Marijke Amelink

Severe adult-onset asthma: A distinct phenotype.

BACKGROUND Some patients with adult-onset asthma have severe disease, whereas others have mild transient disease. It is currently unknown whether patients with severe adult-onset asthma represent a distinct clinical phenotype. OBJECTIVE We sought to investigate whether disease severity in patients with adult-onset asthma is associated with specific phenotypic characteristics. METHODS One hundred seventy-six patients with adult-onset asthma were recruited from 1 academic and 3 nonacademic outpatient clinics. Severe refractory asthma was defined according to international Innovative Medicines Initiative criteria, and mild-to-moderate persistent asthma was defined according to Global Initiative for Asthma criteria. Patients were characterized with respect to clinical, functional, and inflammatory parameters. Unpaired t tests and χ(2) tests were used for group comparisons; both univariate and multivariate logistic regression were used to determine factors associated with disease severity. RESULTS Apart from the expected high symptom scores, poor quality of life, need for high-intensity treatment, low lung function, and high exacerbation rate, patients with severe adult-onset asthma were more often nonatopic (52% vs 34%, P = .02) and had more nasal symptoms and nasal polyposis (54% vs 27%, P ≤ .001), higher exhaled nitric oxide levels (38 vs 27 ppb, P = .02) and blood neutrophil counts (5.3 vs 4.0 10(9)/L, P ≤ .001) and sputum eosinophilia (11.8% vs 0.8%, P ≤ .001). Multiple logistic regression analysis showed that increased blood neutrophil (odds ratio, 10.9; P = .002) and sputum eosinophil (odds ratio, 1.5; P = .005) counts were independently associated with severe adult-onset disease. CONCLUSION The majority of patients with severe adult-onset asthma are nonatopic and have persistent eosinophilic airway inflammation. This suggests that severe adult-onset asthma has a distinct underlying mechanism compared with milder disease.

Three phenotypes of adult-onset asthma.

Adult‐onset asthma differs from childhood‐onset asthma in many respects. It is more heterogeneous, often severe and frequently associated with loss of lung function. To identify underlying mechanisms of adult‐onset asthma and to capture predictors of disease progression, detailed characterization and phenotyping is necessary.

Biomarkers to identify sputum eosinophilia in different adult asthma phenotypes

Several biomarkers have been used to assess sputum eosinophilia in asthma. It has been suggested that the diagnostic accuracy of these biomarkers might differ between asthma phenotypes. We investigated the accuracy of biomarkers in detecting sputum eosinophilia (≥3%) in different adult asthma phenotypes. Levels of eosinophils in blood and sputum, exhaled nitric oxide fraction (FeNO) and total immunoglobulin (Ig)E from 336 adult patients, enrolled in three prospective observational clinical trials and recruited at five pulmonology outpatient departments, were analysed. Areas under the receiver operating characteristics curves (AUC) for detecting sputum eosinophilia were calculated and compared between severe and mild, obese and nonobese, atopic and nonatopic and (ex-)smoking and never-smoking asthma patients. Sputum eosinophilia was present in 116 patients (35%). In the total group the AUC was 0.83 (95% CI 0.78–0.87) for blood eosinophils, 0.82 (0.77–0.87) for FeNO and 0.69 (0.63–0.75) for total IgE. AUCs were similar for blood eosinophils and FeNO between different phenotypes. Total IgE was less accurate in detecting sputum eosinophilia in atopic and obese patients than in nonatopic and nonobese patients. Blood eosinophils and FeNO had comparable diagnostic accuracy (superior to total IgE) in identifying sputum eosinophilia in adult asthma patients, irrespective of asthma phenotype such as severe, nonatopic, obese and smoking-related asthma. FeNO and blood eosinophils can be used to detect sputum eosinophilia in adult asthma patients regardless of phenotype http://ow.ly/MnGqF

