Epigenomic partitioning of a polygenic risk score for asthma reveals distinct genetically driven disease pathways.

BACKGROUND: Individual differences in susceptibility to developing asthma, a heterogeneous chronic inflammatory lung disease, are poorly understood. Whether genetics can predict asthma risk and how genetic variants modulate the complex pathophysiology of asthma are still debated. AIM: To build polygenic risk scores for asthma risk prediction and epigenomically link predictive genetic variants to pathophysiological mechanisms. METHODS: Restricted polygenic risk scores were constructed using single nucleotide variants derived from genome-wide association studies and validated using data generated in the Rotterdam Study, a Dutch prospective cohort of 14 926 individuals. Outcomes used were asthma, childhood-onset asthma, adulthood-onset asthma, eosinophilic asthma and asthma exacerbations. Genome-wide chromatin analysis data from 19 disease-relevant cell types were used for epigenomic polygenic risk score partitioning. RESULTS: The polygenic risk scores obtained predicted asthma and related outcomes, with the strongest associations observed for childhood-onset asthma (2.55 odds ratios per polygenic risk score standard deviation, area under the curve of 0.760). Polygenic risk scores allowed for the classification of individuals into high-risk and low-risk groups. Polygenic risk score partitioning using epigenomic profiles identified five clusters of variants within putative gene regulatory regions linked to specific asthma-relevant cells, genes and biological pathways. CONCLUSIONS: Polygenic risk scores were associated with asthma(-related traits) in a Dutch prospective cohort, with substantially higher predictive power observed for childhood-onset than adult-onset asthma. Importantly, polygenic risk score variants could be epigenomically partitioned into clusters of regulatory variants with different pathophysiological association patterns and effect estimates, which likely represent distinct genetically driven disease pathways. Our findings have potential implications for personalised risk mitigation and treatment strategies.

Younger facial looks are associate with a lower likelihood of several age-related morbidities in the middle-aged to elderly.

BACKGROUND: Looking older for one's chronological age is associated with a higher mortality rate. Yet it remains unclear how perceived facial age relates to morbidity and the degree to which facial ageing reflects systemic ageing of the human body. OBJECTIVES: To investigate the association between ΔPA and age-related morbidities of different organ systems, where ΔPA represents the difference between perceived age (PA) and chronological age. METHODS: We performed a cross-sectional analysis on data from the Rotterdam Study, a population-based cohort study in the Netherlands. High-resolution facial photographs of 2679 men and women aged 51.5-87.8 years of European descent were used to assess PA. PA was estimated and scored in 5-year categories using these photographs by a panel of men and women who were blinded for chronological age and medical history. A linear mixed model was used to generate the mean PAs. The difference between the mean PA and chronological age was calculated (ΔPA), where a higher (positive) ΔPA means that the person looks younger for their age and a lower (negative) ΔPA that the person looks older. ΔPA was tested as a continuous variable for association with ageing-related morbidities including cardiovascular, pulmonary, ophthalmological, neurocognitive, renal, skeletal and auditory morbidities in separate regression analyses, adjusted for age and sex (model 1) and additionally for body mass index, smoking and sun exposure (model 2). RESULTS: We observed 5-year higher ΔPA (i.e. looking younger by 5 years for one's age) to be associated with less osteoporosis [odds ratio (OR) 0.76, 95% confidence interval (CI) 0.62-0.93], less chronic obstructive pulmonary disease (OR 0.85, 95% CI 0.77-0.95), less age-related hearing loss (model 2; B = -0.76, 95% CI -1.35 to -0.17) and fewer cataracts (OR 0.84, 95% CI 0.73-0.97), but with better global cognitive functioning (g-factor; model 2; B = 0.07, 95% CI 0.04-0.10). CONCLUSIONS: PA is associated with multiple morbidities and better cognitive function, suggesting that systemic ageing and cognitive ageing are, to an extent, externally visible in the human face.

Pharmacogenetics of inhaled corticosteroids and exacerbation risk in adults with asthma.

