Mitochondria in the centre 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.© 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/)

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 childhoodonset 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 andmediators 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.Copyright © 2015 Pinja Ilmarinen et al. This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

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.Peer reviewe

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.publishedVersionPeer reviewe

Effect of asthma control on general health-related quality of life in patients diagnosed with adult-onset asthma

Health-related quality of life (HRQoL) is a well-established aspect of health that can be measured by both disease-specific and general instruments. The effect of uncontrolled asthma on generic HRQoL has not been shown in patients with clinically confirmed adult-onset asthma and with asthma control defined according to the Global Initiative for Asthma, so the aim of this study was to determine this. In the 12-year follow-up cohort of the Seinajoki Adult Asthma Study (n = 203), patients with uncontrolled and partially controlled asthma had lower generic HRQoL as determined by 15D compared to the controlled group. On 10 out of 15 dimensions of 15D, the mean scores were significantly lower in patients with uncontrolled asthma compared with those with controlled asthma. The affected dimensions were mobility, breathing, sleeping, usual activities, mental function, discomfort and symptoms, depression, distress, vitality and sexual activity. In the Tobit regression analysis, a poorer 15D score was associated with uncontrolled asthma, lower postbronchodilator FEV1, female sex, depression, treated dyspepsia and poorer 15D score at diagnosis. Our results show that uncontrolled asthma affects everyday life in several aspects, including previously unknown components such as sexual activity and vitality.Peer reviewe

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.publishedVersionPeer reviewe

Low socioeconomic status relates to asthma and wheeze, especially in women

Low socioeconomic status (SES) has been associated with asthma and wheezing. Occupational group, educational level and income are commonly used indicators for SES, but no single indicator can illustrate the entire complexity of SES. The aim was to investigate how different indicators of SES associate with current asthma, allergic and nonallergic, and asthmatic wheeze. In 2016, a random sample of the population aged 20–79 years in Northern Sweden were invited to a postal questionnaire survey, with 58% participating (n=6854). The survey data were linked to the national Integrated Database for Labour Market Research by Statistics Sweden for the previous calendar year, 2015. Included SES indicators were occupation, educational level and income. Manual workers had increased risk for asthmatic wheeze, and manual workers in service for current asthma, especially allergic asthma. Primary school education associated with nonallergic asthma, whereas it tended to be inversely associated with allergic asthma. Low income was associated with asthmatic wheeze. Overall, the findings were more prominent among women, and interaction analyses between sex and income revealed that women, but not men, with low income had an increased risk both for asthmatic wheeze and current asthma, especially allergic asthma. To summarise, the different indicators of socioeconomic status illustrated various aspects of associations between low SES and asthma and wheeze, and the most prominent associations were found among women.Peer reviewe

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.Peer reviewe