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Background: Mepolizumab can induce an early response and clinical remission in people with severe eosinophilic asthma (SEA)., Objective: To find whether early response to mepolizumab (100 mg) could predict future asthma remission and to identify the best predictor of treatment response to mepolizumab for achieving remission., Methods: 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 5-item Asthma Control Questionnaire (ACQ-5), oral corticosteroid (OCS) dose, exacerbation frequency, and postbronchodilator FEV 1 . Clinical remission, assessed at 12 months, was defined as an ACQ-5 score less than or equal to 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 for internal validation., Results: 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 postbronchodilator FEV 1 at 6 months was more predictive of achieving remission than measures at 3 months. The ACQ-5 score at 6 months had the highest optimism-corrected area under the curve of 0.778 (95% CI, 0.719-0.833). An ACQ-5 score less than 1.5 at 6 months had a sensitivity of 85.9% for achieving clinical remission, whereas an ACQ-5 score less than 0.75 had a specificity of 84.7%., Conclusions: The 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, in which treatment response is assessed at 6 months to predict clinical remission., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Biologic effectiveness is often assessed as response, a term that eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging., Objective: To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response., Methods: This was a longitudinal cohort study using data from 21 countries, which shared data with the International Severe Asthma Registry. Changes in four asthma outcome domains were assessed in the 1-year period before and after biologic initiation in patients with a predefined level of prebiologic impairment. Responder cutoffs were 50% or greater reduction in exacerbation rate, 50% or greater reduction in long-term oral corticosteroid daily dose, improvement in one or more category in asthma control, and 100 mL or greater improvement in FEV 1 . Responders were defined using single and multiple domains. The association between prebiologic characteristics and postbiologic initiation response was examined by multivariable analysis., Results: A total of 2,210 patients were included. Responder rate ranged from 80.7% (n = 566 of 701) for exacerbation response to 10.6% (n = 9 of 85) for a four-domain response. Many responders still exhibited significant impairment after biologic initiation: 46.7% (n = 206 of 441) of asthma control responders with uncontrolled asthma before the biologic still had incompletely controlled disease postbiologic initiation. Predictors of response were outcome-dependent. Lung function responders were more likely to have higher prebiologic FeNO (odds ratio = 1.20 for every 25-parts per billion increase), and shorter asthma duration (odds ratio = 0.81 for every 10-year increase in duration). Higher blood eosinophil count and the presence of type 2-related comorbidities were positively associated with higher odds of meeting long-term oral corticosteroid, control, and lung function responder criteria., Conclusions: Our findings underscore the multimodal nature of response, showing that many responders experience residual symptoms after biologic initiation and that predictors of response vary according to the outcome assessed., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Effectiveness of biologics has neither been established in patients with high oral corticosteroid exposure (HOCS) nor been compared with effectiveness of continuing with HOCS alone., Objective: To examine the effectiveness of initiating biologics in a large, real-world cohort of adult patients with severe asthma and HOCS., Methods: This was a propensity score-matched, prospective cohort study using data from the International Severe Asthma Registry. Between January 2015 and February 2021, patients with severe asthma and HOCS (long-term OCSs for ≥1 year or ≥4 courses of rescue OCSs within a 12-month period) were identified. Biologic initiators were identified and, using propensity scores, matched 1:1 with noninitiators. The impact of biologic initiation on asthma outcomes was assessed using generalized linear models., Results: We identified 996 matched pairs of patients. Both groups improved over the 12-month follow-up period, but improvement was greater for biologic initiators. Biologic initiation