RESUMEN
BACKGROUND: Evidence on the role of exogenous female sex steroid hormones in asthma development in women remains conflicting. We sought to quantify the potential causal role of hormonal contraceptives and menopausal hormone therapy (MHT) in the development of asthma in women. METHODS: We conducted a matched case-control study based on the West Sweden Asthma Study, nested in a representative cohort of 15,003 women aged 16-75 years, with 8-year follow-up (2008-2016). Data were analyzed using Frequentist and Bayesian conditional logistic regression models. RESULTS: We included 114 cases and 717 controls. In Frequentist analysis, the odds ratio (OR) for new-onset asthma with ever use of hormonal contraceptives was 2.13 (95% confidence interval [CI] 1.03-4.38). Subgroup analyses showed that the OR increased consistently with older baseline age. The OR for new-onset asthma with ever MHT use among menopausal women was 1.17 (95% CI 0.49-2.82). In Bayesian analysis, the ORs for ever use of hormonal contraceptives and MHT were, respectively, 1.11 (95% posterior interval [PI] 0.79-1.55) and 1.18 (95% PI 0.92-1.52). The respective probability of each OR being larger than 1 was 72.3% and 90.6%. CONCLUSIONS: Although use of hormonal contraceptives was associated with an increased risk of asthma, this may be explained by selection of women by baseline asthma status, given the upward trend in the effect estimate with older age. This indicates that use of hormonal contraceptives may in fact decrease asthma risk in women. Use of MHT may increase asthma risk in menopausal women.
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Asma , Humanos , Femenino , Estudios de Casos y Controles , Teorema de Bayes , Asma/inducido químicamente , Asma/epidemiología , Anticonceptivos , Hormonas Esteroides GonadalesRESUMEN
BACKGROUND: As the prevalence of dog allergy rises, component resolved diagnosis might improve the diagnosis, understanding of the clinical outcomes and the effectiveness of immunotherapy. Considering the paucity of data in adults, the current study characterized the patterns of sensitization to dog molecular allergens in an adult population. METHODS: Data were derived from the West Sweden Asthma Study, a population-based and representative sample of adults from western Sweden. Of the 2006 subjects clinically examined, 313 participants sensitized to whole dog allergen extract were measured for specific immunoglobulin E (sIgE) levels to Can f 1, Can f 2, Can f 3, Can f 4, Can f 5 and Can f 6 using ImmunoCAP™. Polysensitization was defined as sensitization to ≥3 components. Overlapping sensitization was defined as having concomitant sensitization to at least two dog molecular allergen families (lipocalin, albumin or prostatic kallikrein). RESULTS: Of 313, 218 (70%) subjects tested positive to at least one dog allergen component. Sensitization to Can f 1 (43%) was the most common, followed by Can f 5 (33%) among molecular allergens, while sensitization to lipocalins (56%) was the most common among component families. Polysensitization was found in 22% of all participants and was more common in participants with than in those without asthma. Subjects with asthma were less likely to be monosensitized to Can f 5 than those without asthma. Subjects with asthma had higher IgE levels of Can f 3, Can f 4 and Can f 6 than those without asthma. Overlapping sensitizations also differed between those with asthma and allergic rhinitis and those without. CONCLUSION: Increased knowledge about the sensitization patterns of dog allergen components can aid in defining their role in asthma and rhinitis. In complex clinical cases of dog allergy, a detailed analysis of dog allergen components can provide additional information on the nature of sensitization.