BACKGROUND: Inhaled corticosteroids (ICS) are a cornerstone of asthma treatment. However, their efficacy is characterized by wide variability in individual responses. OBJECTIVE: We investigated the association between genetic variants and risk of exacerbations in adults with asthma and how this association is affected by ICS treatment. METHODS: We investigated the pharmacogenetic effect of 10 single nucleotide polymorphisms (SNPs) selected from the literature, including SNPs previously associated with response to ICS (assessed by change in lung function or exacerbations) and novel asthma risk alleles involved in inflammatory pathways, within all adults with asthma from the Dutch population-based Rotterdam study with replication in the American GERA cohort. The interaction effects of the SNPs with ICS on the incidence of asthma exacerbations were assessed using hurdle models adjusting for age, sex, BMI, smoking and treatment step according to the GINA guidelines. Haplotype analyses were also conducted for the SNPs located on the same chromosome. RESULTS: rs242941 (CRHR1) homozygotes for the minor allele (A) showed a significant, replicated increased risk for frequent exacerbations (RR = 6.11, P < 0.005). In contrast, rs1134481 T allele within TBXT (chromosome 6, member of a family associated with embryonic lung development) showed better response with ICS. rs37973 G allele (GLCCI1) showed a significantly poorer response on ICS within the discovery cohort, which was also significant but in the opposite direction in the replication cohort. CONCLUSION: rs242941 in CRHR1 was associated with poor ICS response. Conversely, TBXT variants were associated with improved ICS response. These associations may reveal specific endotypes, potentially allowing prediction of exacerbation risk and ICS response.

Multi-ancestry genome-wide association study of asthma exacerbations.

BACKGROUND: Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi-ancestry meta-analysis of genome-wide association studies (meta-GWAS) for this trait. We aimed to identify common genetic loci associated with asthma exacerbations across diverse populations and to assess their functional role in regulating DNA methylation and gene expression. METHODS: A meta-GWAS of asthma exacerbations in 4989 Europeans, 2181 Hispanics/Latinos, 1250 Singaporean Chinese, and 972 African Americans analyzed 9.6 million genetic variants. Suggestively associated variants (p ≤ 5 × 10-5 ) were assessed for replication in 36,477 European and 1078 non-European asthma patients. Functional effects on DNA methylation were assessed in 595 Hispanic/Latino and African American asthma patients and in publicly available databases. The effect on gene expression was evaluated in silico. RESULTS: One hundred and twenty-six independent variants were suggestively associated with asthma exacerbations in the discovery phase. Two variants independently replicated: rs12091010 located at vascular cell adhesion molecule-1/exostosin like glycosyltransferase-2 (VCAM1/EXTL2) (discovery: odds ratio (ORT allele ) = 0.82, p = 9.05 × 10-6 and replication: ORT allele  = 0.89, p = 5.35 × 10-3 ) and rs943126 from pantothenate kinase 1 (PANK1) (discovery: ORC allele  = 0.85, p = 3.10 × 10-5 and replication: ORC allele  = 0.89, p = 1.30 × 10-2 ). Both variants regulate gene expression of genes where they locate and DNA methylation levels of nearby genes in whole blood. CONCLUSIONS: This multi-ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense.

Trajectory and mortality of preserved ratio impaired spirometry: the Rotterdam Study.

Preserved ratio impaired spirometry (PRISm) is a heterogeneous condition but its course and disease progression remain to be elucidated. We aimed to examine its prevalence, trajectories and prognosis in the general population.In the Rotterdam Study (population-based prospective cohort) we examined prevalence, trajectories and prognosis of subjects with normal spirometry (controls; forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥0.7, FEV1  ≥80%), PRISm (FEV1/FVC ≥0.7, FEV1 <80%) and chronic obstructive pulmonary disease (COPD) (FEV1/FVC <0.7) at two study visits. Hazard ratios with 95% confidence intervals for mortality (until December 30, 2018) were adjusted for age, sex, body mass index, current smoking and pack-years.Of 5487 subjects (age 69.1±8.9 years; 7.1% PRISm), 1603 were re-examined after 4.5 years. Of the re-examined PRISm subjects, 15.7% transitioned to normal spirometry and 49.4% to COPD. Median lung function decline was highest in subjects with incident PRISm (FEV1 -92.8 mL·year-1, interquartile range (IQR) -131.9- -65.8 mL·year-1; FVC -93.3 mL·year-1, IQR -159.8- -49.1 mL·year-1), but similar in persistent PRISm (FEV1 -30.2 mL·year-1, IQR -67.9- -7.5 mL·year-1; FVC -20.1 mL·year-1, IQR -47.7-21.7 mL·year-1) and persistent controls (FEV1 -39.6 mL·year-1, IQR -64.3--12.7 mL·year-1; FVC -20.0 mL·year-1, IQR -55.4-18.8 mL·year-1). Of 5459 subjects with informed consent for follow-up, 692 (12.7%) died during 9.3 years (maximum) follow-up: 10.3% of controls, 18.7% of PRISm subjects and 20.8% of COPD subjects. Relative to controls, subjects with PRISm and COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2-4 had increased all-cause mortality (PRISm: HR 1.6, 95% CI 1.2-2.0; COPD GOLD 2-4: HR 1.7, 95% CI 1.4-2.1) and cardiovascular mortality (PRISm: HR 2.8, 95% CI 1.5-5.1; COPD 2-4: HR 2.1, 95% CI 1.2-3.6). Mortality within <1 year was highest in PRISm, with patients often having cardiovascular comorbidities (heart failure or coronary heart disease; 70.0%).PRISm is associated with increased mortality and this population encompasses at least three distinct subsets: one that develops COPD during follow-up, a second with high cardiovascular burden and early mortality, and a third with persistent PRISm and normal age-related lung function decline.

