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1.
  • Accordini, Simone, et al. (author)
  • The Cost of Persistent Asthma in Europe : An International Population-Based Study in Adults
  • 2013
  • In: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 160:1, s. 93-101
  • Journal article (peer-reviewed)abstract
    • Background: This study is aimed at providing a real-world evaluation of the economic cost of persistent asthma among European adults according to the degree of disease control [as defined by the 2006 Global Initiative for Asthma (GINA) guidelines]. Methods: A prevalence-based cost-of-illness study was carried out on 462 patients aged 30-54 years with persistent asthma (according to the 2002 GINA definition), who were identified in general population samples from 11 European countries and examined in clinical settings in the European Community Respiratory Health Survey II between 1999 and 2002. The cost estimates were computed from the societal perspective following the bottom-up approach on the basis of rates, wages and prices in 2004 (obtained at the national level from official sources), and were then converted to the 2010 values. Results: The mean total cost per patient was EUR 1,583 and was largely driven by indirect costs (i.e. lost working days and days with limited, not work-related activities 62.5%). The expected total cost in the population aged 30-54 years of the 11 European countries was EUR 4.3 billion (EUR 19.3 billion when extended to the whole European population aged from 15 to 64 years). The mean total cost per patient ranged from EUR 509 (controlled asthma) to EUR 2,281 (uncontrolled disease). Chronic cough or phlegm and having a high BMI significantly increased the individual total cost. Conclusions: Among European adults, the cost of persistent asthma drastically increases as disease control decreases. Therefore, substantial cost savings could be obtained through the proper management of adult patients in Europe.
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2.
  • Amaral, Andre F. S., et al. (author)
  • Chronic airflow obstruction and ambient particulate air pollution
  • 2021
  • In: Thorax. - : BMJ Publishing Group Ltd. - 0040-6376 .- 1468-3296. ; 76:12, s. 1236-1241
  • Journal article (peer-reviewed)abstract
    • Smoking is the most well-established cause of chronic airflow obstruction (CAO) but particulate air pollution and poverty have also been implicated. We regressed sex-specific prevalence of CAO from 41 Burden of Obstructive Lung Disease study sites against smoking prevalence from the same study, the gross national income per capita and the local annual mean level of ambient particulate matter (PM2.5) using negative binomial regression. The prevalence of CAO was not independently associated with PM2.5 but was strongly associated with smoking and was also associated with poverty. Strengthening tobacco control and improved understanding of the link between CAO and poverty should be prioritised.
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3.
  • Burney, Peter, et al. (author)
  • Prevalence and Population-Attributable Risk for Chronic Airflow Obstruction in a Large Multinational Study
  • 2021
  • In: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 203:11, s. 1353-1365
  • Journal article (peer-reviewed)abstract
    • Rationale: The Global Burden of Disease program identified smoking and ambient and household air pollution as the main drivers of death and disability from chronic obstructive pulmonary disease (COPD).Objectives: To estimate the attributable risk of chronic airflow obstruction (CAO), a quantifiable characteristic of COPD, due to several risk factors.Methods: The Burden of Obstructive Lung Disease study is a cross-sectional study of adults, aged ≥40, in a globally distributed sample of 41 urban and rural sites. Based on data from 28,459 participants, we estimated the prevalence of CAO, defined as a postbronchodilator FEV1-to-FVC ratio less than the lower limit of normal, and the relative risks associated with different risk factors. Local relative risks were estimated using a Bayesian hierarchical model borrowing information from across sites. From these relative risks and the prevalence of risk factors, we estimated local population attributable risks.Measurements and Main Results: The mean prevalence of CAO was 11.2% in men and 8.6% in women. The mean population attributable risk for smoking was 5.1% in men and 2.2% in women. The next most influential risk factors were poor education levels, working in a dusty job for ≥10 years, low body mass index, and a history of tuberculosis. The risk of CAO attributable to the different risk factors varied across sites.Conclusions: Although smoking remains the most important risk factor for CAO, in some areas, poor education, low body mass index, and passive smoking are of greater importance. Dusty occupations and tuberculosis are important risk factors at some sites.