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Asma , Rinitis Alérgica , Perros , Animales , Alérgenos , Suecia/epidemiología , Asma/diagnóstico , Asma/epidemiologíaRESUMEN
BACKGROUND: Due to the high transmissibility of SARS-CoV-2, accurate diagnosis is essential for effective infection control, but the gold standard, real-time reverse transcriptase-polymerase chain reaction (RT-PCR), is costly, slow, and test capacity has at times been insufficient. We compared the accuracy of clinician diagnosis of COVID-19 against RT-PCR in a general adult population. METHODS: COVID-19 diagnosis data by 30th September 2021 for participants in an ongoing population-based cohort study of adults in Western Sweden were retrieved from registers, based on positive RT-PCR and clinician diagnosis using recommended ICD-10 codes. We calculated accuracy measures of clinician diagnosis using RT-PCR as reference for all subjects and stratified by age, gender, BMI, and comorbidity collected pre-COVID-19. RESULTS: Of 42,621 subjects, 3,936 (9.2%) and 5705 (13.4%) had had COVID-19 identified by RT-PCR and clinician diagnosis, respectively. Sensitivity and specificity of clinician diagnosis against RT-PCR were 78% (95%CI 77-80%) and 93% (95%CI 93-93%), respectively. Positive predictive value (PPV) was 54% (95%CI 53-55%), while negative predictive value (NPV) was 98% (95%CI 98-98%) and Youden's index 71% (95%CI 70-72%). These estimates were similar between men and women, across age groups, BMI categories, and between patients with and without asthma. However, while specificity, NPV, and Youden's index were similar between patients with and without chronic obstructive pulmonary disease (COPD), sensitivity was slightly higher in patients with (84% [95%CI 74-90%]) than those without (78% [95%CI 77-79%]) COPD. CONCLUSIONS: The accuracy of clinician diagnosis for COVID-19 is adequate, regardless of gender, age, BMI, and asthma, and thus can be used for screening purposes to supplement RT-PCR.
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Asma , COVID-19 , Enfermedad Pulmonar Obstructiva Crónica , Masculino , Adulto , Humanos , Femenino , COVID-19/diagnóstico , COVID-19/epidemiología , SARS-CoV-2/genética , Prueba de COVID-19 , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios de Cohortes , Suecia/epidemiología , Sensibilidad y Especificidad , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
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.
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Asma , Bronquitis , Enfermedad Pulmonar Obstructiva Crónica , Adulto , Anciano , Asma/diagnóstico , Asma/epidemiología , Bronquitis/diagnóstico , Bronquitis/epidemiología , Enfermedad Crónica , Tos/diagnóstico , Tos/epidemiología , Femenino , Finlandia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Fumar/epidemiología , Encuestas y Cuestionarios , Suecia/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Asthma is a chronic airway disease affecting millions of people. Better methods to define asthma subgroups using clinical parameters and molecular biomarkers are crucial in the development of personalized medicine. OBJECTIVE: The aim of this study was to determine if circulating microRNAs (miRNAs) may be used to distinguish well-defined asthma groups. METHODS: Blood serum from 116 well-defined subjects, including healthy controls and individuals with allergic or non-allergic asthma, from the West Sweden Asthma Study were included. Serum was analyzed for circulating miRNA expression of miR-126, - 145, -146a, - 155, - 223, and -374a and eosinophil cationic protein (ECP). Correlations between clinical characteristics and circulating miRNA expression as well as potential miRNA gene targets were investigated. RESULTS: A subset of miRNAs were differentially expressed between allergic and non-allergic asthmatic individuals. Alterations in expression of miR-155, -146a, -374a and - 145 were observed in allergic asthmatics in response to inhaled corticosteroid usage. Additionally, miR-223 and miR-374a expression varied in non-allergic asthmatics based on blood eosinophil numbers. Numerous clinical parameters, including lung function measurements, correlated with subsets of miRNAs. Finally, pathway analysis revealed a potential role for inhaled corticosteroid induced miRNAs in leukocyte regulation, IL-6 signaling and glucocorticoid response. CONCLUSION: Circulating miRNA expression was altered in subjects with allergic and non-allergic asthma and correlated to clinical parameters including lung function and potential gene targets involved in immune processes. This combination of clinical and molecular data may be a basis for the further, more precise classification of asthma subgroups. Taken together, these findings would further asthma research and benefit future patients through the discovery of molecular mechanisms as well as identifying asthma subgroups contributing to the development of personalized medicine.
