ACQ Score Research Articles

Early treatment response to mepolizumab predicts clinical remission in severe eosinophilic asthma

Mepolizumab can induce an early response and clinical remission in people with severe eosinophilic asthma (SEA). We questioned whether early response to mepolizumab could predict future asthma remission, and sought to identify the best predictor of treatment response to mepolizumab for achieving remission. The Australian Mepolizumab Registry was used to investigate the early response to mepolizumab at 3 and 6 months and relate this to clinical remission at 12 months. Treatment response was assessed using the Asthma Control Questionnaire (ACQ)-5, oral corticosteroid (OCS) dose, exacerbation frequency, and post-bronchodilator FEV1. Clinical remission, assessed at 12 months, was defined as ACQ-5 ≤1.0 at 12 months, no exacerbations in the previous 6 months, and no OCS use for asthma in the previous 6 months. We estimated the optimism-corrected area under the curve (AUC) for internal validation. We analyzed 255 participants with SEA. Seventy-eight (30.6%) participants achieved clinical remission at 12 months. A prediction model including ACQ-5 score, exacerbation frequency, OCS dose, and post-bronchodilator FEV1 at 6 months was more predictive of achieving remission than measures at 3 months. ACQ-5 score at 6 months had the highest optimism-corrected AUC of 0.778 [95% CI: 0.719-0.833]. ACQ-5 score <1.5 at 6 months had a sensitivity of 85.9% for achieving clinical remission, while ACQ-5 score <0.75 had a specificity of 84.7%. ACQ-5 score at 6 months was the best predictor of achieving clinical remission at 12 months in people with SEA treated with mepolizumab. These results can be used to design a treat-to-target paradigm for asthma, where treatment response is assessed at 6 months to predict clinical remission.

The Analysis Study of Comparison of Effectiveness and Safety of Inhalers in Mild-to Moderate Asthma in Adults: A Comprehensive Systematic Review

Background: Asthma, a prevalent and potentially debilitating chronic disease, is traditionally managed using reliever medications such as short-acting β2-agonists (SABA) or low-dose inhaled corticosteroids (ICS). Recent evidence, however, indicates that a combination of as-needed ICS and a rapid-acting long-acting β2-agonist (LABA) provides superior outcomes compared to SABA alone. Furthermore, this combination therapy is at least as effective as regular ICS in mitigating the risk of exacerbations. This emerging evidence highlights a significant shift in treatment strategies for mild asthma, underscoring the potential for enhanced management and improved patient outcomes with the new therapeutic approach. Methods: Following PRISMA 2020 guidelines, this systematic review focused exclusively on full-text articles published in English between 2014 and 2024. Result: The study conducted a comprehensive review of over 400 publications sourced from reputable databases, including ScienceDirect, SagePub, and PubMed. Folowing an initial screening, eight publications were identified as warranting more in-depth analysis. Conclusion: The study found that as-needed ICS/LABA is effective in preventing exacerbations in mild-to-moderate asthma patients, but less effective than regular ICS in improving FEV1 and ACQ scores. Combining ICS/LABA with SMART regimen was highest for severe exacerbations prevention.

Prospective REALITI-A Study: 2-Year Real-World Benefits of Mepolizumab in Severe Asthma

BackgroundMepolizumab, a monoclonal antibody targeting interleukin-5, is of proven clinical benefit in severe asthma; prospective, long-term, real-world data in severe asthma are required. Research QuestionThis study aimed to assess the real-world benefit of 2 years’ mepolizumab treatment in severe asthma. Study Design and MethodsREALITI-A was a 2-year, international, prospective study enrolling adults with asthma, newly initiating mepolizumab 100 mg subcutaneously (physician decision). Outcomes in the 1-year pre-mepolizumab versus 2-year follow-up periods included rates of clinically significant asthma exacerbations (CSE; deterioration requiring systemic corticosteroids and/or emergency department [ED] visit/hospitalisation), exacerbations requiring ED visit/hospitalisation, exacerbations requiring hospitalisation, proportion of patients with no exacerbations, median daily maintenance oral corticosteroid (mOCS) dose, proportion of patients discontinuing mOCS completely, asthma control questionnaire (ACQ)-5 score, forced expiratory volume in 1s (FEV1) and adverse events (AEs). ResultsAfter 2 years’ follow-up, 73% of patients (n=599/822) had no record of mepolizumab discontinuation. During the 2-year follow-up versus pre-mepolizumab period (N=822), rates of CSEs, exacerbations requiring ED visit/hospitalisation, or hospitalisation only were reduced by 74%, 79% and 73%, respectively (odds ratio for no CSEs: 10.0; 95% confidence interval: 7.55, 13.25). Median (Q1, Q3) daily mOCS dose decreased from 10.0 (5.0, 14.7) mg at Week 0 (n=297) to 0.0 (0.0, 5.0) mg at Weeks 101–104 (n=168), and the proportion of patients discontinuing mOCS increased progressively to 43% at 1 year and 57% at 2 years. There was a 1.53-point reduction in ACQ-5 scores from baseline at 2 years. At Months 21–24, least square mean FEV1 improved by 142 mL from baseline. Ninety (11%) and 7 (<1%) patients experienced mepolizumab-related AEs and serious AEs during the follow-up period, respectively. InterpretationIn patients with severe asthma, real-world mepolizumab treatment for 2 years was well-tolerated, and was associated with sustained reductions in exacerbations and progressive reductions in mOCS use.