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4.
  • Cazzoletti, Lucia, et al. (author)
  • Asthma control in Europe : a real-world evaluation based on an international population-based study
  • 2007
  • In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 120:6, s. 1360-1367
  • Journal article (peer-reviewed)abstract
    • Background: Epidemiologic evidence related to asthma control in   patients from the general population is scanty. Objectives: We sought to assess asthma control in several European   centers according to the Global Initiative for Asthma (GINA) guidelines   and to investigate its determinants. Methods: In the European Community Respiratory Health Survey 11   (1999-2002), 1241 adults with asthma were identified and classified   into inhaled corticosteroid (ICS) users and non-ICS users in the last   year. Control was assessed in both groups by using the GINA proposal   (controlled, partly controlled, and uncontrolled asthma), and it was   related to potential determinants. Results: Only 15% (95% CI, 12% to 19%) of subjects who had used ICSs in   the last year and 45% (95% CI, 41% to 50%) of non-ICS users had their   asthma under control; individuals with uncontrolled asthma accounted   for 49% (95% CI, 44% to 53%) and 18% (95% CI, 15% to 21%),   respectively. Among ICS users, the prevalence of uncontrolled asthma   showed great variability across Europe, ranging from 20% (95% CI, 7% to   41%; Iceland) to 67% (95% CI, 35% to 90%; Italy). Overweight status, chronic cough and phlegm, and sensitization to Cladosporium species   were associated with poor control in ICS users. About 65% and 87% of   ICS users with uncontrolled and partly controlled asthma, respectively,   were on a medication regimen that was less than recommended by the GINA   guidelines. Conclusion: Six of 7 European asthmatic adults using ICSs in the last   year did not achieve good disease control. The large majority of   subjects with poorly controlled asthma were using antiasthma drugs in a   suboptimal way. A wide variability in asthma control emerged across   Europe. Clinical implications: Greater attention should be paid to asthma management and to the implementation of the GINA guidelines.
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5.
  • Cazzoletti, Lucia, et al. (author)
  • Asthma Severity According to Global Initiative for Asthma and Its Determinants : An International Study
  • 2010
  • In: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 151:1, s. 70-79
  • Journal article (peer-reviewed)abstract
    • Background: The identification of the factors associated with severe asthma may shed some light on its etiology and on the mechanisms of its development. We aimed to describe asthma severity using the Global Initiative for Asthma (GINA) classification and to investigate its determinants in a cross-sectional, population-based sample in Europe. Methods: In the European Community Respiratory Health Survey II (1999-2002), 1,241 adults with asthma were identified. Severity was assessed using the 2002 GINA classification (intermittent, mild persistent, moderate persistent, severe persistent) and it was related to potential determinants by a multinomial logistic model, using the intermittent group as the reference category for relative risk ratios. Results: About 30% of asthmatic subjects were affected by moderate-to-severe asthma. Sensitization to Cladosporium was associated with a more than 5-fold greater risk of having (mild, moderate or severe) persistent asthma than intermittent asthma. Persistent asthma was positively associated with sensitization to house dust mite, nonseasonal asthma, an older age at asthma onset, and chronic cough and phlegm. Sensitization to cat increased the risk of severe asthma only. Smoking was more strongly associated with asthma severity in men, while rhinitis was more strongly associated with asthma severity in women. Conclusions: One third of the asthmatic population have moderate-to-severe asthma. Sensitization to perennial indoor allergens, particularly Cladosporium, is strongly associated with asthma severity. The role of smoking and rhinitis in determining asthma severity may differ between the sexes, and it should be further investigated. Copyright (C) 2009 S. Karger AG, Basel
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6.
