Recent developments in occupational asthma.

PURPOSE OF REVIEW: Occupational asthma (OA) is a complex condition that can be difficult to diagnose. The purpose of this review is to describe some recent findings regarding the epidemiology of OA, the occupational sensitizing agents, the prognosis of OA, and its primary prevention. RECENT FINDINGS: The risk of developing OA varies according to the geographic localization of the worker, the type of industry and the type of sensitizing agents. New findings have been reported for several known sensitizing agents, such as isocyanates, seafood & cleaning agents, and their related industries, such as hairdressing salons and schools. Moreover, a few new sensitizing agents, such as cannabis, have been identified in the past few years. The prognosis of OA seems worse than that of nonwork-related asthma. It is mainly determined by the duration and the level of exposure. Primary prevention is crucial to reduce the number of new cases of OA. Complete avoidance of exposure to the causal agent remains the optimal treatment of sensitizer-induced OA. SUMMARY: Improving our knowledge regarding OA and its causative agents is key to enable an early recognition of this condition and improve its prognosis. Further research is still needed to improve primary prevention.

Work-Related Asthma and Its Impact on Quality of Life and Work Productivity.

BACKGROUND: The impact of work-related asthma (WRA) on quality of life (QoL) and work productivity remains largely neglected/uncertain despite its high prevalence. OBJECTIVE: To investigate the association of WRA with QoL and work productivity as compared with subjects with non-WRA and those without asthma and rhinitis. METHODS: A cross-sectional survey was carried out among workers during their periodic occupational health visit in Belgium. The Mini Asthma Quality of Life Questionnaire, the 8-item Medical Outcome Study Short Form instrument, and the Work Productivity and Activity Impairment-General Health questionnaire were administered. Survey participants were divided into 3 groups: (1) WRA (current asthma with ≥2 respiratory symptoms at work; n = 89); (2) non-WRA (current asthma without work-related respiratory symptoms; n = 119); and (3) the reference group (no asthma and no lower respiratory, nasal, or eye symptoms; n = 815). Associations of QoL and work productivity with WRA were evaluated by multivariable regression analyses. RESULTS: WRA and having poor asthma control were significantly associated with lower global Mini Asthma Quality of Life Questionnaire scores compared with non-WRA. Asthmatic subjects had significantly lower physical and mental health component scores of the 8-item Medical Outcome Study Short Form instrument and overall work productivity compared with the reference group, with greater impairment in workers with WRA than in those without WRA. Moreover, workers with WRA had higher percentages of doctor visits and income reduction because of respiratory symptoms than those with non-WRA. Work-related rhinitis and depression were associated with reduced QoL, independent of the effect of WRA. CONCLUSIONS: WRA should be managed comprehensively to reduce the worsening of QoL and work productivity of those affected.

Anticipating undiagnosed asthma in symptomatic adults with normal pre- and post-bronchodilator spirometry: a decision tool for bronchial challenge testing.

BACKGROUND: Some patients with asthma demonstrate normal spirometry and remain undiagnosed without further testing. OBJECTIVE: To determine clinical predictors of asthma in symptomatic adults with normal spirometry, and to generate a tool to help clinicians decide who should undergo bronchial challenge testing (BCT). METHODS: Using random-digit dialling and population-based case-finding, we recruited adults from the community with respiratory symptoms and no previous history of diagnosed lung disease. Participants with normal pre- and post-bronchodilator spirometry subsequently underwent BCT. Asthma was diagnosed in those with symptoms and a methacholine provocative concentration (PC20) of < 8 mg/ml. Sputum and blood eosinophils, and exhaled nitric oxide were measured. Univariate analyses identified potentially predictive variables, which were then used to construct a multivariable logistic regression model to predict asthma. Model sensitivity, specificity, and area under the receiver operating curve (AUC) were calculated. RESULTS: Of 132 symptomatic individuals with normal spirometry, 34 (26%) had asthma. Of those ultimately diagnosed with asthma, 33 (97%) answered 'yes' to a question asking whether they experienced cough, chest tightness or wheezing provoked by exercise or cold air. Other univariate predictors of asthma included female sex, pre-bronchodilator FEV1 percentage predicted, and percent positive change in FEV1 post bronchodilator. A multivariable model containing these predictive variables yielded an AUC of 0.82 (95% CI: 0.72-0.91), a sensitivity of 82%, and a specificity of 66%. The model was used to construct a nomogram to advise clinicians which patients should be prioritized for BCT. CONCLUSIONS: Four readily available patient characteristics demonstrated a high sensitivity and AUC for predicting undiagnosed asthma in symptomatic adults with normal pre- and post-bronchodilator spirometry. These characteristics can potentially help clinicians to decide which individuals with normal spirometry should be investigated with bronchial challenge testing. However, further prospective validation of our decision tool is required.

