aim of the present study was to compare airway and systemic inflammation in obese and nonobese asthmatic children and controls. In a cross-sectional study, children aged 8–17 years were assigned to one of four groups: obese asthma (OA, n=74); nonobese asthma (NOA, n=249); obese control (OC, n=9); nonobese control (NOC, n=29). Lung function, and both sputum and systemic inflammatory biomarkers were measured. Non-eosinophilic asthma was more prevalent among OA females (60.0%) versus OA males (30.8%). However, there were no differences in the percentage of eosinophils or neutrophils between OA and NOA. Leptin was higher in OC, but not OA, versus NOA and NOC, while adiponectin was reduced in OA versus NOC only. Expiratory reserve volume was reduced in OA, versus NOC. Residual volume (RV) and RV/total lung capacity were reduced in OC versus OA, and OC versus OA and NOA, respectively. Obesity was associated with significant lung restriction in children with and without asthma. Obesity was not associated with significantly altered airway or systemic inflammation in asthmatic children. However, the higher prevalence of non-eosinophilic asthma in female obese asthmatics, compared to males, warrants further investigation. Obesity linked to lung restriction in non- and asthmatic children but not altered airway or systemic inflammation http://ow.ly/nm2VY

Vitamin D for the management of asthma

BACKGROUNDnSeveral clinical trials of vitamin D to prevent asthma exacerbation and improve asthma control have been conducted in children and adults, but a meta-analysis restricted to double-blind, randomised, placebo-controlled trials of this intervention is lacking.nnnOBJECTIVESnTo evaluate the efficacy of administration of vitamin D and its hydroxylated metabolites in reducing the risk of severe asthma exacerbations (defined as those requiring treatment with systemic corticosteroids) and improving asthma symptom control.nnnSEARCH METHODSnWe searched the Cochrane Airways Group Trial Register and reference lists of articles. We contacted the authors of studies in order to identify additional trials. Date of last search: January 2016.nnnSELECTION CRITERIAnDouble-blind, randomised, placebo-controlled trials of vitamin D in children and adults with asthma evaluating exacerbation risk or asthma symptom control or both.nnnDATA COLLECTION AND ANALYSISnTwo review authors independently applied study inclusion criteria, extracted the data, and assessed risk of bias. We obtained missing data from the authors where possible. We reported results with 95% confidence intervals (CIs).nnnMAIN RESULTSnWe included seven trials involving a total of 435 children and two trials involving a total of 658 adults in the primary analysis. Of these, one trial involving 22 children and two trials involving 658 adults contributed to the analysis of the rate of exacerbations requiring systemic corticosteroids. Duration of trials ranged from four to 12 months, and the majority of participants had mild to moderate asthma. Administration of vitamin D reduced the rate of exacerbations requiring systemic corticosteroids (rate ratio 0.63, 95% CI 0.45 to 0.88; 680 participants; 3 studies; high-quality evidence), and decreased the risk of having at least one exacerbation requiring an emergency department visit or hospitalisation or both (odds ratio (OR) 0.39, 95% CI 0.19 to 0.78; number needed to treat for an additional beneficial outcome, 27; 963 participants; 7 studies; high-quality evidence). There was no effect of vitamin D on % predicted forced expiratory volume in one second (mean difference (MD) 0.48, 95% CI -0.93 to 1.89; 387 participants; 4 studies; high-quality evidence) or Asthma Control Test scores (MD -0.08, 95% CI -0.70 to 0.54; 713 participants; 3 studies; high-quality evidence). Administration of vitamin D did not influence the risk of serious adverse events (OR 1.01, 95% CI 0.54 to 1.89; 879 participants; 5 studies; moderate-quality evidence). One trial comparing low-dose versus high-dose vitamin D reported two episodes of hypercalciuria, one in each study arm. No other study reported any adverse event potentially attributable to administration of vitamin D. No participant in any included trial suffered a fatal asthma exacerbation. We did not perform a subgroup analysis to determine whether the effect of vitamin D on risk of severe exacerbation was modified by baseline vitamin D status, due to unavailability of suitably disaggregated data. We assessed two trials as being at high risk of bias in at least one domain; neither trial contributed data to the analysis of the outcomes reported above.nnnAUTHORS CONCLUSIONSnMeta-analysis of a modest number of trials in people with predominantly mild to moderate asthma suggests that vitamin D is likely to reduce both the risk of severe asthma exacerbation and healthcare use. It is as yet unclear whether these effects are confined to people with lower baseline vitamin D status; further research, including individual patient data meta-analysis of existing datasets, is needed to clarify this issue. Children and people with frequent severe asthma exacerbations were under-represented; additional primary trials are needed to establish whether vitamin D can reduce the risk of severe asthma exacerbation in these groups.