Risk of deep vein thrombosis and pulmonary embolism in asthma

Increasing evidence suggests that patients with asthma have activated coagulation within the airways. Whether this leads to an increase in venous thromboembolic events is unknown. We therefore assessed the incidence of venous thromboembolic events in patients with mild-to-moderate and severe asthma as compared with an age- and sex-matched reference population. 648 patients with asthma (283 with severe and 365 patients with mild-to-moderate asthma) visiting three Dutch outpatient asthma clinics were studied. All patients completed a questionnaire about a diagnosis of deep vein thrombosis and pulmonary embolism in the past, their risk factors, history of asthma and medication use. All venous thromboembolic events were objectively verified. In total, 35 venous thromboembolic events (16 deep vein thrombosis and 19 pulmonary embolism) occurred at a median age of 39 (range 20–63) years. The incidence of pulmonary embolism in patients with severe asthma was 0.93 (95% CI 0.42–1.44) per 1000 person-years, 0.33 (95% CI 0.07–0.60) in mild-to-moderate asthma and 0.18 (95% CI 0.03–0.33) in the general population, respectively. Severe asthma and oral corticosteroid use were independent risk factors of pulmonary embolism (hazard ratios 3.33 (1.16–9.93) and 2.82 (1.09–7.30), respectively). Asthma was not associated with deep vein thrombosis. Severe asthma greatly enhances the risk of pulmonary embolism, particularly if chronic corticosteroids are used. Severe asthma greatly enhances the risk of pulmonary embolism, particularly if chronic corticosteroids are used http://ow.ly/moNaO

Clinical profile of patients with adult-onset eosinophilic asthma.

Adult-onset eosinophilic asthma is increasingly recognised as a severe and difficult-to-treat subtype of asthma. In clinical practice, early recognition of patients with this asthma subtype is important because it may have treatment implications. Therefore, physicians need to know the distinct characteristics of this asthma phenotype. The objective of the present study was to determine the characteristic profile of patients with adult-onset eosinophilic asthma. 130 patients with adult-onset (>18 years of age) asthma and high blood eosinophil counts (≥0.3×109 L−1) were compared with 361 adult-onset asthma patients with low (<0.3×109 L−1) blood eosinophils. Measurements included a series of clinical, functional and imaging parameters. Patients with high blood eosinophils were more often male, had less well controlled asthma and higher exacerbation rates, despite the use of higher doses of inhaled corticosteroids. They had higher levels of total IgE without more sensitisation to common inhaled allergens. In addition, these patients had worse lung function, and more often showed fixed airflow limitation, air trapping, nasal polyposis and abnormalities on sinus computed tomography scanning. Chronic rhinosinusitis, air trapping and male sex were three independent factors associated with blood eosinophilia (adjusted OR 3.8 (95% CI 1.7–8.1), 3.0 (95% CI 1.1–8.1) and 2.4 (95% CI 1.3–4.4), respectively). Patients with adult-onset asthma with elevated blood eosinophils exhibit a distinct profile, which can readily be recognised in clinical practice. Adult-onset eosinophilic asthma has a distinct clinical profile http://ow.ly/4mQSQk

Anxiety, depression and personality traits in severe, prednisone-dependent asthma

BACKGROUND Anxiety and depression are prevalent in patients with asthma, and associated with more exacerbations and increased health care utilization. Since psychiatric intervention might improve asthma control, we examined whether patients with severe, prednisone-dependent asthma are at higher risk of these disorders than patients with severe non-prednisone dependent asthma or mild-moderate asthma, and whether they exhibit different personality traits. METHODS Sixty-seven adults with severe prednisone-dependent asthma, 47 with severe non-prednisone dependent and 73 patients with mild-moderate asthma completed the HADS depression and anxiety subscale and the NEO-FFI for personality traits. In addition, asthma duration, body mass index and FEV1 were measured. RESULTS The prevalence of clinically significant depressive symptoms (9% vs. 0 vs. 0%; p = 0.009) and anxiety symptoms (19% vs. 6.4 vs. 5.5%; p = 0.01), was higher in patients with severe, prednisone-dependent asthma than in patients with severe non-prednisone dependent or mild-moderate asthma. Patients with prednisone-dependent asthma were respectively 3.4 (95%CI: 1.0-10.8 p = 0.04) and 3.5 (95%CI: 1.3-9.6 p = 0.01) times more likely to have significant depression symptoms and 1.6 (95%CI: 0.7-3.7, p = 0.2) and 2.5 (95%CI: 01.1-5.5, p = 0.02) times more likely to have symptoms of anxiety than patients with severe non-prednisone dependent or mild-moderate asthma. There were no differences found in personality traits between the 3 groups. CONCLUSION Patients with severe, prednisone-dependent asthma have more often psychological distress as compared to patients with severe non-prednisone dependent or mild-moderate asthma.

