Exposure to secondhand tobacco smoke and the frailty syndrome in US older adults

Exposure to secondhand tobacco smoke (SHS) is a well-established risk factor for cardiovascular disease and lung cancer in non-smoking adults. However, few studies have focused on the health consequences of exposure to SHS in older adults. This is the first study to assess the association between SHS and the frailty syndrome in the non-smoking older adult population. Methods. Cross-sectional study among 2059 non-smoking adults aged ≥60 years who participated in the third U.S. National Health and Nutrition Examination Survey and had completed a physical examination. Exposure to SHS was assessed by serum cotinine concentrations and by self-reported data from the home questionnaire. Frailty was ascertained with a slight modification of the Fried criteria. Analyses were performed with logistic regression and adjusted for the main confounders. Results. The median (interquartile range) concentration of serum cotinine was 0.095 (IQR: 0.035-0.211) ng/mL. The prevalence of frailty was 6.0%. The odds ratios (95% CI) of frailty comparing the second, third and fourth to the lowest quartile of serum cotinine were, respectively, 1.44 (0.67-3.06), 1.46 (0.75-2.85) and 2.51 (1.06-5.95); p value for trend 0.04. An increased frequency of frailty was also observed in participants reporting to live with ≥2 smokers at home (odds ratio: 5.37; 95% CI: 1.13-25.5). Conclusions. In the US non-smoking older adult population, exposure to SHS was associated with an increased frequency of frailty. More efforts are needed to protect older adults from SHS, especially at home and in other areas not covered by smoke-free regulations.This work was supported by grants from the Instituto de Salud Carlos III, Ministry of Health of Spain (PI12/1166) and from the European Commission (FRAILOMIC Initiative FP7-HEALTH-2012-Proposal No: 305483-2). Dr. Navas-Acien was supported by the Flight Attendant Medical Research Institut

Diagnosis of alpha1-antitrypsin deficiency not just in severe COPD

Alpha1-antitrypsin deficiency (AATD) is a well known genetic risk factor for pulmonary disease and is the most frequent hereditary disease diagnosed in adults. Despite being one of the most common hereditary diseases, AATD remains under-diagnosed because of its variable clinical presentation and the poor knowledge of this disease by physicians. With the aim of identifying clinical differences that could influence early diagnosis, we compared two groups of six AATD Pi*ZZ patients with different lung function severity and clinical expression at diagnosis. On comparing the two groups, we observed a younger mean age at diagnosis and more exacerbations in the severe group, but the percentage of smokers did not statistically differ between the two groups. Our results suggest that AATD continues being a disease suspected on younger patients with a worse lung function. In addition these findings confirm the clinical variability of the disease and that there are still unknown factors that contribute to its development. Therefore, early diagnosis may modify the prognosis of this disease

Genetic diagnosis of α1-antitrypsin deficiency using DNA from buccal swab and serum samples

Background: α1-Antitrypsin deficiency (AATD) is associated with a high risk of developing lung and liver disease. Despite being one of the most common hereditary disorders worldwide, AATD remains under-diagnosed and prolonged delays in diagnosis are usual. The aim of this study was to validate the use of buccal swab samples and serum circulating DNA for the complete laboratory study of AATD. Methods: Sixteen buccal swab samples from previously characterized AATD patients were analyzed using an allele-specific genotyping assay and sequencing method. In addition, 19 patients were characterized by quantification, phenotyping and genotyping using only serum samples. Results: the 16 buccal swab samples were correctly characterized by genotyping. Definitive results were obtained in the 19 serum samples analyzed by quantification, phenotyping and genotyping, thereby performing the complete AATD diagnostic algorithm. Conclusions: Buccal swab samples may be useful to expand AATD screening programs and family studies. Genotyping using DNA from serum samples permits the application of the complete diagnostic algorithm without delay. These two methods will be useful for obtaining more in depth knowledge of the real prevalence of patients with AATD

The inflammatory potential of diet is related to incident frailty and slow walking in older adults

