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In patients with asthma who had elevated blood eosinophil levels and marginal asthma control despite treatment with high-dose inhaled or oral glucocorticoids, asthma exacerbations were reduced in those receiving a monoclonal antibody that binds to and inactivates interleukin-5. Severe asthma affects less than 10% of patients with asthma and is associated with substantial morbidity and mortality and a large fraction of the health care costs among patients with asthma. 1 – 3 Despite available care, recurrent asthma exacerbations are a major issue in a subgroup of patients with eosinophilic airway inflammation. 4 – 6 Mepolizumab, a humanized monoclonal antibody against interleukin-5, selectively inhibits eosinophilic inflammation 7 , 8 and reduces the number of eosinophils in both sputum and blood, resulting in a reduction in exacerbations and in the need for treatment with systemic glucocorticoids. 7 – 12 In the Dose Ranging Efficacy and Safety with Mepolizumab . . .

Case finding for symptomatic adults with undiagnosed asthma or COPD was coupled with a randomized trial to compare pulmonologist-directed and usual care. Pulmonologist-directed care led to less health care utilization.

Clinical control is difficult to achieve in obese patients with asthma. Bariatric surgery has been recommended for weight loss and to improve asthma control; however, the benefits of nonsurgical interventions have been poorly investigated. To examine the effect of exercise training in a weight-loss program on asthma control, quality of life, inflammatory biomarkers, and lung function. Fifty-five obese patients with asthma were randomly assigned to either a weight-loss program plus exercise (WL + E group, n = 28) or a weight-loss program plus sham (WL + S group, n = 27), where the weight-loss program included nutrition (caloric restriction) and psychological therapies. The WL + E group incorporated aerobic and resistance muscle training, whereas the WL + S group incorporated breathing and stretching exercises. The primary outcome was clinical improvement in asthma control over 3 months. Secondary outcomes included quality of life, lung function, body composition, aerobic capacity, muscle strength, and inflammatory/antiinflammatory biomarkers. After 3 months, 51 patients were analyzed. Compared with the WL + S group, the WL + E group demonstrated improved clinical control scores (median [25th to 75th percentile], -0.7 [-1.3 to -0.3] vs. -0.3 [-0.9 to 0.4]; P = 0.01) and greater weight loss (mean ± SD, -6.8% ± 3.5 vs. -3.1% ± 2.6; P < 0.001) and aerobic capacity (median [25th to 75th percentile], 3.0 [2.4 to 4.0] vs. 0.9 [-0.3 to 1.3] ml O  × kg  × min ; P < 0.001). These improvements in the WL + E group were also accompanied by improvements in lung function, antiinflammatory biomarkers, and vitamin D levels, as well as reductions in airway and systemic inflammation. Adding exercise to a short-term weight-loss program should be considered as a useful strategy for achieving clinical control of asthma in obese patients. Clinical trial registered with www.clinicaltrials.gov (NCT 02188940).

BackgroundHypersensitivity to house dust mite (HDM) allergens is a common cause of allergic asthma symptoms and can be effectively treated with allergy immunotherapy (AIT).ObjectiveTo investigate whether genetic and type 2 (T2) inflammatory biomarkers correlate with disease severity in subjects with allergic asthma, and whether this can be modified by AIT.MethodsMITRA (NCT01433523) was a phase III, randomised, double-blind, placebo-controlled trial of HDM sublingual immunotherapy (SLIT)-tablets in adults with HDM allergic asthma. Post hoc analyses of the study population (N=742) evaluated associations between T2 inflammatory (blood eosinophils, eosinophil cationic protein (ECP), total IgE and tryptase) and genetic (single-nucleotide polymorphisms, SNP) biomarkers (n=582) for the primary study endpoint (time to first moderate/severe asthma exacerbation). SNP associations were verified in HDM-positive subgroup from an independent 3-year Severe Asthma Research Programme (SARP3) subject cohort.ResultsAn increased asthma exacerbation risk in subjects homozygous for SNP rs7216389 (chromosomal locus 17q12-21) was reduced (p=0.037) by treatment with HDM SLIT (HR=0.37 (95% CI 0.22 to 0.64), p<0.001). The associations between exacerbation risk and 17q12-21 SNPs were replicated in the SARP3 HDM-positive subgroup. High levels of T2 biomarkers were associated with increased risk of asthma exacerbations in the placebo group. HDM SLIT-tablet treatment reduced this risk (blood eosinophils: HR=0.50 (95% CI 0.30 to 0.85); ECP: HR=0.45 (95% CI 0.29 to 0.87); tryptase: HR=0.45 (95% CI 0.25 to 0.80)). The treatment effect was higher (p=0.006) for subjects with a higher number of elevated T2 biomarkers.ConclusionsHDM SLIT-tablet AIT is efficacious in HDM-sensitised asthma subjects with a genetic asthma predisposition and/or an underlying T2 endotype.Trial registration number NCT01433523.