Immediate and One-Year Outcomes of an Asthma-Tailored Pulmonary Rehabilitation Programme in Overweight and Obese People with Difficult-to-Treat Asthma.

Management of difficult-to-treat asthma is particularly challenging in people with elevated body mass index (BMI). Our randomised controlled trial of pulmonary rehabilitation (PR) showed improved outcomes at 8weeks. Here we assess immediate and one-year effects of asthma-tailored PR in participants with difficult-to-treat asthma and BMI ≥25 kg/m2, and identify response predictors. A prospective observational study of PR, tailored to asthma, comparing outcomes at baseline (V1), immediately after 8 weeks of PR (V2), and at 1 year (V3). Baseline characteristics were compared in responders/non-responders defined by achievement of minimum clinically important difference (MCID) for asthma control questionnaire (ACQ6) (0.5) at 8weeks and 1 year. Of 92 participants, 56 attended V2 and 45 attended V3. Mean age was 60 (SD 13) years, 60% were female, and median (IQR) BMI was 33.8 (29.5-38.7) kg/m2. At V1, V2, and V3, respectively, there were significant differences in ACQ6 (mean (95% CI): 2.5 (2.1-2.9), 2.2 (1.8-2.5), and 2.3 (1.9-2.7), p<0.003), Borg breathlessness score post-6-minute walk test (median (IQR): 2 (0.5-3), 1 (0-2), and 1 (0.5-2), p<0.035), and annualised exacerbations requiring prednisolone (median (IQR): 3 (2-5), 0 (0-4.7), and 1.5 (0-4.2), p<0.003). A total of 27/56 (48%) had improvements >MCID for ACQ6 at V2 and 16 (33%) at V3. Participants with higher ACQ6 scores at baseline (suggesting poorer asthma control) were more likely to achieve MCID. Baseline BMI, within the range studied, was not predictive. Pulmonary rehabilitation induced improvements in asthma-related outcomes including perception of breathlessness, asthma control, and exacerbation frequency at 1 year. Those with poorer baseline asthma control were more likely to benefit.

Clinical and Economic Burden of Severe Asthma With Low Blood Eosinophil Counts

BackgroundType 2 (T2) low severe asthma phenotype is often a result of corticosteroid-overtreated T2-disease due to persistent symptoms, often not related to asthma, and unlikely to respond to high-dose corticosteroid treatment. ObjectiveThis study aimed to characterise severe asthma patients with low eosinophil counts (<300 cells/μl) and describe their disease burden and treatment across healthcare settings in the UK. MethodsA retrospective cohort study of severe asthma patients using linked Clinical Practice Research Datalink (CPRD) Aurum-Hospital Episode Statistics (HES) and UK Severe Asthma Registry (UKSAR) data indexed patients on latest blood eosinophil count (BEC). Clinical characteristics, treatment patterns, outcomes, and healthcare resource use (HCRU) were described by baseline BEC (≤150 and >150 to <300 cells/μl). ResultsAnalysis included 701 (CPRD-HES) and 1,546 (UKSAR) patients; with 60.5% and 59.4% having BECs ≤150 cells/μl at baseline, respectively. Across BEC groups, the proportion with uncontrolled asthma (≥2 exacerbations) at follow-up (12-months post-index) was 5.4% in CPRD-HES and 45.2% in UKSAR. Maintenance OCS use remained high across BEC groups (CPRD-HES: 29.4%; UKSAR: 51.7%), symptom control remained poor (>200 μg SABA or >500 μg terbutaline/day in CPRD-HES: 48.8%; median ACQ-6 score in UKSAR: 2.0 [1.0-3.3]). HCRU were similar across BEC groups. ConclusionMost patients managed in primary care were infrequent exacerbators, whilst UKSAR patients exacerbated frequently. Large proportions of both patient groups had poor symptom control and continued to receive high levels of maintenance OCS, increasing risk of corticosteroid-induced morbidity. These data highlight the need for rigorous assessment of underlying disease pathology to guide appropriate treatment.