  • Corsico, Angelo G, et al. (author)
  • Factors affecting adherence to asthma treatment in an international cohort of young and middle-aged adults
  • 2007
  • In: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 101:6, s. 1363-1367
  • Journal article (peer-reviewed)abstract
    • Background A major reason of the poor control of asthma is that patients fail to adhere to their treatment. The aim of the study was to identify factors affecting changes in asthma treatment adherence in an international cohort. Methods A follow-up study was carried out by means of a structured clinical interview in 971 subjects with asthma from 12 countries who participated in both the European Community Respiratory Health Survey: ECRHS-I (1990–94) and ECRHS-II (1998–2002). Subjects were considered adherent if they reported they normally took all the prescribed drugs. A logistic model was used to study the adjusted effect of the determinants. Results The net change in adherence to anti-asthmatic treatment per 10 years of follow-up was −2% (95% CI: −9.5, 5.5), 7.5% (−2.6, 17.6), 15.0% (6.6, 23.5) and 19.8% (4.1, 35.5), respectively, in Nordic, Mediterranean, Continental and extra-European areas. Among the 428 non-adherent subjects in ECRHS-I, having regular consultations with health care professionals was the strongest predictor of increased adherence (OR 3.32; 95% CI: 1.08–10.17). Among the 543 adherent subjects in ECRHS-I, using inhaled corticosteroids significantly predicted a persistence of adherence (OR 2.04; 95% CI: 1.11–3.75). No effect of gender, age, duration of the disease, smoking habit and educational level was observed. Conclusions Our findings highlight the key role of doctors and nurses in educating and regularly reviewing the patients and support the efforts for an improvement of clinical communication.
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7.
  • de Marco, Roberto, et al. (author)
  • Inhaled steroids are associated with reduced lung function decline in subjects with asthma with elevated total IgE
  • 2007
  • In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 119:3, s. 611-617
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Few studies have investigated the long-term association between inhaled corticosteroids (ICSs) and lung function decline in asthma. OBJECTIVE: To evaluate whether prolonged treatment with ICSs is associated with FEV(1) decline in adults with asthma. METHODS: An international cohort of 667 subjects with asthma (20-44 years old) was identified in the European Community Respiratory Health Survey (1991-1993) and followed up from 1999 to 2002. Spirometry was performed on both occasions. FEV(1) decline was analyzed according to age, sex, height, body mass index, total IgE, time of ICS use, and smoking, while adjusting for potential confounders. RESULTS: As ICS use increased, the decline in FEV(1) was lower (P trend = .025): on average, decline passed from 34 mL/y in nonusers (half of the sample) to 20 mL/y in subjects treated for 48 months or more (18%). When adjusting for all covariates, there was an interaction (P = .02) between ICS use and total IgE: in subjects with high (>100 kU/L) IgE, ICS use for 4 years or more was associated with a lower FEV(1) decline (23 mL/y; 95% CI, 8-38 compared with nonusers). This association was not seen in those with lower IgE. CONCLUSION: Although confirming a beneficial long-term association between ICSs and lung function in asthma, our study suggests that subjects with high IgE could maximally benefit from a prolonged ICS treatment. CLINICAL IMPLICATIONS: This study adds further evidence to the beneficial effect of inhaled steroids on lung function in asthma; future studies will clarify whether calibrating the corticosteroid dose according to the level of total IgE is a feasible approach in asthma management.
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  • Franklin, Karl, et al. (author)
  • Early life environment and snoring in adulthood
  • 2008
  • In: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 9:1, s. 63-
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: To our knowledge, no studies of the possible association of early life environment with snoring in adulthood have been published. We aimed to investigate whether early life environment is associated with snoring later in life. METHODS: A questionnaire including snoring frequency in adulthood and environmental factors in early life was obtained from 16,190 randomly selected men and women, aged 25-54 years, in Sweden, Norway, Iceland, Denmark and Estonia (response rate 74%). RESULTS: A total of 15,556 subjects answered the questions on snoring. Habitual snoring, defined as loud and disturbing snoring at least 3 nights a week, was reported by 18%. Being hospitalized for a respiratory infection before the age of two years (adjusted odds ratio (OR) = 1.27; 95% confidence interval (CI) 1.01-1.59), suffering from recurrent otitis as a child (OR = 1.18; 95%CI 1.05-1.33), growing up in a large family (OR = 1.04; 95%CI 1.002-1.07) and being exposed to a dog at home as a newborn (OR = 1.26; 95%CI 1.12-1.42) were independently related to snoring later in life and independent of a number of possible confounders in adulthood. The same childhood environmental factors except household size were also related with snoring and daytime sleepiness combined. CONCLUSION: The predisposition for adult snoring may be partly established early in life. Having had severe airway infections or recurrent otitis in childhood, being exposed to a dog as a newborn and growing up in a large family are environmental factors associated with snoring in adulthood.