was associated with a 72.9% reduction in the average number of exacerbations per year versus noninitiators (0.64 vs 2.06; rate ratio, 0.27 [95% CI, 0.10-0.71]). Biologic initiators were 2.2 times more likely than noninitiators to take a daily long-term OCS dose of less than 5 mg (risk probability, 49.6% vs 22.5%; P = .002) and had a lower risk of asthma-related emergency department visits (relative risk, 0.35 [95% CI, 0.21-0.58]; rate ratio, 0.26 [0.14-0.48]) and hospitalizations (relative risk, 0.31 [95% CI, 0.18-0.52]; rate ratio, 0.25 [0.13-0.48])., Conclusions: In a real-world setting, including patients with severe asthma and HOCS from 19 countries, and within an environment of clinical improvement, initiation of biologics was associated with further improvements across multiple asthma outcomes, including exacerbation rate, OCS exposure, and health care resource utilization., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Comorbidities in severe asthma are common and contribute to disease burden. The severe asthma phenotype and treatment response can be impacted by comorbid conditions. Real-world data on the use of mepolizumab in severe eosinophilic asthma (SEA) in the presence of comorbidities are needed to inform clinical practice., Objective: To investigate the impact of comorbid conditions on baseline phenotype in patients with SEA and assess the mepolizumab treatment effect by comorbidity status in SEA., Methods: Patients enrolled in the Australian Mepolizumab Registry (n = 309) were classified into subgroups defined by the presence or absence of comorbidities, including nasal polyps, aspirin-exacerbated airway disease, asthma-chronic obstructive pulmonary disease overlap (ACO), fungal sensitization, and obesity. Patient baseline characteristics were compared, and the impacts of comorbidity on phenotype, identified by differences in patient age and/or baseline biomarker levels and/or asthma severity, were assessed. The mepolizumab treatment effects on clinical and biological outcomes at 12 months were assessed., Results: Across comorbidity subgroups, mepolizumab reduced the rate of clinically significant exacerbations (range: 47%-77%), maintenance oral corticosteroid use (dose reduction: 4.2-13.3 mg/d), and improved symptom control (Asthma Control Questionnaire-5 score: 1.9-2.4 point reduction) and lung function (mean: 3.4-9.3 post-bronchodilator percent predicted forced expiratory volume in 1 second). Peripheral blood eosinophils were reduced (mean: 480-780 cells/μL). Comorbidities (nasal polyps, obesity, ACO, and fungal sensitization) modified the baseline phenotype., Conclusions: Mepolizumab treatment is associated with comparable clinical improvements in patients with SEA and comorbidities. Mepolizumab effectively minimizes the disease impact and corticosteroid burden in patients with SEA., (Copyright © 2023. Published by Elsevier Inc.)

Background: Regulatory bodies have approved five biologics for severe asthma. However, regional differences in accessibility may limit the global potential for personalized medicine., Objective: To compare global differences in ease of access to biologics., Methods: In April 2021, national prescription criteria for omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab were reviewed by severe asthma experts collaborating in the International Severe Asthma Registry. Outcomes (per country, per biologic) were (1) country-specific prescription criteria and (2) development of the Biologic Accessibility Score (BACS). The BACS composite score incorporates 10 prescription criteria, each with a maximum score of 10 points. Referenced to European Medicines Agency marketing authorization specifications, a higher score reflects easier access., Results: Biologic prescription criteria differed substantially across 28 countries from five continents. Blood eosinophil count thresholds (usually ≥300 cells/μL) and exacerbations were key requirements for anti-IgE/anti-IL-5/5R prescriptions in around 80% of licensed countries. Most countries (40% for dupilumab to 54% for mepolizumab) require two or more moderate or severe exacerbations, whereas numbers ranged from none to four. Moreover, 0% (for reslizumab) to 21% (for omalizumab) of countries required long-term oral corticosteroid use. The BACS highlighted marked between-country differences in ease of access. For omalizumab, mepolizumab, benralizumab, and dupilumab, only two, one, four, and seven countries, respectively, scored equal or higher than the European Medicines Agency reference BACS. For