Association Between Blood Eosinophils and Neutrophils With Clinical Features in Adult-Onset Asthma.

BACKGROUND: Asthma is a disease that can be separated into different phenotypes and endotypes based on the clinical characteristics and the molecular mechanisms of the condition, respectively. OBJECTIVE: To assess the association between blood eosinophil and neutrophil counts with clinical and molecular features in patients with adult-onset asthma. METHODS: Blood eosinophil and neutrophil counts were measured from 203 patients who took part in the Seinäjoki Adult Asthma Study and attended the 12-year follow-up visit. The patients were then divided into four groups (paucigranulocytic [n = 108], neutrophilic [n = 60], eosinophilic [n = 21], and mixed granulocytic [n = 14]), according to eosinophil and neutrophil levels. The cutoff values used to define the groups were 0.30 × 109 · L-1 for blood eosinophils and 4.4 × 109 · L-1 for blood neutrophils. RESULTS: The neutrophilic group had highest body mass index. It was dispensed the highest doses of inhaled corticosteroids during the 12-year follow-up and made the most unplanned respiratory visits. The neutrophilic, eosinophilic, and mixed granulocytic groups had more severe asthma compared with the paucigranulocytic group. The neutrophilic and eosinophilic groups were associated with higher dispensed antibiotics. The eosinophilic group had more nasal polyps, more suspected sinusitis, a greater decline in lung function, and increased levels of periostin, FeNO, and IgE. The neutrophilic group had increased high-sensitivity C-reactive protein, matrix metalloproteinase-9, IL-6, leptin, and soluble urokinase plasminogen activator receptor levels. The mixed granulocytic group showed increased resistin levels together with the neutrophilic group. CONCLUSIONS: In addition to blood eosinophils, the blood neutrophil count reflects underlying inflammatory patterns and indicates important differences in asthma clinical features and outcomes.

Documentation of smoking in scheduled asthma contacts in primary health care: a 12-year follow-up study.

Smoking among asthmatics is common and associates with poorer asthma control, more rapid lung function decline and higher health care costs in dose-dependent manner. No previous real-life studies exist, however, on how smoking status and pack-years are documented in scheduled asthma contacts in primary health care (PHC) during long-term follow-up, and how often patients are advised to quit smoking. In this real-life 12-year follow-up study, we showed that out of all scheduled PHC asthma contacts (n = 603) smoking was mentioned only in 17.2% and pack-years only in 6.5%. Smoking data was not recorded even once in 70.9% of never smokers, 64.7% of ex-smokers and 27.3% of current smokers. Smoking including pack-years were mentioned more often if nurse took part on the scheduled contact. For current smokers, smoking cessation was recommended only in 21.7% of their scheduled contacts. Current smokers used more antibiotics and had more unscheduled health care contacts during follow-up.

NSAID-exacerbated respiratory disease: a population study.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) may exacerbate respiratory symptoms. A recent European Academy of Allergy and Clinical Immunology position paper recommended the use of an acronym, N-ERD (NSAID-exacerbated respiratory disease), for this hypersensitivity associated with asthma or chronic rhinosinusitis with or without nasal polyposis. Our aim was to estimate the prevalence of N-ERD and identify factors associated with N-ERD. METHODS: In 2016, a cross-sectional questionnaire survey of a random adult population of 16 000 subjects aged 20-69 years was performed in Helsinki and Western Finland. The response rate was 51.5%. RESULTS: The prevalence was 1.4% for N-ERD, and 0.7% for aspirin-exacerbated respiratory disease (AERD). The prevalence of N-ERD was 6.9% among subjects with asthma and 2.7% among subjects with rhinitis. The risk factors for N-ERD were older age, family history of asthma or allergic rhinitis, long-term smoking and exposure to environmental pollutants. Asthmatic subjects with N-ERD had a higher risk of respiratory symptoms, severe hypersensitivity reactions and hospitalisations than asthmatic subjects without N-ERD. The subphenotype of N-ERD with asthma was most symptomatic. Subjects with rhinitis associated with N-ERD, which would not be included in AERD, had the fewest symptoms. CONCLUSION: We conclude that the prevalence of N-ERD was 1.4% in a representative Finnish adult population sample. Older age, family history of asthma or allergic rhinitis, cumulative exposure to tobacco smoke, secondhand smoke, and occupational exposures increased odds of N-ERD. N-ERD was associated with significant morbidity.