Diet Quality, Measured by Fruit and Vegetable Intake, Predicts Weight Change in Young Women

This study investigates the relationship between diet quality and weight gain in young women. Young women (n = 4,287, with 1,356 women identified as plausible subsample aged 27.6u2009±u20091.5 years at baseline) sampled from the Australian Longitudinal Study on Womens Health study completed food frequency questionnaires in 2003, which were used to evaluate diet quality using three indices: Australian Recommended Food Score (ARFS), Australian Diet Quality Index (Aus-DQI), and Fruit and Vegetable Index (FAVI). Weight was self-reported in 2003 and 2009. Multivariate linear regression was used to examine the association between tertiles of each diet quality index and weight change from 2003 to 2009. The ARFS and FAVI were significant predictors of 6-year weight change in this group of young women, while Aus-DQI did not predict weight change (P > 0.05). In the fully adjusted model, those who were in the top tertile of the ARFS significantly gained lower weight gain compared with the lower tertile for the plausible TEI sub-sample (β = −1.6u2009kg (95% CI: −2.67 to −0.56), P = 0.003). In the fully adjustment model, young women were classified in the highest FAVI tertile and gained significantly less weight than those in the lowest tertile for the plausible TEI (β = −1.6u2009kg (95% CI: −2.4 to −0.3) P = 0.01). In conclusion, overall diet quality measured by the ARFS and the frequency and variety of fruit and vegetable consumption may predict long-term weight gain in young women. Therefore, health promotion programs encouraging frequent consumption of a wide variety of fruits and vegetables are warranted.

The obesity phenotype in children with asthma

Asthma and obesity have been increasing in prevalence internationally among children. Evidence points to an association between these chronic morbidities, suggesting the development of an obese asthma phenotype in childhood. This review summarises the evidence that the proinflammatory environment created by excess adiposity may provide a mechanism leading to obese asthma in children and adolescents. Weight loss studies conducted in children without asthma have demonstrated a reduction in systemic inflammation. However, the impact of weight loss in the obese paediatric population with asthma has not been investigated. The paucity of information highlights the need for high quality randomised controlled trials of weight loss in this population that include assessment of systemic and airway inflammation, and clinical asthma outcomes. This will lead to refinements in management approaches for these patients.

Vitamin D supplementation to prevent asthma exacerbations: a systematic review and meta-analysis of individual participant data

BACKGROUNDnA previous aggregate data meta-analysis of randomised controlled trials showed that vitamin D supplementation reduces the rate of asthma exacerbations requiring treatment with systemic corticosteroids. Whether this effect is restricted to patients with low baseline vitamin D status is unknown.nnnMETHODSnFor this systematic review and one-step and two-step meta-analysis of individual participant data, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science for double-blind, placebo-controlled, randomised controlled trials of vitamin D3 or vitamin D2 supplementation in people with asthma that reported incidence of asthma exacerbation, published between database inception and Oct 26, 2016. We analysed individual participant data requested from the principal investigator for each eligible trial, adjusting for age and sex, and clustering by study. The primary outcome was the incidence of asthma exacerbation requiring treatment with systemic corticosteroids. Mixed-effects regression models were used to obtain the pooled intervention effect with a 95% CI. Subgroup analyses were done to determine whether effects of vitamin D on risk of asthma exacerbation varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration, age, ethnic or racial origin, body-mass index, vitamin D dosing regimen, use of inhaled corticosteroids, or end-study 25(OH)D levels; post-hoc subgroup analyses were done according to sex and study duration. This study was registered with PROSPERO, number CRD42014013953.nnnFINDINGSnOur search identified 483 unique studies, eight of which were eligible randomised controlled trials (total 1078 participants). We sought individual participant data for each and obtained it for seven studies (955 participants). Vitamin D supplementation reduced the rate of asthma exacerbation requiring treatment with systemic corticosteroids among all participants (adjusted incidence rate ratio [aIRR] 0·74, 95% CI 0·56-0·97; p=0·03; 955 participants in seven studies; high-quality evidence). There were no significant differences between vitamin D and placebo in the proportion of participants with at least one exacerbation or time to first exacerbation. Subgroup analyses of the rate of asthma exacerbations treated with systemic corticosteroids revealed that protective effects were seen in participants with baseline 25(OH)D of less than 25 nmol/L (aIRR 0·33, 0·11-0·98; p=0·046; 92 participants in three studies; moderate-quality evidence) but not in participants with higher baseline 25(OH)D levels (aIRR 0·77, 0·58-1·03; p=0·08; 764 participants in six studies; moderate-quality evidence; pinteraction=0·25). p values for interaction for all other subgroup analyses were also higher than 0·05; therefore, we did not show that the effects of this intervention are stronger in any one subgroup than in another. Six studies were assessed as being at low risk of bias, and one was assessed as being at unclear risk of bias. The two-step meta-analysis did not reveal evidence of heterogeneity of effect (I2=0·0, p=0·56).nnnINTERPRETATIONnVitamin D supplementation reduced the rate of asthma exacerbations requiring treatment with systemic corticosteroids overall. We did not find definitive evidence that effects of this intervention differed across subgroups of patients.nnnFUNDINGnHealth Technology Assessment Program, National Institute for Health Research (reference number 13/03/25).

