Agreement between self-reported and registered age at asthma diagnosis in Finland.

INTRODUCTION: In epidemiological studies, the age at asthma onset is often defined by patients' self-reported age at diagnosis. The reliability of this report might be questioned. Our objective was to evaluate the agreement between self-reported and registered age at asthma diagnosis and assess features contributing to the agreement. METHODS: As part of the FinEsS respiratory survey in 2016, randomly selected population samples of 13,435 from Helsinki and 8000 from Western Finland were studied. Self-reported age at asthma diagnosis was compared to age at asthma diagnosis registered in the Finnish register on special reimbursement for asthma medication. The reimbursement right is based on lung function criteria according to GINA and Finnish guidelines. If the difference was less than 5 years, self-reported diagnosis was considered reliable. Features associated with the difference between self-reported and registered age at asthma diagnosis were evaluated. RESULTS: Altogether 197 subjects from Helsinki and 144 from Western Finland were included. Of these, 61.9% and 77.8%, respectively, reported age at diagnosis reliably. Median difference between self-reported and registered age at diagnoses was - 2.0 years (IQR - 9.0 to 0) in Helsinki and - 1.0 (IQR - 4.3 to 0) in Western Finland indicating earlier self-reported age at diagnosis. More reliable self-report was associated with non-allergic subjects and subjects who reported having asthma diagnosis more recently. CONCLUSIONS: Agreement between self-reported and registered age at asthma diagnosis was good especially with adult-onset asthma patients. Poor agreement in early-onset asthma could be related to delay in registration due to reimbursement criteria.

Level of education and asthma control in adult-onset asthma.

OBJECTIVE: Education in itself and as a proxy for socioeconomic status, may influence asthma control, but remains poorly studied in adult-onset asthma. Our aim was to study the association between the level of education and asthma control in adult-onset asthma. METHODS: Subjects with current asthma with onset >15 years were examined within the Obstructive Lung Disease in Northern Sweden study (OLIN, n = 593), Seinäjoki Adult Asthma Study (SAAS, n = 200), and West Sweden Asthma Study (WSAS, n = 301) in 2009-2014 in a cross-sectional setting. Educational level was classified as primary, secondary and tertiary. Uncontrolled asthma was defined as Asthma Control Test (ACT) score ≤19. Altogether, 896 subjects with complete data on ACT and education were included (OLIN n = 511, SAAS n = 200 and WSAS n = 185). RESULTS: In each cohort and in pooled data of all cohorts, median ACT score was lower among those with primary education than in those with secondary and tertiary education. Uncontrolled asthma was most common among those with primary education, especially among daily ICS users (42.6% primary, 28.6% secondary and 24.2% tertiary; p = 0.001). In adjusted analysis, primary education was associated with uncontrolled asthma in daily ICS users (OR 1.92, 95% CI 1.15-3.20). When stratified by atopy, the association between primary education and uncontrolled asthma was seen in non-atopic (OR 3.42, 95% CI 1.30-8.96) but not in atopic subjects. CONCLUSIONS: In high-income Nordic countries, lower educational level was a risk factor for uncontrolled asthma in subjects with adult-onset asthma. Educational level should be considered in the management of adult-onset asthma.

Participation in scheduled asthma follow-up contacts and adherence to treatment during 12-year follow-up in patients with adult-onset asthma.

BACKGROUND: Poor treatment compliance is a common problem in the treatment of asthma. To our knowledge, no previous long-term follow-up studies exist on how scheduled asthma follow-up contacts occur in primary health care (PHC) versus secondary care and how these contacts relate to adherence to medication and in participation to further scheduled asthma contacts. The aim of this study was to evaluate occurrence of scheduled asthma contacts and treatment compliance in PHC versus secondary care, and to identify the factors associated with non-participation to scheduled contacts. METHODS: Patients with new adult-onset asthma (n = 203) were followed for 12 years in a real-life asthma cohort of the Seinäjoki Adult Asthma Study (SAAS). The first contacts were mainly carried out in secondary care and therefore the actual follow-up time including PHC visits was 10 years. RESULTS: A majority (71%) of the patients had ≥ 2 scheduled asthma contacts during 10-year follow-up and most of them (79%) mainly in PHC. Patients with follow-up contacts mainly in PHC had better adherence to inhaled corticosteroid (ICS) medication during the whole 12-year period compared to patients in secondary care. In the study population, 29% of the patients had only 0-1 scheduled asthma contacts during the follow-up. Heavy alcohol consumption predicted poor participation in scheduled contacts. CONCLUSIONS: Patients with mainly PHC scheduled asthma contacts were more adherent to ICS medication than patients in the secondary care. Based on our results it is necessary to pay more attention to actualization of asthma follow-up visits and systematic assessment of asthma patients including evaluation of alcohol consumption. Trial registration Seinäjoki Adult Asthma Study is retrospectively registered at www.ClinicalTrials.gov with identifier number NCT02733016. Registered 11 April 2016.

