Health-related quality of life, anxiety, depression, beliefs of medication, and self-efficacy in individuals with severe asthma - a population-based study.

OBJECTIVE: Individuals with severe asthma often report poor Health-related quality of life (HRQoL) and more research is essential to increase understanding of how they may be helped to improve HRQoL. The main aim of the current paper is to evaluate HRQoL, and possible factors influencing HRQoL, in individuals with severe asthma. The aim is also to explore associations among anxiety, depression, beliefs of medication, self-efficacy, and HRQoL among individuals with severe and other asthma as well as those with no asthma. METHODS: Participants with severe asthma (n = 59), other asthma (n = 526), and no asthma (n = 902) were recruited from West Sweden Asthma Study, a population-based study, which includes both questionnaire surveys and clinical examinations. RESULTS: Individuals with severe asthma had worse physical HRQoL (measured with SF-8) than those with other and no asthma (median 48.4, 51.9, and 54.3, respectively). They also had worse mental HRQoL (median 46.7) and reported higher anxiety and depression scores (measured using HADS, median 5.0 and 3.5, respectively) compared to no asthma (median 4.0 and 2.0, respectively). HRQoL was particularly affected among women with severe asthma. Individuals with severe asthma believed that their asthma medication was more necessary than those with other asthma, but they reported more concern for the medication. Asthma control and packyears predicted physical HRQoL and anxiety predicted mental HRQoL among individuals with severe asthma. CONCLUSIONS: Efforts to improve asthma control and to reduce anxiety may improve HRQoL in individuals with severe asthma. Especially, women with severe asthma seem to need support to improve their HRQoL. Reducing concerns with asthma medication is most likely essential as high concerns may lead to poor adherence, which in turn may negatively affect asthma control and HRQoL.

Prevalence of food hypersensitivity in relation to IgE sensitisation to common food allergens among the general adult population in West Sweden.

BACKGROUND: The prevalence of self-experienced adverse reactions to foods seems to have an increasing trend in both adults and children. However, it is unclear if the prevalence of food hypersensitivity in the Swedish adult population is still rising, what symptoms are caused by different foods and which are the most common foods to which adults are more frequently IgE-sensitised. METHODS: In a cross-sectional study based on questionnaire responses, interviews and clinical examinations as part of the West Sweden Asthma Study, 1042 subjects from the general population, 17-78 years of age, living in Västra Götaland, Sweden, were included. The subjects reported symptoms for 56 specified foods and blood samples were taken to examine the IgE-sensitisation pattern for 9 common foods. RESULTS: Approximately 32% of adults reported food hypersensitivity, affecting mostly women and subjects less than 61 years old. The foods most often reported to cause adverse reactions were hazelnut (8.9%), apple (8.4%), milk (7.4%) and kiwi (7.3%). Less than one percent (0.9%) reported symptoms from ingestion of meat. Symptoms mostly affected the gastrointestinal tract (15%) and the skin (2.7%). Sixteen per cent were IgE-sensitised to common foods, most often to hazelnut (13.3%), peanut (4.9%) and almond (3.0%), while 5.9% reported symptoms and were IgE-sensitised to the same food, mainly to hazelnut (5.3%). CONCLUSIONS: The prevalence of self-reported food hypersensitivity in West Sweden indicates a rising trend. The correspondence between self-reported symptoms and IgE-sensitisation to foods is generally poor, except for hazelnut and almond which exhibit moderate or fair correlation.

Altered miR-155 Expression in Allergic Asthmatic Airways.