Background: Certain foods and dietary patterns have been associated with both inflammation and frailty. As chronic inflammation may play a role in frailty and disability, we examined the association of the inflammatory potential of diet with these outcomes. Methods: Data were taken from 1948 community-dwelling individuals =60 years old from the Seniors-ENRICA cohort, who were recruited in 2008–2010 and followed-up through 2012. Baseline diet data, obtained with a validated diet history, was used to calculate Shivappa's Dietary Inflammatory Index (DII), an “a priori” pattern score which is based on known associations of foods and nutrients with inflammation, and Tabung's Empirical Dietary Inflammatory Index (EDII), an “a posteriori” pattern score which was statistically derived from an epidemiological study. At follow-up, incident frailty was assessed with Fried's criteria, and incident limitation in instrumental activities of daily living (IADL) with the Lawton-Brody index. Statistical analyses were performed with logistic regression, and adjusted for the main confounders. Results: Compared with individuals in the lowest tertile of DII, those in the highest tertile showed higher risk of frailty (odds ratio [OR] 2.48; 95% confidence interval [CI]: 1.42, 4.44, p-trend = 0.001) and IADL disability (OR: 1.96; 95% CI: 1.03, 3.86, p-trend = 0.035). By contrast, EDII did not show an association with these outcomes. The DII score was associated with slow gait speed, both as a low score in the Short Physical Performance Battery test (OR: 1.82; 95% CI: 1.27, 2.62, p-trend = 0.001) and as a positive Fried's criterion (OR: 1.64; 95% CI: 1.08, 2.51, p-trend = 0.021), which use different thresholds. Conclusions: DII predicted frailty and IADL while EDII did not. DII is able to measure diet healthiness in terms of physical decline in addition to avoidance of inflammation

Application of a diagnostic algorithm for the rare deficient variant Mmalton of alpha-1-antitrypsin deficiency: a new approach

Background and objectives: alpha-1-antitrypsin deficiency (AATD) is associated with a high risk for the development of early-onset emphysema and liver disease. A large majority of subjects with severe AATD carry the ZZ genotype, which can be easily detected. Another rare pathologic variant, the Mmalton allele, causes a deficiency similar to that of the Z variant, but it is not easily recognizable and its detection seems to be underestimated. Therefore, we have included a rapid allele-specific genotyping assay for the detection of the Mmalton variant in the diagnostic algorithm of AATD used in our laboratory. The objective of this study was to test the usefulness of this new algorithm for Mmalton detection. Materials and methods: we performed a retrospective revision of all AATD determinations carried out in our laboratory over 2 years using the new diagnostic algorithm. Samples with a phenotype showing one or two M alleles and AAT levels discordant with that phenotype were analyzed using the Mmalton allele-specific genotyping assay. Results: we detected 49 samples with discordant AAT levels; 44 had the MM and five the MS phenotype. In nine of these samples, a single rare Mmalton variant was detected. During the study period, two family screenings were performed and four additional Mmalton variants were identified. Conclusion: the incorporation of the Mmalton allele-specific genotyping assay in the diagnostic algorithm of AATD resulted in a faster and cheaper method to detect this allele and avoided a significant delay in diagnosis when a sequencing assay was required. This methodology can be adapted to other rare variants. Standardized algorithms are required to obtain conclusive data of the real incidence of rare AAT alleles in each region

Rapid detection of Mmalton α1-antitrypsin deficiency allele by real-time PCR and melting curves in whole blood, serum and dried blood spot samples

Background: α1-Antitrypsin deficiency (AATD) is an autosomal codominant disorder associated with a high risk of developing lung and liver disease. The most common deficient alleles are known as Z and S. However, another deficient variant, called Mmalton, which causes a deficiency similar to variant Z, is considered to be the second cause of severe AATD in Spain. Nevertheless, the Mmalton allele is not recognizable by usual diagnostic techniques and therefore, its real prevalence is underestimated. We describe a rapid real-time PCR and melting curves assay designed for the detection of Mmalton AATD. Methods: we tested the applicability of this new technique for the identification of the Mmalton allele in AATD screening using whole blood, dried blood spot (DBS) and serum samples. Mmalton heterozygote and homozygote samples and samples without this allele were included in the study. Results: this new assay is able to detect homozygous and heterozygous genotypes in the same reaction and in a single step, giving matching results with those obtained by SERPINA1 gene sequencing. Conclusions: this technology is optimal for working with small amounts of DNA, such as in DBS and even with residual DNA present in serum samples, allowing improvement in routine algorithms of AATD diagnosis or large-scale screening. This method will be useful for obtaining more in depth knowledge of the real incidence of the Mmalton variant

