Asthma Control Questionnaire Score Research Articles

Benralizumab in Severe Eosinophilic Asthma and Chronic Rhinosinusitis with Nasal Polyps: The Real-World, Multi-Country RANS Observational Study.

Real-world evidence of benralizumab effectiveness on nasal polyps (NP) and asthma outcomes in patients with severe eosinophilic asthma (SEA) and comorbid chronic rhinosinusitis with NP are limited. The objective of this study was to assess NP and asthma outcomes in benralizumab-treated patients with SEA and comorbid NP in a real-world setting. RANS was a retrospective, multi-country observational study (ClinicalTrials.gov: NCT05180357) using medical chart reviews of adults with SEA and comorbid NP. Total NP Score (NPS), SinoNasal Outcome Test-22 (SNOT-22) total score, annualized exacerbation rate (AER), and 6-item Asthma Control Questionnaire (ACQ-6) and Asthma Control Test (ACT) scores during the 12 months pre-index (baseline) and post-index (follow-up) were measured. Clinically meaningful improvement from baseline following treatment, in terms of total NPS (≥1-point reduction), SNOT-22 total (≥8.9-point reduction), ACQ-6 (≥0.5-point reduction) or ACT (≥3-point increase) scores, were reported. A total of 233 patients were included. Baseline mean (standard deviation [SD]) NPS and SNOT-22 total scores were 3.8 (2.4) and 47.5 (22.6), respectively. The mean change (95% confidence interval [CI]) from baseline was -1.2 (-1.7, -0.6) for NPS, and -19.8 (-23.6, -15.9) for SNOT-22. The AER (95% CI) was 1.2 (0.96, 1.41) at baseline and 0.2 (0.13, 0.28) at follow-up. Mean (SD) ACQ-6 and ACT scores were 1.6 (1.3) and 15.0 (5.2) at baseline and 0.8 (1.0) and 22.0 (3.9) at follow-up, respectively. The proportion of patients who achieved clinically meaningful improvements in NPS, SNOT-22 total, ACQ-6, and ACT scores was 49.1%, 67.6%, 56.6%, and 81.1%, respectively. In this real-world study, improvements in NP and asthma outcomes in patients with SEA and comorbid NP were observed during the 12 months following benralizumab initiation.

Suboptimal Response to Biologics in Severe Asthma—A Marker of Humoral Immunodeficiencies

BackgroundAsthmatic patients with antibody deficiencies (AD) have more severe disease and higher risk of exacerbations. No data exists about the efficacy of biologics in severe asthma (SA) patients with AD.The objective of this study was to evaluate the efficacy of biologics in SA patients with and without AD. MethodsA case-control real-life study was conducted including 68 patients divided in two groups: group 1 with SA-AD and group 2 with SA. ResultsTreatment by biologics for 6 months was effective to decrease the number of exacerbations, hospitalizations, and emergency department (ED) visits, to improve the Asthma Control Questionnaire (ACQ) score and proved a systemic corticosteroid sparing effect. Despite benefits, the number of exacerbations, hospitalizations, and ED visits, the mean ACQ score, and the cumulative dose of systemic corticosteroids remain higher in group 1 vs 2, with lower lung function parameters. The rates of responses were inferior in group 1 vs 2 with a decrease by ≥50% of exacerbation rate in 76% vs 97% of patients (p=.006), no hospitalization in 44% vs 91% of patients (p<.001), no ED visit 56% vs 82% of patients (p=.018), significant improvement of ACQ score by ≥0.5 in 68% vs 100% of patients (p<.001), and increase of forced expiratory volume in the first second by >10% in 32% vs 65% of patients (p=.007). ConclusionDespite evident benefits, SA patients with AD have suboptimal responses to biologics compared to those immunocompetent. A multidisciplinary approach is necessary to optimize the management of these patients in practice.