We and others have previously identified microRNAs (miRNAs) with pathological roles in animal models of asthma, where miR-146a and miR-155 have been described to play important roles in inflammatory responses. To date, few studies have investigated miRNA expression in human asthmatics. In the current study, significantly lower levels of miR-155 were detected in cell-free sputum from allergic asthmatics compared to healthy controls. Induced sputum isolated from allergic asthmatics in and out of pollen season revealed that miR-155 expression, but not miR-146a, is reduced in lymphocytes in season compared to post-season. In contrast, miR-155 was found to increase, whereas miR-146a decreased in PBMCs and cell-free PBMC culture media upon T cell receptor stimulation via αCD3/CD28 in both allergic asthmatics and healthy controls. Our findings suggest that miR-155 is differentially expressed ex vivo in airways of allergic asthmatics compared to healthy controls, which may have implications in the local immune response in allergic asthma.

Important non-disease-related determinants of exhaled nitric oxide levels in mild asthma - results from the Swedish GA(2) LEN study.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) has a potential clinical role in asthma management. Constitutive factors such as age, height and gender, as well as individual characteristics, such as IgE sensitization and smoking, affect the levels of FeNO in population-based studies. However, their effect on FeNO in subjects with asthma has been scarcely studied. OBJECTIVE: To study the effects on FeNO of these commonly regarded determinants, as demonstrated in healthy subjects, as well as menarche age and parental smoking, in a population of asthmatics. MATERIAL AND METHODS: Fractional exhaled nitric oxide was measured in 557 subjects with asthma from the Swedish GA(2) LEN study. Allergic sensitization was assessed by skin prick tests to most common aeroallergens. Upper airway comorbidities, smoking habits, smoking exposure during childhood and hormonal status (for women) were questionnaire-assessed. RESULTS: Male gender (P < 0.001), greater height (P < 0.001) and sensitization to both perennial allergens and pollen (P < 0.001) are related to higher FeNO levels. Current smoking (P < 0.001) and having both parents smoking during childhood, vs. having neither (P < 0.001) or only one parent smoking (P = 0.002), are related to lower FeNO. Women with menarche between 9 and 11 years of age had lower FeNO than those with menarche between 12 and 14 years of age (P = 0.03) or 15 and 17 years of age (P = 0.003). CONCLUSIONS AND CLINICAL RELEVANCE: Interpreting FeNO levels in clinical practice is complex, and constitutional determinants, as well as smoking and IgE sensitisation, are of importance in asthmatic subjects and should be accounted for when interpreting FeNO levels. Furthermore, menarche age and parental smoking during childhood and their effects on lowering FeNO deserve further studies.

Increase in pollen sensitization in Swedish adults and protective effect of keeping animals in childhood.

BACKGROUND: To date, most studies of the 'allergy epidemic' have been based on self-reported data. There is still limited knowledge on time trends in allergic sensitization, especially among adults. OBJECTIVE: To study allergic sensitization, its risk factors and time trends in prevalence. METHODS: Within West Sweden Asthma Study (WSAS), a population-based sample of 788 adults (17-60 years) underwent skin prick tests (SPTs) for 11 aeroallergens 2009-2012. Specific IgE was analysed in 750 of the participants. Those aged 20-46 years (n = 379) were compared with the European Community Respiratory Health Survey sample aged 20-46 year from the same area (n = 591) in 1991-1992. RESULTS: Among those aged 20-46 years, the prevalence of positive SPT to pollen increased, timothy from 17.1% to 29.0% (P < 0.001) and birch from 15.6% to 23.7% (P = 0.002) between 1991-1992 and 2009-2012. Measurements of specific IgE confirmed these increases. Prevalence of sensitization to all other tested allergens was unchanged. In the full WSAS sample aged 17-60 years, any positive SPT was seen in 41.9%, and the dominating sensitizers were pollen (34.3%), animals (22.8%) and mites (12.6%). Pollen sensitization was strongly associated with rhinitis, whereas indoor allergens were more associated with asthma. Growing up with livestock or furred pets decreased the risk of sensitization, adjusted odds ratio 0.53 (0.28-0.995) and 0.68 (0.47-0.98), respectively. CONCLUSION: Pollen sensitization has increased in Swedish adults since the early 1990s, while the prevalence of sensitization to other allergens has remained unchanged. This is one plausible explanation for the increase in rhinitis 1990-2008 in Swedish adults, during which time the prevalence of asthma, which is more associated with perennial allergens, was stable. Contact with animals in childhood seems to reduce the risk of sensitization well into adulthood. One major factor contributing to the rise in pollen allergy is a significant increase in levels of birch and grass pollen over the past three decades.