Efficacy of dupilumab for severe chronic rhinosinusitis with nasal polyps and asthma: A prospective study

BackgroundDupilumab exerts clinical effects, including improved sinus opacification, olfactory function, and quality of life, in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNPs). Meanwhile, only a few studies have reported its effects on nasal airway resistance and olfactory function, particularly in the Japanese population. Predictors of response remain unclear. ObjectiveTo assess the comprehensive efficacy and therapeutic response to dupilumab in patients with severe CRSwNP with comorbid asthma. MethodsIn 16 adult patients with severe CRSwNP with comorbid asthma, the efficacy of 48-week dupilumab treatment, including olfactory function measured by a T&T olfactometer, nasal airway resistance measured by rhinomanometry, nasal polyp score, Lund-Mackay computed tomography score, and 22-item Sinonasal Outcome Test (SNOT-22), was assessed. Regarding asthma, the annualized rate of exacerbations, 7-item Asthma Control Questionnaire (ACQ-7), and spirometry were assessed. Treatment responsiveness was analyzed. ResultsWith 48-week dupilumab treatment, olfactory function, nasal airway resistance, nasal polyp score, Lund-Mackay computed tomography score, and SNOT-22 scores improved significantly. Regarding comorbid asthma, the annualized rate of exacerbations decreased, and ACQ-7 scores and lung function improved significantly. According to the European Position Paper on Rhinosinusitis and Nasal Polyps 2020/European Forum for Research and Education in Allergy and Airway Diseases criteria, 15 patients (94%) were moderate-to-excellent responders at 48 weeks of treatment. Patients with higher SNOT-22 scores, ACQ-7 scores, the rate of asthma exacerbations in the previous year, and blood eosinophil counts benefited more from the treatment. ConclusionDupilumab improved upper and lower airway outcomes especially in patients with severe CRSwNP with comorbid, poorly controlled asthma. Trial RegistrationUMIN Clinical Trials Registry: UMIN000038669.

Long-term Safety and Efficacy of Dupilumab in Patients With Uncontrolled, Moderate-to-Severe Asthma Recruited From Korean Centers: A Subgroup Analysis of the Phase 3 LIBERTY ASTHMA TRAVERSE Trial.

Long-term data are limited on the safety and efficacy of dupilumab in patients with uncontrolled, moderate-to-severe asthma from Korea. The current subgroup analysis was designed to evaluate the long-term safety and efficacy of dupilumab in patients enrolled from Korean centers in the parent studies (phase 2b and QUEST) and who participated in the TRAVERSE open-label extension (OLE) study. TRAVERSE was a global, multicenter, OLE study that assessed the safety and efficacy of dupilumab 300 mg every 2 weeks for up to 96 weeks in patients (n = 2,282) with uncontrolled, moderate-to-severe asthma who completed prior dupilumab asthma clinical trials. The primary outcome was the incidence of any treatment-emergent adverse events (TEAEs); the secondary outcomes included annualized severe exacerbation rate, pre-bronchodilator forced expiratory volume in 1 second (pre-BD FEV1), and 5-item Asthma Control Questionnaire (ACQ-5) score. Safety outcomes were consistent with the parent studies and the overall TRAVERSE population; out of 74 patients, 70 experienced ≥ 1 TEAE, and 6 (8.1%) discontinued because of adverse events. During the treatment period, the unadjusted annualized severe exacerbation rate was low (0.470). Improvement in pre-BD FEV1 was seen as early as Week 2 with a mean change from the parent study baseline (PSBL), standard deviation (SD) of 0.42 L (0.47), which was sustained until Week 96. Mean change from PSBL (SD) in ACQ-5 score was -1.32 (0.76) at Week 48. This subgroup analysis of TRAVERSE showed the long-term safety and efficacy of dupilumab in patients with uncontrolled, moderate-to-severe asthma enrolled from Korean centers. ClinicalTrials.gov Identifier: NCT02134028.

