Characterisation of patients with severe asthma in the UK Severe Asthma Registry in the biologic era.

BACKGROUND: The UK Severe Asthma Registry (UKSAR) is the world's largest national severe asthma registry collecting standardised data on referrals to UK specialist services. Novel biologic therapies have transformed the management of type 2(T2)-high severe asthma but have highlighted unmet need in patients with persisting symptoms despite suppression of T2-cytokine pathways with corticosteroids. METHODS: Demographic, clinical and treatments characteristics for patients meeting European Respiratory Society / American Thoracic Society severe asthma criteria were examined for 2225 patients attending 15 specialist severe asthma centres. We assessed differences in biomarker low patients (fractional exhaled nitric oxide (FeNO) <25 ppb, blood eosinophils <150/μL) compared with a biomarker high population (FeNO ≥25 ppb, blood eosinophils ≥150/µL). RESULTS: Age (mean 49.6 (14.3) y), age of asthma onset (24.2 (19.1) y) and female predominance (62.4%) were consistent with prior severe asthma cohorts. Poor symptom control (Asthma Control Questionnaire-6: 2.9 (1.4)) with high exacerbation rate (4 (IQR: 2, 7)) were common despite high-dose treatment (51.7% on maintenance oral corticosteroids (mOCS)). 68.9% were prescribed biologic therapies including mepolizumab (50.3%), benralizumab (26.1%) and omalizumab (22.6%). T2-low patients had higher body mass index (32.1 vs 30.2, p<0.001), depression/anxiety prevalence (12.3% vs 7.6%, p=0.04) and mOCS use (57.9% vs 42.1%, p<0.001). Many T2-low asthmatics had evidence of a historically elevated blood eosinophil count (0.35 (0.13, 0.60)). CONCLUSIONS: The UKSAR describes the characteristics of a large cohort of asthmatics referred to UK specialist severe asthma services. It offers the prospect of providing novel insights across a range of research areas and highlights substantial unmet need with poor asthma control, impaired lung function and high exacerbation rates. T2-high phenotypes predominate with significant differences apparent from T2-low patients. However, T2-low patients frequently have prior blood eosinophilia consistent with possible excessive corticosteroid exposure

An examination of factorial invariance of the Asthma Control Questionnaire among adults with severe asthma

BackgroundThe Asthma Control Questionnaire (ACQ) is used to assess asthma symptom control. The relationship between the questionnaire items and symptom control has not been fully studied in severe asthmatic patients, and its validity for making comparisons between subgroups of patients is unknown.MethodsData was obtained from patients in the United Kingdom Severe Asthma Registry whose symptom control was assessed using the five-item ACQ (ACQ5) (n = 2,951). Confirmatory factor analysis determined whether a latent factor for asthma symptom control, as measured by the ACQ5, was consistent with the data. Measurement invariance was examined in relation to ethnicity, sexand age; this included testing for approximate measurement invariance using Bayesian Structural Equation Modelling (BSEM). The fitted models were used to estimate the internal consistency reliability of the ACQ5. Invariance of factor means across subgroups was assessed.ResultsA one-factor construct with residual correlations for the ACQ5 was an excellent fit to the data in all subgroups (Root Mean Square Error Approximation 0.03 [90%CI 0.02,0.05], p close fit 0.93, Comparative Fit Index 1.00, Tucker Lewis Index 1.00}. Expected item responses were consistent for Caucasian and non-Caucasian patients with the same absolute level of symptom control. There was some evidence that females and younger adults reported wakening more frequently during the night than males and older adults respectivelywith the same absolute level of symptom control (p&lt;0.001). However approximate measurement invariance was tenable and any failure to observe strong measurement invariance had minimal impact when comparing mean levels of asthma symptom control between patients of different sexes or ages. Average levels of asthma symptom control were lower for non-Caucasians (p = 0.001), females (p&lt;0.01)and increased with age (p&lt;0.01). Reliability of theinstrument was high (over 88%) in all subgroups studied.ConclusionThe ACQ5 is informative in comparing levels of symptom control between severe asthmatic patients of different ethnicities, sexes and ages. It is important that analyses are replicated in other severe asthma registries to determine whether measurement invariance is observed

Ethnic differences in severe asthma clinical care and outcomes: an analysis of United Kingdom primary and specialist care.