Self-reported adverse reactions and IgE sensitization to common foods in adults with asthma.

BACKGROUND: There is very few data available on the prevalence of food hypersensitivity among adults with asthma. The aim of this study was to explore the prevalence of self-reported adverse reactions and IgE sensitization to the different foods and to determine the spectrum and the prevalence of food-related gastrointestinal symptoms in adults with and with no asthma. METHODS: A cross sectional study based on interviews and questionnaire responses from 1527 subjects, aged 18-75 years of age, from Västra Götaland in Sweden, as part of the larger West Sweden Asthma Study. IgE analyses were performed in sera from all subjects. RESULTS: Fifty three percent of adults with asthma reported adverse reactions to foods compared to 30 % of non-asthmatics. Most asthmatics reported symptoms from eating hazelnut, followed by other nuts, birch-related foods, milk, peanut and shellfish. Furthermore, adults with asthma experienced significantly more often gastrointestinal symptoms from hazelnut, apple and milk and were found to significantly more often be sensitized to the most common foods compared to the non-asthmatic subjects. The asthmatics showed a significant correlation between IgE to both hazelnut and birch and self-reported symptoms after ingestion of hazelnut and to a lesser extent to almonds. CONCLUSIONS: The prevalence of self-reported adverse reactions and sensitization to the most common foods was much higher among the asthmatic subjects. Hazelnut was the food that asthmatics most frequently experienced adverse reactions from, and the strong correlation between IgE to hazelnut and birch indicate that the observed adverse reactions are partly due to sensitization to allergens from the PR-10 family.

Gas, dust, and fumes exposure is associated with mite sensitization and with asthma in mite-sensitized adults.

Occupational exposure to gas, dust, and fumes (GDF) increases the risk of asthma and eczema. We investigated the role of sensitization in the association between GDF and allergic conditions. A population-based sample of 788 adults from the West Sweden Asthma Study completed questionnaires and skin prick tests. After adjustment for confounders, GDF exposure was associated with a doubled risk of sensitization to mites, but not with other allergens. Mite sensitization also modified the effect of GDF on asthma. In mite-sensitized subjects, GDF was associated with physician-diagnosed asthma, adjusted OR 2.9 (1.2-7.2), and with wheeze, OR 2.4 (1.1-5.3). In non-mite-sensitized subjects, the corresponding ORs were 1.1 (0.5-2.6) and 0.6 (0.3-1.3). GDF was independently associated with eczema regardless of mite sensitization, but not with rhinitis. These novel findings suggest that components of GDF may act as adjuvants that facilitate sensitization to mites and that mite-sensitized individuals may be especially susceptible to inhalant occupational exposures.

Aspirin-intolerant asthma in the population: prevalence and important determinants.

BACKGROUND: Population-based studies on aspirin-intolerant asthma (AIA) are very few, and no previous population study has investigated risk factors for the condition. OBJECTIVE: To investigate the prevalence and risk factors of AIA in the general population. METHODS: A questionnaire on respiratory health was mailed to 30,000 randomly selected subjects aged 16-75 years in West Sweden, 29,218 could be traced and 18,087 (62%) responded. The questionnaire included questions on asthma, respiratory symptoms, aspirin-induced dyspnoea and possible determinants. RESULTS: The prevalence of AIA was 0.5%, 0.3% in men and 0.6% in women (P = 0.014). Sick leave, emergency visits due to asthma and all investigated lower respiratory symptoms were more common in AIA than in aspirin-tolerant asthma (ATA). Obesity was a strong risk factor for AIA (BMI > 35: odds ratio (OR) 12.1; 95% CI 2.49-58.5), and there was a dose-response relationship between increasing body mass index (BMI) and risk of AIA. Obesity, airborne occupational exposure and visible mould at home were considerably stronger risk factors for AIA than for ATA. Current smoking was a risk factor for AIA (OR 2.55; 95% CI 1.47-4.42), but not ATA. CONCLUSION: Aspirin-intolerant asthma identified in the general population was associated with a high burden of symptoms, uncontrolled disease and a high morbidity. Increasing BMI increased the risk of AIA in a dose-response manner. A number of risk factors, including obesity and current smoking, were considerably stronger for AIA than for ATA.

