Disease marker combination enhances patient characterization in the Finnish sarcoidosis patients

Sarcoidosis is an inflammatory disease of unknown etiology and multiple clinical phenotypes. Clinical manifestations range from asymptomatic disease to severe loss-of-function leading to the hypothesis that sarcoidosis might not be just one disease, but consists of several distinct disease entities each with potentially distinct genetic associations. We have previously demonstrated that in our series HLADRB1* 03:01 and haplotype HLA-DRB1*04:01-DPB1*04:01 are associated with good prognosis sarcoidosis. In our recent work, we found a novel SNP (rs9905945) in the 50upstream region of the ACE gene to be associated with favorable disease prognosis as well. The main objective of this study was to expand the previous results and analyse combined influence of the found ACE SNP rs9905945 with the protective HLA markers HLADRB1*03:01 and HLA-DRB1*04:01-DPB1*04:01 in 188 Finnish sarcoidosis patients (resolved disease, n = 90; persistent disease, n = 98). When combining the frequencies of the rs9905945 and of the HLA markers, the strongest association was found for a combination of either/or both HLA markers and rs9905945 for good disease prognosis (37.1% in resolved vs. 11.3% in persistent, p <0.001, OR = 4.61, (95% CI 2.15-9.86)). In conclusion, we discovered that a combination of the ACE SNP rs9905945 and HLA markers enhance the accuracy for predicting disease course in Finnish sarcoidosis patients further characterizing genetic differences between Finnish sarcoidosis patients with different prognosis. (c) 2017 Elsevier Ltd. All rights reserved.Peer reviewe

The Angiotensin Converting Enzyme Insertion/Deletion polymorphism is not associated with an increased risk of death or bronchopulmonary dysplasia in ventilated very low birth weight infants

BACKGROUND: The ACE gene contains a polymorphism consisting of either the presence (insertion, I) or absence (deletion, D) of a 287 bp alu repeat in intron 16. The D allele is associated with increased ACE activity in both tissue and plasma. The DD genotype is associated with risk of developing ARDS and mortality. The frequency of the D allele is higher in patients with pulmonary fibrosis, sarcoidosis and berylliosis. The role of this polymorphism has not been studied in the development of BPD in the premature newborn. METHODS: ACE I/D genotype was determined in 245 (194 African-American, 47 Caucasian and 4 Hispanic) mechanically ventilated infants weighing less than 1250 grams at birth and compared to outcome (death and/or development of BPD). RESULTS: The incidence of the D allele in the study population was 0.58. Eighty-eight (35.9%) infants were homozygous DD, 107 (43.7%) were heterozygous ID and 50 (20.4%) were homozygous II. There were no significant differences between genotype groups with respect to ethnic origin, birth weight, gestation, or gender. There was no effect of the ACE I/D polymorphism on mortality or development of BPD (O(2 )on 28 days or 36 weeks PCA). Secondary outcomes (intraventricular hemorrhage and periventricular leukomalacia) similarly were not influenced by the ACE ID polymorphism. CONCLUSIONS: The ACE I/D polymorphism does not significantly influence the development of BPD in ventilated infants less than 1250 grams

The development of socio-economic health differences in childhood: results of the Dutch longitudinal PIAMA birth cohort

Background: People with higher socio-economic status (SES) are generally in better health. Less is known about when these socio-economic health differences set in during childhood and how they develop over time. The goal of this study was to prospectively study the development of socio-economic health differences in the Netherlands, and to investigate possible explanations for socio-economic variation in childhood health. Methods: Data from the Dutch Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study were used for the analyses. The PIAMA study followed 3,963 Dutch children during their first eight years of life. Common childhood health problems (i.e. eczema, asthma symptoms, general health, frequent respiratory infections, overweight, and obesity) were assessed annually using questionnaires. Maternal educational level was used to indicate SES. Possible explanatory lifestyle determinants (breastfeeding, smoking during pregnancy, smoking during the first three months, and day-care centre attendance) and biological determinants (maternal age at birth, birthweight, and older siblings) were analysed using generalized estimating equations. Results: This study shows that socio-economic differences in a broad range of health problems are already present early in life, and persist during childhood. Children from families with low socio-economic backgrounds experience more asthma symptoms (odds ratio (OR) 1.27; 95% Confidence Interval (CI) 1.08-1.49), poorer general health (OR 1.36; 95% CI 1.16-1.60), more frequent respiratory infections (OR 1.57; 95% CI 1.35-1.83), more overweight (OR 1.42; 95% CI 1.16-1.73), and more obesity (OR 2.82; 95% CI 1.80-4.41). The most important contributors to the observed childhood socio-economic health disparities are socio-economic differences in maternal age at birth, breastfeeding, and day-care centre attendance. Conclusions: Socio-economic health disparities already occur very early in life. Socio-economic disadvantage takes its toll on child health before birth, and continues to do so during childhood. Therefore, action to reduce health disparities needs to start very early in life, and should also address socio-economic differences in maternal age at birth, breastfeeding habits, and day-care centre attendance

