Mark K. Hew

Rationale: Although clinical trials have documented the oral corticosteroid (OCS)-sparing effect of biologics in patients with severe asthma, little is known about whether this translates to a reduction of new-onset OCS-related adverse outcomes. Objective: To compare the risk of developing new-onset OCS-related adverse outcomes between biologic initiators and noninitiators. Methods: This was a longitudinal cohort study using pooled data from the International Severe Asthma Registry (ISAR; 16 countries) and the Optimum Patient Care Research database (OPCRD; United Kingdom). For biologic initiators, the index date was the date of biologic initiation. For noninitiators, it was the date of enrollment (for ISAR) or a random medical appointment date (for OPCRD). Inverse probability of treatment weighting was used to improve comparability between groups, and weighted Cox proportional hazard models were used to estimate the hazard ratios (HRs) of developing OCS-related adverse outcomes for up to 5 years from the index date. Measurements and Main Results: A total of 42,908 patients were included. Overall, 27.3% and 4.7% of biologic initiators and noninitiators were long-term OCS users (daily intake ⩾90 consecutive days in year before the index date), with a mean prednisolone-equivalent daily dose of 10.2 mg and 6.2 mg, respectively. Compared with noninitiators, biologic initiators had decreased rate of developing any OCS-related adverse outcome (HR [95% confidence interval (CI)]: 0.82 [0.72-0.93]; P = 0.002), primarily driven by reduced rate of developing diabetes (0.62 [0.45-0.87]; P = 0.006), major cardiovascular events (0.65 [0.44-0.97]; P = 0.034), and anxiety and/or depression (0.68 [0.55-0.85]; P = 0.001). There were no significant differences in the rates of new-onset cataract (HR, 0.77 [95% CI, 0.47-1.25]), sleep apnea (HR, 0.82 [95% CI, 0.78-1.41]), or other OCS-related adverse outcomes assessed (e.g., osteoporosis). The results were consistent across both datasets. Conclusions: Our findings highlight the role for biologics in preventing new-onset OCS-related adverse outcomes in patients with severe asthma.

Rationale: Although clinical trials have documented the oral corticosteroid (OCS)-sparing effect of biologics in patients with severe asthma, little is known about whether this translates to a reduction of new-onset OCS-related adverse outcomes. Objective: To compare the risk of developing new-onset OCS-related adverse outcomes between biologic initiators and noninitiators. Methods: This was a longitudinal cohort study using pooled data from the International Severe Asthma Registry (ISAR; 16 countries) and the Optimum Patient Care Research database (OPCRD; United Kingdom). For biologic initiators, the index date was the date of biologic initiation. For noninitiators, it was the date of enrollment (for ISAR) or a random medical appointment date (for OPCRD). Inverse probability of treatment weighting was used to improve comparability between groups, and weighted Cox proportional hazard models were used to estimate the hazard ratios (HRs) of developing OCS-related adverse outcomes for up to 5 years from the index date. Measurements and Main Results: A total of 42,908 patients were included. Overall, 27.3% and 4.7% of biologic initiators and noninitiators were long-term OCS users (daily intake ⩾90 consecutive days in year before the index date), with a mean prednisolone-equivalent daily dose of 10.2 mg and 6.2 mg, respectively. Compared with noninitiators, biologic initiators had decreased rate of developing any OCS-related adverse outcome (HR [95% confidence interval (CI)]: 0.82 [0.72-0.93]; P = 0.002), primarily driven by reduced rate of developing diabetes (0.62 [0.45-0.87]; P = 0.006), major cardiovascular events (0.65 [0.44-0.97]; P = 0.034), and anxiety and/or depression (0.68 [0.55-0.85]; P = 0.001). There were no significant differences in the rates of new-onset cataract (HR, 0.77 [95% CI, 0.47-1.25]), sleep apnea (HR, 0.82 [95% CI, 0.78-1.41]), or other OCS-related adverse outcomes assessed (e.g., osteoporosis). The results were consistent across both datasets. Conclusions: Our findings highlight the role for biologics in preventing new-onset OCS-related adverse outcomes in patients with severe asthma.