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10.
  • Gronseth, Rune, et al. (author)
  • Predictors of dyspnoea prevalence : results from the BOLD study
  • 2014
  • In: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 43:6, s. 1610-1620
  • Journal article (peer-reviewed)abstract
    • Dyspnoea is a cardinal symptom for cardiorespiratory diseases. No study has assessed worldwide variation in dyspnoea prevalence or predictors of dyspnoea. We used cross-sectional data from population-based samples in 15 countries of the Burden of Obstructive Lung Disease (BOLD) study to estimate prevalence of dyspnoea in the full sample, as well as in an a priori defined low-risk group (few risk factors or dyspnoea-associated diseases). Dyspnoea was defined by the modified Medical Research Council questions. We used ordered logistic regression analysis to study the association of dyspnoea with site, sex, age, education, smoking habits, low/high body mass index, self-reported disease and spirometry results. Of the 9484 participants, 27% reported any dyspnoea. In the low-risk subsample (n = 4329), 16% reported some dyspnoea. In multivariate analyses, all covariates were correlated to dyspnoea, but only 13% of dyspnoea variation was explained. Females reported more dyspnoea than males (odds ratio similar to 2.1). When forced vital capacity fell below 60% of predicted, dyspnoea was much more likely. There was considerable geographical variation in dyspnoea, even when we adjusted for known risk factors and spirometry results. We were only able to explain 13% of dyspnoea variation.
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11.
  • Gulsvik, Amund, et al. (author)
  • A critical evaluation of the guidelines of obstructive lung disease and their implementation
  • 2006
  • In: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 100, s. S22-S30
  • Journal article (peer-reviewed)abstract
    • Guidelines or recommendations for diagnosis and treatment of obstructive lung diseases defined as asthma and/or chronic obstructive pulmonary disease (COPD) have been numerous in the Nordic countries during the last 25 years. A better-shared care between on one side the general practitioners or chest physicians and on the other side the patients and their closest surroundings of care has to be implemented in future guidelines. Guidelines are based on efficacy and not effectiveness studies, and do not property focus the process of behavioural changes of health care professionals and patients. Primary care physicians treat the vast majority of patients with chronic airway disease of moderate severity. However, they find the evidence-based practice guidelines often complicated. Furthermore, less than 50% of the recommendations in guidelines may be evidence based. As rapid changes may occur in diagnosis and treatment options, future guidelines must be able to adapt to such rapid adjustments. No randomised studies are available on the effect of patient-relevant outcomes using guidelines on management of obstructive lung disease. More outcome research is necessary on both change of procedures and health endpoints after launching guidelines. Cost-effectiveness studies are important to make medical staff and administrative health care systems cooperate in the construction of future health care systems with both an improved medical and system quality.
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12.
  • Gulsvik, Amund, et al. (author)
  • The burden of obstructive lung disease in the Nordic countries
  • 2006
  • In: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 100, s. S2-S9
  • Journal article (peer-reviewed)abstract
    • About 25 million people are living in the Nordic countries, which include Denmark, Finland, Iceland, Norway and Sweden. Population demography, growth and economic status of the countries as well as distribution of known risk factors for obstructive diseases are of importance for building the evidence base for a health program. Immigration, changes in lifestyle, increased mobility of the population and changes of health care services may have an effect on the frequency of the disease. However, the increase in average age, tobacco smoking and the cumulative exposure to occupational agents or indoor pollution will cause the greatest impact on the frequency of obstructive pulmonary disease. This report shows that there is a huge discrepancy in data availability and reliability and implies an urgent need to collect accurate and comprehensive vital statistics on obstructive lung diseases in the Nordic countries.