A Simulation Study of the Effect of Clinical Characteristics and Treatment Choice on Reliever Medication Use, Symptom Control and Exacerbation Risk in Moderate-Severe Asthma.

The relationship between immediate symptom control, reliever medication use and exacerbation risk on treatment response and factors that modify it have not been assessed in an integrated manner. Here we apply simulation scenarios to evaluate the effect of individual baseline characteristics on treatment response in patients with moderate-severe asthma on regular maintenance dosing monotherapy with fluticasone propionate (FP) or combination therapy with fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR). Reduction in reliever medication use (puffs/24h), change in symptom control scores (ACQ-5), and annualised exacerbation rate over 12months were simulated in a cohort of patients with different baseline characteristics (e.g. time since diagnosis, asthma control questionnaire (ACQ-5) symptom score, smoking status, body mass index (BMI) and sex) using drug-disease models derived from large phaseIII/IV clinical studies. Simulation scenarios show that being a smoker, having higher baseline ACQ-5 and BMI, and long asthma history is associated with increased reliever medication use (p < 0.01). This increase correlates with a higher exacerbation risk and higher ACQ-5 scores over the course of treatment, irrespective of the underlying maintenance therapy. Switching non-responders to ICS monotherapy to combination therapy after 3months resulted in immediate reduction in reliever medication use (i.e. 1.3 vs. 1.0 puffs/24h for FP/SAL and BUD/FOR, respectively). In addition, switching patients with ACQ-5 > 1.5 at baseline to FP/SAL resulted in 34% less exacerbations than those receiving regular dosing BUD/FOR (p < 0.01). We have identified baseline characteristics of patients with moderate to severe asthma that are associated with greater reliever medication use, poor symptom control and higher exacerbation risk. Moreover, the effects of different inhaled corticosteroid (ICS)/long-acting beta agonist (LABA) combinations vary significantly when considering long-term treatment performance. These factors should be considered in clinical practice as a basis for personalised management of patients with moderate-severe asthma symptoms.

Sleeve Gastrectomy is Associated with Longitudinal Improvements in Lung Function and Patient-Reported Respiratory Outcomes.

Obesity exerts negative effects on pulmonary function through proven mechanical and biochemical pathways. Multiple studies have suggested that bariatric surgery can improve lung function. However, the timing of these effects on lung function and its association with patient reported outcomes is not known. A prospective cohort study of patients undergoing laparoscopic sleeve gastrectomy (LSG) at a tertiary care hospital was undertaken. Spirometry tests, laboratory tests, and self-reported questionnaires on asthma symptoms and asthma control (ACQ and ACT) were administered. All data were recorded pre-operatively (T0) and every 3 months post-operatively for 1 year (T3, T6, T9, T12) and were compared using a mixed-models approach for repeated measures. For the 23 participants, mean age was 44.2 ± 12.3 years, mean BMI was 45.2 ± 7.2 kg/m2, 18(78%) were female, 9(39%) self-reported as non-white and 6(26%) reported to have asthma. Following LSG, % total body weight loss was significant at all follow-up points (P < 0.0001). Rapid improvement in forced expiratory volume (FEV)% predicted and forced vital capacity (FVC)% predicted was seen at T3. Although the overall ACQ and ACT score remained within normal range throughout the study, shortness of breath declined significantly at 3 months post-op (P < 0.05) and wheezing resolved for all patients by twelve months. Patients also reported reduced frequency of sleep interruption and inability to exercise by the end of the study (P < 0.05). Improvements in objective lung function assessments and patient-reported respiratory outcomes begin as early as 3 months and continue until 12 months after sleeve gastrectomy.

Alpha-1 deficiency in severe asthma patients.

<sec id="st1"><title>INTRODUCTION</title>Alpha-1 antitrypsin (AAT) deficiency, an autosomal co-dominant condition, decreases protein concentration and activity at both serum and tissue levels. Few studies investigated whether the type of SERPINA1 gene phenotype in patients with severe asthma can influence symptoms and disease control during follow-up.</sec><sec id="st2"><title>OBJECTIVE</title>To assess whether the presence of a non-MM genotype of SERPINA1 in patients with severe asthma is associated with disease control, systemic and airway inflammation, lung function and comorbidities prevalence compared to severe asthma patients with a homozygous genotype (MM).</sec><sec id="st3"><title>METHODS</title>Asthmatic patients belonging to Global Initiative for Asthma (GINA) step 5 were retrospectively analysed in an Italian reference asthma clinic. We collected clinical, biological and functional variables at baseline and for the three following years.</sec><sec id="st4"><title>RESULTS</title>Out of 73 patients enrolled, 14 (19.18%) were non-MM and 59 (80.8%) were MM. Asthmatics with non-MM genotype had lower serum AAT concentration (P = 0.004) and higher emphysema prevalence than the MM group (P = 0.003) at baseline. During follow up, only MM patients showed a significant improvement of both ACQ-6 score (P < 0.0001) and eosinophilic systemic inflammation (P < 0.0001).</sec><sec id="st5"><title>CONCLUSIONS</title>Our findings emphasise the importance of a screening for AAT deficiency in severe asthma, as alleles mutation may influence patient's follow-up.</sec>.