reslizumab, all countries scored lower., Conclusions: Although some differences were expected in country-specific biologic prescription criteria and ease of access, the substantial differences found in the current study present a challenge to implementing precision medicine across the world., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Inhaled therapy is the cornerstone of chronic airway disease therapy, but poor adherence to controller inhalers worsens clinical outcomes and increases cost. Monitoring of controller use is needed to improve adherence, and monitoring of reliever use can predict impending exacerbations. Both can be accurately achieved by electronic inhaler monitoring (EIM). However, evidence for EIM use in clinical practice is limited and varied, and knowledge gaps remain across different outcomes and health settings. We aimed to develop a framework to assess EIM systematically across all aspects of efficacy, apply this framework to the current literature, and identify gaps in efficacy to inform future development in the field. We adapted an existing framework for diagnostic tests, consisting of six levels of efficacy with ascending clinical relevance: technical, diagnostic accuracy, diagnostic thinking, therapeutic, patient outcome, and societal efficacy. Tailoring this framework to EIM, we incorporated expert feedback and applied it to the EIM efficacy literature. We found that EIM has good diagnostic accuracy, diagnostic thinking, and therapeutic efficacies, but evidence is lacking for specific aspects of technical, patient outcome, and societal efficacies. Further development of EIM requires improved reliability, usability, and data security for patients, and optimal integration with electronic medical records and overall patient care. Defining appropriate target patient groups and pairing EIM data with effective interventions, in conjunction with reducing costs through technological innovation and economies of scale, will enhance patient and societal outcome efficacies., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Vocal cord dysfunction (VCD) is present in 25% to 50% of patients with asthma. When both diagnoses are suspected, accurate diagnosis and targeted management represent a clinical challenge., Objective: To evaluate diagnostic and therapeutic outcomes following systematic assessment for patients with concurrent suspected VCD and asthma., Methods: Patients underwent systematic evaluation by clinical assessment and validated questionnaires, followed by multidisciplinary management. VCD was confirmed by visualization of paradoxical vocal fold motion at baseline or following provocation. Asthma was confirmed by demonstrating variable airflow obstruction. Asthma medications were deescalated in those with low clinical probability of asthma and no variable airflow obstruction. Response to 2 or more sessions of speech pathology was assessed by subjective report and standardized questionnaires., Results: Among 212 consecutive patients, 62 (29%) patients had both VCD and asthma, 54 (26%) had VCD alone, 51 (24%) had asthma alone, and 45 (21%) had neither. Clinician assessment and the Laryngeal Hypersensitivity Questionnaire both predicted laryngoscopy-confirmed VCD. Deescalation or discontinuation of asthma therapy was possible in 37 of 59 (63%) patients without variable airflow obstruction, and was most successful (odds ratio, 5.5) in the presence of laryngoscopy-confirmed VCD (25 of 31, or 81%) Patients with VCD responded subjectively to 2 or more sessions of speech pathology, but laryngeal questionnaire scores did not improve., Conclusions: Expert clinician assessment and the Laryngeal Hypersensitivity Questionnaire predict the presence of laryngoscopy-confirmed VCD. Systematic assessment for both VCD and asthma facilitates deescalation or discontinuation of unnecessary asthma medications. Subjective symptom improvement following speech pathology was not paralleled by laryngeal questionnaire scores in this cohort., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: We developed an eosinophil phenotype gradient algorithm and applied it to a large severe asthma cohort (International Severe Asthma Registry)., Objective: We sought to reapply this algorithm in a UK primary care asthma cohort, quantify the eosinophilic phenotype, and assess the relationship between the likelihood of an eosinophilic phenotype and asthma severity/health care resource use (HCRU)., Methods: Patients age 13 years and older with active asthma and blood eosinophil count