Long-term prognosis of new adult-onset asthma in obese patients.

BACKGROUND: Obesity has been associated with poor outcomes of asthma in cross-sectional studies, but long-term effect of obesity on asthma remains unknown. AIMS: To study the effects of obesity, found at the time of diagnosis of adult-onset asthma, on 12-year prognosis by focusing on oral corticosteroid (OCS) use and respiratory-related hospital admissions. METHODS: Patients diagnosed with adult-onset asthma (n=203) were divided into three categories based on diagnostic body mass index (BMI) (<25 kg·m-2, 25-29.9 kg·m-2, ≥30 kg·m-2) and followed for 12 years as part of the Seinäjoki Adult Asthma Study. Self-reported and dispensed OCS were assessed for the 12-year period. Data on hospital admissions were analysed based on medical records. RESULTS: 12 years after diagnosis, 86% of the patients who were obese (BMI ≥30 kg·m-2) at diagnosis remained obese. During the follow-up, no difference was found in weight gain between the BMI categories. During the 12-year follow-up, patients obese at diagnosis reported more frequent use of OCS courses (46.9% versus 23.1%, p=0.028), were dispensed OCS more often (81.6% versus 56.9%, p=0.014) and at higher doses (median 1350 (interquartile range 280-3180) mg versus 600 (0-1650) mg prednisolone, p=0.010) compared to normal-weight patients. Furthermore, patients who were obese had more often one or more respiratory-related hospitalisations compared to normal-weight patients (38.8% versus 16.9%, p=0.033). In multivariate logistic regression analyses, obesity predicted OCS use and hospital admissions. CONCLUSIONS: In adult-onset asthma, patients obese at diagnosis mostly remained obese at long-term and had more exacerbations and respiratory-related hospital admissions compared to normal-weight patients during 12-year follow-up. Weight loss should be a priority in their treatment to prevent this outcome.

Differences in diagnostic patterns of obstructive airway disease between areas and sex in Sweden and Finland - the Nordic EpiLung study.

OBJECTIVE: To investigate the current prevalence of physician-diagnosed obstructive airway diseases by respiratory symptoms and by sex in Sweden and Finland. METHOD: In 2016, a postal questionnaire was answered by 34,072 randomly selected adults in four study areas: Västra Götaland and Norrbotten in Sweden, and Seinäjoki-Vaasa and Helsinki in Finland. RESULTS: The prevalence of asthma symptoms was higher in Norrbotten (13.2%), Seinäjoki-Vaasa (14.8%) and Helsinki (14.4%) than in Västra Götaland (10.7%), and physician-diagnosed asthma was highest in Norrbotten (13.0%) and least in Västra Götaland (10.1%). Chronic productive cough was most common in the Finnish areas (7.7-8.2% versus 6.3-6.7%) while the prevalence of physician-diagnosed chronic bronchitis (CB) or chronic obstructive pulmonary disease (COPD) varied between 1.7 and 2.7% in the four areas. Among individuals with respiratory symptoms, the prevalence of asthma was most common in Norrbotten, while a diagnosis of COPD or CB was most common in Västra Götaland and Seinäjoki-Vaasa. More women than men with respiratory symptoms reported a diagnosis of asthma in Sweden and Seinäjoki-Vaasa but there were no sex differences in Helsinki. In Sweden, more women than men with symptoms of cough or phlegm reported a diagnosis of CB or COPD, while in Finland the opposite was found. CONCLUSION: The prevalence of respiratory symptoms and corresponding diagnoses varied between and within the countries. The proportion reporting a diagnosis of obstructive airway disease among individuals with respiratory symptoms varied, indicating differences in diagnostic patterns both between areas and by sex.

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 .