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13.
  • Hedman, Linnea, 1979- (author)
  • Epidemiological studies of asthma and allergic diseases in teenagers : methodological aspects and tobacco use
  • 2010
  • Doctoral thesis (other academic/artistic)abstract
    • Parental reports are often used in studies of asthma and allergic diseases in children. A change in respondent from parent to index subject usually occurs during adolescence. Little is known about the effects this change in method might have on the outcomes of a longitudinal study. Smoking is a major cause of respiratory symptoms among adults and environmental tobacco smoke (ETS) is a risk factor for asthma among children. Less is known about these associations among teenagers. In order to improve prevention of smoking, it is important to identify populations at risk of becoming smokers.      The aim of this thesis were to 1) evaluate the methodological change from parental to self-completion of a questionnaire about asthma and allergic diseases, and 2) to study determinants for, and respiratory health effects of ETS and personal smoking in teenagers.In 1996, a longitudinal study of asthma and allergic diseases among schoolchildren started within the Obstructive Lung Disease in Northern Sweden (OLIN) studies. All children in first and second grades (aged 7-8 years) in three municipalities, Luleå, Kiruna and Piteå (n=3,525) were invited and 97% participated by parental completion of a questionnaire. The cohort has been followed with annual questionnaires until age 16-17 years and with high participation rates (>91%). From age 12-13 years, the teenagers were the respondents and questions about their tobacco use were included. In addition to the questionnaire completed by the teenagers at age 13-14 years, a questionnaire was also distributed to a random sample of 10% of the parents and 294 participated (84%).  The parents and the teenagers reported a similar prevalence of asthma, respiratory symptoms, rhinitis, eczema and environmental factors. Two statistically significant differences were found: the teenagers reported a higher prevalence of wheezing during or after exercise (14% vs 8%, p<0.05), and having a dog in the home in the last 12 months (42% vs 29%, p<0.001). Answer agreement between parents and teenagers on questions about asthma was almost perfect with kappa values of 0.8-0.9. Corresponding kappa values for questions about respiratory symptoms and rhinitis were 0.3-0.6 and for eczema 0.5-0.6. Agreement about environmental factors varied from 0.2-0.9. Kappa values for parental smoking were 0.8-0.9. The risk factor pattern for allergic diseases was similar regardless of respondent, ie parent or teenager.The prevalence of smoking increased from 3% at 12-13 years to 6% at 14-15 years. Smoking was more common among girls, while the use of snus was more common among boys. Significant risk factors related to smoking among teenagers were smoking family members, female sex and living in an apartment. Having physician-diagnosed asthma did not prevent the teenagers from becoming smokers. Factors related to using snus were a smoking mother and male sex. Daily smokers aged 16-17 years (9%) reported a significantly higher prevalence of wheezing and physician-diagnosed asthma compared to non-smokers. There was a significant dose-response association with higher prevalence of wheeze among those who smoked ≥11 cigarettes per day compared to those who smoked ≤10 per day. In multivariate analyses, maternal environmental tobacco smoke exposure was a significant risk factor for ever wheeze and physician-diagnosed asthma at age 16-17 years, while daily smoking was a risk factor for current wheeze.In conclusion, the methodological change of questionnaire respondent from parent to index subject did not substantially alter the findings of this longitudinal study. There were significant sex differences in the tobacco use: smoking was more common among girls and snus was more common among boys. The most important factor related to tobacco use was presence of family members who smoke. Both maternal ETS exposure and personal smoking was associated with asthma and wheeze in adolescence. ETS was associated with lifetime symptoms but daily smoking was more strongly associated with current symptoms.