or 1 or greater, who were included from the Optimum Patient Care Research Database and the Clinical Practice Research Datalink, were categorized according to the likelihood of eosinophilic phenotype using the International Severe Asthma Registry gradient eosinophilic algorithm. Patient demographic, clinical and HCRU characteristics were described for each phenotype., Results: Of 241,006 patients, 50.3%, 22.2%, and 21.9% most likely (grade 3), likely (grade 2), and least likely (grade 1), respectively, had an eosinophilic phenotype, and 5.6% had a noneosinophilic phenotype (grade 0). Compared with patients with noneosinophilic asthma, those most likely to have an eosinophilic phenotype tended to have more comorbidities (percentage with Charlson comorbidity index of ≥2: 28.2% vs 6.9%) and experienced more asthma attacks (percentage with one or more attack: 24.8% vs 15.3%). These patients were also more likely to have asthma that was difficult to treat (31.1% vs 18.3%), to receive more intensive treatment (percentage on Global Initiative for Asthma 2020 step 4 or 5: 44.2% vs 27.5%), and greater HCRU (eg, 10.8 vs 7.9 general practitioner all-cause consultations per year)., Conclusions: The eosinophilic asthma phenotype predominates in primary care and is associated with greater asthma severity and HCRU. These patients may benefit from earlier and targeted asthma therapy., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Allergy, eosinophilic inflammation, and epithelial dysregulation are implicated in severe asthma pathogenesis., Objective: We characterized biomarker expression in adults with severe asthma., Methods: Within the International Severe Asthma Registry (ISAR), we analyzed data from 10 countries in North America, Europe, and Asia, with prespecified thresholds for biomarker positivity (serum IgE ≥ 75 kU/L, blood eosinophils ≥ 300 cells/μL, and FeNO ≥ 25 ppb), and with hierarchical cluster analysis using biomarkers as continuous variables., Results: Of 1,175 patients; 64% were female, age (mean ± SD) 53 ± 15 years, body mass index (BMI) 30 ± 8, postbronchodilator forced expiratory volume in 1 second (FEV 1 ) predicted 72% ± 20%. By prespecified thresholds, 59% were IgE positive, 57% eosinophil positive, and 58% FeNO positive. There was substantial inflammatory biomarker overlap; 59% were positive for either 2 or 3 biomarkers. Five distinct clusters were identified: cluster 1 (61%, low-to-medium biomarkers) comprised highly symptomatic, older females with elevated BMI and frequent exacerbations; cluster 2 (18%, elevated eosinophils and FeNO) older females with lower BMI and frequent exacerbations; cluster 3 (14%, extremely high FeNO) older, highly symptomatic, lower BMI, and preserved lung function; cluster 4 (6%, extremely high IgE) younger, long duration of asthma, elevated BMI, and poor lung function; cluster 5 (1.2%, extremely high eosinophils) younger males with low BMI, poor lung function, and high burden of sinonasal disease and polyposis., Conclusions: There is significant overlap of biomarker positivity in severe asthma. Distinct clusters according to biomarker expression exhibit unique clinical characteristics, suggesting the occurrence of discrete patterns of underlying inflammatory pathway activation and providing pathogenic insights relevant to the era of monoclonal biologics., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Oral corticosteroids (OCS) carry serious health risks. Innovative treatment options are required to reduce excessive exposure and promote OCS stewardship., Objectives: This study evaluated the trajectories of OCS exposure (prednisolone-equivalent) in patients with severe eosinophilic asthma before and after starting mepolizumab and the predictors of becoming OCS free after 6 months of mepolizumab therapy., Methods: This real-world observational study included 309 patients from the Australian Mepolizumab Registry who were followed up for 1 year (n = 225)., Results: Patients had a median age of 60 (interquartile range: 50, 68) years, and 58% were female. At baseline, 48% used maintenance OCS, 96% had ≥1 OCS burst, and 68% had received ≥1 g of OCS in the previous year. After commencing mepolizumab, only 55% of those initially on maintenance OCS remained on this treatment by 12 months. Maintenance OCS dose reduced from median 10 (5.0, 12.5) mg/day at baseline to 2 (0, 7.0) mg/day at 12 months (P < .001). Likewise, proportions of patients receiving OCS bursts in the previous year reduced from 96% at baseline to 50% at 12 months (P < .001). Overall, 137 (48%) patients required OCS (maintenance/burst) after 6 months' mepolizumab therapy. Becoming OCS free was predicted by a lower body mass index (odds ratio: 0.925; 95% confidence interval: 0.872-0.981), late-onset asthma (1.027; 1.006-1.048), a lower Asthma Control Test score (1.111; 0.011-1.220), and not receiving maintenance OCS therapy at baseline (0.095; 0.040-0.227)., Conclusion: Mepolizumab led to a significant and sustained reduction in OCS dependence in patients with severe eosinophilic asthma. This study supports the OCS-sparing effect of mepolizumab and highlights the pivotal role of mepolizumab in OCS stewardship initiatives., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Where an ongoing requirement for intravenous iron replacement exists after an index infusion reaction, current recommendations are limited to expert opinion and isolated case reports., Objective: To evaluate the safety of recommencing an infusion or subsequent rechallenge following an infusion reaction to intravenous iron., Methods: Infusion reactions to intravenous iron occurring between January 1, 2010, and December 31, 2019, at a metropolitan health network were identified. Patient characteristics, reaction type (mild, moderate, or severe hypersensitivity, delayed, or Fishbane: transient flushing and truncal myalgias), and outcomes of recommencing the index infusion or subsequent rechallenge were examined., Results: Among 13,509 iron infusions, 195 infusion reactions occurred in 195 patients (1.4% of infusions). Recommencement of the index infusion (generally with a reduced infusion rate and premedication) was tolerated in 33 of 33 patients with Fishbane (20 of 20) or mild (9 of 9) and moderate (4 of 4) hypersensitivity reactions. Subsequent rechallenge (generally at standard infusion rates to an alternative formulation, ferric carboxymaltose) was successful in 68 of 69 patients with Fishbane (23 of 23), mild (26 of 26), moderate (16 of 17), and severe (3 of 3) hypersensitivity, or delayed (2 of 2) reactions. All 9 patients rechallenged to the original formulation (iron polymaltose) completed the infusion., Conclusions: Following an infusion reaction to intravenous iron infusion, recommencement of the index infusion is safe for Fishbane or mild and moderate hypersensitivity reactions. Subsequent rechallenge to an alternative formulation is tolerated, including in severe hypersensitivity reactions (albeit based on limited numbers). Where alternative formulations are not available, rechallenge to the same formulation could be considered, depending on the risk-benefit profile., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Difficult-to-treat asthma affects a minority of adults and children with asthma but represents a challenging mix of misdiagnosis, multimorbidity, inadequate self-management, severe airway pathobiology, and treatment complications. Management of these patients extends beyond asthma pharmacotherapy, because multiple other patient-related domains need to be addressed as well. Such complexity can hinder adequate clinical assessment even when performed in specialist practice. Systematic assessment undertaken by specialized multidisciplinary teams brings a broad range of resources to bear on patients with difficult-to-treat asthma. Although the concept of systematic assessment is not new, practices vary considerably and implementation is not universal. Nevertheless, assessment protocols are already in place in several institutions worldwide, and outcomes after such assessments have been highly encouraging. This review discusses the rationale, components, and benefits of systematic assessment, outlining its clinical utility and the available evidence for improved outcomes. It describes a range of service configurations and assessment approaches, drawing examples from severe asthma centers around the world to highlight common essential elements. It also provides a framework for establishing such services and discusses practical considerations for implementation., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Many patients with difficult asthma also have coexisting vocal cord dysfunction (VCD), evident by paradoxical vocal fold motion (PVFM) on laryngoscopy., Objective: Among patients with difficult asthma, we sought to identify clinical features associated with laryngoscopy-diagnosed PVFM., Methods: Consecutive patients with "difficult asthma" referred by respiratory specialists underwent systematic assessment in this observational study. Those with a high