Age-specific incidence of allergic and non-allergic asthma.

BACKGROUND: Onset of allergic asthma has a strong association with childhood but only a few studies have analyzed incidence of asthma from childhood to late adulthood in relation to allergy. The purpose of the study was to assess age-specific incidence of allergic and non-allergic asthma. METHODS: Questionnaires were sent to 8000 randomly selected recipients aged 20-69 years in Finland in 2016. The response rate was 52.3% (n = 4173). The questionnaire included questions on e.g. atopic status, asthma and age at asthma diagnosis. Asthma was classified allergic if also a physician-diagnosed allergic rhinitis was reported. RESULTS: The prevalence of physician-diagnosed asthma and allergic rhinitis were 11.2 and 17.8%, respectively. Of the 445 responders with physician-diagnosed asthma, 52% were classified as allergic and 48% as non-allergic. Median ages at diagnosis of allergic and non-allergic asthma were 19 and 35 years, respectively. Among subjects with asthma diagnosis at ages 0-9, 10-19, 20-29, 30-39, 40-49, 50-59 and 60-69 years, 70, 62, 58, 53, 38, 19 and 33%, respectively, were allergic. For non-allergic asthma, the incidence rate was lowest in children and young adults (0.7/1000/year). It increased after middle age and was highest in older age groups (2.4/1000/year in 50-59 years old). CONCLUSIONS: The incidence of allergic asthma is highest in early childhood and steadily decreases with advancing age, while the incidence of non-allergic asthma is low until it peaks in late adulthood. After approximately 40 years of age, most of the new cases of asthma are non-allergic.

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.

Transient Receptor Potential Ankyrin 1 Enhances Ovalbumin-Induced Acute Allergic Inflammation in Murine Models.

BACKGROUND: Transient receptor potential ankyrin 1 (TRPA1) is an ion channel known to mediate nociception and neurogenic inflammation, and to be activated by reactive oxygen and nitrogen species (ROS and RNS) produced at the sites of inflammation. Because neurogenic inflammation as well as the release of ROS and RNS are typical features of early stages of allergic responses, we hypothesized that TRPA1 may be involved in triggering and/or amplifying allergic inflammation. OBJECTIVE: This study aims at exploring the role of TRPA1 ion channel in acute ovalbumin-induced allergic inflammation in applicable murine models. METHODS: The effects of pharmacological blockade and genetic deletion of TRPA1 in ovalbumin-induced allergic conjunctivitis and acute paw inflammation were studied in mice sensitized to ovalbumin. RESULTS: Ovalbumin-induced allergic conjunctivitis was milder in TRPA1-deficient mice and alleviated in wild-type mice treated with the TRPA1 antagonist TCS 5861528. Subcutaneous challenge with ovalbumin caused a significant paw edema and interleukin (IL)-4 production in sensitized mice; these responses were attenuated in animals treated with the TRPA1 antagonist and in TRPA1-deficient mice. Interestingly, blockade of the major secondary effector of TRPA1, substance P, also resulted in attenuated ovalbumin-induced paw edema and IL-4 production. However, the splenocytes' responses to ovalbumin were similar in cells from wild-type and TRPA1-deficient mice sensitized to ovalbumin. CONCLUSION: These results introduce a novel concept that TRPA1 mediates early events in allergic inflammation, but does not seem to affect allergic sensitization, and could therefore be a novel drug target to treat conditions associated with allergic inflammation.

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.

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.

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.

Emerging Comorbidities in Adult Asthma: Risks, Clinical Associations, and Mechanisms.

Asthma is a heterogeneous disease with many phenotypes, and age at disease onset is an important factor in separating the phenotypes. Most studies with asthma have been performed in patients being otherwise healthy. However, in real life, comorbid diseases are very common in adult patients. We review here the emerging comorbid conditions to asthma such as obesity, metabolic syndrome, diabetes mellitus type 2 (DM2), and cardiac and psychiatric diseases. Their role as risk factors for incident asthma and whether they affect clinical asthma are evaluated. Obesity, independently or as a part of metabolic syndrome, DM2, and depression are risk factors for incident asthma. In contrast, the effects of comorbidities on clinical asthma are less well-known and mostly studies are lacking. Cross-sectional studies in obese asthmatics suggest that they may have less well controlled asthma and worse lung function. However, no long-term clinical follow-up studies with these comorbidities and asthma were identified. These emerging comorbidities often occur in the same multimorbid adult patient and may have in common metabolic pathways and inflammatory or other alterations such as early life exposures, systemic inflammation, inflammasome, adipokines, hyperglycemia, hyperinsulinemia, lung mechanics, mitochondrial dysfunction, disturbed nitric oxide metabolism, and leukotrienes.