Multimorbidity in Finnish and Swedish speaking Finns; association with daily habits and socioeconomic status - Nordic EpiLung cross-sectional study.

Multimorbidity is an emerging public health priority. This study aims to assess the role of lifestyle and socioeconomic status in the prevalence of multimorbidity and chronic diseases by using two language groups that are part of the same genetic subgroup but differ by daily habits. We conducted a cross-sectional survey in 2016 with randomly selected population sample with 4173 responders (52.3%) aged 20-69 years in Western Finland. We included 3864 Finnish participants with Swedish (28.1%) or Finnish (71.9%) as a native language. We used a questionnaire to assess participants' chronic diseases and lifestyle. We determined multimorbidity as a disease count ≥ 2. Finnish speakers were more likely to have a diagnosis of COPD, heart failure, diabetes, reflux disease, chronic kidney failure, and painful conditions than Swedish speakers. The prevalence of multimorbidity was higher for Finnish speakers in the age group of 60-69 years (41.0% vs. 32.0%, p = 0.018) than Swedish speakers. A higher proportion of Finnish speakers smoked, were obese, inactive, and had lower socioeconomic status compared to Swedish speakers. All these factors, in addition to age and female sex, were significant risk factors for multimorbidity. Prevalence of multimorbidity was different in two language groups living in the same area and was associated with differences in lifestyle factors such as smoking, physical inactivity and obesity.

Dyspnea has an association with lifestyle: differences between Swedish and Finnish speaking persons in Western Finland.

Background Difference in dyspnea mMRC ≥2 between Finnish speaking and Swedish-speaking populations in Finland has not been previously studied. Methods In February 2016, a respiratory questionnaire was sent to 8000 randomly selected subjects aged 20-69 years in western Finland with a response rate of 52.3%. The registered native language of each subject determined whether questionnaire in Finnish or Swedish was applied. Multiple logistic regression was performed to calculate Odds Ratios (OR) with 95% CI for the simultaneous effects of independent variables on dyspnea mMRC ≥2. Results Of all participants, 2780 (71.9%) were Finnish speakers and 1084 (28.1%) were Swedish speakers. Finnish speakers had a higher prevalence of dyspnea mMRC ≥2 (11.1% vs 6.5% p < 0.001) when compared to Swedish speakers. Finnish speakers smoked more often, had higher BMI, spent less time moving during the day, had more often occupational exposure to vapours, gases, dusts or fumes (VGDF), and had lower socioeconomic status based on occupation. Significant risk factors for dyspnea mMRC ≥2 were COPD (OR = 10.94), BMI >35 (OR = 9.74), asthma (OR = 4.78), female gender (OR = 2.38), older age (OR = 2.20), current smoking (OR = 1.59), and occupational exposure to VGDF (OR = 1.47). Conclusions Swedish speakers had less dyspnea mMRC ≥2 which is explained by a healthier lifestyle. Smoking, obesity, and occupational exposures should be in focus to improve respiratory health.

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.

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.

Comorbidities and elevated IL-6 associate with negative outcome in adult-onset asthma.

The effect of systemic inflammation and comorbidities on treatment and outcome of adult-onset asthma remains unknown and is the objective of this study.As part of the Seinäjoki Adult Asthma Study (SAAS) with a 12-year follow-up, serum interleukin (IL)-6, high-sensitivity C-reactive protein (hsCRP) and lung function were measured and clinical information on comorbidities and medication collected from 170 patients with adult-onset asthma without chronic obstructive pulmonary disease.At follow-up visit, 54% of the patients had systemic inflammation as indicated by elevated IL-6 or hsCRP, 58% had at least one comorbidity and 30% at least two comorbidities (other than asthma related). Patients with systemic inflammation were treated with higher dose of inhaled corticosteroid (ICS) and they had lower lung function and higher blood neutrophils compared with patients without. Patients having ≥2 comorbidities had lower Asthma Control Test score and this association remained significant in adjusted analysis. Patients with both systemic inflammation and comorbidities showed poorest outcome of asthma. In multivariate regression analysis, high ICS dose was predicted by elevated IL-6, elevated blood neutrophils and eosinophils and poorer lung function at baseline and follow-up.Altogether, in patients with adult-onset asthma, elevated IL-6 was associated with use of high-dose ICS while multi-morbidity was linked to worse symptoms of asthma.