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Asma/sangre , Asma/epidemiología , MicroARN Circulante/sangre , Hipersensibilidad/sangre , Hipersensibilidad/epidemiología , Adulto , Asma/diagnóstico , Biomarcadores/sangre , Femenino , Humanos , Hipersensibilidad/diagnóstico , Masculino , Persona de Mediana Edad , Suecia/epidemiologíaRESUMEN
BACKGROUND: COPD has increased in prevalence worldwide over several decades until the first decade after the millennium shift. Evidence from a few recent population studies indicate that the prevalence may be levelling or even decreasing in some areas in Europe. Since the 1970s, a substantial and ongoing decrease in smoking prevalence has been observed in several European countries including Sweden. The aim of the current study was to estimate the prevalence, characteristics and risk factors for COPD in the Swedish general population. A further aim was to estimate the prevalence trend of COPD in Northern Sweden from 1994 to 2009. METHODS: Two large random population samples were invited to spirometry with bronchodilator testing and structured interviews in 2009-2012, one in south-western and one in northern Sweden, n = 1839 participants in total. The results from northern Sweden were compared to a study performed 15 years earlier in the same area and age-span. The diagnosis of COPD required both chronic airway obstruction (CAO) and the presence of respiratory symptoms, in line with the GOLD documents since 2017. CAO was defined as post-bronchodilator FEV1/FVC < 0.70, with sensitivity analyses based on the FEV1/FVC < lower limit of normal (LLN) criterion. RESULTS: Based on the fixed ratio definition, the prevalence of COPD was 7.0% (men 8.3%; women 5.8%) in 2009-2012. The prevalence of moderate to severe (GOLD ≥ 2) COPD was 3.5%. The LLN based results were about 30% lower. Smoking, occupational exposures, and older age were risk factors for COPD, whereof smoking was the most dominating risk factor. In northern Sweden the prevalence of COPD, particularly moderate to severe COPD, decreased significantly from 1994 to 2009, and the decrease followed a decrease in smoking. CONCLUSIONS: The prevalence of COPD has decreased in Sweden, and the prevalence of moderate to severe COPD was particularly low. The decrease follows a major decrease in smoking prevalence over several decades, but smoking remained the dominating risk factor for COPD.
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Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Fumar Tabaco/epidemiología , Fumar Tabaco/tendencias , Anciano , Femenino , Volumen Espiratorio Forzado/fisiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Espirometría/métodos , Espirometría/tendencias , Suecia/epidemiología , Factores de Tiempo , Fumar Tabaco/efectos adversosRESUMEN
BACKGROUND: There are paucity of data on sensitization to furry animal allergen components in adults. Furry animals are major sensitizers and contributors to asthma burden in northern Europe and North America. OBJECTIVE: To characterize sensitization patterns to furry animal allergen components in Swedish adults. METHODS: Based on the West Sweden Asthma Study, a random population (n = 1103) and an asthma sample (n = 769) were tested for allergen sensitization using Phadiatop® . Those with IgE ≥ 0.35 kUA /L were tested for cat (Fel d 1, 2, and 4), dog (Can f 1, 2, 3, and 5), and horse (Equ c 1) allergen component sensitization. We defined allergen component poly-sensitization patterns, identified data-driven sensitization clusters, described component sensitization overlaps, and assessed determinants of sensitization patterns. RESULTS: The prevalence of allergen component sensitization ranged from 0.8% for Fel d 2 and Can f 3 to 8.9% for Fel d 1. The most common dog component was Can f 5 (3.6%); 2.1% were sensitized to Equ c 1. Those sensitized to Fel d 2 and Fel d 4 were commonly sensitized to Fel d 1. The most common dog component overlap was between Can f 1/Can f 2 and Can f 5. Mono-sensitization was 5.6%, double sensitization 1.5% and poly-sensitization 2.1%. Sensitization was always higher in the asthma than in the random sample. Three sensitization clusters were derived, namely non-sensitized (90% in random vs 66% in asthma sample); Fel d 1-driven sensitized (7% vs 19%); and multi-sensitized (3% vs 15%). Key determinants of sensitization were gender, age, raised on a farm, family history of allergy or asthma, smoking, and occupational exposure to dust or fumes. CONCLUSIONS & CLINICAL RELEVANCE: Fel d 1 and Can f 5 are the most common cat and dog components sensitization in this adult Swedish population. Mono-sensitization is more common than poly-sensitization. This detailed characterization highlights the current distribution of furry animal allergen components in Swedish adults, and their impact on clinical outcomes of asthma will be further explored.