Evidence for 2 clusters among patients with noneosinophilic asthma

BackgroundAlthough asthma is often seen as an eosinophilic disease associated with atopy, patients with noneosinophilic asthma represent a substantial part of the population with asthma. ObjectiveTo apply an unsupervised clustering method in a cohort of 588 patients with noneosinophilic asthma (sputum eosinophils < 3%) recruited from an asthma clinic of a secondary care center. MethodsOur cluster analysis of the whole cohort identified 2 subgroups as cluster 1 (n = 417) and cluster 2 (n = 171). ResultsCluster 1 comprised a predominantly female group with late disease onset, a low proportion of atopy (24%), and a substantial smoking history (53%). In this cluster, treatment burden was low (<50% of inhaled corticosteroid users); asthma control and quality of life were poor, with median Asthma Control Test, Asthma Control Questionnaire, and Asthma Quality of Life scores of 16, 1.7, and 4.5, respectively, whereas lung function was preserved with a median postbronchodilation forced expiratory volume in 1 second of 93% predicted. Cluster 2 was a predominantly male group, almost exclusively comprising patients with atopy (99%) with early disease onset and a moderate treatment burden (median inhaled corticosteroids dose 800 µg/d equivalent beclomethasone). In cluster 2, asthma was partially controlled, with median Asthma Control Test and Asthma Control Questionnaire scores reaching 18 and 1.3, respectively, and lung function well preserved with a median postbronchodilation of 95% predicted. Although systemic and airway neutrophilic inflammation was the dominant pattern in cluster 1, cluster 2 essentially comprised paucigranulocytic asthma with moderately elevated fraction exhaled nitric oxide. ConclusionNoneosinophilic asthma splits into 2 clusters distinguishing by disease onset, atopic status, smoking history, systemic and airway inflammation, and disease control and quality of life.

Super-responder and clinical remission in patients with asthma on treatment with single biologic therapy or cycling therapy using dupilumab in a real-world setting.

Regarding the therapeutic target in asthma, super-responder status (SR) is a status without systemic corticosteroids. Recently, clinical remission (CR), being a status of prolonged absence of asthma symptoms without systemic corticosteroids and/or normal pulmonary function, has gained attention as a new therapeutic target in asthma. Here, we examined the percentage and features of asthma patients on treatment with dupilumab showing SR and CR. 49 asthma patients used subcutaneous dupilumab for >1 year between April 2019 and November 2022. The status of SR and CR for 1 year was evaluated. Patients without any maintenance oral corticosteroids and exacerbations requiring systemic corticosteroids were classified as SR. CR was defined using three definitions based on changes in asthma symptoms and pulmonary function in addition to achieving SR for 1 year: CR without pulmonary function criteria (CR w/o F), fulfilment of asthma symptom improvement (asthma control questionnaire score <0.75 or asthma control test score ≥23); and CR-70 or CR-80, pulmonary function improvement (%forced expiratory volume in 1 second ≥70% or ≥80%) in addition to achieving CR w/o F, respectively. 38 (77.6%), 22 (44.9%), 13 (26.5%), 12 (24.5%) of patients had SR, CR w/o F, CR-70, and CR-80, respectively. Severe eosinophilic chronic rhinosinusitis was significantly more found in patients with SR and CR based on all three definitions than in those without. This study identified the percentage and features of patients on treatment with dupilumab showing SR and CR in a real-world setting. The outcome beyond CR on biologic treatment should be clarified.

Effect of Individual Patient Characteristics and Treatment Choices on Reliever Medication Use in Moderate-Severe Asthma: A Poisson Analysis of Randomised Clinical Trials.

Even though increased use of reliever medication, including short-acting beta agonists (SABA), provides an indirect measure of symptom worsening, there have been limited efforts to assess how different patterns of reliever use correlate with symptom control and future risk of exacerbations. Here, we evaluate the effect of individual baseline characteristics on reliever use in patients with moderate-severe asthma on regular maintenance therapy with fluticasone propionate (FP) or combination therapy with fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR). A drug-disease model describing the number of 24-h puffs and overnight occasions was developed with data from five clinical studies (N = 6212). The model was implemented using a nonlinear mixed effects approach and a Poisson function, considering clinical and demographic baseline characteristics. Goodness of fit and model predictive performance were assessed. Heatmaps were created to summarise the effect of concurrent baseline factors on reliever utilisation. The final model accurately described individual patterns of reliever use, which is significantly increased with time since diagnosis, smoking, higher Asthma Control Questionnaire (ACQ-5) score and higher body mass index (BMI) at baseline. Whilst the number of puffs decreases slowly after an initial drop relative to the start of treatment, exacerbating patients utilise significantly more reliever than those who do not exacerbate. The mean effect of FP/SAL (median dose: 250/50μg BID) on reliever use was slightly higher than that of BUD/FOR (median dose: 160/4.5μg BID), i.e. a 75.3% vs 69.3% reduction in reliever use, respectively. The availability of individual-level patient data in conjunction with a parametric approach enabled the characterisation of interindividual differences in the patterns of reliever use in patients with moderate-severe asthma. Taken together, individual demographic and clinical characteristics, as well as exacerbation history, can be considered an indicator of the degree of asthma control. High SABA reliever use suggests suboptimal clinical management of patients on maintenance therapy.