Prevalence and early-life risk factors of school-age allergic multimorbidity: The EuroPrevall-iFAAM birth cohort.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadBackground: Coexistence of childhood asthma, eczema and allergic rhinitis is higher than can be expected by chance, suggesting a common mechanism. Data on allergic multimorbidity from a pan-European, population-based birth cohort study have been lacking. This study compares the prevalence and early-life risk factors of these diseases in European primary school children. Methods: In the prospective multicentre observational EuroPrevall-iFAAM birth cohort study, we used standardized questionnaires on sociodemographics, medical history, parental allergies and lifestyle, and environmental exposures at birth, 12 and 24 months. At primary school age, parents answered ISAAC-based questions on current asthma, rhinitis and eczema. Allergic multimorbidity was defined as the coexistence of at least two of these. Results: From 10,563 children recruited at birth in 8 study centres, we included data from 5,572 children (mean age 8.2 years; 51.8% boys). Prevalence estimates were as follows: asthma, 8.1%; allergic rhinitis, 13.3%; and eczema, 12.0%. Allergic multimorbidity was seen in 7.0% of the whole cohort, ranging from 1.2% (Athens, Greece) to 10.9% (Madrid, Spain). Risk factors for allergic multimorbidity, identified with AICc, included family-allergy-score, odds ratio (OR) 1.50 (95% CI 1.32-1.70) per standard deviation; early-life allergy symptoms, OR 2.72 (2.34-3.16) for each symptom; and caesarean birth, OR 1.35 (1.04-1.76). Female gender, OR 0.72 (0.58-0.90); older siblings, OR 0.79 (0.63-0.99); and day care, OR 0.81 (0.63-1.06) were protective factors. Conclusion: Allergic multimorbidity should be regarded as an important chronic childhood disease in Europe. Some of the associated early-life factors are modifiable and may be considered for prevention strategies. Keywords: allergic multimorbidity; allergic rhinitis; asthma; children; eczema.European Commission under the 6th Framework Programme within the collaborative research initiative 'EuroPrevall' European Commission under 7th Framework Programme (FP7-KBBE-2012-6) within the collaborative project 'iFAAM' Icelandic birth cohort centre from Landspitali University Hospital Iceland Science Fund GlaxoSmithKline UK birth cohort centre from the UK Food Standards Agenc

Asma e gravidez: repercussões no recém-nascido

OBJETIVO: Descrever, numa coorte de nascimentos, aspectos socioeconômicos e comportamentais de gestantes com asma e analisar as repercussões desta sobre alguns parâmetros perinatais. MÉTODOS: Estudo observacional, transversal e analítico a partir de informações de parturientes da coorte de nascimentos ocorridos no período entre 8 de março e 15 de julho de 2005 nas maternidades da Grande Aracaju (SE). A identificação de asma nas gestantes foi obtida segundo informação destas a partir do diagnóstico emitido anteriormente por um médico. Foram analisadas variáveis epidemiológicas, obstétricas e perinatais. RESULTADOS: Das 4.757 parturientes incluídas no estudo, 299 (6,3%) eram asmáticas. As mães asmáticas tinham menor renda familiar e mais frequentemente procuraram assistência no pré-natal e no parto em serviços públicos que as mães sem asma. Embora somente 9,4% das gestantes asmáticas fumaram, e 27,6% ingeriram bebidas alcoólicas, as proporções em relação ao grupo controle foram significativamente maiores. Não se detectou associação entre asma e problemas obstétricos ou do recém-nascido. Não foi encontrada associação entre asma e parto cesariano, prematuridade ou recém-nascido sendo pequeno para a idade gestacional. CONCLUSÕES: O nível socioeconômico inferior parece ser um fator de risco para a asma

Proteomic Changes of Alveolar Lining Fluid in Illnesses Associated with Exposure to Inhaled Non-Infectious Microbial Particles

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Asthma control and steroid doses 5 years after early or delayed introduction of inhaled corticosteroids in asthma: a real-life study

We evaluated asthma control and medication use 5 years after introduction of an inhaled corticosteroid (budesonide via Turbuhaler(R)) in 462 patients with persistent asthma and symptoms of different duration. An early treatment group with symptoms for <2 years (group A) was compared with a delayed treatment group (group B) (median duration 5 years and 3 months). Most patients received budesonide 400 μg twice daily as initial dose. We report 5-year follow-up data on 404 patients (group A n = 253; group B n = 151) and on a few more patients after treatment for 6 months, 1 year and 3 years. At 5 years the mean maintenance doses of budesonide were 412 μg (A) and 825 μg (B), respectively (P < 0.001). Nevertheless, treatment goals (normal lung function, normal exercise tolerance, minimal use of reliever medication, no asthma exacerbations) were all statistically significantly more frequently achieved in group A. At 5 years group B patients also used significantly more additional asthma medications, e.g. inhaled tong-acting beta(2)-agonists by 64% compared with 6% in group A. In group A 43 patients (117%) had been able to stop budesonide treatment compared to five patients (3%) in group B. A subgroup of group B patients with higher mean baseline FEV1 values than group A showed nevertheless significantly poorer response. No treatment-related serious adverse events were reported. Budesonide was well tolerated in both groups. Conclusion: Duration of asthma symptoms when starting treatment with an inhaled corticosteroid is an important determinant for the response. Early treatment gives significantly better airway function and asthma control than delayed treatment and at tower maintenance doses