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Alérgenos/inmunología , Pelaje de Animal/inmunología , Asma/epidemiología , Asma/inmunología , Adolescente , Adulto , Anciano , Animales , Especificidad de Anticuerpos/inmunología , Gatos , Perros , Exposición a Riesgos Ambientales/efectos adversos , Humanos , Inmunización , Inmunoglobulina E/inmunología , Persona de Mediana Edad , Vigilancia de la Población , Prevalencia , Encuestas y Cuestionarios , Suecia/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Asthma is a common chronic inflammatory disease of the airways, with a noticeable increase in prevalence during the second half of the 20th century. Recent studies assessing the prevalence trends among adults have been inconsistent. We investigated the changes in the prevalence of asthma, respiratory symptoms, and risk factors between 2008 and 2016 in western Sweden. METHODS: The West Sweden Asthma Study (WSAS) is a population-based study which started in 2008 (WSAS I) and then repeated in 2016 (WSAS II) in western Sweden. Randomly selected individuals aged 16-75 years (N = 18 087 in 2008 and N = 24 534 in 2016) completed a questionnaire regarding obstructive lung diseases, respiratory symptoms, potential risk factors, and also questions from the GA2 LEN survey. RESULTS: The prevalence of reported ever asthma, physician-diagnosed asthma, use of asthma medication, and current asthma increased significantly from 9.6% to 11%, 8.3% to 10%, 8.6% to 9.8%, and 8.1% to 9.1%, respectively, between 2008 and 2016. There were also increases in the prevalence of respiratory symptoms during the same period. The greatest increase occurred in young adults aged 16-25 years. Female gender, allergic rhinitis, obesity, and family history of asthma remained the strongest risk factors for asthma in 2016 as it was in 2008. CONCLUSION: There were moderate increases in asthma and respiratory symptoms in adults in western Sweden between 2008 and 2016, the greatest increase occurring in younger adults. The potential risk factors for asthma remained the same during the study period.
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Asma/epidemiología , Adolescente , Adulto , Anciano , Asma/diagnóstico , Asma/historia , Estudios Transversales , Demografía , Femenino , Historia del Siglo XXI , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Vigilancia en Salud Pública , Factores Socioeconómicos , Encuestas y Cuestionarios , Suecia/epidemiología , Evaluación de Síntomas , Adulto JovenRESUMEN
BACKGROUND: The prevalence of asthma severity is not well described at a population level. OBJECTIVE: We sought to determine the prevalence of phenotypic signs of asthma severity among asthmatic patients in a general population and to describe risk factors for asthma severity. METHODS: We performed an epidemiologic study conducted between 2008 and 2012 (West Sweden Asthma Study). A postal questionnaire was sent to a random population (n = 30,000) in west Sweden, with 18,087 responses. A total of 2,006 subjects were carefully phenotyped. Only subjects with "active asthma" (symptoms or medication in the last year, n = 744) were analyzed in this study to determine the degree of severity of the disease within an asthma cohort. Phenotypes of severity were calculated based on (1) multiple symptoms during the day despite ongoing use of asthma medications, (2) FEV1 of less than 70% of predicted value, (3) daily or almost daily use of rescue medications, (4) nighttime symptoms once a week or more, and (5) oral corticosteroid use/emergency department visits. Asthmatic patients were grouped as having nonsevere disease, 1 sign of severity, or 2 or more signs of severity. RESULTS: A total of 36.2% of asthmatic patients expressed at least 1 sign of asthma severity, and 13.2% had 2 or more signs. The group with 2 or more signs was older in age and had higher body mass index, a higher rate of tobacco smoking, and lower lung function. Bronchial hyperreactivity, airway inflammation, and sensitization were significantly different among the 3 groups. At a population level, the prevalence of asthma severity was 3.1% for 1 sign and 1.3% for at least 2 signs. CONCLUSION: More than 1 in 3 asthmatic patients show at least 1 sign of asthma severity. The phenotypes of asthma severity are highly diverse, which is important to consider when implementing personalized medicine in asthmatic patients.
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Asma/epidemiología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Encuestas y Cuestionarios , Suecia/epidemiologíaRESUMEN
OBJECTIVE: Although asthma and chronic obstructive pulmonary disease (COPD) have been regarded as distinct conditions, emerging literature suggests that overlapping phenotypes, called asthma-COPD overlap (ACO), exists. The aim of this study was to describe prevalence, patient characteristics and morbidity of ACO. METHODS: From a cross-sectional population sample, the West Sweden Asthma Study, subjects with suspected asthma, chronic bronchitis or COPD, and a random sample, were invited to clinical examinations. ACO was defined as doctor-diagnosed asthma, or clear clinical signs of asthma at examination, with a FEV1/FVC < 0.7. RESULTS: Subjects were categorized as ACO (N = 181), COPD only (N = 89), asthma only (N = 651) or healthy (n = 1036) based on clinical examinations. Prevalence of ACO was 3.4% in the random sample (N = 1172) and 18.1% among asthmatics (N = 138) in the random sample. Subjects with ACO (mean age 59 years, 54% women) had an age and gender distribution in between asthma only (45 years, 63% women) and COPD only (62 years, 41% women). Ever-smoking was reported by 71%, 48% and 74% in the ACO, asthma only and COPD only groups, respectively. Subjects with ACO had worse lung function (mean FEV1% of predicted normal 76%) than asthma only (100%) and COPD only (87%) and reported more respiratory symptoms. Also respiratory related emergency visits were more common in ACO compared to asthma only and COPD only, respectively. CONCLUSIONS: ACO is present in 3.4% of the population and common among subjects with both asthma and COPD. Subjects with ACO had worse lung function and more symptoms than subjects with asthma or COPD only.