Efectividad del consumo de frutas y verduras sobre los síntomas y episodios asmáticos: Una revisión sistemática

Introduction: Asthma is a chronic disease, so it is essential to adhere to good treatment and follow the recommendations appropriatel, Objective: to determine the effectiveness of recommending the consumption of fruits and vegetables (FV) on the reduction of asthma attacks, including Asthma Control Questionnaire (ACQ) and Interleukin-6 (IL-6) scores, Methods: The search was performed in the electronic databases: Pubmed, Web of Science, Scopus and Cochrane Library. Studies were included that applied at least one intervention or recommendation for FV consumption in patients with asthma, airway inflammation and other associated problems. Two independent reviewers assessed the selected studies and measured risk of bias. Relevant information was summarized and combined with random effect meta-analysis (DerSimonian-Laird). RevMan 5.4 was applied. Finally, the degree of recommendation was evaluated with GRADE-pro, Results: Three randomized clinical trials (RCTs) totaling 197 subjects were identified. A decrease in asthma symptoms was observed according to the ACQ, but not statistically significant (-0.20; 95% CI: -0.59, 0.19). Furthermore, interleukin-6 also did not present significance 0.20 (95% CI: -0.06, 0.46). The nature of the design of the meta-analyzed studies allows a high and moderate degree of recommendation to be scored, respectively. The findings in general suggest that FV intake can generate favorable changes in asthma and its prevention. However, this study failed to demonstrate this statistically, Conclusion: It is necessary that more RCTs be carried out to increase the power of the evidence and update the available information.

Low Serum IL-18 Levels May Predict the Effectiveness of Dupilumab in Severe Asthma.

Objective Dupilumab, a monoclonal antibody specific for the human interleukin (IL)-4 receptor α, is used to treat severe asthma, especially in patients with elevated blood eosinophil counts and fractional exhaled nitric oxide (FeNO). The therapeutic response to dupilumab is highly variable. In this study, we explored new serum biomarkers to accurately predict the effect of dupilumab and examine the effect of dupilumab based on changes in the clinical parameters and cytokine levels. Methods Seventeen patients with severe asthma treated with dupilumab were enrolled. Responders, defined as those with a >0.5-point decrease in the Asthma Control Questionnaire (ACQ) score after 6 months of treatment, were included. Results There were 10 responders and 7 non-responders. Serum type 2 cytokines were equivalent between responders and non-responders; the baseline serum IL-18 level was significantly lower in responders than in non-responders (responders, 194.9±51.0 pg/mL; non-responders, 323.4±122.7 pg/mL, p=0.013). The cut-off value of IL-18 at 230.5 pg/mL could be used to distinguish non-responders from responders (sensitivity 71.4, specificity 80.0, p=0.032). Conclusion A low baseline serum IL-18 level may be a useful predictor of an unfavorable response to dupilumab in terms of the ACQ-6.

Effect of Buteyko breathing technique on clinical and functional parameters in adult patients with asthma: a randomized, controlled study

BackgroundThe established therapy of asthma might be supported by additional non-pharmaceutical measures, such as the Buteyko breathing technique (BBT); however, the available data are mixed. To clarify the effects of BBT in patients with asthma, we investigated whether it led to clinical improvements with correlation to functional parameters.MethodsUsing a randomized, controlled design, we studied two groups (n = 30 each) of patients with asthma under either BBT or usual therapy (UT) w/o BBT over a period of 3 months. The primary outcome comprised the voluntary control pause (CP) after 3 months, secondary outcomes an additional breathhold parameter, forced expiratory volume in 1 s (FEV1), capnovolumetry, exhaled nitric oxide (FeNO), Asthma Control Questionnaire (ACQ) and Nijmegen Questionnaire (NQ), and the use of medication (β2-agonists; inhaled corticosteroids, ICS).ResultsCP showed significant time-by-group interaction [F(1,58.09) = 28.70, p < 0.001] as well as main effects for study group [F(1,58.27) = 5.91, p = 0.018] and time [F(1,58.36) = 17.67, p < 0.001]. ACQ and NQ scores were significantly (p < 0.05 each) improved with BBT. This was associated with reductions in the use of β2-agonists and ICS (p < 0.05 each) by about 20% each. None of these effects occurred in the UT group. While FEV1 and the slopes of the capnovolumetric expiratory phases 2 and 3 did not significantly change, the capnovolumetric threshold volume at tidal breathing increased (p < 0.05) with BBT by about 10 mL or 10%, compared to baseline, suggesting a larger volume of the central airways. No significant changes were seen for FeNO.ConclusionsBBT was clinically effective, as indicated by the fact that the improvement in symptom scores and the small increase in bronchial volume occurred despite the significant reduction of respiratory pharmacotherapy. As the self-controlled Buteyko breathing therapy was well-accepted by the participants, it could be considered as supporting tool in asthma therapy being worth of wider attention in clinical practice.Trial registration Retrospectively registered on 10 March 2017 at ClinicalTrials.gov (NCT03098849).

