Subtypes of Adult-Onset Asthma at the Time of Diagnosis: A Latent Class Analysis

Introduction: Only a few previous studies have investigated the subtypes of adult-onset asthma. No previous study has assessed whether these subtypes are different between men and women, or whether these subtypes have different risk factors. Methods: We applied latent class analyses to the Finnish Environment and Asthma Study population, including 520 new cases of adult-onset asthma. We formed subtypes separately between women and men and analyzed the following determinants as potential predictors for these subtypes: age, body mass index, smoking, and parental asthma. Results: Among women, the subtypes identified were: 1. Moderate asthma, 2. Cough-variant asthma, 3. Eosinophilic asthma, 4. Allergic asthma, and 5. Difficult asthma. Among men, the subtypes were: 1. Mild asthma, 2. Moderate asthma, 3. Allergic asthma, and 4. Difficult asthma. Three of the subtypes were similar among women and men: Moderate, Allergic, and Difficult asthma. In addition, women had two distinct subtypes: Cough-variant asthma, and Eosinophilic asthma. These subtypes had different risk factor profiles, e.g., heredity was important for Eosinophilic and Allergic asthma (RR for Both parents having asthma in Eosinophilic 3.55 (1.09 to 11.62)). Furthermore, smoking increased the risk of Moderate asthma among women (RR for former smoking 2.21 (1.19 to 4.11)) and Difficult asthma among men but had little influence on Allergic or Cough-variant asthma. Conclusion: This is an original investigation of the subtypes of adult-onset asthma identified at the time of diagnosis. These subtypes differ between women and men, and these subtypes have different risk factor profiles. These findings have both clinical and public health importance for the etiology, prognosis, and treatment of adult-onset asthma

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

A genome-wide association search for type 2 diabetes genes in African Americans.

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations

Smoking and lung function among adults with newly onset asthma

Introduction Smoking increases the risk of asthma and reduces lung function among subjects with and without asthma. We assessed the effects of smoking on lung function reflecting both central and small airways among adults with newly onset asthma. Methods In a population-based study, 521 (response rate 86%) working-aged adults with clinically defined newly diagnosed asthma answered a questionnaire on personal smoking and other factors potentially influencing lung function, and performed spirometry. We applied multiple linear regression analysis to estimate the relations between smoking and lung function adjusting for confounding. Results Among asthmatics, FEV1 level was reduced significantly, on average 208 mL, related to regular smoking (adjusted effect estimate -0.208, 95% CI -0.355 to -0.061) and 245 mL in relation to former smoking, that is, among those who quit less than a year ago (-0.245, 95% CI -0.485 to -0.004). In contrast, FEV1 was not significantly related to occasional smoking or former smoking among those who quit over a year ago. Forced expiratory flow (FEF) levels (L/s) were also significantly reduced among regular smokers (FEF25-75%: -0.372, 95% CI -0.607 to -0.137; FEF50%: -0.476, 95% CI -0.750 to -0.202). An exposure-response pattern related to both daily smoking rate and lifetime cumulative smoking was seen both among men and women. Conclusions This study provides new evidence that among working-aged adults with new asthma, regular smoking and former smoking reduce lung function levels with a dose-response pattern. The lung function parameters applied as outcomes reflect both larger and smaller airways.Peer reviewe

Occupation and occurrence of respiratory infections among adults with newly diagnosed asthma

Abstract Background Work environments are potential areas for spreading respiratory infections. We hypothesized that certain occupations increase susceptibility to respiratory infections among adults with asthma. Our objective was to compare the occurrence of respiratory infections among different occupations in adults with newly diagnosed asthma. Methods We analysed a study population of 492 working-age adults with newly diagnosed asthma who were living in the geographically defined Pirkanmaa Area in Southern Finland during a population-based Finnish Environment and Asthma Study (FEAS). The determinant of interest was occupation at the time of diagnosis of asthma. We assessed potential relations between occupation and occurrence of both upper and lower respiratory tract infections during the past 12 months. The measures of effect were incidence rate ratio (IRR) and risk ratio (RR) adjusted for age, gender, and smoking habits. Professionals, clerks, and administrative personnel formed the reference group. Results The mean number of common colds in the study population was 1.85 (95% CI 1.70, 2.00) infections in the last 12 months. The following occupational groups showed increased risk of common colds: forestry and related workers (aIRR 2.20, 95% CI 1.15–4.23) and construction and mining (aIRR 1.67, 95% CI 1.14–2.44). The risk of lower respiratory tract infections was increased in the following groups: glass, ceramic, and mineral workers (aRR 3.82, 95% CI 2.54–5.74), fur and leather workers (aRR 2.06, 95% CI 1.01–4.20) and metal workers (aRR 1.80, 95% CI 1.04–3.10). Conclusions We provide evidence that the occurrence of respiratory infections is related to certain occupations