Association between a Mediterranean lifestyle and growth differentiation factor 15: The seniors ENRICA-2 cohort

Background: Growth Differentiation Factor 15 (GDF-15) is a marker of inflammation and oxidative stress that has been associated with multiple age-related chronic diseases. Since lifestyle is key for preventing these adverse health outcomes, we examined the association between a Mediterranean lifestyle and GDF-15 serum concentrations in Spanish older adults. Methods: We used cross-sectional data from 2502 older adults participating in the Seniors ENRICA-2 cohort. Adherence to the Mediterranean lifestyle was assessed with the 27-item MEDLIFE index, divided into three blocks: 1) "Mediterranean food consumption, 2) Mediterranean dietary habits, 3) Physical activity, rest, social habits, and conviviality". Analyses of the association between the MEFLIFE index and GDF-15 concentrations were performed using multivariable linear regression models adjusting for the main potential confounders. Results: The MEDLIFE index was inversely associated with GDF-15. Compared with participants in the lowest quartile of the MEDLIFE score, GDF-15 mean percentage differences (95% CI) were -3.0% (-8.0, 2.3) for the second quartile, -8.7% (-13.0, -4.1) for the third quartile, and -10.1% (-15.0, -4.9) for the fourth quartile (p-trend<0.001). Block 3 of MEDLIFE, and particularly doing sufficient physical activity, adequate sleep duration, and participating in collective sports, was individually linked to lower concentrations of GDF-15. Results remained similar after excluding participants with cardiovascular disease, type 2 diabetes, or obesity. Conclusions: A Mediterranean lifestyle was associated with reduced levels of GDF-15, suggesting that a combination of multiple lifestyles may be an integral approach to reduce chronic inflammation and disease burden in older adults.This work was supported by the Institute of Health Carlos III; the Secretary of R+D+I; the European Regional Development Fund/European Social Fund (FIS grants 19/319, 20/00896); the National Plan on Drugs (grant 2020/17); Fundación Soria Melguizo (MITOFUN project); Ministry of Science, Innovation and Universities (RYC 2018-02069I to MSP); Universidad Autonóma de Madrid (FPI contract to JMR); FACINGLCOVID-CM project, Funding REACT EU Program (Comunidad de Madrid, European Regional Development Fund). Reagents for measuring Growth Differentiation Factor 15 have been provided by Roche Diagnostics International through a Research Agreement with the FUAM (Fundación de la Universidad Autonóma de Madrid). The funding agencies had no role in study design, data collection and analysis, interpretation of results, manuscript preparation or the decision to submit this manuscript for publication.S

Diagnosis of alpha-1 antitrypsin deficiency : a population-based study

Altres ajuts: This study was funded by unrestricted grants from Grifols, Fundació Catalana de Pneumologia, and the Spanish Society of Pneumology and Thoracic Surgery.Alpha-1 antitrypsin deficiency (AATD) remains an underdiagnosed condition despite initiatives developed to increase awareness. The objective was to describe the current situation of the diagnosis of AATD in primary care (PC) in Catalonia, Spain. We performed a population-based study with data from the Information System for Development in Research in Primary Care, a population database that contains information of 5.8 million inhabitants (80% of the population of Catalonia). We collected the number of alpha-1 antitrypsin (AAT) determinations performed in the PC in two periods (2007-2008 and 2010-2011) and described the characteristics of the individuals tested. A total of 12,409 AAT determinations were performed (5,559 in 2007-2008 and 6,850 in 2010-2011), with 10.7% of them in children. As a possible indication for AAT determination, 28.9% adults and 29.4% children had a previous diagnosis of a disease related to AATD; transaminase levels were above normal in 17.7% of children and 47.1% of adults. In total, 663 (5.3%) individuals had intermediate AATD (50-100 mg/dL), 24 (0.2%) individuals had a severe deficiency (<50 mg/dL), with a prevalence of 0.19 cases of severe deficiency per 100 determinations. Nine (41%) of the adults with severe deficiency had a previous diagnosis of COPD/emphysema, and four (16.7%) were diagnosed with COPD within 6 months. The number of AAT determinations in the PC is low in relation to the prevalence of COPD but increased slightly along the study period. The indication to perform the test is not always clear, and patients detected with deficiency are not always referred to a specialist