Real-World Safety and Effectiveness of Benralizumab in Japanese Patients with Severe Asthma: A Multicenter Prospective Observational Study.

This study aimed to demonstrate whether benralizumab maintained the safety and effectiveness profiles established in randomized controlled trials among all patients with severe uncontrolled asthma initially prescribed benralizumab in the real-world setting in Japan. This was a prospective, observational, multicenter post-marketing study (ClinicalTrial.gov, NCT03588546). The safety and tolerability of benralizumab over 1 year were assessed by the incidence of adverse events (AEs), serious AEs, adverse drug reactions (ADRs), and serious ADRs. Patient background characteristics indicating a more frequent onset of ADRs with benralizumab were explored. The main effectiveness assessment was the change in Asthma Control Questionnaire-5 (ACQ-5) score from baseline. Patients with baseline ACQ-5 scores ≥1.5 were defined as having severe uncontrolled asthma. In total, 632 patients were evaluated for safety and 274 for effectiveness; 139 patients were included in the severe uncontrolled asthma subgroup. ADRs were reported in 12.7% and serious AEs in 13.0% of patients. Serious infections occurred in 3.8%, serious hypersensitivity in 0.3%, and malignancy in 0.3% of patients. No helminthic infections occurred. In the effectiveness population, benralizumab improved the mean (standard deviation [95% confidence interval]) ACQ-5 score by -1.16 (1.40 [-1.36, -0.96]) from baseline; forced expiratory volume in 1 second by 0.151 (0.440 [0.09, 0.21]) L; and Mini-Asthma Quality of Life questionnaire score by 1.16 (1.29 [0.94, 1.38]) at the last observation. The annual asthma exacerbation rate was 0.42. A greater ACQ-5 score improvement was observed among patients with eosinophilic asthma characteristics. No new safety concerns were raised, and patients experienced benefits consistent with previous studies of benralizumab, thus supporting the use of benralizumab for the add-on maintenance treatment of patients with eosinophilic severe uncontrolled asthma.

Characteristics and outcomes of patients enrolled in the Connect 360 benralizumab patient support programme in the UK: a retrospective cohort study

BackgroundPatient support programmes (PSPs) allow patients with chronic diseases to receive treatment and support at home. This study describes the Connect 360 PSP delivery and impact on patient-reported outcomes, satisfaction...

Application of different counseling strategies for better adult asthma control

Objective We aimed to compare the effectiveness of three distinct counseling methods to determine the most effective approach. Methods In this prospective cohort study with a two-month follow-up, A group of non-smoking adults, aged 19-60 years, were randomly collected at outpatients clinic with prior asthma diagnosis, based on the forced expiratory volume in one seconds to forced vital capacity ratio (FEV1/FVC) and the guidelines outlined by the Global Initiative for Asthma (GINA), At the baseline assessment, all patients, underwent FEV1/FVC measurements, asthma symptom evaluations using Asthma Control Test (ACT), Asthma Control Questionnaire (ACQ), and GINA symptoms control assessment questionnaire, and assessment of pressurized metered-dose inhaler (pMDI) usage. The patients were divided into three groups, each assigned a distinct counseling strategy: traditional verbal counseling, advanced counseling utilizing the Asthma smartphone-application, and a combination of advanced-verbal counseling. We conducted a two-month monitoring period for all three groups. Results Significant differences (p < .001) were observed among the three counseling groups in ACT, FEV1/FVC ratio, and GINA symptoms control assessment scores from the first month to the second month visit. Regarding ACQ, the study unveiled a noteworthy disparity in ACQ scores during the second week, with a significant difference (p = .025) observed between the verbal and advanced-verbal counseling groups. Similarly, a significant difference (p = .016) was noted between the advanced counseling group and the advanced-verbal counseling groups. Conclusion The study findings indicate that the combining advanced-verbal counseling by incorporating the Asthma smartphone-application alongside traditional verbal counseling is a more effective approach for improving asthma control in adults.