Background: Dysfunctional breathing is common and leads to worse asthma outcomes. Objective: To describe the characteristics of nonpharmacological interventions to treat dysfunctional breathing, and evidence for their efficacy. Methods: We searched electronic databases (MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, and Physiotherapy Evidence Database) to identify studies that involved nonpharmacological interventions for people with the diagnosis of dysfunctional breathing. The primary aim was to determine the characteristics of intervention protocols according to the Template for Intervention Description and Replication checklist. Secondary aims included the assessment tools used, outcomes measured, and the clinical impact of the intervention. We assessed the risk of bias using the Cochrane Risk of Bias 1.0 tool or the Standard Quality Assessment Criteria, depending on the study design. Results: A total of 68 trials met review criteria (26 cohort studies, 20 case series, 19 randomized trials, and three nonrandomized trials), with 2,119 participants. Most studies had a high or unclear risk of bias across multiple domains. Five groups of nonpharmacological interventions were identified: breathing retraining with or without biofeedback, psychological therapy, acupoint therapy, manual therapy, and exercise therapy. Intervention components were highly variable and inadequately reported. Breathing retraining was the most reported intervention and showed positive effects across biochemical (29 of 34 studies; 85%), biomechanical (10 of 10 studies; 100%), and psychophysiological (15 of 19; 79%) domains of dysfunctional breathing. There was marked heterogeneity across studies and outcomes. Conclusions: A variety of nonpharmacological interventions have been applied in people with dysfunctional breathing. Breathing retraining was frequently studied, with low-quality evidence for efficacy. Future studies should report intervention components in sufficient detail to allow replication and use consistent objective measurements to assess outcomes.

Background: Dysfunctional breathing is common and leads to worse asthma outcomes. Objective: To describe the characteristics of non-pharmacological interventions to treat dysfunctional breathing, and evidence for their efficacy. Methods: Electronic databases (MEDLINE, Embase, CINAHL, CENTRAL and PEDro) were searched to identify studies that involved non-pharmacological interventions for people diagnosed with dysfunctional breathing. The primary aim was to determine the characteristics of intervention protocols according to the Template for Intervention Description and Replication checklist. Secondary aims included the assessment tools used, outcomes measured, and the clinical impact of the intervention. Risk of bias was assessed using the Cochrane Risk of Bias 1.0 tool or the Standard Quality Assessment Criteria depending on study design. Results: Sixty-eight trials met review criteria (26 cohort studies, 20 case series, 19 randomised trials, and 3 non-randomised trials) with a total of 2119 participants. Most studies had high or unclear risk of bias across multiple domains. Five groups of non-pharmacological interventions were identified: breathing re-training ± biofeedback, psychological therapy, acupoint therapy, manual therapy, and exercise therapy. Intervention components were highly variable and inadequately reported. Breathing re-training was the most reported intervention and showed positive effects across biochemical (29/34 studies, 85%), biomechanical (10/10 studies, 100%) and psychophysiological (15/19, 79%) domains of dysfunctional breathing. There was marked heterogeneity across studies and outcomes. Conclusions: A variety of non-pharmacological interventions have been applied in people with dysfunctional breathing. Breathing re-training was frequently studied with low quality evidence for efficacy. Future studies should report intervention components in sufficient detail to allow replication and use consistent objective measurements to assess outcomes.

Background: For severe asthma (SA) management, real-world evidence on the effects of biologic therapies in reducing the burden of oral corticosteroid (OCS) use is limited. Objective: To estimate the efficacy of biologic initiation on total OCS (TOCS) exposure in patients with SA from real-world specialist and primary care settings. Methods: From the International Severe Asthma Registry (ISAR, specialist care) and the Optimum Patient Care Research Database (OPCRD, primary care, United Kingdom), adult biologic initiators were identified and propensity score-matched with non-initiators (ISAR, 1:1; OPCRD, 1:2). The impact of biologic initiation on TOCS (including bursts for exacerbations) daily dose in the first- and second-year follow-up period was estimated using multivariable generalized linear models. Results: Among 5,663 patients (ISAR 48%, OPCRD 52%), the odds ratios (ORs) of biologic initiators achieving TOCS cessation in the first and second years of follow-up were 2.38 (95% CI, 1.87-3.04) and 2.11 (95% CI, 1.65-2.70), whereas the ORs of low (0- to 5-mg) TOCS intake were 1.62 (95% CI, 1.40-1.86) and 1.40 (95% CI, 1.21-1.61), respectively. Compared with non-initiators, biologic initiators had a substantially higher chance of achieving greater than 75% reduction from baseline (OR [95% CI] = 2.35 [2.06-2.68] and 1.53 [1.35-1.73] in first and second years, respectively). These findings remained persistent and robust when analyses were repeated with one country setting removed at a time. Conclusions: Biologic initiation in patients with SA led to substantial reduction in TOCS exposure, particularly in the first year. Future analyses will explore the impact on OCS-related adverse health events.

Immunological Mechanisms of Oralair® (5 Grass Mix Sublingual Allergen Immunotherapy Tablet) in Patients With Seasonal Allergic Rhinitis