BACKGROUND Understanding the effects of ethnicity in severe asthma is important for optimal personalised patient care. OBJECTIVE To assess ethnic differences in disease control, exacerbations, biological phenotype and treatment in UK severe asthma. METHODS We compared demographics, type-2 biomarkers, lung function, asthma control, medications and healthcare utilisation between White and ethnic minority group [EMG] patients in the UK Severe Asthma Registry (UKSAR) and Optimum Patient Care Research Database (OPCRD). RESULTS 3,637 patients (665 EMG) were included from UKSAR and 10,549 (577 EMG) from OPCRD. EMG patients had higher levels of uncontrolled disease when measured using the asthma control questionnaire in UKSAR (OR:1.47, 95%CI: 1.12-1.93) and the Royal College of Physicians 3 Questions in OPCRD (OR:1.82, 95%CI: 1.27-2.60). Although exacerbation rates were similar, EMG patients were more likely to have recently attended ED (OR:1.55, 95%CI: 1.26-1.92) or been hospitalised (OR:1.31, 95% CI: 1.07-1.59) due to their asthma. Inflammatory biomarkers were consistently higher in EMG severe asthma including blood eosinophils in OPCRD (Ratio:1.12, 95%CI: 1.05-1.20) and in UKSAR blood eosinophils (Ratio:1.16, 95%CI: 1.06-1.27), FeNO (Ratio:1.14, 95%CI: 1.04-1.26) and IgE (Ratio:1.70, 95%CI: 1.47-1.97). EMG patients were more likely to be atopic in the UKSAR (OR:1.32; 95%CI: 1.07-1.63) and OPCRD (OR:1.67; 95%CI: 1.26-2.21), and less likely to be using maintenance oral corticosteroids at referral (OR:0.75 [95%CI: 0.61-0.92]). CONCLUSIONS Severe asthma patients from EMGs presented with higher disease burden and were more likely to attend ED. They had a distinct phenotypic presentation, and differences in medicine utilisation, with higher levels of type-2 biomarkers

Ethnic differences in severe asthma clinical care and outcomes: An analysis of United Kingdom primary and specialist care

BACKGROUND: Understanding the effects of ethnicity in severe asthma is important for optimal personalized patient care.OBJECTIVE: To assess ethnic differences in disease control, exacerbations, biological phenotype, and treatment in severe asthma in the United Kingdom.METHODS: We compared demographics, type 2 biomarkers, lung function, asthma control, medications, and health care use between White and underrepresented ethnic group patients in the UK Severe Asthma Registry (UKSAR) and Optimum Patient Care Research Database (OPCRD).RESULTS: A total of 3637 patients (665 from the underrepresented ethnic group) were included from UKSAR and 10,549 (577 from the underrepresented ethnic group) from OPCRD. Patients in the underrepresented ethnic group had higher levels of uncontrolled disease when measurements were made using the asthma control questionnaire in UKSAR (odds ratio [OR] = 1.47; 95% confidence interval [CI], 1.12-1.93) and the Royal College of Physicians 3 Questions in OPCRD (OR = 1.82; 95% CI, 1.27-2.60). Although exacerbation rates were similar, patients in the underrepresented ethnic group were more likely to have recently attended the emergency department (OR = 1.55; 95% CI, 1.26-1.92) or to have been hospitalized (OR = 1.31; 95% CI, 1.07-1.59) owing to asthma. Inflammatory biomarkers were consistently higher in the underrepresented ethnic group, including blood eosinophils in OPCRD (ratio = 1.12; 95% CI, 1.05-1.20) and in UKSAR blood eosinophils (ratio = 1.16; 95% CI, 1.06-1.27), FeNO (ratio = 1.14; 95% CI, 1.04-1.26), and IgE (ratio = 1.70; 95% CI, 1.47-1.97). Patients in the underrepresented ethnic group were more likely to be atopic in the UKSAR (OR = 1.32; 95% CI, 1.07-1.63) and OPCRD (OR = 1.67; 95% CI, 1.26-2.21), and less likely to be using maintenance oral corticosteroids at referral (OR = 0.75; 95% CI, 0.61-0.92).CONCLUSIONS: Severe asthma patients from underrepresented ethnic groups presented with a higher disease burden and were more likely to attend the emergency department. They had a distinct phenotypic presentation and differences in medicine use, with higher levels of type 2 biomarkers.</p