Reduction of daily maintenance inhaled corticosteroids in patients with severe eosinophilic asthma treated with benralizumab (SHAMAL): a randomised, multicentre, open-label, phase 4 study

Stepwise intensification of inhaled corticosteroids (ICS) is routine for severe eosinophilic asthma, despite some poor responses to high-dose ICS. Dose reductions are recommended in patients responding to biologics, but little supporting safety evidence exists. SHAMAL was a phase 4, randomised, open-label, active-controlled study done at 22 study sites in four countries. Eligible participants were adults (aged ≥18 years) with severe eosinophilic asthma and a five-item Asthma Control Questionnaire score below 1·5 and who received at least three consecutive doses of benralizumab before screening. We randomly assigned patients (3:1) to taper their high-dose ICS to a medium-dose, low-dose, and as-needed dose (reduction group) or continue (reference group) their ICS-formoterol therapy for 32 weeks, followed by a 16-week maintenance period. The primary endpoint was the proportion of patients reducing their ICS-formoterol dose by week 32. The primary outcome was assessed in the reduction group, and safety analyses included all randomly assigned patients receiving study treatment. This study is registered at ClinicalTrials.gov, NCT04159519. Between Nov 12, 2019, and Feb 16, 2023, we screened and enrolled in the run-in period 208 patients. We randomly assigned 168 (81%) to the reduction (n=125 [74%]) and reference arms (n=43 [26%]). Overall, 110 (92%) patients reduced their ICS-formoterol dose: 18 (15%) to medium-dose, 20 (17%) to low-dose, and 72 (61%) to as-needed only. In 113 (96%) patients, reductions were maintained to week 48; 114 (91%) of patients in the reduction group had zero exacerbations during tapering. Rates of adverse events were similar between groups. 91 (73%) patients had adverse events in the reduction group and 35 (83%) in the reference group. 17 patients had serious adverse events in the study: 12 (10%) in the reduction group and five (12%) in the reference group. No deaths occurred during the study. These findings show that patients controlled on benralizumab can have meaningful reductions in ICS therapy while maintaining asthma control. AstraZeneca.

Increased expression of ficolin-1 is associated with airway obstruction in asthma

BackgroundThe activated complement cascade is involved in asthmatic airway inflammation. Ficolins are essential for innate immunity and can activate the complement lectin pathway. Despite this, the significance of ficolins in asthma has yet to be determined. This study aimed to explore the presence of ficolins in individuals with asthma and to determine the relationship between ficolins and clinical characteristics.MethodsFor the study, 68 asthmatic patients and 30 healthy control subjects were recruited. Enzyme-linked immunosorbent assay was used to determine plasma ficolin-1, ficolin-2, and ficolin-3 concentrations both before and after inhaled corticosteroid (ICS) therapy. Further, the associations of plasma ficolin-1 level with pulmonary function and asthma control questionnaire (ACQ) score were examined in the asthma patients.ResultsPatients with asthma exhibited significantly elevated plasma ficolin-1 levels (median, 493.9 ng/mL; IQR, 330.2–717.8 ng/mL) in comparison to healthy controls (median, 330.6 ng/mL; IQR, 233.8–371.1 ng/mL). After ICS treatment, plasma ficolin-1 (median, 518.1 ng/mL; IQR, 330.2–727.0 ng/mL) in asthmatic patients was significantly reduced (median, 374.7 ng/mL; IQR, 254.8–562.5 ng/mL). Additionally, ficolin-1 expressions in plasma were significantly correlated with pulmonary function parameters and ACQ score in asthmatic patients. Asthma patients with higher plasma ficolin-1 levels demonstrated poorer lung function than those with lower plasma ficolin-1 levels.ConclusionsThe results revealed that asthmatic patients had higher plasma ficolin-1 concentrations, which decreased after ICS treatment and were linked to their lung function, implying a potential involvement of ficolin-1 in asthma pathogenesis.