clinical suspicion for VCD were referred for laryngoscopy, either at rest or after mannitol provocation. Statistical analyses were performed to identify clinical factors associated with PVFM, and a multivariate logistic regression model was fitted to control for confounders., Results: Of 169 patients with difficult asthma, 63 (37.3%) had a high clinical probability of VCD. Of 42 who underwent laryngoscopy, 32 had PVFM confirmed. Patients with PVFM more likely had preserved lung function (prebronchodilator forced expiratory ratio 74% ± 11 vs 62% ± 16, P < .001); physiotherapist-confirmed dysfunctional breathing (odds ratio [OR] = 5.52, 95% confidence interval [CI]: 2.4-12.7, P < .001), gastro-oesophageal reflux (OR = 2.6, 95% CI: 1.16-5.8, P = .02), and a lower peripheral eosinophil count (0.09 vs 0.23, P = .004). On multivariate logistic regression, independent predictors for PVFM were dysfunctional breathing (OR = 4.93, 95% CI: 2-12, P < .001) and preserved lung function (OR = 1.07, 95% CI: 1.028-1.106, P < .001)., Conclusion: Among specialist-referred patients with difficult asthma, VCD pathogenesis may overlap with dysfunctional breathing but is not associated with severe airflow obstruction. Dysfunctional breathing and preserved lung function may serve as clinical clues for the presence of VCD., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Global Initiative for Asthma step 5 therapies (GINA-5), other than inhaled corticosteroids and long-acting β-agonists in fixed dose combinations (ICS/LABA FDC), often entail more expensive (eg, monoclonal biologics) or less safe (eg, maintenance oral corticosteroids [OCS]) treatments. It is therefore important to assess poor inhaler adherence as a possible cause of suboptimal response to ICS/LABA FDC before additional GINA-5., Objective: To determine rates of, and time to, additional GINA-5 after first-year ICS/LABA FDC use, and their association with inhaler adherence., Methods: Patients initiating ICS/LABA FDC between 2013 and 2017 were identified from Australian national dispensing data. Group-based trajectory modeling was used to estimate medication adherence patterns. Multivariable Cox proportional hazards models were used to examine the association between adherence trajectories and GINA-5 addition during 2-year follow-up., Results: In total, 3062 new ICS/LABA FDC users were identified, of whom 120 (3.9%) received additional GINA-5 (OCS: 89; long-acting muscarinic antagonists: 39; biologics: <3). Mean time to commencing additional GINA-5 was 705.2 (standard deviation, 1.7) days. Adherence trajectories were nonpersistent use (20%), seasonal use (8%), poor adherence (58%), and good adherence (13%). Although poor adherence was associated with longer time to additional GINA-5 (adjusted hazard ratio: 0.58; 95% confidence interval: 0.35-0.95), over 80% of additional GINA-5 was commenced in poorly adherent patients. Use of ≥2 OCS/antibiotic courses also predicted additional GINA-5., Conclusions: Almost 1 in 20 people with asthma commenced additional GINA-5 after ICS/LABA initiation, most of whom (>80%) were poorly adherent to inhaled preventers. There is a substantial unmet need for inhaler adherence to be addressed before prescribing additional GINA-5., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Guidelines endorse systematic assessment for severe asthma, with data indicating benefit across multiple outcome domains., Objective: We examined which patients respond to systematic assessment and whether oral corticosteroid burden can be decreased independent of monoclonal biologic use., Methods: Specialist-referred patients are assessed systematically for difficult asthma at our center. We undertook a responder analysis for improvements in the domains of symptom control, quality of life, exacerbations, and airflow obstruction, assessed 6 months after initial assessment. Multivariate analyses were performed for each domain to identify predictors of response. Changes in oral corticosteroid burden were also measured, stratified by monoclonal biologics commenced during assessment., Results: Among 161 patients assessed systematically, 64% had a reduction in exacerbations, 54% achieved minimum clinically important differences for both symptom control and quality of life, and 40% increased their forced expiratory volume in 1 second by ≥100 mL. Altogether, 87% of patients with asthma improved in at least 1 domain. The most consistent predictor of response across domains was poorer baseline asthma status. There was a substantial reduction