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Asma/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Adulto , Anciano , Asma/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Morbilidad , Prevalencia , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad , Suecia/epidemiologíaRESUMEN
OBJECTIVE: Previous studies have found that excessive daytime sleepiness (EDS) is a more common problem in asthmatic subjects than in the general population. The aim of this study was to investigate whether the prevalence of EDS is increased in asthmatic subjects and, if so, to analyse the occurrence of potential risk factors for EDS in asthmatics. METHODS: Cross-sectional epidemiological study. In 2008, a postal questionnaire was sent out to a random sample of 45,000 individuals aged 16-75 years in four Swedish cities. RESULTS: Of the 25,160 persons who participated, 7.3% were defined as having asthma. The prevalence of EDS was significantly higher in asthmatic subjects (42.1% vs. 28.5%, p < 0.001) compared with non-asthmatic subjects. Asthma was an independent risk factor for EDS (adjusted OR 1.29) and the risk of having EDS increased with asthma severity. Risk factors for EDS in subjects with asthma included insomnia (OR, 3.87; 95% CI, 3.10-4.84); chronic rhinosinusitis (OR, 2.00; 95% CI, 1.53-2.62); current smoking (OR, 1.60; 95% CI, 1.15-2.22) and obesity (OR, 1.53; 95% CI, 1.09-2.13). CONCLUSIONS: EDS is a common problem among subjects with asthma. Asthma is an independent risk factor for having EDS. Furthermore, subjects with asthma often have other risk factors for EDS, many of them potentially modifiable.
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Asma/complicaciones , Trastornos del Sueño-Vigilia/epidemiología , Somnolencia , Adolescente , Adulto , Anciano , Asma/diagnóstico , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Índice de Severidad de la Enfermedad , Trastornos del Sueño-Vigilia/etiología , Suecia/epidemiología , Adulto JovenRESUMEN
Cardiovascular diseases are the most common comorbidities in COPD, due to common risk factors such as smoking. The prevalence of current smokers in Sweden has decreased over four decades to around 10%. The aim of the present study was to investigate the prevalence, distribution and associations of cardiovascular comorbidities in COPD by disease severity in two large areas of Sweden, both with low-smoking prevalence. Data from clinical examinations in 2009-2012, including spirometry and structured interview, from two large-scale population studies, the West Sweden Asthma Study (WSAS) and the OLIN Studies in Northern Sweden, were pooled. COPD was defined using post-bronchodilator spirometry according to the fixed ratio FEV1/FVC <0.70 and the lower limit of normal (LLN5th percentile) of the ratio of FEV1/FVC. Of the 1839 subjects included, 8.7% and 5.7% had COPD according to the fixed ratio and the LLN criterion. Medication for heart disease or hypertension among those with moderate-to-severe COPD was more common than among those without COPD (fixed ratio definition of COPD: 51% vs. 23%, p < 0.001; LLN definition: 42% vs. 24%, p = 0.002). After adjusting for known risk factors for COPD, including smoking, age, socio-economic status, and occupational exposure for gas, dust and fumes, only heart failure remained significantly, and independently, associated with COPD, irrespective of the definitions of COPD. Though a major decrease in smoking prevalence, the pattern of cardiovascular comorbidities in COPD still remains similar with previously performed studies in Sweden and in other Westernized countries as well.