Impact of Undiagnosed Chronic Obstructive Pulmonary Disease and Asthma on Symptoms, Quality of Life, Healthcare Use, and Work Productivity.

Rationale: A significant proportion of individuals with chronic obstructive pulmonary disease (COPD) and asthma remain undiagnosed. Objectives: The objective of this study was to evaluate symptoms, quality of life, healthcare use, and work productivity in subjects with undiagnosed COPD or asthma compared with those previously diagnosed, as well as healthy control subjects. Methods: This multicenter population-based case-finding study randomly recruited adults with respiratory symptoms who had no previous history of diagnosed lung disease from 17 Canadian centers using random digit dialing. Participants who exceeded symptom thresholds on the Asthma Screening Questionnaire or the COPD Diagnostic Questionnaire underwent pre- and post-bronchodilator spirometry to determine if they met diagnostic criteria for COPD or asthma. Two control groups, a healthy group without respiratory symptoms and a symptomatic group with previously diagnosed COPD or asthma, were similarly recruited. Measurements and Main Results: A total of 26,905 symptomatic individuals were interviewed, and 4,272 subjects were eligible. Of these, 2,857 completed pre- and post-bronchodilator spirometry, and 595 (21%) met diagnostic criteria for COPD or asthma. Individuals with undiagnosed COPD or asthma reported greater impact of symptoms on health status and daily activities, worse disease-specific and general quality of life, greater healthcare use, and poorer work productivity than healthy control subjects. Individuals with undiagnosed asthma had symptoms, quality of life, and healthcare use burden similar to those of individuals with previously diagnosed asthma, whereas subjects with undiagnosed COPD were less disabled than those with previously diagnosed COPD. Conclusions: Undiagnosed COPD or asthma imposes important, unmeasured burdens on the healthcare system and is associated with poor health status and negative effects on work productivity.

Canadian multidisciplinary expert consensus on the use of biologics in upper airways: a Delphi study.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) often coexists with lower airway disease. With the overlap between upper and lower airway disease, optimal management of the upper airways is undertaken in conjunction with that of the lower airways. Biologic therapy with targeted activity within the Type 2 inflammatory pathway can improve the clinical signs and symptoms of both upper and lower airway diseases. Knowledge gaps nevertheless exist in how best to approach patient care as a whole. There have been sixteen randomized, double-blind, placebo-controlled trails performed for CRSwNP targeted components of the Type 2 inflammatory pathway, notably interleukin (IL)-4, IL-5 and IL-13, IL- 5R, IL-33, and immunoglobulin (Ig)E. This white paper considers the perspectives of experts in various disciplines such as rhinology, allergy, and respirology across Canada, all of whom have unique and valuable insights to contribute on how to best approach patients with upper airway disease from a multidisciplinary perspective. METHODS: A Delphi Method process was utilized involving three rounds of questionnaires in which the first two were completed individually online and the third was discussed on a virtual platform with all the panelists. A national multidisciplinary expert panel of 34 certified specialists was created, composed of 16 rhinologists, 7 allergists, and 11 respirologists who evaluated the 20 original statements on a scale of 1-9 and provided comments. All ratings were quantitively reviewed by mean, median, mode, range, standard deviation and inter-rater reliability. Consensus was defined by relative interrater reliability measures-kappa coefficient ([Formula: see text]) value > 0.61. RESULTS: After three rounds, a total of 22 statements achieved consensus. This white paper only contains the final agreed upon statements and clear rationale and support for the statements regarding the use of biologics in patients with upper airway disease. CONCLUSION: This white paper provides guidance to Canadian physicians on the use of biologic therapy for the management of upper airway disease from a multidisciplinary perspective, but the medical and surgical regimen should ultimately be individualized to the patient. As more biologics become available and additional trials are published we will provide updated versions of this white paper every few years.