in mean chronic oral corticosteroid dose (11-5 mg, n = 46, P < .001), even after excluding 7 patients commenced on monoclonal biologics (11-5.6 mg, n = 39, P < .001)., Conclusions: Almost 90% of patients undergoing systematic assessment for difficult asthma improve significantly in at least 1 key asthma outcome, with few reliable predictors of response. The halving of oral corticosteroid burden during systematic assessment is independent of, and comparable in magnitude with, that achieved by monoclonal biologics., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Chronic rhinosinusitis (CRS) is an extrapulmonary manifestation in some individuals with bronchiectasis, but the prevalence of CRS in this population and its clinical impact has not been systematically reviewed., Objective: To systematically review the prevalence of CRS in bronchiectasis and identify its clinical implications., Methods: Four databases were searched from inception to August 2018 for studies reporting the prevalence and/or clinical impact of CRS in individuals with bronchiectasis. Clinical outcomes included health-related quality of life (HRQOL), severity of bronchiectasis, lung function, clinical and psychological symptoms, exacerbation frequency, and health care utilization. Two independent reviewers rated the quality of evidence using the risk of bias for prevalence trials tool., Results: Of 80 studies identified, 8 studies with 797 participants (all adults) were included. Mean FEV 1 % predicted was 77.7%. Overall, 5 studies were classed as low risk of bias and 3 were of moderate risk of bias. The pooled prevalence of clinical and/or radiological CRS was 62% (95% CI, 50%-74%). CRS was associated with a greater degree of bronchiectasis severity, poorer HRQOL, reduction in smell detection, elevated levels of inflammatory markers, and reduced time to first exacerbation. However, the association with airflow obstruction was inconsistent and there was no impact on anxiety or depression., Conclusions: CRS is present in 62% of adults with bronchiectasis. Its presence is associated with poorer HRQOL, greater degree of disease severity, and more extensive radiological bronchiectasis., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Understanding of dysfunctional breathing in patients with difficult asthma who remain symptomatic despite maximal inhaler therapy is limited., Objective: We characterized the pattern of dysfunctional breathing in patients with difficult asthma and identified possible contributory factors., Methods: Dysfunctional breathing was identified in patients with difficult asthma using the Nijmegen Questionnaire (score >23). Demographic characteristics, asthma variables, and comorbidities were assessed. Multivariate logistic regression was performed for dysfunctional breathing, adjusted for age, sex, body mass index, and airflow obstruction., Results: Of 157 patients with difficult asthma, 73 (47%) had dysfunctional breathing. Compared with patients without dysfunctional breathing, those with dysfunctional breathing experienced poorer asthma status (symptom control, quality of life, and exacerbation rates) and greater unemployment. In addition, more frequently they had elevated sino-nasal outcome test scores, anxiety, depression, sleep apnea, and gastroesophageal reflux. On multivariate analysis, anxiety (odds ratio [OR], 3.26; 95% CI, 1.18-9.01; P = .02), depression (OR, 2.8; 95% CI, 1.14-6.9; P = .03), and 22-item sino-nasal outcome test score (OR, 1.03; 95% CI, 1.003-1.05; P = .03) were independent risk factors for dysfunctional breathing., Conclusions: Dysfunctional breathing is common in difficult asthma and associated with worse asthma status and unemployment. The independent association with psychological disorders and nasal obstruction highlight an important interaction between comorbid treatable traits in difficult asthma., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Severe asthma is complex and heterogeneous; ad hoc outpatient assessment can be suboptimal. Systematic evaluation improves outcomes and is recommended by international guidelines. Electronic templates improve physician performance and clinical processes, and may be useful in severe asthma systematic evaluation. We developed the Severe Asthma Global Evaluation (SAGE) electronic platform to streamline this process, via Research Electronic Data Capture (REDCap). It incorporates: a questionnaire battery for patient completion before clinical consultation; asthma and comorbidity modules; a clinical summary page