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Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Exposición Profesional/efectos adversos , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Fumar/efectos adversos , Adulto , Factores de Edad , Anciano , Estudios de Cohortes , Comorbilidad , Polvo , Femenino , Volumen Espiratorio Forzado , Gasolina , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Distribución de Poisson , Prevalencia , Factores de Riesgo , Clase Social , Espirometría , Encuestas y Cuestionarios , Suecia/epidemiología , Adulto JovenRESUMEN
MicroRNAs (miRs) represent a part of epigenetic control of autoimmunity gaining increasing attention in rheumatoid arthritis (RA). Since cigarette smoking plays important role in RA pathogenesis and reprograms transcriptional profile of miRNAs, we ask if the onco-protein survivin, a novel biomarker of RA, may provide a link between smoking and miRNA. Studying survivin expression in leukocytes of 144 female RA patients we observed that smoking patients had higher survivin transcription and a remarkable spreading of survivin isoforms. This was associated with restricted pattern and low production of miRs. Additionally, miRNA processing enzymes Dicer and DGRC8 were decreased in the patients with survivin isoform spreading. The direct contribution of survivin in miRs biogenesis was confirmed by a massive increase of miRs production following inhibition of survivin in leukocyte cultures. Dicer is shown to mediate these effects of survivin. Chromatin immunoprecipitation analysis demonstrated binding of survivin to the Dicer promoter region. Dicer expression increased 5-folds following survivin inhibition. Taken together, this study presents experimental evidence of a novel cellular function of survivin, control of miRs biogenesis. Up-regulation of survivin in smokers suggests its role as effector of the adverse epigenetic control in RA.
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Artritis Reumatoide/genética , Fumar Cigarrillos/genética , Proteínas Inhibidoras de la Apoptosis/genética , MicroARNs/genética , Activación Transcripcional , Transcriptoma , Adulto , Anciano , Artritis Reumatoide/etiología , Fumar Cigarrillos/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Isoformas de Proteínas/genética , Fumadores , SurvivinRESUMEN
CD8+ T cells have an emerging role in RA. Resent research indicates a causal relationship between the non-exhausted state of CD8+ T cells, defined by lost function of PD-1, and development of arthritis. We investigated how smoking contributes to the non-exhausted phenotype of CD8+ T cells and cause survivin release to serum. We compared serum survivin levels between smokers and non-smokers in 252 RA and 168 healthy subjects. Nicotine effects on CD8+ T cells were studied in peripheral blood of smoking women, bone marrow of nicotine treated mice and in sorted CD8 spleen cells in vitro using flow cytometry and quantitative PCR. Smoking increased the frequency of survivin release in serum of healthy women (OR 3.64, p = 0.025) and in RA patients (OR 1.98, p = 0.039). CD8+ T cells of smokers gained a non-exhausted PD-1 deficient phenotype. Expression of the cytotoxic marker CD107 correlated to survivin levels in serum. In the experimental setting, nicotine exposure led to an accumulation of non-exhausted PD-1-IL-7R+ CD8+ T cells in the bone marrow that is abundant with survivin producing cells. The production of the cytolytic protein perforin in bone marrow correlated to serum survivin levels. In vitro stimulation of nicotinic receptors on murine CD8+ T cells induced repressive transcription factors T-bet and Blimp-1 in support of the non-exhausted phenotype. We conclude that nicotine contributes to autoimmunity by supporting the non-exhausted state of CD8+ T cells resulting in the release of survivin. This presents a new mechanism by which smoking may contribute to the pathogenesis of RA.