Diagnosis and Assessment of the Asthmas.

Optimizing asthma diagnosis is an essential part of global strategies to reduce the excessive illness burden from asthma. New understanding about how to address the complexity and heterogeneity of the different forms of asthma means that asthma diagnosis now requires a compound diagnostic approach and label. Eliciting the typical symptoms and abnormal physiology of variable airflow limitation permits the recognition of asthma, and the identification of further features, such as eosinophilic or type 2 inflammation, allows a compound diagnostic label of eosinophilic asthma. This conveys key information about future exacerbation risk and likely treatment responsiveness. Treatable traits are a useful way to implement this new approach to diagnosis. Targeted assessment is used to inform a specific treatment plan in a pragmatic and iterative process.

Patient and physician factors associated with symptomatic undiagnosed asthma or COPD.

BACKGROUND: It remains unclear why some symptomatic individuals with asthma or COPD remain undiagnosed. Here, we compare patient and physician characteristics between symptomatic individuals with obstructive lung disease (OLD) who are undiagnosed and individuals with physician-diagnosed OLD. METHODS: Using random-digit dialling and population-based case finding, we recruited 451 participants with symptomatic undiagnosed OLD and 205 symptomatic control participants with physician-diagnosed OLD. Data on symptoms, quality of life and healthcare utilisation were analysed. We surveyed family physicians of participants in both groups to elucidate differences in physician practices that could contribute to undiagnosed OLD. RESULTS: Participants with undiagnosed OLD had lower mean pre-bronchodilator forced expiratory volume in 1 s percentage predicted compared with those who were diagnosed (75.2% versus 80.8%; OR 0.975, 95% CI 0.963-0.987). They reported greater psychosocial impacts due to symptoms and worse energy and fatigue than those with diagnosed OLD. Undiagnosed OLD was more common in participants whose family physicians were practising for >15 years and in those whose physicians reported that they were likely to prescribe respiratory medications without doing spirometry. Undiagnosed OLD was more common among participants who had never undergone spirometry (OR 10.83, 95% CI 6.18-18.98) or who were never referred to a specialist (OR 5.92, 95% CI 3.58-9.77). Undiagnosed OLD was less common among participants who had required emergency department care (OR 0.44, 95% CI 0.20-0.97). CONCLUSIONS: Individuals with symptomatic undiagnosed OLD have worse pre-bronchodilator lung function and present with greater psychosocial impacts on quality of life compared with their diagnosed counterparts. They were less likely to have received appropriate investigations and specialist referral for their respiratory symptoms.

Airway inflammation and hyperresponsiveness in subjects with respiratory symptoms and normal spirometry.

BACKGROUND: Subjects without a previous history of asthma, presenting with unexplained respiratory symptoms and normal spirometry, may exhibit airway hyperresponsiveness (AHR) in association with underlying eosinophilic (type 2 (T2)) inflammation, consistent with undiagnosed asthma. However, the prevalence of undiagnosed asthma in these subjects is unknown. METHODS: In this observational study, inhaled corticosteroid-naïve adults without previously diagnosed lung disease reporting current respiratory symptoms and showing normal pre- and post-bronchodilator spirometry underwent fractional exhaled nitric oxide (F ENO) measurement, methacholine challenge testing and induced sputum analysis. AHR was defined as a provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 s (PC20) <16 mg·mL-1 and T2 inflammation was defined as sputum eosinophils >2% and/or F ENO >25 ppb. RESULTS: Out of 132 subjects (mean±sd age 57.6±14.2 years, 52% female), 47 (36% (95% CI 28-44%)) showed AHR: 20/132 (15% (95% CI 9-21%)) with PC20 <4 mg·mL-1 and 27/132 (21% (95% CI 14-28%)) with PC20 4-15.9 mg·mL-1. Of 130 participants for whom sputum eosinophils, F ENO or both results were obtained, 45 (35% (95% CI 27-43%)) had T2 inflammation. 14 participants (11% (95% CI 6-16%)) had sputum eosinophils >2% and PC20 ≥16 mg·mL-1, suggesting eosinophilic bronchitis. The prevalence of T2 inflammation was significantly higher in subjects with PC20 <4 mg·mL-1 (12/20 (60%)) than in those with PC20 4-15.9 mg·mL-1 (8/27 (30%)) or ≥16 mg·mL-1 (25/85 (29%)) (p=0.01). CONCLUSIONS: Asthma, underlying T2 airway inflammation and eosinophilic bronchitis may remain undiagnosed in a high proportion of symptomatic subjects in the community who have normal pre- and post-bronchodilator spirometry.