In patients with asthma, an active bronchodilator improved lung function; two inactive treatments and no intervention had no effect. The same patients reported subjective improvements after both inactive and active interventions but not after no intervention at all. Placebo effects (i.e., benefits resulting from simulated treatment or the experience of receiving care) are reported to improve signs and symptoms of many diseases in clinical trials and in clinical practice. 1 On this basis, the accepted standards for clinical-trial design specify that the effects of active treatment should ideally be compared with the effects of placebo. 2 , 3 Despite this common practice, it is unclear whether placebo effects observed in clinical trials (or those that presumably occur in clinical care) influence both objective and subjective outcomes and whether placebo effects differ from the natural course of disease or regression to the . . .

BackgroundThe benefits of aerobic training for the main features of asthma, such as bronchial hyperresponsiveness (BHR) and inflammation, are poorly understood. We investigated the effects of aerobic training on BHR (primary outcome), serum inflammatory cytokines (secondary outcome), clinical control and asthma quality of life (Asthma Quality of Life Questionnaire (AQLQ)) (tertiary outcomes).MethodsFifty-eight patients were randomly assigned to either the control group (CG) or the aerobic training group (TG). Patients in the CG (educational programme+breathing exercises (sham)) and the TG (same as the CG+aerobic training) were followed for 3 months. BHR, serum cytokine, clinical control, AQLQ, induced sputum and fractional exhaled nitric oxide (FeNO) were evaluated before and after the intervention.ResultsAfter 12 weeks, 43 patients (21 CG/22 TG) completed the study and were analysed. The TG improved in BHR by 1 doubling dose (dd) (95% CI 0.3 to 1.7 dd), and they experienced reduced interleukin 6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1) and improved AQLQ and asthma exacerbation (p<0.05). No effects were seen for IL-5, IL-8, IL-10, sputum cellularity, FeNO or Asthma Control Questionnaire 7 (ACQ-7; p>0.05). A within-group difference was found in the ACQ-6 for patients with non-well-controlled asthma and in sputum eosinophil and FeNO in patients in the TG who had worse airway inflammation.ConclusionsAerobic training reduced BHR and serum proinflammatory cytokines and improved quality of life and asthma exacerbation in patients with moderate or severe asthma. These results suggest that adding exercise as an adjunct therapy to pharmacological treatment could improve the main features of asthma.Trial registration numberNCT02033122.

Abstract Rationale Allergen exposure in sensitized individuals with asthma interacts with viruses to increase the risk of asthma exacerbation. Objectives To evaluate the use of house dust mite–impermeable bedding and its impact on severe asthma exacerbations in children. Methods We randomized mite-sensitized children with asthma (ages 3–17 yr) after an emergency hospital attendance with an asthma exacerbation to receive mite-impermeable (active group) or control (placebo group) bed encasings. Measurements and Main Results Over a 12-month intervention period, the occurrence of severe asthma exacerbations was investigated. Of 434 children with asthma who consented, 286 (mean age, 7.7 yr; male sex, 65.8%) were mite sensitized, and 284 were randomized (146 to the active group and 138 to the placebo group). At 12 months, significantly fewer children in the active group than in the placebo group had attended the hospital with an exacerbation (36 [29.3%] of 123 vs. 49 [41.5%] of 118; P = 0.047). In the multivariable analysis, the risk of emergency hospital attendance was 45% lower in the active group (hazard ratio, 0.55; 95% confidence interval [CI], 0.36–0.85; P = 0.006) than in the placebo group. The annual rate of emergency hospital attendance with exacerbations was 27% lower in the active group than in the placebo group, but this did not reach significance (estimated marginal mean [95% CI], active, 0.38 [0.26–0.56] vs. placebo, 0.52 [0.35–0.76]; P = 0.18). No difference between the groups in the risk of prednisolone use for exacerbation was found (hazard ratio, 0.82; 95% CI, 0.58–1.17; P = 0.28). Conclusions Mite-impermeable encasings are effective in reducing the number of mite-sensitized children with asthma attending the hospital with asthma exacerbations but not the number requiring oral prednisolone. This simple measure may reduce the health care burden of asthma exacerbations in children. Clinical trial registered with www.isrctn.com (ISRCTN 69543196).