A 12-year prognosis of adult-onset asthma: Seinäjoki Adult Asthma Study.

RATIONALE: Long-term prognosis of adult-onset asthma is poorly known. OBJECTIVE: To evaluate 12-year prognosis of adult-onset asthma and the factors associated with disease prognosis. METHODS: Seinäjoki Adult-onset Asthma Study (SAAS) is a 12-year real-life single-center follow-up study of new-onset asthma diagnosed at adult age and treated in primary and specialized care. Remission was defined by no symptoms and no asthma medication use for 6 months. Asthma control was evaluated according to Global Initiative for Asthma 2010. Factors associated with current asthma control were analyzed by multinomial multivariate logistic regression. MAIN RESULTS: A total of 203 patients (79% of the baseline population) were followed for 12 years. Remission occurred in 6 (3%) patients. In 34% asthma was controlled, in 36% it was partially controlled and in 30% uncontrolled. Uncontrolled asthma was predicted by elevated body-mass index at baseline, smoking (pack-years) and current allergic or persistent rhinitis. Elevated blood eosinophils and good lung function (FEV1) at baseline protected from uncontrolled asthma. In contrast, gender, age at the onset or baseline symptoms (Airways Questionnaire 20) were not significant predictors of uncontrolled disease. CONCLUSIONS: During a 12-year follow-up, remission of adult-onset asthma was rare occurring in only 3% of patients. The majority of patients (66%) presented either with uncontrolled or partially controlled asthma. This study is registered at ClinicalTrials.gov with identifier number NCT02733016.

Phenotypes, Risk Factors, and Mechanisms of Adult-Onset Asthma.

Asthma is a heterogeneous disease with many phenotypes, and age at disease onset is an important factor in separating the phenotypes. Genetic factors, atopy, and early respiratory tract infections are well-recognized factors predisposing to childhood-onset asthma. Adult-onset asthma is more often associated with obesity, smoking, depression, or other life-style or environmental factors, even though genetic factors and respiratory tract infections may also play a role in adult-onset disease. Adult-onset asthma is characterized by absence of atopy and is often severe requiring treatment with high dose of inhaled and/or oral steroids. Variety of risk factors and nonatopic nature of adult-onset disease suggest that variety of mechanisms is involved in the disease pathogenesis and that these mechanisms differ from the pathobiology of childhood-onset asthma with prevailing Th2 airway inflammation. Recognition of the mechanisms and mediators that drive the adult-onset disease helps to develop novel strategies for the treatment. The aim of this review was to summarize the current knowledge on the pathogenesis of adult-onset asthma and to concentrate on the mechanisms and mediators involved in establishing adult-onset asthma in response to specific risk factors. We also discuss the involvement of these mechanisms in the currently recognized phenotypes of adult-onset asthma.

The Finnish national asthma programme: communication in asthma care--quality assessment of asthma referral letters.

AIMS AND OBJECTIVES: The Finnish National Asthma Programme, which was launched in year 1994, considered the management of asthma as a community problem. The role of the primary health care in the management of asthma was emphasized. Optimal asthma management includes good communication between health care professionals. Referral letters are an accepted tool for evaluation of the communication process. The aim of this study was to assess the quality of asthma-related referral letters. METHODS: All non-acute referral letters (n=3176) to three pulmonary departments were screened in 2001 and all those related to asthma were included (n=1289). The 14 previously derived asthma-specific criteria were applied: occupation, smoking, known allergies, current medication, other diseases, onset of symptoms, wheezing, dyspnoea, specified dyspnoea, cough, specified cough, use of asthma medication, peak-flow follow-up or spirometry with bronchodilatation test as an attachment. The study group was prepared to accept the maximum of 30% of the referral letters to be of poor quality. RESULTS: Twenty-one per cent of the referral letters were graded good, 34% satisfactory and 45% poor. Information on wheezing, smoking habits and current medication was mentioned in 44%, 42% and 41% of asthma letters respectively. CONCLUSIONS: The Finnish National Asthma Programme calls for optimizing communication between doctors. The proportion of poor letters was 50% higher than the preset standard and clearly indicates a need for improvement. We found several issues, which need to be better communicated (smoking, lung function tests, wheezing, medication) when referring a patient with suspected asthma.