The efficacy of citalopram or escitalopram in patients with asthma and major depressive disorder

BackgroundMajor depressive disorder is common in people with asthma. Yet, few studies have evaluated depression treatment in those with asthma. ObjectiveTo explore the relationship between antidepressant use, depressive symptoms, and asthma control, pooled data from 3 randomized trials of either citalopram or escitalopram were assessed. MethodsLinear fixed effects and binary logistic regression analyses were conducted with between-subject covariates including treatment group, (original) study, and demographics. The within-subject effect of visit, and a treatment group–visit (between-within) interaction effect, were also evaluated. Analyses were repeated in a high asthma exacerbation subgroup having at least 3 oral corticosteroid bursts in the previous 12 months. Outcomes included the Hamilton rating scale for depression (HAM-D17), the 7-item asthma control questionnaire (ACQ), and oral corticosteroid use (yes or no). ResultsIn the pooled sample (n = 255), the antidepressant treatment group exhibited lower HAM-D17 overall (P ≤ .001) and a lower likelihood for oral corticosteroid use (P ≤ .001) relative to the placebo group. In the high-exacerbation subgroup (n = 96), treatment group participants had lower overall asthma control questionnaire (P = .004) and HAM-D17 scores (P ≤ .001), and a lower likelihood of oral corticosteroid use (P = .003), relative to placebo participants. All treatment group interaction effects were not significant. ConclusionCitalopram or escitalopram exhibited efficacy in reducing depressive symptoms and the need for rescue oral corticosteroids in patients with asthma and major depressive disorder. Future work should determine whether selective serotonin reuptake inhibitors are effective at improving asthma outcomes in those with asthma who are not depressed. Trial RegistrationClinicaltrials.gov Identifier: NCT00621946 and NCT01324700 (one study was conducted before ClinicalTrials.gov requirements).

Benralizumab in severe eosinophilic asthma in real life: confirmed effectiveness and contrasted effect on sputum eosinophilia versus exhaled nitric oxide fraction - PROMISE.

Randomised controlled trials have shown that benralizumab, an anti-interleukin-5 receptor monoclonal antibody, reduces exacerbations and oral corticosteroid dose and improves asthma control and lung function in severe eosinophilic asthma. The aim of this study was to confirm results of randomised controlled trials in real life in a population of 73 patients with severe eosinophilic asthma treated with benralizumab for at least 12 months. Patients underwent careful monitoring of asthma exacerbations, exhaled nitric oxide fraction, lung function, asthma control and quality of life questionnaire responses and sputum induction, and gave a blood sample at baseline, after 6 months and then every year. We found significant reductions in exacerbations (by 92%, p<0.0001) and oral corticosteroid dose (by 83%, p<0.001) after 6 months that were maintained over time, with 78% of patients able to stop oral corticosteroid therapy. Patients improved their Asthma Control Test (ACT) score (from 11.7±5.1 to 16.9±5.35, p<0.0001), Asthma Control Questionnaire (ACQ) score (from 2.88±1.26 to 1.77±1.32, p<0.0001) and Asthma Quality of Life Questionnaire score (+1.04, p<0.0001) at 6 months and this was maintained during follow-up. Only 35% and 43% of patients reached asthma control according to an ACT score ≥20 and ACQ score <1.5, respectively. We observed stable post-bronchodilation lung function over time and a significant reduction in sputum eosinophil count, with 85% of patients exhibiting sputum eosinophil counts <3% after 6 months (p<0.01) with no effect on exhaled nitric oxide fraction. In our real-life study, we confirm the results published in randomised controlled trials showing a sharp reduction in exacerbations and oral corticosteroid therapy, an improvement in asthma control and quality of life, and a dramatic reduction in sputum eosinophil count.

