New-Onset Asthma in Adults: What Does the Trigger History Tell Us?

BACKGROUND: Adult-onset asthma is an important asthma phenotype and, in contrast to childhood asthma, is often associated with specific triggers of onset. It is unknown whether these triggers correspond with specific phenotypic characteristics or predict a specific asthma outcome. OBJECTIVE: To compare clinical, functional, and inflammatory characteristics between patients with different triggers of asthma onset, and relate these triggers to asthma outcome. METHODS: Two hundred adults with recently diagnosed (<1 year) asthma were prospectively followed for 5 years. The trigger of asthma onset was patient reported and defined by the question: "What, in your opinion, elicited your asthma?" Asthma remission was defined as no asthma symptoms and no asthma medication use for ≥1 year. Kruskal-Wallis and Fisher's exact test were used to compare categories containing >10 patients. RESULTS: Ten categories of triggers were identified, of which 5 contained >10 patients. Clinical and inflammatory characteristics and remission rates differed significantly between categories. "New allergic sensitization" (11%) was associated with mild atopic asthma and a relatively young age at onset; "pneumonia" (8%) with previous smoking, low IgE, and the highest remission rates (one third); "upper respiratory symptoms" (22%) with high exhaled NO and eosinophilia; "no trigger identified" (38%) did not show any specific characteristics; and "stressful life event" (7%) with high medication usage, low type 2 markers, and no disease remission. CONCLUSIONS: Patients with adult-onset asthma can be characterized by the trigger that seemingly incited their asthma. These triggers might represent underlying mechanisms and may be important to phenotype patients and predict disease outcome.

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.

Predictors of accelerated decline in lung function in adult-onset asthma.

Little is known about the prognosis of adults with new-onset asthma. Cross-sectional studies suggest that these patients may exhibit accelerated decline in forced expiratory volume in 1 s (FEV1). However, risk factors for accelerated decline in lung function have not yet been identified.We aimed to identify these risk factors in a prospective 5-year follow-up study in 200 adults with newly diagnosed asthma. In the current study, clinical, functional and inflammatory parameters were assessed annually for 5 years. Linear mixed-effects models were used to identify predictors.Evaluable lung function sets of 141 patients were available. Median (interquartile range) change in post-bronchodilator FEV1 was -17.5 (-54.2 to +22.4) mL per year. Accelerated decline in FEV1 was defined by the lower quartile of decline (>54.2 mL per year). Nasal polyps, number of blood and sputum eosinophils, body mass index, and level of exhaled nitric oxide were univariably associated with decline in lung function. Only the latter two were independently associated. Using cut-off values to identify patients at highest risk showed accelerated decline in FEV1 in all patients with combined exhaled nitric oxide fraction (FeNO) ≥57 ppb and body mass index (BMI) ≤23 kg·m-2We conclude that adults with new-onset asthma with both high levels of exhaled nitric oxide and low BMI are at risk of accelerated decline in lung function.

Clinical predictors of remission and persistence of adult-onset asthma.

BACKGROUND: Adult-onset asthma is an important but relatively understudied asthma phenotype and little is known about its natural course and prognosis. The remission rate is believed to be low, and it is still obscure which factors predict remission or persistence of the disease. OBJECTIVE: This study sought to determine the remission rate and identify predictors of persistence and remission of adult-onset asthma. METHODS: Two hundred adult patients with recently diagnosed (<1 year) asthma were recruited from secondary and tertiary pulmonary clinics and prospectively followed for 5 years. Clinical, functional, and inflammatory parameters were assessed at baseline and at yearly visits. Asthma remission was defined as absence of asthma symptoms for ≥1 year and no asthma medication use for ≥1 year. Descriptive statistics and logistic regression analysis were performed. RESULTS: Five-year follow-up data of 170 patients (85%) was available. Of these, 27 patients (15.9%) experienced asthma remission. Patients with asthma persistence were older, had worse asthma control, required higher doses of inhaled corticosteroids, had more severe airway hyperresponsiveness, more often nasal polyps, and higher levels of blood neutrophils as compared to patients who experienced clinical remission. In a multivariable logistic regression analysis, only moderate to severe bronchial hyperresponsiveness and nasal polyps were independent predictors of asthma persistence. Patients with these 2 characteristics had <1% chance of asthma remission. CONCLUSIONS: One in 6 patients with adult-onset asthma experiences remission within the first 5 years of the disease. In patients with moderate to severe bronchial hyperresponsiveness and nasal polyposis, the chance of remission is close to zero.

Improving the diagnosis of eosinophilic asthma.

INTRODUCTION: Diagnosing eosinophilic asthma is important, because uncontrolled eosinophilic airway inflammation is associated with reduced response to glucocorticoids and increased risk of severe exacerbations. AREAS COVERED: Currently, the diagnosis of eosinophilic asthma is based on measurements of sputum eosinophils, which is time consuming and requires specific technical expertise. Therefore, biomarkers such as blood eosinophils, FeNO, serum IgE and periostin are being used as surrogates. These biomarkers can be used separately or in combination, and their accuracy to detect sputum eosinophilia depends on cut-off values. The demonstration of eosinophils in sputum is no guarantee for response to treatment with current biological agents targeting Type 2 inflammation, because several molecular pathways may lead to eosinophilic inflammation. In the near future, the results of large trials using 'omics' technologies will certainly identify new, more 'upstream' biomarkers of eosinophilic inflammation, that will ultimately lead to the ideal targeted treatment for patients with eosinophilic asthma. Expert commentary: Of currently used surrogate markers to diagnose eosinophilic asthma, blood eosinophils and FeNO have the highest diagnostic accuracy, in particular if used in combination to rule in or rule out eosinophilic asthma. For patients who cannot be classified by these biomarkers alone, the clinical profile may be of help.