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  • Jõgi, Rain (author)
  • Asthma : Respiratory Symptoms, Atopy and Bronchial Hyperresponsiveness in Young Adults in Estonia and Sweden
  • 2001
  • Doctoral thesis (other academic/artistic)abstract
    • Morbidity of asthma has increased over the world. The reasons for this increase have remained unclear. Studies in children have reported considerable East-West difference in the prevalence of atopy and respiratory allergies.The aim of this thesis was to compare the prevalence and risk factors of respi-ratory symptoms, atopic sensitisation and bronchial hyperresponsiveness (BHR) in young adults in Estonia and Sweden. Following the protocol of the European Community Respiratory Health Survey (ECRHS), two random population samples, 3000 from Tartu, Estonia, and 3600 from Uppsala, Sweden were investigated with postal questionnaires. Random sub samples and subjects with asthma-like complaints were subsequently interviewed, BHR was tested and serum samples analysed for total and specific IgE and eosinophil cationic protein (ECP). In a separate study two methacholine challenge methods, using either Spira Elektro2 or Mefar MB3 as dosimeters, were compared on 28 mild to moderate asthma patients.Symptoms of asthma and hay fever were less common in Esto-nia than in Sweden, while respiratory symptoms in general were more common in Estonia. The prevalence of BHR was high and the prevalence of atopy and the levels of serum ECP were low in Tartu. The differences between the two centres in the prevalence of atopy and allergic rhinitis diminished with age, indicating a probable cohort effect. Current smoking was a dominant risk factor for BHR and for all respiratory symptoms, except attacks of asthma, both in Tartu and Uppsala. There was some difference between risk factors for BHR and atopy between Tartu and Uppsala, mostly of social and environmental origin. The low prevalence of hay fever and asthma in Tartu seemed to be partly explained by a lack of awareness of atopy and allergic diseases in the Estonian society. The estimated cumulative dose causing a 20% fall in FEV1 was smaller and the decline of FEV1 /log(dose) curve steeper, using the Spira, compared to the Mefar protocol.
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  • Kato, Bernet, et al. (author)
  • Can spirometric norms be set using pre- or post- bronchodilator test results in older people?
  • 2012
  • In: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 13:1, s. 102-
  • Journal article (peer-reviewed)abstract
    • BACKGROUND:Chronic Obstructive Pulmonary Disease (COPD) is defined by post-bronchodilator spirometry. Data on "normal values" come predominantly from pre-bronchodilator spirometry. The effects of this on diagnosis are unknown.METHODS:Lower limits of normal (LLN) were estimated from "normal" participants in the Burden of Obstructive Lung Disease (BOLD) programme. Values separately derived using pre- and post-bronchodilator spirometry were compared. Sensitivity and specificity of criteria derived from pre-bronchodilator spirometry and pre-bronchodilator spirometry adjusted by a constant were assessed in the remaining population. The "gold standard" was the LLN for the post-bronchodilator spirometry in the "normal population". For FEV1/FVC, sensitivity and specificity of criteria were assessed when a fixed value of < 70% was used rather than LLN.RESULTS:Of 6,600 participants with full data, 1,354 were defined as "normal". Mean differences between pre- and post- bronchodilator measurements were small and the Bland-Altman plots showed no association between difference and mean value. Compared with using the gold standard, however, tests using pre-bronchodilator spirometry had a sensitivity and specificity of detecting a low FEV1 of 78.4% and 100%, a low FVC of 99.6% and 99.1% and a low FEV1/FVC ratio of 65% and 100%. Adjusting this by a constant improved the sensitivity without substantially altering the specificity for FEV1 (99%, 99.8%), FVC (97.4%, 99.9%) and FEV1/FVC (98.7%, 99.5%).CONCLUSIONS: Using pre-bronchodilator spirometry to derive norms for lung function reduces sensitivity compared to a post-bronchodilator gold standard. Adjustment of these values by a constant can improve validity of the test.