Feasibility of implementing a web-based tool built from pharmacy claims data (e-MEDRESP) to monitor adherence to respiratory medications in primary care.

OBJECTIVE: e-MEDRESP is a novel web-based tool that provides easily interpretable information on patient adherence to asthma/chronic obstructive pulmonary disease (COPD) medications, using pharmacy claims data. This study investigated the feasibility of implementing e-MEDRESP in primary care. MATERIAL AND METHODS: In this 16-month prospective cohort study, e-MEDRESP was integrated into electronic medical records. Nineteen family physicians and 346 of their patients were enrolled. Counters embedded in the tool tracked physician use during the follow-up. Patient/physician satisfaction with e-MEDRESP was evaluated though telephone interviews and online questionnaires. The capacity of e-MEDRESP to improve adherence was explored using a pre-post analysis. RESULTS: Overall, 245 patients had at least one medical visit during follow-up. e-MEDRESP was consulted by 15 (79%) physicians for 85 (35%) patients during clinic visits. Seventy-three patients participated in telephone interviews; 84% reported discussing their medication use with their physician; 33% viewed their e-MEDRESP report and indicated that it was easy to interpret. The physicians reported that the tool facilitated their evaluation of their patients' medication adherence (mean ± standard deviation rating: 4.8 ± 0.7, on a 5-point Likert scale). Although the pre-post analysis did not reveal improved adherence in the overall cohort, adherence improved significantly in patients whose adherence level was <80% and who were prescribed inhaled corticosteroids (26.9% [95% CI 14.3-39.3%]) or long-acting muscarinic agents (26.4% [95% CI 12.4-40.2%]). CONCLUSIONS: e-MEDRESP was successfully integrated in clinical practice. It could serve as a useful tool to help physicians monitor their patients' medication adherence.

Development of a community pharmacy-based intervention for patients with uncontrolled asthma.

Background: Achieving asthma control is often difficult, despite the availability of effective medications. Because of their expertise, regular contact with patients, and accessibility, community pharmacists can play an important role in helping patients manage uncontrolled asthma. Objective: To develop a community pharmacy-based intervention for improving asthma control in patients with uncontrolled moderate to severe asthma. Methods: A qualitative study involving two focus groups with six and five community pharmacists, respectively, five individual interviews with community pharmacists, and three individual interviews with asthma patients was conducted using semi-structured interview guides. Focus groups aimed to develop the first prototype of the intervention and the topics included criteria to identify patients with uncontrolled asthma, content of the intervention to manage uncontrolled asthma, and potential logistical issues. Interviews were subsequently conducted with individual pharmacists and asthma patients to evaluate the prototype and finalize the intervention. The interviews and focus group transcripts were analyzed thematically, using an iterative process. Results: In focus groups and interviews, the pharmacists discussed how they screen patients with uncontrolled asthma using prescriptions refills, their needs for a convenient tool to assess asthma control, the necessity to identify causes of uncontrolled asthma to guide asthma management strategies, and the importance of patient follow-up. During interviews, patients shared their interest for the commitment of pharmacists to managing asthma. The final intervention consists of structured face-to-face counselling sessions at community pharmacies, with six steps: screening of patients with potential uncontrolled moderate to severe asthma, assessment of asthma control, identification of the causes of uncontrolled asthma, strategies for controlling asthma, an optional follow-up at the next prescription refill, and a follow-up 3 months after the initial intervention. Conclusions: The patients and community pharmacists reached consensus on the intervention's key elements and provided support for implementing the intervention in community pharmacies.