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.

Usefulness of Computed Tomography for Evaluating the Effects of Bronchial Thermoplasty in Japanese Patients with Severe Asthma.

Bronchial thermoplasty (BT) improves clinical outcomes and quality of life for patients with severe asthma and has shown sustained reductions in airway narrowing and air trapping in previous CT studies. However, there is a lack of a comprehensive analysis, including CT evaluation, of clinical outcomes in Japanese patients who have undergone BT for severe asthma. This study aimed to evaluate the impact of BT in Japanese asthma patients, with a focus on the CT metric "WA at Pi10" to assess airway disease. Twelve patients with severe persistent asthma who underwent BT were assessed using ACQ6, AQLQ, pulmonary function tests, FeNO measurement, blood sampling, and chest CT before BT and one year after the third procedure for the upper lobes. The median age of the patient was 62.0 years, 7/12 (58.3%) were male, 4/12 (33.3%) used regular oral corticosteroids, and 8/12 (66.7%) received biologics. Median FEV1% was 73.6%, and median peripheral eosinophil count was 163.8/μL. After one year of BT, ACQ6 scores improved from 2.4 to 0.8 points (p = 0.007), and AQLQ scores improved from 4.3 to 5.8 points (p < 0.001). Significant improvements were also observed in asthma exacerbations, unscheduled visits due to exacerbations, FeNO, and √WA at Pi10 (p < 0.05). The baseline mucus score on the CT findings was negatively correlated with FEV1 (r = -0.688, p = 0.013) and with the maximum mid-expiratory flow rate (r = -0.631, p = 0.028), and positively correlated with the peripheral blood eosinophil count (r = -0.719, p = 0.008). Changes in √WA at Pi10 after one year were positively correlated with changes in the mucus score (r = 0.742, p = 0.007). This study has limitations, including its single-arm observational design and the small sample size. However, BT led to a symptomatic improvement in patients with severe asthma. The validated "√WA at Pi10" metric on CT effectively evaluated the therapeutic response in Japanese asthma patients after BT.

Physical Activity and Sedentary Behavior as Treatable Traits for Clinical Control in Moderate-to-Severe Asthma

Physical activity and sedentary behavior are treatable traits that may impact asthma control in distinct manners, but this impact remains poorly understood. To evaluate the influence of physical activity and sedentary behavior on clinical control in adults with moderate-to-severe asthma. This cross-sectional, multicentric study included 426 individuals with moderate-to-severe asthma. Assessments included physical activity and sedentary time (actigraphy), clinical asthma control (Asthma Control Questionnaire [ACQ]), quality of life (Asthma Quality of Life Questionnaire), anxiety and depression symptoms (Hospital Anxiety and Depression Scale), anthropometric data, and lung function. Participants were grouped according to physical activity levels and sedentary behavior. Participants who walked ≥7500 steps/day presented better ACQ scores than those who walked <7500 steps/day (P<.05), independent of sedentary status. The percentage of patients with controlled asthma was higher in the active/sedentary (43.9%) and active/nonsedentary (43.8%) groups than in the inactive/sedentary (25.4%) and inactive/nonsedentary (23.9%) groups (P < .02). The likelihood of having uncontrolled asthma according to the treatable traits of physical inactivity (odds ratio [95% confidence interval]: 2.36 [1.55-3.59]), higher anxiety (2.26 [1.49-3.42]), and depression symptoms (1.95 [1.28-2.95]) was significant (P ≤ .002). Obesity and sedentary time were not associated with asthma control. Our results show that ≥7500 steps/day is associated with better asthma control independent of sedentary time in adults with moderate-to-severe asthma. Physical inactivity, anxiety, and depression symptoms are associated with higher odds of uncontrolled asthma. These results suggest that interventions should mainly focus on increasing physical activity rather than reducing sedentary time.

