| 1. |
- Melen, Erik, et al.
(author)
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Spirometric phenotypes from early childhood to young adulthood - A CADSET (Chronic Airway Disease Early Stratification) study
- 2020
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In: European Respiratory Journal. - : ERS Publications. - 0903-1936 .- 1399-3003. ; 56:Suppl 64
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Journal article (other academic/artistic)abstract
- Background: Results from longitudinal cohort studies show that the lower the lung function in childhood and adulthood, the higher the risk of later chronic airway disease such as COPD. Yet, reliable data is sparse on the prevalence of different types of lung function impairments in the general population of children and young adults, as well as their major determinants.Aim: To report age- and sex-specific prevalences and characteristics of spirometric phenotypes from childhood up to young adulthood.Methods: Lung function data from independent European population-based cohorts involved in the CADSET collaboration were analysed. Pre-bronchodilator FEV1 and FVC data from each cohort were converted into z-scores according to the Global Lung Initiative (GLI) reference system. Overall fit with the GLI spirometry equations was assessed. Airway limitation was defined as a FEV1/FVC z-score < -1.65.Results: Five cohorts provided spirometry data from 10,842 observations in subjects aged 7 to 25 years. Airway limitation was found in around 6-10% across all ages in the cohorts. No evidence of differences between males and females in different age groups were observed. In unadjusted analyses of all cohorts, we found maternal smoking during pregnancy to be associated with airway limitation (p<0.05).Conclusion: Analyses of spirometry data from population-based cohorts in Europe show that the prevalence of airflow limitation according to GLI is substantial (6-10%) and quite similar across cohorts and age groups. These results suggest that airflow limitation can develop early in life and that there are rather small changes in prevalence during childhood.
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| 2. |
- Nicoletti, Paola, et al.
(author)
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Genetic Risk Factors in Drug-Induced Liver Injury Due to Isoniazid-Containing Antituberculosis Drug Regimens
- 2021
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In: Clinical Pharmacology and Therapeutics. - : John Wiley & Sons. - 0009-9236 .- 1532-6535. ; 109:4, s. 1125-1135
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Journal article (peer-reviewed)abstract
- Drug-induced liver injury (DILI) is a complication of treatment with antituberculosis (TB) drugs, especially in isoniazid (INH)-containing regimens. To investigate genetic risk factors, we performed a genomewide association study (GWAS) involving anti-TB DILI cases (55 Indian and 70 European) and controls (1,199 Indian and 10,397 European). Most cases were treated with a standard anti-TB drug regimen; all received INH. We imputed single nucleotide polymorphism and HLA genotypes and performed trans-ethnic meta-analysis on GWAS and candidate gene genotypes. GWAS found one significant association (rs117491755) in Europeans only. For HLA, HLA-B*52:01 was significant (meta-analysis odds ratio (OR) 2.67, 95% confidence interval (CI) 1.63-4.37, P = 9.4 × 10-5 ). For N-acetyltransferase 2 (NAT2), NAT2*5 frequency was lower in cases (OR 0.69, 95% CI 0.57-0.83, P = 0.01). NAT2*6 and NAT2*7 were more common, with homozygotes for NAT2*6 and/or NAT2*7 enriched among cases (OR 1.89, 95% CI 0.84-4.22, P = 0.004). We conclude HLA genotype makes a small contribution to TB drug-related DILI and that the NAT2 contribution is complex, but consistent with previous reports when differences in the metabolic effect of NAT2*5 compared with those of NAT2*6 and NAT2*7 are considered.
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| 3. |
- Yasinska, Valentyna, et al.
(author)
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Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids
- 2023
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In: ERJ Open Research. - : European Respiratory Society. - 2312-0541. ; 9:5
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Journal article (peer-reviewed)abstract
- Rationale: Patients with severe asthma are dependent upon treatment with high doses of inhaled corticosteroids (ICS) and often also oral corticosteroids (OCS). The extent of endogenous androgenic anabolic steroid (EAAS) suppression in asthma has not previously been described in detail. The objective of the present study was to measure urinary concentrations of EAAS in relation to exogenous corticosteroid exposure.Methods: Urine collected at baseline in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcomes) study of severe adult asthmatics (SA, n=408) was analysed by quantitative mass spectrometry. Data were compared to that of mild-to-moderate asthmatics (MMA, n=70) and healthy subjects (HC, n=98) from the same study.Measurements and main results: The concentrations of urinary endogenous steroid metabolites were substantially lower in SA than in MMA or HC. These differences were more pronounced in SA patients with detectable urinary OCS metabolites. Their dehydroepiandrosterone sulfate (DHEA-S) concentrations were <5% of those in HC, and cortisol concentrations were below the detection limit in 75% of females and 82% of males. The concentrations of EAAS in OCS-positive patients, as well as patients on high-dose ICS only, were more suppressed in females than males (p<0.05). Low levels of DHEA were associated with features of more severe disease and were more prevalent in females (p<0.05). The association between low EAAS and corticosteroid treatment was replicated in 289 of the SA patients at follow-up after 12–18 months.Conclusion: The pronounced suppression of endogenous anabolic androgens in females might contribute to sex differences regarding the prevalence of severe asthma.
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