Implementation of a Work-Related Asthma Screening Questionnaire in Clinical Settings: Multimethods Study.

BACKGROUND: A work-related asthma (WRA) screening questionnaire is currently being validated for implementation in clinical settings. To minimize barriers to integrating tools into clinical practice, a discussion of strategies for the implementation of the questionnaire has begun. OBJECTIVE: This study aimed to understand the benefits, feasibility, barriers, and limitations of implementing the Work-related Asthma Screening Questionnaire-Long version (WRASQ[L]) and asthma e-tools in clinical settings and propose dissemination and implementation strategies for the WRASQ(L). METHODS: This study was conducted in Kingston, Ontario, Canada, from September 2019 to August 2021. A workshop and 2 questionnaires were used to understand the benefits of and barriers to implementing the questionnaire in clinical settings. An expert advisory committee was established to develop the implementation and dissemination strategies. Workshops were semistructured and used thematic qualitative analysis to identify themes that provided an understanding of the benefits and limitations of and barriers to using the WRASQ(L), and e-tools in general, in clinical settings. Workshop participants included patients and health care providers, including physicians, nurses, and asthma educators, who were implementation specialists and expert electronic medical record users. A questionnaire focusing on providers' knowledge and awareness of WRA and another focusing on WRASQ(L) feedback was administered at the workshops. Advisory committee members from relevant stakeholders met 3 times to strategize implementation opportunities. RESULTS: A total of 6 themes were identified in the workshop: involving and addressing patient needs, novel data collection, knowledge translation, time considerations, functional and practical barriers, and human limitations. Questionnaire responses yielded positive feedback on the utility of the WRASQ(L) in clinical settings. All participants agreed that it is an easy way of collecting information on occupational and exposure history and could prompt a discussion between the health care provider and patient on how the workplace and exposures could affect one's asthma, increase awareness of WRA in patients and providers, and increase awareness of exposures in the workplace. Implementation and dissemination strategies were generated with input from the advisory committee. CONCLUSIONS: Stakeholders and workshop participants consider the WRASQ(L) to be a useful tool that satisfies many provider needs in their clinical settings. Once validated, dissemination strategies will include developing educational materials that include the WRASQ(L), linking the questionnaire to stakeholder websites or e-toolkits, translation into other languages, leveraging health care and research networks, conference presentations, and peer-reviewed publications. Implementation strategies will include integration into electronic medical records; designing multifaceted interventions; and targeting nontraditional settings such as workplaces, pharmacies, and research settings. The WRASQ(L) addresses many benefits of and barriers to implementation, as identified in the workshop themes. These themes will guide future implementation and dissemination strategies, noting that human limitations identified in providers and patients will need to be overcome for successful implementation.

Disease burden in individuals with symptomatic undiagnosed asthma or COPD.

BACKGROUND: The actual burden of COPD and asthma may be much higher than appreciated, since a large proportion of individuals are not diagnosed. Our study objective was to compare health care utilization, burden of symptoms and quality of life in subjects with self-reported respiratory symptoms who were subsequently found to have undiagnosed airflow obstruction compared to those having no airflow obstruction. METHODS: This cross-sectional case-finding study used data from the Undiagnosed COPD and Asthma Population (UCAP) study. Adult subjects with respiratory symptoms who had no history of diagnosed lung disease were recruited in a two-step case-finding process using random digit-dialling of land lines and cell phones located within a 90-min radius of 16 Canadian study sites. Participants were assessed for COPD, asthma or no airflow obstruction using pre- and post-bronchodilator spirometry based on American Thoracic Society diagnostic criteria. RESULTS: 1660 participants were recruited, of these 1615 had adequate spirometry and 331 (20.5%) subjects met spirometry criteria for undiagnosed asthma or COPD. Subjects with undiagnosed asthma or COPD had increased respiratory symptoms as assessed by the COPD Assessment Test (CAT), and higher St. George's Respiratory Questionnaire (SGRQ) scores indicating worse health-related quality of life, compared to subjects with no airflow obstruction. No between-group differences were found in health care utilization or work or school absenteeism. CONCLUSION: Undiagnosed asthma and COPD are common in Canadian adults experiencing breathing problems and are associated with a greater burden of symptoms and poorer health-related quality of life. These results suggest that patients may benefit from early identification and treatment of undiagnosed asthma and COPD.