Digitally monitored inhaled therapy: a ‘smart’ way to manage severe asthma?

Introduction One of the fundamental challenges of managing patients with severe asthma is treatment adherence, particularly with inhaled corticosteroids. Adherence is difficult to measure objectively and poor adherence is associated with worse outcomes. In this study, assess the ability of a ‘smart’ inhaler to record adherence in severe asthma patients and measure the impact of this on asthma control. Methods Consecutive consenting patients meeting criteria for biologics had their existing high-dose ICS/LABA//LAMA combination inhaler/s switched to mometasone/indacaterol/glycopyrronium (114/46/136). Routine clinical data, including blood eosinophils, FeNO, and ACQ-6 scores were collected at baseline and at 4 wk. Adherence was then checked on the Propeller Health app, and good adherence was defined as >80% of prescribed usage. Participants were then followed-up at 12 months to record the proportion of patients who were initiated on biologics Results 77 patients (mean [SD] age = 50.4 [15.7] years, 67.5% female [n = 52]) participated. 71 participants were able to use the device and 65% (n = 46) of these attained good asthma control and were not initiated on biologics at 12-month follow-up. Both groups demonstrated a significant reduction in ACQ6 score at follow-up (2.81 vs. 1.92, p < 0.001 and 3.05 vs. 2.60, p < 0.001, respectively), but there was no statistically significant difference in improvement between groups. Patients with optimal adherence also demonstrated a significant reduction in median FeNO at follow-up (47 ppb vs. 40 ppb, p = 0.003). Conclusions In severe asthma patients, ‘smart’ inhalers may represent an effective management tool to improve adherence and asthma control, therefore avoiding the need for patients to commence biological therapies.

Baseline Characteristics and ICS/LAMA/LABA Response in Asthma: Analyses From the CAPTAIN Study

BackgroundFindings from CAPTAIN (NCT02924688) suggest treatment response to fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) differs according to baseline type 2 (T2) inflammation markers in patients with moderate-to-severe asthma. Understanding how other patient physiologic and clinical characteristics affect response to inhaled therapies may guide physicians toward a personalized approach for asthma management. ObjectiveTo investigate, using CAPTAIN data, the predictive value of key demographic and baseline physiologic variables in patients with asthma (lung function, bronchodilator reversibility, age, age at asthma onset) on response to addition of the long-acting muscarinic antagonist UMEC to inhaled corticosteroid/long-acting β2-agonist combination FF/VI, or doubling FF dose. MethodsPrespecified and post hoc analyses of CAPTAIN data were performed using categorical and continuous variables of key baseline characteristics to understand their influence on treatment outcomes (lung function [trough forced expiratory volume in 1 second, FEV1], annualized rate of moderate/severe exacerbations, and asthma control [Asthma Control Questionnaire, ACQ]) following addition of UMEC to FF/VI or doubling FF dose in FF/VI or FF/UMEC/VI. ResultsAdding UMEC to FF/VI led to greater improvements in trough FEV1 versus doubling FF dose across all baseline characteristics assessed. Doubling FF dose was generally associated with numerically greater reductions in the annualized rate of moderate/severe exacerbations compared with adding UMEC, independent of baseline characteristics. Adding UMEC and/or doubling FF dose generally led to improvements in ACQ scores irrespective of baseline characteristics. ConclusionUnlike previous findings with T2 biomarkers, lung function, bronchodilator reversibility, age and age at asthma onset do not appear to predict response to inhaled therapy.

Long-term efficacy of house dust mite sublingual immunotherapy on clinical and pulmonary function in patients with asthma and allergic rhinitis

