Clinical value of bronchodilator response for diagnosing asthma in steroid-naïve adults.

Spirometry and testing for bronchodilator response have been recommended to detect asthma, and a bronchodilator response (BDR) of ≥12% and ≥200 mL has been suggested to confirm asthma. However, the clinical value of bronchodilation tests in newly diagnosed steroid-naïve adult patients with asthma remains unknown. We evaluated the sensitivity of BDR in forced expiratory volume in 1 s (FEV1) as a diagnostic test for asthma in a real-life cohort of participants in the Seinäjoki Adult Asthma Study. In the diagnostic phase, 369 spirometry tests with bronchodilation were performed for 219 steroid-naïve patients. The fulfilment of each test threshold was assessed. According to the algorithm of the National Institute for Health and Care Excellence, we divided the patients into obstructive (FEV1/forced vital capacity (FVC) <0.70) and non-obstructive (FEV1/FVC ≥0.70) groups. Of the overall cohort, 35.6% fulfilled ΔFEV1 ≥12% and ≥200 mL for the initial FEV1, 18.3% fulfilled ΔFEV1 ≥15% and ≥400 mL for the initial FEV1, and 36.1% fulfilled ΔFEV1 ≥9% of predicted FEV1 at least once. One-third (31%) of these steroid-naïve patients was obstructive (pre-bronchodilator FEV1/FVC <0.7). Of the obstructive patients, 55.9%, 26.5% and 48.5%, respectively, met the same thresholds. In multivariate logistic regression analysis, different thresholds recognised different kinds of asthma patients. In steroid-naïve adult patients, the current BDR threshold (ΔFEV1 ≥12% and ≥200 mL) has low diagnostic sensitivity (36%) for asthma. In obstructive patients, sensitivity is somewhat higher (56%) but far from optimal. If the first spirometry test with bronchodilation is not diagnostic but asthma is suspected, spirometry should be repeated, and other lung function tests should be used to confirm the diagnosis.

Relationship between age and bronchodilator response at diagnosis in adult-onset asthma.

BACKGROUND: Possible variation in bronchodilator response (BDR) according to age at the diagnosis of adult-onset asthma is unknown. Our aim was to assess if BDR in FEV1 is related to age at diagnosis of adult-onset asthma and how many subjects fulfill the 400 mL criterion of BDR, the suggested cut-off for asthma-like reversibility in asthma-COPD overlap (ACO). METHODS: A total of 1030 patients with adult-onset asthma were included; 245 from SAAS (Seinäjoki Adult Asthma Study, Finland) and 785 from COREA (Cohort for Reality and Evolution of Adult Asthma in Korea) cohorts. BDR in FEV1 at the diagnosis of asthma was assessed. Patients were divided into groups based on age at asthma diagnosis: < 40, 40-59.9, and ≥ 60 years. The cohorts were analyzed separately. RESULTS: BDR % in FEV1 did not differ between the groups of different age at asthma diagnosis and no correlation between BDR and age was found. Of patients aged ≥40 years, only 18% (SAAS-cohort) and 5% (COREA-cohort) reached the 400 mL BDR in FEV1. After exclusion of possible ACO patients, the results remained similar. CONCLUSION: By using two large cohorts of steroid-naive patients with asthma, we have shown that BDR at diagnosis of asthma is constant over large age span range, and the limit of 400 mL in BDR in FEV1 is rarely reached. TRIAL REGISTRATION: Seinäjoki Adult Asthma Study is registered at ClinicalTrials.gov with identifier number NCT02733016 .

12-year adherence to inhaled corticosteroids in adult-onset asthma.

Adherence to inhaled corticosteroids (ICS) has been suggested to be poor but long-term follow-ups are lacking. The objective of the present study was to assess adherence to ICS treatment in patients with adult-onset asthma during 12-year follow-up. A total of 181 patients with clinically confirmed, new-onset adult asthma were followed for 12 years as part of the Seinäjoki Adult Asthma Study. Adherence to ICS was assessed individually as the percentage of true dispensed ICS in micrograms per true prescribed daily ICS in micrograms over 12 years. Mean 12-year adherence to ICS was 69% (mean±sd dispensed 2.5±1.8 g and prescribed 3.6±1.5 g budesonide equivalent per patient for 12 years), annual adherence varying between 81% (year 1) and 67% (year 12). Patients with good 12-year adherence (≥80%) used oral corticosteroids more often, and had add-on drugs in use and asthma-related visits to healthcare more often. In addition, they showed less reversibility in forced expiratory volume in 1 s and had higher peripheral blood neutrophil counts. However, lung function decline was steeper in patients with poorer adherence (<80%) and this association remained in multiple linear regression analysis. No difference was found in symptom scores, blood eosinophil counts, exhaled nitric oxide or immunoglobulin E between the patients with different levels of adherence. In patients with adult-onset asthma, adherence to ICS was moderate. Poorer adherence (<80%) to ICS was associated with more rapid decline in lung function but was not associated to symptoms or markers of inflammatory endotypes.