Psychometric evaluation of an electronic Asthma Symptom Diary for young children

BackgroundPatient-reported outcome measures that facilitate self-report by children are needed to reduce the bias of proxy report. We previously developed an electronic Pediatric Asthma Symptom Diary (ePASD) to assess the severity of daily asthma symptoms and proximal impacts in children aged 6–11 years with mild to severe asthma. The ePASD, administered via a digital application with visuals, sounds, and text, is uniquely designed to minimize the importance of reading skills on children’s ability to self-report accurately. Here, we describe the ePASD’s psychometric properties.MethodsNinety-one children aged 6–11 years with mild to severe asthma and their caregivers participated in 2 study visits, which consisted of training on the provisioned device and completing asthma-specific clinical outcome assessment (COA) questionnaires. The children self-completed the ePASD at home twice daily for 8 consecutive days. The scoring of the ePASD was guided by factor analyses, inter-item correlations, and internal consistencies. Reliability, discriminating ability, construct validity, and responsiveness were evaluated for ePASD items and candidate scores.ResultsAll COAs included in the study—the ePASD, Asthma Control Questionnaire (ACQ), Childhood Asthma Control Test, Pediatric Asthma Quality of Life Questionnaire–Standardized (PAQLQ[S]), and global ratings—demonstrated that the children exhibited few asthma-related symptoms and impacts at all timepoints, and consequently, showed little change over time. Internal consistencies (all Cronbach’s alphas ≥ 0.52) and test-retest reliabilities (all intraclass correlation coefficients ≥ 0.60) were largely satisfactory. Patterns of convergent and divergent correlations supported the construct validity of ePASD scores. The ePASD symptom scores correlated moderately to strongly with PAQLQ(S) Symptom scores (all correlations ≥ − 0.46) and with ACQ scores (all correlations ≥ 0.42), as predicted. Evidence of the discriminating ability of ePASD items and composite scores was demonstrated by known-groups analyses.ConclusionsThe ePASD is a reliable and valid measure of asthma symptoms and proximal impacts in children aged 6–11 years with mild, moderate, or severe asthma. These results lay the psychometric groundwork for use of the ePASD in future clinical trials for the management of pediatric asthma. An ongoing pediatric asthma treatment trial is anticipated to provide evidence of the ePASD’s responsiveness to change.

Efficacy of Bhramari pranayama and Om chanting on asthma control, quality of life, and airway inflammation in asthmatic children: an open-label randomized controlled trial

Objectives To explore the efficacy of combination of Bhramari pranayama and om chanting as an adjunct to standard pharmacological treatment on asthma control, quality of life, pulmonary function, and airway inflammation in asthmatic children. Methods Children (n = 110; 8–15 years) with uncontrolled or partly controlled asthma were recruited from the Pediatric Chest Clinic of All India Institute of Medical Sciences, New Delhi. Eligible participants were randomized to either home-based online Bhramari pranayama and om chanting plus standard treatment (YI + ST) group, or standard treatment (ST) alone group. Primary outcome measures were 12-week change in level of asthma symptom control; asthma control questionnaire (ACQ) score, spirometry indices, impulse oscillometry parameters, and pediatric asthma quality of life questionnaire (PAQLQ) score. Secondary outcome was a change in fractional exhaled nitric oxide (FeNO) levels at 12 weeks. Beginning from the enrollment, every participant was evaluated at 0, 2, 6, and 12 weeks. Results After 12 weeks of intervention, higher proportion (68.2%) of children were found to have controlled asthma symptoms in the YI + ST group as compared to ST group (38.5%) according to per protocol analysis (p = 0.03). When compared to ST group, children in YI + ST group showed significantly lower ACQ score, higher PAQLQ score and reduced FeNO levels. No significant changes were observed for the lung function parameters. Conclusion Children practicing Bhramari pranayama and om chanting for 12 weeks have better asthma symptom control, quality of life, and reduced airway inflammation than those taking standard pharmacotherapy alone.

Dupilumab efficacy in high sleep disturbance management among patients with type 2 asthma

BackgroundPatients with asthma often experience sleep disturbances. We assessed the 5-item Asthma Control Questionnaire (ACQ-5) score ≥2.5 as a useful threshold to identify patients with moderate-to-severe type 2 asthma and high sleep disturbance (HSD) and investigated dupilumab efficacy on clinical and sleep-related outcomes among patients with HSD. MethodsQUEST (NCT02414854) data were used in this post hoc analysis. A composite endpoint from validated patient-reported outcomes was developed to identify patients with HSD using sleep-related items from the ACQ-5, Asthma-Related Quality-of-Life Questionnaire, Rhino-Conjunctivitis Quality-of-Life Questionnaire, and Sino-Nasal Outcome Test-22. Impairment in at least 1 item was considered an indication of HSD. Change from baseline to Week 52 in nighttime symptoms, ACQ-5 score, lung function, annualized severe exacerbation rates (AER), and short-acting β-agonists use during treatment was used to assess dupilumab efficacy. ResultsIn type 2 asthma patients, 64% had HSD at baseline; of those with ACQ-5 ≥2.5 at baseline, 82% had HSD. In this population, dupilumab reduced nighttime symptoms and ACQ-5 score by 0.31 and 0.56 points, respectively, by Week 52 versus placebo, and led to a 66% reduction in AER during QUEST and 0.34 L improvement in pre-bronchodilator (pre-BD) forced expiratory volume in 1 s (FEV1) at Week 52. ConclusionA majority of patients with moderate-to-severe type 2 asthma with ACQ-5 ≥2.5 at baseline had HSD. Dupilumab reduced nighttime symptoms and exacerbations, and improved lung function, overall asthma control, and quality of life. Further studies are needed to confirm the association between ACQ-5 score ≥2.5 and higher sleep disturbance rates.