Rationale Knowledge about the clinical importance of patient-reported outcome measures (PROMs) in severe asthma is limited. Objectives To assess whether and to what extent asthma exacerbations affect changes in PROMS over time and asthma-specific PROMs can predict exacerbations in adult patients with severe asthma in usual care. Methods Data of 421 patients with severe asthma (62% female; mean age 51.9 ± 13.4 years; mean FEV 1 67.5 ± 21.3%pred) from the U-BIOPRED cohort were analyzed. The included PROMs were: Asthma Control Questionnaire (ACQ5); Asthma Quality of Life Questionnaire (AQLQ); Hospital Anxiety and Depression scale (HADS); Epworth Sleepiness Scale (ESS); Medication Adherence Report Scale (MARS); Sino-Nasal Outcomes Test (SNOT20). Participants were assessed at baseline and after 12–18 months of usual care. Results PROMs showed very weak to weak correlations with clinical characteristics such as age, body mass index, FEV 1 , FeNO and eosinophilic cell count. Patients presenting no exacerbations during follow-up showed a statistically significant improvement in all PROMs (except for MARS), whereas individuals experiencing > 2 exacerbations showed a deterioration. Baseline ACQ5 was a predictor of exacerbations with an AUC of 0.590 (95%CI 0.514–0.666). Conclusions The association of PROMs with clinical measures was poor in severe asthmatics. Moreover, PROMs were prone to changes in usual care, with exacerbations playing a key role. PROMs need to be systematically evaluated in severe asthma to improve clinical care based on specific patient’s needs.

Increases in symptoms may occur before exacerbations fully develop. In a trial involving adults and adolescents, quadrupling the dose of inhaled glucocorticoids when symptoms occurred resulted in fewer severe asthma exacerbations than not increasing the dose. Increases in symptoms may occur before exacerbations fully develop. In two trials, when symptoms occurred, the dose of inhaled glucocorticoids was increased by a factor of 5 (pediatric trial) or 4 (adult trial). There was no benefit, and perhaps some harm, in children, and a modest benefit in adults.

Clinical decision support (CDS) tools leveraging electronic health records (EHRs) have been an approach for addressing challenges in asthma care but remain under-studied through clinical trials. To assess the effectiveness and efficiency of Asthma-Guidance and Prediction System (A-GPS), an Artificial Intelligence (AI)-assisted CDS tool, in optimizing asthma management through a randomized clinical trial (RCT). This was a single-center pragmatic RCT with a stratified randomization design conducted for one year in the primary care pediatric practice of the Mayo Clinic, MN. Children (<18 years) diagnosed with asthma receiving care at the study site were enrolled along with their 42 primary care providers. Study subjects were stratified into three strata (based on asthma severity, asthma care status, and asthma diagnosis) and were blinded to the assigned groups. Intervention was a quarterly A-GPS report to clinicians including relevant clinical information for asthma management from EHRs and machine learning-based prediction for risk of asthma exacerbation (AE). Primary endpoint was the occurrence of AE within 1 year and secondary outcomes included time required for clinicians to review EHRs for asthma management. Out of 555 participants invited to the study, 184 consented for the study and were randomized (90 in intervention and 94 in control group). Median age of 184 participants was 8.5 years. While the proportion of children with AE in both groups decreased from the baseline (P = 0.042), there was no difference in AE frequency between the two groups (12% for the intervention group vs. 15% for the control group, Odds Ratio: 0.82; 95%CI 0.374-1.96; P = 0.626) during the study period. For the secondary end points, A-GPS intervention, however, significantly reduced time for reviewing EHRs for asthma management of each participant (median: 3.5 min, IQR: 2-5), compared to usual care without A-GPS (median: 11.3 min, IQR: 6.3-15); p<0.001). Mean health care costs with 95%CI of children during the trial (compared to before the trial) in the intervention group were lower than those in the control group (-$1,036 [-$2177, $44] for the intervention group vs. +$80 [-$841, $1000] for the control group), though there was no significant difference (p = 0.12). Among those who experienced the first AE during the study period (n = 25), those in the intervention group had timelier follow up by the clinical care team compared to those in the control group but no significant difference was found (HR = 1.93; 95% CI: 0.82-1.45, P = 0.10). There was no difference in the proportion of duration when patients had well-controlled asthma during the study period between the intervention and the control groups. While A-GPS-based intervention showed similar reduction in AE events to usual care, it might reduce clinicians' burden for EHRs review resulting in efficient asthma management. A larger RCT is needed for further studying the findings. ClinicalTrials.gov Identifier: NCT02865967.