Occupational exposures and asthma-COPD overlap in a clinical cohort of adult-onset asthma.

Occupational exposure to vapours, gases, dusts or fumes (VGDF) increases the prevalence of asthma-COPD overlap (ACO) in adult-onset asthma. VGDF exposure is independently associated with ACO and an additive effect with smoking is proposed. http://bit.ly/2LiMiXW.

Immediate bronchodilator response in FEV1 as a diagnostic criterion for adult asthma.

Asthma is characterised by variable and reversible expiratory airflow limitations. Thus, it is logical to use the change in forced expiratory volume in 1 s (FEV1) in response to a bronchodilator (ΔFEV1BDR) as a diagnostic tool; increases of ≥12% and ≥200 mL from the baseline FEV1 are commonly used values. We aimed to evaluate the historical development of diagnostic cut-off levels for the ΔFEV1BDR for adults and the evidence behind these recommendations.We searched for studies from the reference lists of all the main statements, reports and guidelines concerning the interpretation of spirometry and diagnostics for asthma and conducted a literature search.A limited amount of evidence regarding the ΔFEV1BDR in healthy populations was found, and even fewer patient studies were found. In healthy persons, the upper 95th percentile for the absolute ΔFEV1BDR ranges between 240 mL and 320 mL, the relative ΔFEV1BDR calculated from the initial FEV1 ranges from 5.9% to 13.3% and the ΔFEV1BDR calculated from the predicted FEV1 ranges from 8.7% to 11.6%. However, the absolute and percentage ΔFEV1BDR values calculated from the initial FEV1 are dependent on age, sex, height and the degree of airway obstruction. Thus, the use of the ΔFEV1BDR calculated from the predicted FEV1 might be more appropriate.Not enough data exist to assess the sensitivity of any of the cut-off levels for the ΔFEV1BDR to differentiate asthma patients from healthy subjects. Further studies in newly diagnosed asthma patients are needed.

Daily physical activity and lung function decline in adult-onset asthma: a 12-year follow-up study.

Background: There is a lack of knowledge on the association between daily physical activity and lung function in patients with asthma. Objective: This study aims to examine the association between daily physical activity and asthma control, lung function, and lung function decline in patients with adult-onset asthma. Design: This study is part of Seinäjoki Adult Asthma Study (SAAS), where 201 patients were followed for 12 years after asthma diagnosis. Daily physical activity was assessed at follow-up by a structured questionnaire and used to classify the population into subgroups of low (≤240 min) or high (>240 min) physical activity. Three spirometry evaluation points were used: 1. diagnosis, 2. the maximum lung function during the first 2.5 years after diagnosis (Max0-2.5), 3. follow-up at 12 years. Results: High physical activity group had slower annual FEV1 (p<0.001) and FVC (p<0.018) decline. Additionally, the high physical activity group had higher FEV1 values at follow-up, and higher FEV1/FVC ratios at follow-up and diagnosis. There was no difference in BMI, smoking, medication, or frequency of physical exercise between high and low physical activity groups. Differences remained significant after adjustments for possible confounding factors. Conclusion: This is the first demonstration of an association between long-term FEV1 decline and daily physical activity in clinical asthma. Low physical activity is independently associated with faster decline in lung function. Daily physical activity should be recommended in treatment guidelines in asthma.

Differences between asthma-COPD overlap syndrome and adult-onset asthma.