Chronic rhinosinusitis in asthma is a negative predictor of quality of life: results from the Swedish GA(2)LEN survey.

BACKGROUND: Asthma and chronic rhinosinusitis (CRS) both impair quality of life, but the quality-of-life impact of comorbid asthma and CRS is poorly known. The aim of this study was to evaluate the impact of CRS and other relevant factors on quality of life in asthmatic subjects. METHODS: This Swedish cohort (age 17-76 years) consists of 605 well-characterized asthmatics with and without CRS, 110 individuals with CRS only, and 226 controls and is part of the Global Allergy and Asthma European Network (GA(2) LEN) survey. The Mini Asthma Quality of Life Questionnaire (mAQLQ), the Euro Quality of Life (EQ-5D) health questionnaire, spirometry, skin prick test (SPT), exhaled nitric oxide (FeNO), smell test, and peak nasal inspiratory flow were used. RESULTS: Subjects having both asthma and CRS have lower mAQLQ scores in all domains (P < 0.001) and a lower EQ-5D index value and EQ-5D VAS value (P < 0.001) compared to those with asthma only. Asthmatics with CRS have significantly lower FEV1%pred and FVC%pred (88.4 [85.1-91.7] and 99.9 [96.7-103.0], respectively) compared with asthma only (91.9 [90.3-93.4] and 104.0 [102.5-105.5], respectively P < 0.05). Multiple regression analysis shows that low asthma quality of life is associated with having CRS (P < 0.0001), lower lung function (P = 0.008), current smoking (P = 0.01), BMI > 30 kg/m2 (P = 0.04), high age (P = 0.03), and a negative SPT (P = 0.04). CONCLUSIONS: Comorbid CRS was a significant and independent negative predictor of quality of life in asthmatics. Other negative factors were lower lung function, current smoking, obesity, advanced age, and having nonatopic asthma.

Cigarette smoking is associated with high prevalence of chronic rhinitis and low prevalence of allergic rhinitis in men.

BACKGROUND: The harmful effects of tobacco smoke on human health, including respiratory health, are extensive and well documented. Previous data on the effect of smoking on rhinitis and allergic sensitization are inconsistent. We sought to investigate how smoking correlates with prevalence of allergic and chronic rhinitis among adults in Sweden. METHODS: The study population comprised 27 879 subjects derived from three large randomly selected cross-sectional population surveys conducted in Sweden between 2006 and 2008. The same postal questionnaire on respiratory health was used in the three surveys, containing questions about obstructive respiratory diseases, rhinitis, respiratory symptoms and possible determinants of disease, including smoking habits. A random sample from one of the cohorts underwent a clinical examination including skin prick testing. RESULTS: Smoking was associated with a high prevalence of chronic rhinitis in both men and women and a low prevalence of allergic rhinitis in men. These associations were dose dependent and remained when adjusted for a number of possible confounders in multiple logistic regression analysis. Prevalence of chronic rhinitis was lowest in nonsmokers and highest in very heavy smokers (18.5% vs 34.5%, P < 0.001). Prevalence of sensitization to common airborne allergens was lower in current smokers (25.9%, P = 0.008) and ex-smokers (28.2%, P = 0.022) than in nonsmokers (38.5%). CONCLUSION: We found that smoking was associated with a high prevalence of chronic rhinitis in both sexes and a low prevalence of allergic rhinitis in men. The associations were dose dependent and remained when adjusting for several possible confounders.