Comorbidities in Difficult-to-Control Asthma

BACKGROUND Difficult-to-control asthma is associated with significant medical and financial burden. Comorbidities are known to contribute to uncontrolled asthma. Better insight into the prevalence, nature, and risk factors of comorbidities may optimize treatment strategies in patients with difficult-to-control asthma and decrease disease burden. OBJECTIVES The objectives of this study were to assess the prevalence, number, and type of comorbidities in difficult-to-control asthma compared with not-difficult-to-control asthma, and to investigate whether specific patient characteristics are associated with particular comorbidities. METHODS A total of 5,002 adult patients with a prescription for high-dose (>1,000 μg) fluticasone or oral corticosteroids, extracted from 65 Dutch pharmacy databases, were sent questionnaires about patient characteristics. Of the 2,312 patients who returned the questionnaires, 914 were diagnosed with difficult-to-control asthma. Diagnoses of comorbidities (gastroesophageal reflux, nasal polyps, cardiovascular disease, anxiety/depression, obesity, and diabetes) were based on treatment prescriptions or questionnaires. Associations were assessed using multivariable logistic regression analyses. RESULTS A total of 92% of patients with difficult-to-control asthma had ≥1 comorbidity. Patients with difficult-to-control asthma had more comorbidities (mean ± SD comorbidities 2.22 ± 1.27 vs 1.69 ± 1.32; P < .01), and a significantly higher prevalence of each comorbidity, compared with patients with not-difficult-to-control asthma, except for diabetes and nasal polyposis. Comorbidities were associated with specific patient characteristics, including older age, female gender, smoking history, and chronic prednisone use. CONCLUSIONS Almost all patients with difficult-to-control asthma have comorbidities, in particular asthmatic women of older age, former smokers, and asthmatics who are prednisone dependent. Recognition of these typical characteristics can help physicians in the diagnostic workup, so that adequate preventive measures can be taken.

Diagnosing persistent blood eosinophilia in asthma with single blood eosinophil or exhaled nitric oxide level

BACKGROUND Eosinophilic asthma is characterized by persistently elevated blood eosinophils, adult-onset asthma and corticosteroid resistance. For stratified medicine purposes one single measurement of blood eosinophils or exhaled nitric oxide (FeNO) is commonly used. The aim of this study was to investigate in patients with new-onset asthma whether persistent blood eosinophilia can be predicted with one single measurement of these biomarkers. METHODS Blood eosinophils and exhaled nitric oxide levels were measured at yearly intervals over 5 years in 114 adults with new-onset asthma on inhaled corticosteroid treatment. Two definitions of persistent blood eosinophilia were used (1); blood eosinophils at every visit ≥0.30 × 109/L, or (2) ≥0.40 × 109/L. Receiver operating characteristic analyses were performed. Diagnostic cut-off values were defined at a positive predictive value of 95% (or the highest achievable). RESULTS Using definition 1 (blood eosinophils ≥0.30 × 109/L) the cut-off value for a single measurement of blood eosinophils was 0.47 × 109/L. For definition 2 (≥0.40 × 109/L) the cut-off value was 0.49 × 109/L. Cut-off values for persistently low blood eosinophils were 0.17 × 109/L for definition (1) and 0.21 × 109/L for definition (2), respectively. For FeNO no cut-off values with sufficient accuracy could be defined. CONCLUSION We showed that by using high and low cut-off values, one single measurement of blood eosinophils, but not FeNO in the initial phase of new-onset asthma in adults can be used to predict persistence or absence of blood eosinophilia in asthma.