Differences between asthma-COPD overlap syndrome (ACOS) and adult-onset asthma are poorly understood. This study aimed to evaluate these differences in a clinical cohort of patients with adult-onset asthma, as a part of the Seinäjoki Adult Asthma Study (SAAS).188 patients were diagnosed with adult-onset asthma and re-evaluated 12 years after diagnosis. They were divided into three groups based on smoking history and post bronchodilator spirometry values: 1) never- and ex-smokers with <10 smoked pack-years; 2) non-obstructive (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥0.7) patients with ≥10 pack-years; and 3) ACOS patients with ≥10 pack-years and FEV1/FVC <0.7.ACOS patients had lower diffusing capacity (DLCO/VA 86% predicted versus 98 or 96% predicted; p<0.001), higher blood neutrophil levels (4.50 versus 3.60 or 3.85×109 L-1; p=0.008), and higher IL-6 levels (2.88 versus 1.52 or 2.10 pg·mL-1, p<0.001) as compared to never- and ex-smokers with <10 pack-years, or non-obstructive patients with ≥10 pack-years smoking history, respectively. ACOS patients also showed reduced lung function, higher remaining bronchial reversibility and a higher number of comorbidities.This study shows distinct differences in diffusing capacity, blood neutrophil and IL-6 levels, bronchial reversibility, lung function and comorbidities between ACOS and adult-onset asthma. The present findings should be considered in the comprehensive assessment of adult asthma patients.

Cluster Analysis on Longitudinal Data of Patients with Adult-Onset Asthma.

BACKGROUND: Previous cluster analyses on asthma are based on cross-sectional data. OBJECTIVE: To identify phenotypes of adult-onset asthma by using data from baseline (diagnostic) and 12-year follow-up visits. METHODS: The Seinäjoki Adult Asthma Study is a 12-year follow-up study of patients with new-onset adult asthma. K-means cluster analysis was performed by using variables from baseline and follow-up visits on 171 patients to identify phenotypes. RESULTS: Five clusters were identified. Patients in cluster 1 (n = 38) were predominantly nonatopic males with moderate smoking history at baseline. At follow-up, 40% of these patients had developed persistent obstruction but the number of patients with uncontrolled asthma (5%) and rhinitis (10%) was the lowest. Cluster 2 (n = 19) was characterized by older men with heavy smoking history, poor lung function, and persistent obstruction at baseline. At follow-up, these patients were mostly uncontrolled (84%) despite daily use of inhaled corticosteroid (ICS) with add-on therapy. Cluster 3 (n = 50) consisted mostly of nonsmoking females with good lung function at diagnosis/follow-up and well-controlled/partially controlled asthma at follow-up. Cluster 4 (n = 25) had obese and symptomatic patients at baseline/follow-up. At follow-up, these patients had several comorbidities (40% psychiatric disease) and were treated daily with ICS and add-on therapy. Patients in cluster 5 (n = 39) were mostly atopic and had the earliest onset of asthma, the highest blood eosinophils, and FEV1 reversibility at diagnosis. At follow-up, these patients used the lowest ICS dose but 56% were well controlled. CONCLUSIONS: Results can be used to predict outcomes of patients with adult-onset asthma and to aid in development of personalized therapy (NCT02733016 at ClinicalTrials.gov).

The effect of smoking on lung function: a clinical study of adult-onset asthma.

The aim of this study was to evaluate the effect of smoking on lung function decline in adult-onset asthma in a clinical, 12-year follow-up study.In the Seinäjoki Adult Asthma Study, 203 patients were followed for 12 years (1999-2013) after diagnosis of new-onset adult asthma. Patients were divided into two groups based on smoking history: <10 or ≥10 pack-years. Spirometry evaluation points were: 1) baseline, 2) the maximum lung function during the first 2.5 years after diagnosis (Max0-2.5) and 3) after 12 years of follow-up.Between Max0-2.5 and follow-up, the median annual decline in absolute forced expiratory volume in 1 s (FEV1) was 36 mL in the group of patients with <10 pack-years of smoking and 54 mL in those with smoking history ≥10 pack-years (p=0.003). The annual declines in FEV1 % pred (p=0.006), forced vital capacity (FVC) (p=0.035) and FEV1/FVC (p=0.045) were also accelerated in the group of patients with ≥10 pack-years smoked. In multivariate regression analysis, smoking history ≥10 pack-years became a significant predictor of accelerated decline in FEV1Among patients with clinically defined adult-onset asthma, smoking history ≥10 pack-years is associated with accelerated loss of lung function.