Eczema among adults: prevalence, risk factors and relation to airway diseases. Results from a large-scale population survey in Sweden.

BACKGROUND: In contrast to asthma and rhinitis, few studies among adults investigating the prevalence and risk factors of eczema have been published. OBJECTIVES: To investigate the prevalence and risk factors of eczema among adults in West Sweden. A further aim was to study the associations between asthma, rhinitis and eczema. METHODS: A questionnaire on respiratory health was mailed in 2008 to 30,000 randomly selected subjects in West Sweden aged 16-75 years; 62% responded. The questionnaire included questions about eczema, respiratory symptoms and diseases and their possible determinants. A subgroup of 669 subjects underwent skin prick testing against common airborne allergens. RESULTS: 'Eczema ever' was reported by 40·7% and 'current eczema' by 11·5%. Both conditions were significantly more common among women. The prevalence decreased with increasing age. The coexistence of both asthma and rhinitis with eczema was common. The main risk factors were family history of allergy and asthma. The dominant environmental risk factor was occupational exposure to gas, dust or fumes. Smoking increased the risk. Eczema was associated with urbanization, while growing up on a farm was associated with a decreased risk. Added one by one to the multivariate model, asthma, allergic rhinitis and any positive skin prick test were associated with eczema. CONCLUSIONS: Eczema among adults is a common disease with more women than men having and having had eczema. Eczema is associated with other atopic diseases and with airway symptoms. Hereditary factors and exposure to gas, dust and fumes are associated with eczema.

Multi-symptom asthma as an indication of disease severity in epidemiology.

Epidemiological questionnaires have failed to identify individuals with severe asthma. The extent of symptoms of asthma can, however, be easily established in epidemiology, by identification of multiple symptoms. We hypothesise that reporting of multiple symptoms of asthma reflects uncontrolled disease and is a sign of more severe asthma. The aims of the current study were, therefore, to determine the prevalence and determinants of multi-symptom asthma. A postal questionnaire was sent to 30,000 randomly selected individuals aged 16-75 yrs. A subgroup underwent clinical examinations. Multi-symptom asthma was defined as reported physician-diagnosed asthma, use of asthma medication, recurrent wheeze, attacks of shortness of breath and at least one additional respiratory symptom. The prevalence of multi-symptom asthma was 2.0%, and it was more common among females (2.4 versus 1.5%; p<0.001) and those with a body mass index >30 kg · m(-2). Multi-symptom asthmatics had lower forced expiratory volume in 1 s, higher exhaled nitric oxide fraction and more pronounced hyperresponsiveness. Family history of both asthma and allergy (OR 7.3), and occupational exposure to gas dust or fumes (OR 2.0) were also significant risk factors. Multi-symptom asthmatics comprise 2% of the general population; multi-symptom asthma is related to signs of more severe disease and could be used as an epidemiological marker of disease severity.

Growing up on a farm leads to lifelong protection against allergic rhinitis.

BACKGROUND: Various studies have reported a low prevalence of allergic rhinitis in farmers and farmers' children. We sought to investigate whether the protective effect of childhood farm environment is conserved throughout adulthood and how it corresponds to different degrees of urbanization. METHODS: A questionnaire on respiratory health was mailed in 2008 to 30,000 randomly selected subjects aged 16-75 in West Sweden, 29,218 could be traced and 18,087 (62%) responded. The questionnaire included questions on allergic rhinitis, asthma, respiratory symptoms and possible determinants. RESULTS: When stratified into age groups of 15 years, subjects that lived on a farm during their first 5 years of life had a lower prevalence of allergic rhinitis in all groups, even among the oldest (61-75 years). The negative correlation between childhood farm living and prevalence of allergic rhinitis was similar in 46-75 years of age (OR 0.82; 95% CI 0.70-0.95) as in 16-45 years of age (OR 0.78; 0.64-0.95). There was a significant trend of increasing prevalence of allergic rhinitis with increasing degree of urbanization independent of the effect of childhood farm living. CONCLUSIONS: We found a lifelong protective effect of childhood farm living on the prevalence of allergic rhinitis. In addition, we found an increasing prevalence of allergic rhinitis with increasing degree of urbanization both in those raised on a farm and those not, thus emphasizing the influence of both childhood and adult exposure for the development of allergic disease.