BackgroundA previous study reported that house dust mite (HDM) sublingual immunotherapy (SLIT) for 48 weeks was effective as add on treatment for allergic asthma; however, data regarding its long-term efficacy is scarce. ObjectiveThis open-label extension study aimed to evaluate the effect of HDM SLIT on asthma control, pulmonary function, airway inflammation and remodeling throughout the 5-year treatment period. MethodsA total of 140 patients with asthma and allergic rhinitis sensitized to HDM were randomized to receive either drugs alone or drugs plus SLIT for 5 years. Asthma Control Questionnaire (ACQ)-5, Asthma Quality of Life Questionnaire (AQLQ), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), spirometry, quantitative computed tomography, and type 2 biomarkers were assessed. ResultsAn improvement in the ACQ-5, AQLQ, and RQLQ scores was observed in the SLIT group compared with the control group. HDM SLIT increased lung function and reduced the percentage of airway wall area (WA/Ao). The levels of fractional exhaled nitric oxide (FeNO), blood eosinophil, serum specific IgE (s-IgE) for HDM, and total IgE decreased and were sustained during the 5 years. The change in type 2 biomarkers correlated with change in AQLQ score. Based on receiver operating characteristic (ROC) analysis for predicting responders, the area under the ROC curve in FEV1% predicted, WA/Ao, FeNO, and s-IgE was high. Multivariate regression analysis showed that the strongest predictor of responders was FeNO. ConclusionsHDM SLIT continued to provide sustained efficacy, improve lung function, and prevent progression of airway inflammation and remodeling in asthma through to year 5.

Real-world effectiveness and predictors of super-responders to dupilumab in a Chinese uncontrolled asthma cohort.

Background: Dupilumab has been shown to be effective in clinical trials for moderate-to-severe uncontrolled asthma. However, the efficacy of dupilumab in the real world and the prediction of treatment response have not been well studied in patients with asthma. Objective: To investigate the efficacy of dupilumab and explore predictors of super-responders in a Chinese retrospective cohort. Methods: From January 2021 through December 2022, the patients with uncontrolled asthma who were treated with dupilumab for 4 months were included. Symptom control, type 2 inflammatory biomarkers, and lung function were collected at baseline and follow-up for efficacy assessment. Super-responders were defined as exacerbation-free, off maintenance of oral corticosteroids (mOCS), and with a score of the five-item Asthma Control Questionnaire (ACQ-5) of <0.5. The uni- and multivariable logistic regressions were used to construct predictive models for super-responders based on baseline features. Results: A total of 53 patients were included. After 4 months treatment, the median (interquartile range [IQR]) ACQ-5 score decreased from 1.8 (1.6-2.4) to 0.4 (0.2-0.8) (p < 0.001), the median (IQR) number of exacerbations, from 0.0 (0.0-1.0) to 0.0 (0.0-0.0) (p = 0.005). The median (IQR) dose of mOCS (prednisone equivalent) decreased from 15.0 mg/day (8.8-22.5 mg/day) to 2.5 mg/day (0.0-10.0 mg/day) (p = 0.008) in nine patients who were receiving mOCS. All efficacy assessment parameters, including sputum eosinophil were significantly improved, while blood eosinophil count did not decline (530 cells/mm³ [300-815 cells/mm³] versus 560 cells/mm³ [220-938 cells/mm³], p = 0.710). After taking dupilumab, 25 of 53 patients (47.2%) achieved a super-response. The age of onset < 42 years (odds ratio [OR] 7.471 [95% confidence interval {CI}, 1.286-43.394) and the baseline fractional exhaled nitric oxide (FeNO) of 25-50 ppb (OR 35.038 [95% CI, 3.104-395.553]) predicted super-responders, which showed a C-index of 0.822 (95% CI, 0.697-0.947). Conclusion: Dupilumab significantly improved symptom control, type 2 inflammatory markers, and lung function in Chinese patients with uncontrolled asthma. Airway eosinophils, rather than blood eosinophils, can be a reliable indicator of therapeutic efficacy. The early-onset asthma as well as the medium-high level of baseline FeNO contributed to the prediction of super-responders.

Effectiveness and Safety of Oral Triamcinolone in the Management of Acute Exacerbations of Asthma: A Prospective Interventional Study