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  • Laerum, Birger N, et al. (author)
  • Young maternal age at delivery is associated with asthma in adult offspring
  • 2007
  • In: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 101:7, s. 1431-1438
  • Journal article (peer-reviewed)abstract
    • Objective: Some studies have shown an association between lower maternal age at delivery and increased asthma in children and young adults. It is unclear whether this represents an effect of maternal ageing or a protective effect of siblings. In a North-European population based study, we investigated whether mother's age at delivery was associated with risk for asthma and hay fever in adult offspring, taking into account relevant confounders. Methods: A total of 16,190 subjects (74%) aged 23-54yr answered a postal questionnaire in a follow-up of the European Community Respiratory Health Survey (ECRHS I). Results: The associations of maternal age at delivery with hay fever, respiratory symptoms and diagnosed asthma were analysed using logistic regression, adjusting for household size, dwelling, parental education, centre, gender, adult hay fever, smoking, age and body mass index (BMI). The adjusted odds ratios (95% CI) for wheeze with breathlessness, wheeze without a cold and asthma in the offspring were 0.94 (0.90-0.99), 0.89 (0.86-0.94) and 0.92 (0.88-0.97), respectively, per 5yr increase in maternal age. No heterogeneity between centres was found (p = 0.84). The estimates remained similar in sub-sample analyses when adjusting for siblings, maternal smoking (n = 3109) and for birth weight (n = 1686). Hay fever was more common among those with the youngest and oldest mothers. Conclusions: In this large North-European multi-centre study, asthma was less common with increasing maternal age. This effect was consistent between centres and persisted with adjustment for several potential confounders, suggesting that the association may possibly be explained by biological changes related to maternal ageing.
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  • Marcon, Alessandro, et al. (author)
  • Body mass index, weight gain, and other determinants of lung function decline in adult asthma
  • 2009
  • In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 123:5, s. 1069-1074
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Little is known about factors associated with lung function decline in asthma. OBJECTIVE: To identify the determinants of FEV(1) decline in adults with asthma with and without airflow obstruction at baseline. METHODS: An international cohort of 638 subjects with asthma (20-44 years old) was identified in the European Community Respiratory Health Survey (1991-1993) and followed up from 1998 to 2002. Spirometry was performed on both occasions. FEV(1) decline was related to potential determinants evaluated at baseline and during the follow-up by random intercept linear regression models. The analyses were stratified by the presence of airflow obstruction (FEV(1)/forced vital capacity < 0.70) at baseline. RESULTS: In the group of individuals without airflow obstruction (n = 544), a faster FEV(1) decline was observed for subjects with intermediate body mass index (BMI) than for lean and obese subjects. FEV(1) decline was associated with weight gain independently of baseline BMI, and this association was stronger in men (20; 95% CI, 10-30, mL/y/kg gained) than in women (6; 95% CI, 1-11, mL/y). In the group of individuals with airflow obstruction (n = 94), the absence of allergen sensitization and a low BMI at baseline were associated with a faster FEV(1) decline, whereas weight gain was not associated with decline. CONCLUSIONS: The detrimental effect of weight gain on FEV(1) decline is particularly relevant in subjects with asthma who still do not have an established airflow obstruction. Our findings support the importance of weight management in asthma and recommend weight loss in overweight or obese individuals with asthma.