in an asthma management module; a nurse educator module; a structured panel discussion record; and an automatically generated report incorporating all key data. SAGE incorporates 282 clinician input fields, with a typical consultation requiring completion of 169. To streamline the process SAGE contains 34 autocalculations and 20 decision support tools. It incorporates all 95 core variables of the International Severe Asthma Registry, with which it is directly compatible. SAGE improves symptom control and exacerbations in patients with difficult asthma. In conclusion, we developed and validated an electronic platform that facilitates a comprehensive but streamlined systematic evaluation of severe asthma that is available for free download via REDCap. Its use enhances management of patients with severe asthma and facilitates audit and international research collaboration., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The lack of centralized data on severe asthma has resulted in a scarcity of information about the disease and its management. The development of a common data collection tool for the International Severe Asthma Registry (ISAR) will enable standardized data collection, subsequently enabling data interoperability., Objectives: To create a standardized list of variables for the first international registry for severe asthma via expert consensus., Methods: A modified Delphi process was used to reach consensus on a minimum set of variables to capture in ISAR: the core variables. The Delphi panel brought together 27 international experts in the field of severe asthma research. The process consisted of 3 iterative rounds. In each round, all Delphi panel members were issued an electronic ISAR Delphi workbook to complete and return to the ISAR Delphi administrator. Workbooks and result summaries were anonymously distributed by the Delphi administrator to all panel members at subsequent rounds. Finalization of the core variable list was facilitated by 2 face-to-face meetings., Results: Of the initial 747 selected variables, the Delphi panel reached a consensus on 95. The chosen variables will allow severe asthma to be assessed against patient demographics and medical history, patient-reported outcomes, diagnostic information, and clinical characteristics. Physician-reported outcomes such as nonadherence and information about treatment and management strategies will also be recorded., Conclusions: This is the first global attempt to generate an ISAR using a common set of core variables to ensure that data collected across all participating countries are standardized., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Systematic evaluation is advocated for difficult asthma, but how best to deliver such care is unclear and outcome data are scarce., Objective: We describe our institution's structured approach to difficult asthma management and report on the outcomes of such an approach., Methods: Eighty-two consecutive patients with difficult asthma referred to our clinic from respiratory specialists were evaluated in 3 key areas: diagnostic confirmation, comorbidity detection, and inflammatory phenotyping. We then optimized treatment including relevant comorbidity interventions. The outpatient protocol was supported by comorbidity questionnaires, an electronic clinic template, and standardized panel discussion. Asthma outcomes were assessed at 6 months., Results: Sixty-eight patients completed follow-up. Asthma diagnosis was refuted in 3 patients and the remaining 65 patients were included in the study analysis. There was no overall escalation of inhaled or oral corticosteroids. Patients had a median of 3 comorbidities, and a median of 3 comorbidity interventions. Control of chronic rhinosinusitis and dysfunctional breathing improved among patients with these diagnoses (22-item Sino-Nasal Outcome Test score from 47 ± 20 to 37 ± 22, P = .017; Nijmegen score from 32 ± 6 to 25 ± 9, P = .003). There were overall improvements in the Asthma Control Test score (from 14 ± 5 to 16 ± 6, P < .001), the Asthma Quality of Life Questionnaire (from 4.29 ± 1.4 to 4.65 ± 1.5, P = .073), and the frequency of exacerbations over 6 months (from 2 [interquartile range, 0-4] to 0 [interquartile range, 0-2], P < .001)., Conclusions: In patients referred with difficult asthma from respiratory specialists, a structured approach coupled with targeted comorbidity interventions improved control of key comorbidities and enhanced asthma outcomes., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)