Increased sleep latency and reduced sleep duration in children with asthma

Study objectiveSleep disturbance is reported to be more prevalent in children and adolescents with asthma than those without. However, this has not been described adequately using objective measures. The aim of this study was to objectively characterise sleep disturbance in asthmatic and non-asthmatic children and adolescents.MethodsA retrospective analysis of polysomnography recordings from children aged 5–17xa0years old, with (nu2009=u2009113) and without asthma (nu2009=u2009104), referred for a sleep study over the period 2005–2010 at the Paediatric Sleep Unit, John Hunter Children’s Hospital in Newcastle, NSW Australia, was carried out.ResultsPolysomnographic recordings were analysed to compare sleep quality and quantity between asthmatic and non-asthmatic children. Sleep latency was significantly longer in asthmatic children compared to controls. However, this result was significant for females only (46.2 (5.6) vs 33.2 (2.7) min, pu2009<u20090.05). Male asthmatics had significantly shorter sleep duration (425.9 (5.4) vs 441.8 (5.4) min, pu2009<u20090.05) than male controls.ConclusionsSleep disturbance exists in children with asthma and manifests differently in males and females. Further investigation into the clinical implication of increased sleep latency and reduced sleep duration upon daytime functioning and lifestyle behaviours in children and adolescents with asthma is warranted.

Short-chain fatty acids, prebiotics, synbiotics, and systemic inflammation: a systematic review and meta-analysis

BackgroundnPrebiotic soluble fibers are fermented by beneficial bacteria in the colon to produce short-chain fatty acids (SCFAs), which are proposed to have systemic anti-inflammatory effects.nnnObjectivenThis review examines the effect of SCFAs, prebiotics, and pre- and probiotic combinations (synbiotics) on systemic inflammation.nnnDesignnRelevant English language studies from 1947 to May 2017 were identified with the use of online databases. Studies were considered eligible if they examined the effects of SCFAs, prebiotics, or synbiotics; were delivered orally, intravenously, or per rectum; were on biomarkers of systemic inflammation in humans; and performed meta-analysis where possible.nnnResultsnSixty-eight studies were included. Fourteen of 29 prebiotic studies and 13 of 26 synbiotic studies reported a significant decrease in ≥1 marker of systemic inflammation. Eight studies compared prebiotic and synbiotic supplementation, 2 of which reported a decrease in inflammation with synbiotics only, with 1 reporting a greater anti-inflammatory effect with synbiotics than with prebiotics alone. Meta-analyses indicated that prebiotics reduce C-reactive protein (CRP) [standardized mean difference (SMD): -0.60; 95% CI: -0.98, -0.23], and synbiotics reduce CRP (SMD: -0.40; 95% CI: -0.73, -0.06) and tumor necrosis factor-α (SMD -0.90; 95% CI: -1.50, -0.30).nnnConclusionsnThere is significant heterogeneity of outcomes in studies examining the effect of prebiotics and synbiotics on systemic inflammation. Approximately 50% of included studies reported a decrease in ≥1 inflammatory biomarker. The inconsistency in reported outcomes may be due to heterogeneity in study design, supplement formulation, dosage, duration, and subject population. Nonetheless, meta-analyses provide evidence to support the systemic anti-inflammatory effects of prebiotic and synbiotic supplementation.

Macrophage activation, age and sex effects of immunometabolism in obese asthma

Obese asthma is characterised by infiltration of adipose tissue by activated macrophages and mast cells. The aim of this study was to examine the age and sex effects of immunometabolism in obese asthma. Obese and non-obese asthmatic children and adults underwent spirometry, body composition assessment by dual energy X-ray absorptiometry and measurement of serum soluble CD163 (sCD163), tryptase, C-reactive protein (CRP) and other adipocytokines. Plasma CRP (p<0.01) and leptin (p<0.01) were elevated in obese asthmatic adults, and sCD163 (p=0.003) was elevated in obese asthmatic children. We observed significantly higher sCD163 in obese female children compared to obese female adults and male children, and higher CRP in obese female adults compared to obese male children and adults. Serum tryptase concentrations were not significantly different across age groups. sCD163 positively correlated with the proportion of android fat in obese female children (r=0.70, p=0.003) and obese female adults (r=0.65, p=0.003). In obese female children, sCD163 was inversely associated with forced expiratory volume in 1u2009su2009% predicted (r=−0.55, p=0.02) and was positively associated with the Asthma Control Questionnaire (r=0.57, p=0.02). Obese children with asthma have sex-specific macrophage activation, which may contribute to worse asthma control and lung function. The heterogeneous systemic inflammatory profile across age and sex suggests the existence of sub-phenotypes in obese asthma at the molecular level. Macrophage activation is a determinant of pro-inflammatory effects of immunometabolism in childhood obese asthma http://ow.ly/ArCAH