Irritant-Induced Asthma.

Irritant-induced asthma (IIA) is a phenotype of asthma caused by the inhalation of irritant agents. Definite, probable, or possible IIA have been described, depending on the concentration of the inhaled irritants and the onset of respiratory symptoms respective to the time of exposure. Definite IIA represents approximately 4% to 14% of all cases of new-onset work-related asthma. Agents responsible for IIA can be encountered as fumes, gases, aerosols, or dusts. The most frequent are chlorine, nitrogen oxides, sulfur dioxide, ammonia, acetic acid, solvents, and cleaning materials. Although the diagnosis of definite IIA is based on a suggestive clinical history along with evidence of reversible airflow limitation and/or nonspecific bronchial hyperresponsiveness, possible IIA cannot be diagnosed with certainty because the relationship between exposure and the onset of symptoms is difficult to establish. This article reviews the epidemiology, pathophysiology, diagnostic approach, and management of IIA.

Derivation and validation of the UCAP-Q case-finding questionnaire to detect undiagnosed asthma and COPD.

BACKGROUND: Many people with asthma and COPD remain undiagnosed. We developed and validated a new case-finding questionnaire to identify symptomatic adults with undiagnosed obstructive lung disease. METHODS: Adults in the community with no prior history of physician-diagnosed lung disease who self-reported respiratory symptoms were contacted via random-digit dialling. Pre- and post-bronchodilator spirometry was used to confirm asthma or COPD. Predictive questions were selected using multinomial logistic regression with backward elimination. Questionnaire performance was assessed using sensitivity, predictive values and area under the receiver operating characteristic curve (AUC). The questionnaire was assessed for test-retest reliability, acceptability and readability. External validation was prospectively conducted in an independent sample and predictive performance re-evaluated. RESULTS: A 13-item Undiagnosed COPD and Asthma Population Questionnaire (UCAP-Q) case-finding questionnaire to predict undiagnosed asthma or COPD was developed. The most appropriate risk cut-off was determined to be 6% for either disease. Applied to the derivation sample (n=1615), the questionnaire yielded a sensitivity of 92% for asthma and 97% for COPD; specificity of 17%; and an AUC of 0.69 (95% CI 0.64-0.74) for asthma and 0.82 (95% CI 0.78-0.86) for COPD. Prospective validation using an independent sample (n=471) showed sensitivities of 93% and 92% for asthma and COPD, respectively; specificity of 19%; with AUCs of 0.70 (95% CI 0.62-0.79) for asthma and 0.81 (95% CI 0.74-0.87) for COPD. AUCs for UCAP-Q were higher compared to AUCs for currently recommended case-finding questionnaires for asthma or COPD. CONCLUSIONS: The UCAP-Q demonstrated high sensitivities and AUCs for identifying undiagnosed asthma or COPD. A web-based calculator allows for easy calculation of risk probabilities for each disease.

EAACI position paper on the clinical use of the bronchial allergen challenge: Unmet needs and research priorities.

Allergic asthma (AA) is a common asthma phenotype, and its diagnosis requires both the demonstration of IgE-sensitization to aeroallergens and the causative role of this sensitization as a major driver of asthma symptoms. Therefore, a bronchial allergen challenge (BAC) would be occasionally required to identify AA patients among atopic asthmatics. Nevertheless, BAC is usually considered a research tool only, with existing protocols being tailored to mild asthmatics and research needs (eg long washout period for inhaled corticosteroids). Consequently, existing BAC protocols are not designed to be performed in moderate-to-severe asthmatics or in clinical practice. The correct diagnosis of AA might help select patients for immunomodulatory therapies. Allergen sublingual immunotherapy is now registered and recommended for controlled or partially controlled patients with house dust mite-driven AA and with FEV1 ≥ 70%. Allergen avoidance is costly and difficult to implement for the management of AA, so the proper selection of patients is also beneficial. In this position paper, the EAACI Task Force proposes a methodology for clinical BAC that would need to be validated in future studies. The clinical implementation of BAC could ultimately translate into a better phenotyping of asthmatics in real life, and into a more accurate selection of patients for long-term and costly management pathways.