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Artritis Reumatoide/inmunología , Artritis Reumatoide/metabolismo , Proteínas Inhibidoras de la Apoptosis/biosíntesis , Activación de Linfocitos/inmunología , Fumar , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Artritis Reumatoide/genética , Biomarcadores , Médula Ósea/efectos de los fármacos , Médula Ósea/metabolismo , Estudios de Casos y Controles , Niño , Preescolar , Modelos Animales de Enfermedad , Femenino , Humanos , Inmunofenotipificación , Proteínas Inhibidoras de la Apoptosis/sangre , Activación de Linfocitos/genética , Masculino , Ratones , Ratones Noqueados , Persona de Mediana Edad , Nicotina/farmacología , Fenotipo , Receptor de Muerte Celular Programada 1/deficiencia , Receptor de Muerte Celular Programada 1/metabolismo , Survivin , Linfocitos T Citotóxicos/efectos de los fármacos , Adulto JovenRESUMEN
BACKGROUND: Asthma is a complex disease presenting with variable symptoms which are sometimes hard to control. The purpose of the study was to describe the prevalence of asthma symptoms, use of asthma medications and allergic sensitization in subjects with asthma. We also related those indices to the level of asthma control, lung function and in particular, cough. METHODS: An extensive questionnaire was sent to randomly selected adults from the West Sweden region. Clinical examinations and interview were performed in a subset. Of the participants, 744 were defined as having an ongoing asthma - reported ever having asthma or physician diagnosed asthma and one of the following - use of asthma medications, recurrent wheeze or attacks of shortness of breath with or without wheeze in the last 12 months. A respiratory disease-free control group of 847 subjects was also described. RESULTS: According to GINA guidelines, 40.6% of the asthmatics had partly controlled and 17.8% had uncontrolled asthma. Asthmatic subjects reported significantly more symptoms in the last 12 months than the control group - wheezing (79.4 vs 9.2%), shortness of breath (36.1 vs 2.5%), wheezing with shortness of breath (58.7 vs 1.3%). Important complaints were morning cough (42.5 vs 15.5%), cough with sputum production (36.1 vs 6.8%) and longstanding cough (32.5 vs 11.1%), which bothered two thirds of the uncontrolled and one third of partly controlled subjects. Asthma medications were used by 87.5% of the asthmatics, although around 30% of them who had insufficiently controlled disease used only short-acting beta-agonists. Asthmatics also had lower lung function, reacted to lower doses of methacholine that the controls and 13.6% of them had a FEV1/FVC ratio below 0.7. Allergic rhinitis was reported by 73.8% of the asthmatics and they were more frequently sensitized to several common allergens. CONCLUSIONS: Approximately 60% of asthmatics from this population-based study had insufficiently controlled asthma and persistent complaints, despite a high use of asthma medications. These self-reported symptoms were supported by clinical examination data. Increased cough frequency is an indicator of a more severe and difficult to control disease and should be considered when asthma is characterized.
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Asma/diagnóstico , Asma/epidemiología , Tos/diagnóstico , Tos/epidemiología , Satisfacción del Paciente , Vigilancia de la Población , Adulto , Anciano , Asma/terapia , Tos/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vigilancia de la Población/métodos , Encuestas y Cuestionarios , Suecia/epidemiologíaRESUMEN
The prevalence of COPD and its risk factor pattern varies between different areas of the world. The aim of this study was to investigate the prevalence of COPD by disease severity in men and women and risk factors for COPD in northern Vietnam. From all 5782 responders to a questionnaire survey, a randomly selected sample of 1500 subjects was invited to a clinical follow-up study. The methods included a structured interview using a modified GA2LEN study questionnaire for registration of symptoms and possible determinants of disease. Spirometry was performed before and after bronchodilation. The age distribution of the sample was 23-72 years. Of 684 subjects attending, 565 completed acceptable spirometric measurements. The prevalence of COPD defined by the GOLD criteria was 7.1%; in men 10.9% and in women 3.9% (p = 0.002). Of those 3.4% had a mild disease, 2.8% a moderate and 0.9% a severe disease. In ages >50 years, 23.5% of men and 6.8% of women had COPD. Among smokers aged >60 years (all men), 47.8% had COPD. None of the women with COPD had been smokers. Increasing age, smoking and male sex were the dominating risk factors, although male sex lost its significance in a multivariate setting. The prevalence of COPD among adults in northern Vietnam was 7.1% and was considerably higher among men than women. The prevalence increased considerably with age. Increasing age and smoking, the latter among men only, were the most important determinants of COPD.
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Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Fumar/epidemiología , Adulto , Factores de Edad , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Espirometría , Vietnam/epidemiología , Adulto JovenRESUMEN
BACKGROUND/OBJECTIVES: Quantification of diamine oxidase (DAO) concentrations in serum has been proposed as an adjunctive diagnostic modality for the evaluation of histamine intolerance (HIT). Limited empirical data exist concerning the influence of dietary patterns on DAO levels. SUBJECTS/METHODS: In the context of a prospective study employing a crossover design, 18 individuals diagnosed with HIT were randomized to initiate either a low histamine diet (LHD) or a conventional mixed diet (MXD). Serum DAO concentrations were measured at the commencement of the study and following each dietary phase. A control group underwent analogous DAO assessments without imposition of dietary constraints. RESULTS: During the time when a diet restricted in histamine was implemented, noticeable differences in changes in DAO levels did not become apparent when compared to the changes observed during the mixed (MXD) phase. Specifically, among the group, 10 of the 18 patients exhibited elevated DAO values subsequent to the LHD regimen, while the remaining eight displayed either reduced or unchanging DAO levels. The prevalence of elevated DAO levels in the LHD group did not differ significantly from that observed in the control group during the MXD phase. Additionally, during the LHD phase, patients reported a significant reduction in gastrointestinal and cutaneous symptoms. CONCLUSIONS: This prospective investigation underscores the enduring utility of a histamine-restricted diet, coupled with structured dietary reintroduction, as an efficacious diagnostic approach for individuals presenting with suspected food-related histamine hypersensitivity. Notably, the measurement of DAO levels appears to furnish only a limited capacity to discern dietary-induced fluctuations. Notwithstanding, the dynamics of DAO alteration do not appear to exhibit a discernible association with specific dietary patterns, a finding consistent across both patient and control groups.