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  • Ratanachina, Jate, et al. (author)
  • Association of respiratory symptoms and lung function with occupation in the multinational Burden of Obstructive Lung Disease (BOLD) study
  • 2023
  • In: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 61:1
  • Journal article (peer-reviewed)abstract
    • Background Chronic obstructive pulmonary disease has been associated with exposures in the workplace. We aimed to assess the association of respiratory symptoms and lung function with occupation in the Burden of Obstructive Lung Disease study.Methods We analysed cross-sectional data from 28 823 adults (≥40 years) in 34 countries. We considered 11 occupations and grouped them by likelihood of exposure to organic dusts, inorganic dusts and fumes. The association of chronic cough, chronic phlegm, wheeze, dyspnoea, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)/FVC with occupation was assessed, per study site, using multivariable regression. These estimates were then meta-analysed. Sensitivity analyses explored differences between sexes and gross national income.Results Overall, working in settings with potentially high exposure to dusts or fumes was associated with respiratory symptoms but not lung function differences. The most common occupation was farming. Compared to people not working in any of the 11 considered occupations, those who were farmers for ≥20 years were more likely to have chronic cough (OR 1.52, 95% CI 1.19–1.94), wheeze (OR 1.37, 95% CI 1.16–1.63) and dyspnoea (OR 1.83, 95% CI 1.53–2.20), but not lower FVC (β=0.02 L, 95% CI −0.02–0.06 L) or lower FEV1/FVC (β=0.04%, 95% CI −0.49–0.58%). Some findings differed by sex and gross national income.Conclusion At a population level, the occupational exposures considered in this study do not appear to be major determinants of differences in lung function, although they are associated with more respiratory symptoms. Because not all work settings were included in this study, respiratory surveillance should still be encouraged among high-risk dusty and fume job workers, especially in low- and middle-income countries.
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22.
  • Sakornsakolpat, Phuwanat, et al. (author)
  • Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations
  • 2019
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 494-505
  • Journal article (peer-reviewed)abstract
    • Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 x 10-8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.
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23.
  • Sator, Lea, et al. (author)
  • Overdiagnosis of COPD in Subjects With Unobstructed Spirometry A BOLD Analysis
  • 2019
  • In: Chest. - : Elsevier BV. - 0012-3692 .- 1931-3543. ; 156:2, s. 277-288
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: There are several reports on underdiagnosis of COPD, while little is known about COPD overdiagnosis and overtreatment. We describe the overdiagnosis and the prevalence of spirometrically defined false positive COPD, as well as their relationship with overtreatment across 23 population samples in 20 countries participating in the BOLD Study between 2003 and 2012.METHODS: A false positive diagnosis of COPD was considered when participants reported a doctor's diagnosis of COPD, but postbronchodilator spirometry was unobstructed (FEV1/FVC > LLN). Additional analyses were performed using the fixed ratio criterion (FEV1/FVC < 0.7).RESULTS: Among 16,177 participants, 919 (5.7%) reported a previous medical diagnosis of COPD. Postbronchodilator spirometry was unobstructed in 569 subjects (61.9%): false positive COPD. A similar rate of overdiagnosis was seen when using the fixed ratio criterion (55.3%). In a subgroup analysis excluding participants who reported a diagnosis of "chronic bronchitis" or "emphysema" (n = 220), 37.7% had no airflow limitation. The site-specific prevalence of false positive COPD varied greatly, from 1.9% in low- to middle-income countries to 4.9% in high-income countries. In multivariate analysis, overdiagnosis was more common among women, and was associated with higher education; former and current smoking; the presence of wheeze, cough, and phlegm; and concomitant medical diagnosis of asthma or heart disease. Among the subjects with false positive COPD, 45.7% reported current use of respiratory medication. Excluding patients with reported asthma, 34.4% of those with normal spirometry still used a respiratory medication.CONCLUSIONS: False positive COPD is frequent. This might expose nonobstructed subjects to possible adverse effects of respiratory medication.
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24.
  • Shrine, Nick, et al. (author)
  • New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries
  • 2019
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 481-493
  • Journal article (peer-reviewed)abstract
    • Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function-associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.
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25.
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26.
  • Wain, Louise V, et al. (author)
  • Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.
  • 2017
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:3, s. 416-425
  • Journal article (peer-reviewed)abstract
    • Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97. A genetic risk score was associated with COPD susceptibility (odds ratio per 1 s.d. of the risk score (∼6 alleles) (95% confidence interval) = 1.24 (1.20-1.27), P = 5.05 × 10(-49)), and we observed a 3.7-fold difference in COPD risk between individuals in the highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in genes for development, elastic fibers and epigenetic regulation pathways. We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications.
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