Efficacy, Safety, and Systemic Exposure of Once-Daily Indacaterol Acetate in Pediatric Asthma: A Randomized, Double-Blind, Controlled Dose-Finding Study.

Indacaterol acetate (IND), a long-acting β2-agonist in combination with mometasone furoate (MF), an inhaled corticosteroid (ICS), is being explored as a once-daily (od) treatment for asthma in children. This study examined the efficacy, safety, and systemic exposure of IND 75 µg and IND 150 µg in children with persistent asthma. In this Phase IIb, multicenter, randomized, double-blind, parallel-group study, pediatric patients (aged ≥6 to <12 years) with persistent asthma were randomized (1:1) to receive either IND 75 µg od or IND 150 µg od via Breezhaler® in combination with ICS background therapy. The primary endpoint was change from baseline in pre-dose trough forced expiratory volume in one second (FEV1) after two weeks of treatment. In total, 80 patients received IND 75 µg (n = 39) or IND 150 µg (n = 41). The study met its primary endpoint; both doses demonstrated improvements in pre-dose trough FEV1 from baseline to Day 14 (mean change [Δ]: 212 mL, IND 75 µg; 171 mL, IND 150 µg). The secondary spirometry parameters (post-dose FEV1 after 1-h, post-dose forced vital capacity; morning and evening peak expiratory flow) also improved. Overall, 36.1% in IND 75 μg group and 25% patients in IND 150 μg group achieved a decrease from baseline in Pediatric Interviewer-administered Asthma Control Questionnaire score of ≥0.5 units. A dose-dependent increase in plasma IND concentration was noted between the two groups. Both IND doses demonstrated an acceptable safety profile. Once-daily IND 75 μg and IND 150 μg via Breezhaler® in combination with background ICS therapy provided substantial bronchodilation in children with asthma and were well tolerated. Taken together, these clinical and systemic exposure findings support IND 75 μg as the most appropriate dose for evaluation in Phase III trials in combination with MF in pediatric asthma. ClinicalTrials.gov (NCT02892019; 08-Sep-2016).

Benralizumab and mepolizumab treatment outcomes in two severe asthma clinics.

This study compared the clinical outcomes of severe asthmatics treated with mepolizumab and benralizumab in a tertiary care severe asthma service setting. Patient data at baseline, six and 12 months were collected prospectively at two large tertiary hospital severe asthma clinics following treatment initiation. Two hundred and four patients received treatment with mepolizumab (117) or benralizumab (87). Baseline characteristics between groups were similar in regard to age, gender, body mass index, steroid dose and blood eosinophil count. However, the mepolizumab cohort had a higher Asthma Control Questionnaire Score (ACQ) at baseline (4.0 ± 1.1 vs. 3.6 ± 0.9, p = 0.018), accompanied by more frequent reliever medication usage and lower prebronchodilator FEV1 % (56.0 ± 20.1 vs. 63.8 ± 18.9, p = 0.008). After 6 months treatment, both treatments induced significant improvements in (i) ACQ of 2.3 ± 0.1 (p < 0.001), (ii) oral steroid requiring exacerbations (incident rate ratio 0.26 (0.18-0.37), p < 0.001) and (iii) FEV1 . However, the improvement in FEV1 was 0.18 (0.05-0.30) litres greater with benralizumab than with mepolizumab (p = 0.002) even when adjusting statistically for baseline differences between groups. These differences were even more pronounced at 12 months post-treatment initiation, when the improvement in exacerbation frequency with benralizumab was 64% greater than with mepolizumab (p = 0.01). Whilst both treatments significantly reduced the blood eosinophil count at 6 and 12 months, this reduction was substantially greater with benralizumab than mepolizumab (-260 cells/μL [-400 to -110, p = 0.001]). In this large group of severe eosinophilic asthmatics, mepolizumab and benralizumab both improved disease parameters. However, benralizumab treatment appeared significantly more effective than mepolizumab in reducing exacerbations, improving FEV1 and depleting blood eosinophils.