Blood eosinophil count correlates with severity of respiratory failure in life-threatening asthma and predicts risk of subsequent exacerbations.

BACKGROUND: An elevated blood eosinophil count when asthma is stable predicts exacerbations and therapeutic response to corticosteroids or biologics targeting eosinophils. Few studies have examined the prognostic value of blood eosinophils measured at exacerbation. AIM: To elucidate the relationship between a spot blood eosinophil count-measured at the onset of a life-threatening asthma exacerbation-with indices of exacerbation severity and risk of subsequent exacerbations. METHODS: Real-world, retrospective review of all life-threatening asthma cases admitted at 4 public hospitals in Singapore between 2011-2015. We assessed the trends and correlations between blood eosinophil count on admission with arterial blood gas values, duration of mechanical ventilation, and risk of death, hypoxic ischemic encephalopathy or respiratory arrest. Risk of future exacerbations among survivors was modelled using Cox regression and survival curves. RESULTS: There were 376 index life-threatening exacerbations with median blood eosinophil count (5-95th percentiles) of 0.270 × 109 /L (0-1.410 × 109 /L). Arterial pH decreased and PCO2 increased with increasing eosinophil count. Duration of mechanical ventilation and risk of death, hypoxic ischaemic encephalopathy or respiratory arrest did not vary with eosinophils. Among 329 survivors who were followed-up over a median of 52 months, blood eosinophils ≥1.200 × 109 /L was associated with an increased hazard of emergency visits and/or admissions for asthma (hazard ratio 1.8, 95% confidence interval 1.1-2.9, P = .02). CONCLUSION: In this study of life-threatening asthma, we found that a spot blood eosinophil count correlates with severity of respiratory failure and predicts risk of subsequent exacerbations.

Characteristics of non-smoking adult asthma patients with chronic airflow limitation.

OBJECTIVE: Chronic airflow limitation (CAL) can develop in a subgroup of patients with asthma. Characterising these patients is important because reduced lung function is a risk factor for adverse asthma outcomes. We hypothesised that heterogeneity in patients with CAL may be influenced by age at asthma onset. We first compared never-smoking asthma patients with and without CAL, and subsequently examined the differences between patients with late and early-onset asthma within the CAL cohort. METHODS: Patients seen in our hospital's respiratory clinic between 1 Jan 2015 and 31 December 2015 were recruited to the study. CAL was defined as post-bronchodilator forced expiratory volume in 1 second (FEV1)<80% predicted, in the presence of post-bronchodilator ratio <70%. Variables independently associated with CAL were determined using a multivariate logistic regression model. Comparisons between patients with late-onset asthma (age ≥18 years) and early-onset asthma were made within the CAL cohort. RESULTS: 247 patients were included in the study. Age was the only variable independently associated with CAL after regression analysis, with an increase in odds of 3.8% (95% CI 0.4-7.3%) for every 1 year increase in age, p = 0.027. 63.2% of patients with CAL had late-onset asthma. Compared to patients with early-onset asthma, those with late-onset asthma had higher fractional exhaled nitric oxide levels (43 ± 32 ppb vs 20 ± 8 pb, p = 0.008). CONCLUSIONS: An increase in age is associated with CAL in never-smoking asthma patients. In addition, age at asthma onset appears to influence airway inflammation in patients with CAL.

Systematic Assessment for Difficult and Severe Asthma Improves Outcomes and Halves Oral Corticosteroid Burden Independent of Monoclonal Biologic Use.

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.

Factors Associated with Dysfunctional Breathing in Patients with Difficult to Treat Asthma.

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.

Severe Asthma Global Evaluation (SAGE): An Electronic Platform for Severe Asthma.

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.