Introduction: Acute exacerbation of asthma leads to increased morbidity, mortality, and healthcare costs. Oral Corticosteroids (OCS) are critical in the management of asthma exacerbations; however, the response varies between patients. While there are some studies about a good response to Intramuscular (IM) triamcinolone, there is no data about the effect of oral triamcinolone on objective parameters during asthma exacerbations. Aim: To evaluate the effectiveness and safety of oral triamcinolone as an adjunct to Standard-Of-Care (SOC) comprising Inhaled Corticosteroids (ICS) with or without Long-Acting β2-Agonist (LABA) in treating mild-to-moderate exacerbations of asthma. Materials and Methods: This was a prospective, interventional, single-arm, single-centre, open-label study. Adults with bronchial asthma on stable doses of asthma medications for at least three months and presenting with mild-to-moderate exacerbation were recruited. Oral triamcinolone 4-16 mg/day for seven days was prescribed depending on exacerbation severity. Improvements in the Asthma Control Questionnaire (ACQ-6) score, Forced Expiratory Volume in 1 second (FEV1), and Peak Expiratory Flow Rate (PEFR) were evaluated. All patients in the study who had taken at least one dose of the study medication were included in the Intention-To-Treat (ITT) set. All patients in the ITT set who completed the study as Per Protocol (PP) were included in the PP set and considered for effectiveness analysis. Qualitative data are presented as numbers (n) and percentages (%), and quantitative data as n, mean, and Standard Deviation (SD). Quantitative variables were further evaluated using paired t-test at a 5% level of significance. Results: A total of 100 (38 males and 62 females) patients with a mean±SD age of 45.2±12.7 years were enrolled. The mean ACQ score decreased from 2.2 to 1.4 (p-value&lt;0.001), mean FEV1 increased from 1.6 to 1.7 L/s (p-value&lt;0.001), and the mean±SD PEFR increased significantly from 251.5±90.0 to 270.4±88.3 L/ min (p-value&lt;0.001) on day 7. Overall, triamcinolone was welltolerated with no serious Adverse Events (AE). Conclusion: In patients with mild-to-moderate asthma exacerbations, oral triamcinolone as an adjunct to SOC improved ACQ-6 score, FEV1, and PEFR with a favourable safety profile. These findings support the use of oral triamcinolone for treating acute exacerbations of asthma.

Comparison of health-related quality of life measures in asthma-COPD overlap.

The Asthma Quality of Life Questionnaire (AQLQ) and COPD assessment test (CAT) are used to assess the health status of asthma and chronic obstructive pulmonary disease (COPD), respectively. However, whether these questionnaires are appropriate in patients with asthma-COPD overlap (ACO) has not been reported. This study aimed to evaluate the performance of the AQLQ and CAT in subjects with ACO. Subjects were enrolled from two previously described observational studies in Beijing, China. ACO was defined by a consensus definition from a roundtable discussion. All subjects completed the AQLQ, CAT, St George's Respiratory Questionnaire (SGRQ), pulmonary function tests, and the Asthma Control Questionnaire (ACQ)-5. Cross-sectional construct validity was evaluated by correlating the AQLQ and CAT with SGRQ score and other measures of asthma and COPD severity. 147 subjects with ACO were recruited. There were floor effects on non-respiratory components of the CAT, and ceiling effects on emotion domains of the AQLQ. Both questionnaires were significantly correlated with ACQ-5 score but were not correlated with FEV1% predicted or FVC% predicted. The AQLQ and CAT were strongly correlated with SGRQ score (r = -0.657 and r = 0.623, respectively). Multivariable linear regression analysis showed that the AQLQ (standardized β-coefficient = -0.449, p < .001) had a stronger association with SGRQ score compared with CAT (standardized β-coefficient = 0.211, p = .023). The AQLQ and CAT were both valid for assessing the health-related quality of life in subjects with ACO, but the AQLQ performed better than CAT.

The perceived waning of biologics in severe asthma

BackgroundBiologics are highly effective in severe asthma and used at fixed dosing intervals. However, in clinical practice, dosing intervals are sometimes shortened if patients perceive a decreased biologic effect before the next administration. The occurrence and clinical relevance of this perceived waning of biological effect is unknown. ObjectiveTo explore (1) the frequency, severity and conditions, (2) associated symptoms and (3) relationship with clinical characteristics of the patient-perceived waning effect of biologics before the next administration. MethodsSevere asthma patients receiving biological treatment ≥4 months were included. Based on 17 semi-structured patient interviews, we developed a questionnaire focusing on the waning effect of biologics before the next administration, which was distributed among 129 patients. Clinical characteristics, including asthma control (ACQ) and quality of life (AQLQ) scores, were collected from patient files. Results65/101 patients who completed the questionnaire reported a waning of biological effect, graded as severe (median (IQR) 6.5 (5–7.5) on a 0–10 BORG-scale). Waning manifested in a broad spectrum of symptoms. Patients reporting waning had higher ACQ and lower AQLQ scores versus those without (p < 0.05) and higher BORG-scores were associated with higher exacerbation rate (ρ = 0.309, p = 0.013). A third of all patients were in favor of extending or shortening their dosing interval. ConclusionTwo-thirds of severe asthma patients report waning of biologic effect at the end of the dosing interval, which is associated with poorer asthma control and quality of life. The diversity in observed waning of effect opens the way for research into more individualized dosing of biologics.