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.

Mitochondria in the center of human eosinophil apoptosis and survival.

Eosinophils are abundantly present in most phenotypes of asthma and they contribute to the maintenance and exacerbations of the disease. Regulators of eosinophil longevity play critical roles in determining whether eosinophils accumulate into the airways of asthmatics. Several cytokines enhance eosinophil survival promoting eosinophilic airway inflammation while for example glucocorticoids, the most important anti-inflammatory drugs used to treat asthma, promote the intrinsic pathway of eosinophil apoptosis and by this mechanism contribute to the resolution of eosinophilic airway inflammation. Mitochondria seem to play central roles in both intrinsic mitochondrion-centered and extrinsic receptor-mediated pathways of apoptosis in eosinophils. Mitochondria may also be important for survival signalling. In addition to glucocorticoids, another important agent that regulates human eosinophil longevity via mitochondrial route is nitric oxide, which is present in increased amounts in the airways of asthmatics. Nitric oxide seems to be able to trigger both survival and apoptosis in eosinophils. This review discusses the current evidence of the mechanisms of induced eosinophil apoptosis and survival focusing on the role of mitochondria and clinically relevant stimulants, such as glucocorticoids and nitric oxide.

Documentation of comorbidities, lifestyle factors, and asthma management during primary care scheduled asthma contacts.

Systematically assessing asthma during follow-up contacts is important to accomplish comprehensive treatment. No previous long-term studies exist on how comorbidities, lifestyle factors, and asthma management details are documented in scheduled asthma contacts in primary health care (PHC). We showed comorbidities and lifestyle factors were poorly documented in PHC in this real-life, 12-year, follow-up study. Documented information on rhinitis was found in 8.9% and BMI, overweight, or obesity in ≤1.5% of the 542 scheduled asthma contacts. Of the 145 patients with scheduled asthma contacts, 6.9% had undergone revision of their inhalation technique; 16.6% had documentation of their asthma action plan. Screening of respiratory symptoms was recorded in 79% but nasal symptoms in only 15.5% of contacts. Lifestyle guidance interventions were found in <1% of contacts. These results, based on documented patient data, indicate a need exists to further improve the assessment and guidance of asthma patients in PHC.

Comorbidity Burden in Severe and Nonsevere Asthma: A Nationwide Observational Study (FINASTHMA).

BACKGROUND: Asthma, affecting more than 330 million people worldwide, is associated with a high level of morbidity, mortality, and socioeconomic costs. OBJECTIVE: In this cross-sectional study, we analyzed the comorbidity burden in patients with severe asthma compared with nonsevere asthma and investigated the role of corticosteroid use on the risk of comorbidities. METHODS: All adults (≥18 y) with a diagnosis of asthma (International Classification of Diseases-10th revision code J45.x) between 2014 and 2017 were identified and data were collected until 2018 from Finnish nationwide registers. Asthma was defined as continuously or transiently severe or nonsevere based on annual dispensed inhaled corticosteroids (ICS), oral corticosteroids (OCS), and hospitalizations. RESULTS: Of 193,730 adult identified patients diagnosed with asthma, 86.3% had nonsevere, 8.1% transiently severe, and 5.6% continuously severe asthma. Excess prevalence of pneumonia was observed in continuously (22%) and transiently severe (14%) compared with nonsevere patients after adjusting for age and sex. Cataract, osteoporosis, obesity, heart failure, and atrial fibrillation were also more frequent in severe asthma patients. The ICS and/or OCS use contributed to the risk of several comorbidities in a dose-dependent manner, particularly pneumonia, osteoporosis, obesity, heart failure, and atrial fibrillation. High OCS use and the presence of comorbidities were associated with increased health care resource use. CONCLUSIONS: Patients with severe asthma have a high burden of comorbidities, especially pneumonia. Many of the comorbidities have a strong dose-dependent association with ICS and OCS treatment, suggesting that corticosteroid doses should be carefully evaluated in clinical practice.

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.