Development of an operational definition of treatment escalation in adults with asthma adapted to healthcare administrative databases: A Delphi study.

BACKGROUND: In recent years, there has been growing interest in studying asthma treatment escalation patterns in the real-world setting, particularly with the advent of expensive biologic therapies. Healthcare administrative claims databases can be used to study treatment escalation patterns at a population-level; however, the reported definitions for claims-based asthma treatment escalation are highly variable in the literature. OBJECTIVE: The aim of this study was to develop an operational definition of treatment escalation in adults with asthma that can be applied to healthcare administrative data. METHODS: A mixed-methods research design incorporating the Delphi process was used to establish an expert consensus for this definition. A multi-disciplinary expert panel participated in three iterative rounds of online questionnaires covering treatment escalation criteria inspired by a systematic review, which was conducted as part of this study. The final definition was constructed using criteria for which a 75% level of agreement was achieved among the experts. RESULTS: We developed a claims-based treatment escalation definition that was adapted from the Global Initiative for Asthma (GINA) strategy. The definition comprised seven treatment steps, as well as escalation options for treatments that are not typically included in clinical guidelines. The definition also incorporated methods to identify treatments in severe asthma, such as oral corticosteroid maintenance therapy and chronic azithromycin use. CONCLUSIONS: The operational definition of treatment escalation developed in this study bridges the gap between clinical guidelines and real-world clinical practice and lays the groundwork for future observational studies on treatment escalation patterns among patients with asthma.

Impact of baseline clinical asthma characteristics on the response to mepolizumab: a post hoc meta-analysis of two Phase III trials.

BACKGROUND: Severe asthma is associated with a broad range of phenotypes and clinical characteristics. This analysis assessed whether select baseline patient characteristics could prognosticate mepolizumab efficacy in severe eosinophilic asthma. METHODS: This was a post hoc meta-analysis of data from the Phase III MENSA (NCT01691521/MEA115588) and MUSCA (NCT02281318/200862) studies. Patients aged ≥ 12 years with severe eosinophilic asthma and a history of exacerbations were randomised to receive placebo (MENSA/MUSCA), mepolizumab 75 mg intravenously (MENSA) or 100 mg subcutaneously (SC) (MENSA/MUSCA) every 4 weeks for 32 (MENSA) or 24 (MUSCA) weeks. The primary endpoint was the annual rate of clinically significant exacerbations; other outcomes included the proportion of patients with no exacerbations and changes from baseline in pre-bronchodilator forced expiratory volume in 1 s (FEV1), St George's Respiratory Questionnaire (SGRQ) total score and Asthma Control Questionnaire (ACQ)-5 score. Analyses were performed by baseline age of asthma onset (< 18 years; 18-40 years; ≥ 40 years); lung function (% predicted FEV1 ≤ 60; 60-80; > 80); airway reversibility (reversible [≥ 12% change in FEV1]; non-reversible [< 12% change in FEV1]); perennial and/or seasonal allergen sensitivity (yes/no); asthma control (uncontrolled [ACQ-5 score ≥ 1.5]; partial/complete control [ACQ-5 score < 1.5]). RESULTS: Overall, 936 patients received mepolizumab 100 mg SC or placebo. Across age at asthma onset, lung function and airway reversibility subgroups, mepolizumab reduced the rate of clinically significant exacerbations by 49-63% versus placebo. Improvements in lung function, SGRQ total score and ACQ-5 score were also seen with mepolizumab versus placebo across most age and lung function subgroups. Clinically significant exacerbations were reduced with mepolizumab versus placebo irrespective of season or allergen sensitivity; SGRQ total and ACQ-5 scores were generally improved across seasons. CONCLUSIONS: Mepolizumab efficacy was consistent for patients with varying age at asthma onset, lung function, airway reversibility and allergen sensitivities at baseline. Our results indicate that mepolizumab is likely to be beneficial for patients with severe eosinophilic asthma with a broad range of baseline clinical characteristics; large-scale real-world studies are needed to confirm the external validity of these findings. Trial registration Post hoc meta-analysis of data from MENSA (NCT01691521/MEA115588) and MUSCA (NCT02281318/200862).