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Amina Oxidasa (conteniendo Cobre) , Estudios Cruzados , Dieta , Histamina , Humanos , Amina Oxidasa (conteniendo Cobre)/sangre , Histamina/sangre , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Adulto , Dieta/métodos , Intolerancia Alimentaria/sangre , AncianoRESUMEN
BACKGROUND: Rhinitis encompasses diverse forms. Each form has distinct pathophysiology and clinical manifestations and may be influenced by differential risk factors. The association between socioeconomic status (SES) and different forms of rhinitis remains poorly understood. Our aim was to examine SES variations in allergic rhinitis, chronic rhinitis, and chronic rhinosinusitis in adults. METHODS: Based on a 2016 postal questionnaire survey within the West Sweden Asthma Study, we analyzed data from 36,213 subjects aged 16-75 years. The measures of SES were levels of education and occupation. Adjusted logistic regression was used to examine associations between SES and the rhinitis outcomes. RESULTS: Attaining a secondary school and tertiary education, compared to a primary school, were associated with increased risk of allergic rhinitis (secondary OR 1.33, 95% CI 1.22-1.45; tertiary 1.54, 1.41-1.69) and chronic rhinitis (secondary 1.18, 1.08-1.29; tertiary 1.17, 1.06-1.28). The influence of occupation was consistent with respect to allergic rhinitis. For instance, compared to the lowest occupational skill level, the highest level (OR 1.24, 95% CI 1.04-1.48) and the lower high occupation levels (1.24, 1.04-1.49) were associated with an increased risk of allergic rhinitis. No significant link was found between education and chronic rhinosinusitis or between occupation levels and risk of either chronic rhinitis or chronic rhinosinusitis. CONCLUSION: Individuals with higher education and those at higher occupational levels may be at higher risk of having different forms of rhinitis than those at lower education and occupation levels. Assessment of rhinitis burden via SES can be one strategy to develop preventive strategies.
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INTRODUCTION: How e-cigarette use relates to changes in smoking status and respiratory symptoms in the population remains controversial. The aim was to study the association between e-cigarette use and, changes in smoking status and changes in respiratory symptoms. METHODS: A prospective, population-based study of random samples of the population (age 16-69 years) was performed within The Obstructive Lung Disease in Northern Sweden (OLIN) study and West Sweden Asthma Study (WSAS). A validated postal questionnaire containing identical questions was used in OLIN and WSAS at baseline in 2006-2008 and at follow-up in 2016. In total, 17325 participated on both occasions. Questions about respiratory symptoms and tobacco smoking were included in both surveys, while e-cigarette use was added in 2016. RESULTS: In 2016, 1.6% used e-cigarettes, and it was significantly more common in persistent tobacco smokers (10.6%), than in those who quit smoking (2.1%), started smoking (7.8%), or had relapsed into tobacco smoking at follow-up (6.4%) (p<0.001). Among current smokers at baseline, tobacco smoking cessation was less common in e-cigarette users than e-cigarette non-users (14.2% vs 47.6%, p<0.001) and there was no association with a reduction in the number of tobacco cigarettes smoked per day. Those who were persistent smokers reported increasing respiratory symptoms. In contrast, the symptoms decreased among those who quit tobacco smoking, but there was no significant difference in respiratory symptoms between quitters with and without e-cigarette use. CONCLUSIONS: E-cigarette use was associated with persistent tobacco smoking and reporting respiratory symptoms. We found no association between e-cigarette use and tobacco smoking cessation, reduction of number of tobacco cigarettes smoked per day or reduction of respiratory symptoms.
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CONCLUSION: Education, but not occupation, was differentially associated with adult asthma phenotypes in the general population. Further research into socioeconomic status variation in various asthma phenotypes is warranted.