Different effects of smoking on atopic and non-atopic adult-onset asthma

Abstract Background: Both tobacco smoking and atopy increase the risk of adult-onset asthma. We studied if there are differences in the effects of smoking on the risks of atopic and non-atopic adult-onset asthma, and if gender modifies these effects. Methods: The Finnish Environment and Asthma Study (FEAS) includes 521 incident cases of adult-onset asthma and 932 population-based controls, aged 21 to 63 years, recruited from a geographically defined area of Pirkanmaa, South Finland. Asthma was defined based on symptoms and lung function measurements, atopy by IgE antibodies to common aeroallergens and smoking by the study questionnaire. Results: Altogether 212 cases were atopic, and 251 cases were non-atopic. Regular smoking increased the risk of atopic asthma (adjusted OR 1.24, 95% CI 0.83–1.85), this effect was seen in women (aOR 1.77, 1.06–2.95) but not in men (aOR 0.75, 0.39–1.45). Among regular smokers, the amount smoked was lowest among women with atopic asthma. Recent quitting of smoking was related to increased risk of both atopic (aOR 4.91, 2.26–10.65) and non-atopic (aOR 4.37, 1.87–10.21) asthma. Having quitted smoking over a year ago was related to increased risk of non-atopic asthma (aOR 1.57, 1.08–2.28), mainly in men (aOR 2.03, 1.06–3.88). Conclusions: In women, rather small amounts of regular smoking increase the risk of atopic asthma. However, for non-atopic asthma, the smoking induced risk continues for longer after quitting, especially in men. In conclusion, the effects of smoking on the risks of atopic and non-atopic asthma differ, and gender modifies these effects

Indoor mold odor in the workplace increases the risk of Asthma-COPD Overlap Syndrome:a population-based incident case–control study

Abstract Background: Previous studies have suggested an increased risk of asthma related to indoor dampness problems, but their role in the etiology of Asthma-COPD Overlap Syndrome has not been studied. We utilized a population-based incident case–control study to assess potential effect of indoor dampness and molds at home and at work on development of ACOS. Methods: We recruited systematically all new cases of asthma diagnosed during a 2.5-year study period (1997–2000) and randomly selected controls from the source population of adults 21–63 years old and representing 500,000 persons-years in the Pirkanmaa Hospital District, South Finland. Exposure indicators included water damage, damp stains or paint peeling, visible mold, and mold odor, asked separately for home and workplace. The clinically diagnosed case series consisted of 521 adults with newly diagnosed asthma. Altogether 25 of them satisfied the criteria for ACOS-cases, i.e. FEV1/FVC &lt; 0.70 in post-bronchodilator spirometry. The control series, including 932 controls, were from a random sample of source population, after excluding 76 (7.5%) controls with asthma. Results: In logistic regression analysis adjusting for confounders, the risk of ACOS was significantly related to presence of mold odor in the workplace (OR 3.43; 95% CI 1.04–11.29), but not to other dampness indicators. The fraction of ACOS attributable to workplace mold odor was 70.8% (95% CI 3.8–91.1%) among the exposed. The risk of ACOS was not related to mold exposures at home. Conclusions: Present results provide new evidence of the significant relation between workplace exposure to mold odor and adult-onset ACOS

Subtypes of Adult-Onset Asthma at the Time of Diagnosis: A Latent Class Analysis

Introduction: Only a few previous studies have investigated the subtypes of adult-onset asthma. No previous study has assessed whether these subtypes are different between men and women, or whether these subtypes have different risk factors. Methods: We applied latent class analyses to the Finnish Environment and Asthma Study population, including 520 new cases of adult-onset asthma. We formed subtypes separately between women and men and analyzed the following determinants as potential predictors for these subtypes: age, body mass index, smoking, and parental asthma. Results: Among women, the subtypes identified were: 1. Moderate asthma, 2. Cough-variant asthma, 3. Eosinophilic asthma, 4. Allergic asthma, and 5. Difficult asthma. Among men, the subtypes were: 1. Mild asthma, 2. Moderate asthma, 3. Allergic asthma, and 4. Difficult asthma. Three of the subtypes were similar among women and men: Moderate, Allergic, and Difficult asthma. In addition, women had two distinct subtypes: Cough-variant asthma, and Eosinophilic asthma. These subtypes had different risk factor profiles, e.g., heredity was important for Eosinophilic and Allergic asthma (RR for Both parents having asthma in Eosinophilic 3.55 (1.09 to 11.62)). Furthermore, smoking increased the risk of Moderate asthma among women (RR for former smoking 2.21 (1.19 to 4.11)) and Difficult asthma among men but had little influence on Allergic or Cough-variant asthma. Conclusion: This is an original investigation of the subtypes of adult-onset asthma identified at the time of diagnosis. These subtypes differ between women and men, and these subtypes have different risk factor profiles. These findings have both clinical and public health importance for the etiology, prognosis, and treatment of adult-onset asthma