Has the increase in the prevalence of asthma and respiratory symptoms reached a plateau in Stockholm, Sweden?

SETTING: An increase in the prevalence of asthma has previously been reported worldwide. However, the current trend is debatable. OBJECTIVE: To assess changes in the prevalence of asthma and respiratory symptoms in a defined study area in Stockholm, Sweden, using identical methods. DESIGN: A questionnaire was sent by mail in 1996 and 2007 to randomly selected subjects aged 20-69 years. On both occasions, 8000 subjects received the questionnaire, with response rates of 72% and 68%, respectively. Questions on asthma, respiratory symptoms, asthma medication and possible determinants were included. Logistic regression analysis was used to assess determinants. RESULTS: Ever asthma increased from 8.7% in 1996 to 11.0% in 2007 and physician-diagnosed asthma from 7.6% to 9.3%. The proportion of asthma patients reporting one to two symptoms increased by 14% during the study period. There were few significant changes in the prevalence of respiratory symptoms: wheeze in the previous 12 months (15.9-17.3%), wheezing with breathlessness apart from cold (3.2-4.1%) and recurrent wheeze (8.3-6.8%). There was no major difference in the risk factor pattern between the surveys. CONCLUSION: An increase in the prevalence of asthma with few symptoms as well as an unchanged prevalence of symptoms was demonstrated, which may indicate a change in diagnostic practices.

Effects of an EGFR-binding affibody molecule on intracellular signaling pathways.

Effects on intracellular signaling were studied in cells treated with the affibody molecule (ZEGFR:955)2 that targets the epithelial growth factor receptor (EGFR). EGFR is overexpressed in many types of cancers and plays a fundamental role in cell signaling and it is of interest to find targeting agents capable of blocking the receptor. The clinically approved antibody cetuximab (Erbitux) and the natural ligand EGF were included as reference molecules. Two EGFR-rich cell lines, A-431 and U-343, were exposed to the three targeting agents and lysed. The cell lysates were immunoprecipitated with the receptors, or directly separated by SDS-Page. Autophosphorylation of the receptors and phosphorylation of the downstream signaling proteins Erk and Akt, were evaluated by Western blotting. Although the three different agents compete for the same binding site on EGFR, they influenced the signaling differently. The affibody molecule did not induce autophosphorylation of EGFR or any other receptor in the EGFR-family but, in spite of this, induced phosphorylation of Erk in both cell lines and Akt in the A-431 cells. Thus, the results suggest that the signaling pattern induced by (ZEGFR:955)2 is only partly similar to that induced by cetuximab. This makes the affibody molecule a potentially interesting alternative to cetuximab for EGFR-targeted therapy since it might give different therapy-related effects on tumor cells and different side effects on normal tissues.

FinEsS-Stockholm and the Stockholm adult asthma study.

Two major studies on asthma and respiratory symptoms are presently in progress in Stockholm. The FinEsS-studies has been ongoing since 1996, with a follow-up study preformed in 2006 and a new cohort selected in 2007. The FinEsS studies focus on prevalence and incidence of asthma and respiratory symptoms in a general population. Clinical follow-up surveys will also target COPD. Further aims include remission and relapse of disease and symptoms and their determinants. The Stockholm adult Asthma Study (SaAS) began in the spring of 2007 and data is being collected presently. The SaAS study focus on the medical care and medication given to asthmatics in Stockholm, and the study population consists of asthmatics found in the two Swedish cohort studies.