Lifetime risk and multimorbidity of non-communicable diseases and disease-free life expectancy in the general population: A population-based cohort study.

BACKGROUND: Non-communicable diseases (NCDs) are leading causes of premature disability and death worldwide. However, the lifetime risk of developing any NCD is unknown, as are the effects of shared common risk factors on this risk. METHODS AND FINDINGS: Between July 6, 1989, and January 1, 2012, we followed participants from the prospective Rotterdam Study aged 45 years and older who were free from NCDs at baseline for incident stroke, heart disease, diabetes, chronic respiratory disease, cancer, and neurodegenerative disease. We quantified occurrence/co-occurrence and remaining lifetime risk of any NCD in a competing risk framework. We additionally studied the lifetime risk of any NCD, age at onset, and overall life expectancy for strata of 3 shared risk factors at baseline: smoking, hypertension, and overweight. During 75,354 person-years of follow-up from a total of 9,061 participants (mean age 63.9 years, 60.1% women), 814 participants were diagnosed with stroke, 1,571 with heart disease, 625 with diabetes, 1,004 with chronic respiratory disease, 1,538 with cancer, and 1,065 with neurodegenerative disease. NCDs tended to co-occur substantially, with 1,563 participants (33.7% of those who developed any NCD) diagnosed with multiple diseases during follow-up. The lifetime risk of any NCD from the age of 45 years onwards was 94.0% (95% CI 92.9%-95.1%) for men and 92.8% (95% CI 91.8%-93.8%) for women. These risks remained high (>90.0%) even for those without the 3 risk factors of smoking, hypertension, and overweight. Absence of smoking, hypertension, and overweight was associated with a 9.0-year delay (95% CI 6.3-11.6) in the age at onset of any NCD. Furthermore, the overall life expectancy for participants without these risk factors was 6.0 years (95% CI 5.2-6.8) longer than for those with all 3 risk factors. Participants aged 45 years and older without the 3 risk factors of smoking, hypertension, and overweight at baseline spent 21.6% of their remaining lifetime with 1 or more NCDs, compared to 31.8% of their remaining life for participants with all of these risk factors at baseline. This difference corresponds to a 2-year compression of morbidity of NCDs. Limitations of this study include potential residual confounding, unmeasured changes in risk factor profiles during follow-up, and potentially limited generalisability to different healthcare settings and populations not of European descent. CONCLUSIONS: Our study suggests that in this western European community, 9 out of 10 individuals aged 45 years and older develop an NCD during their remaining lifetime. Among those individuals who develop an NCD, at least a third are subsequently diagnosed with multiple NCDs. Absence of 3 common shared risk factors is associated with compression of morbidity of NCDs. These findings underscore the importance of avoidance of these common shared risk factors to reduce the premature morbidity and mortality attributable to NCDs.

The interrelationship of chronic cough and depression: a prospective population-based study.

Background: Chronic cough is a debilitating medical condition that is often complicated by psychomorbidities such as depressive symptoms. Nevertheless, little is known about the impact of chronic cough on the risk of developing depression. Therefore, we investigated the association between chronic cough and prevalent, incident and recurrent depression in a population-based sample of middle-aged and older persons. Methods: Within the Rotterdam Study, a population-based cohort, we defined chronic cough as reporting daily coughing for ⩾3 months. Depression was assessed using the Center for Epidemiologic Studies Depression scale, clinical interviews and medical records. Associations between chronic cough and depression were determined with linear, logistic and Cox regression analyses. Results: The study included 5877 participants (mean±sd age 72±8 years, 59% female) who contributed 37 287 person-years of follow-up. At baseline, participants with chronic cough reported more depressive symptoms (adjusted standardised mean difference 0.15, 95% CI 0.07-0.22) compared to those without chronic cough. Over time, chronic cough was associated with an increased risk of depression in participants with a history of depression (hazard ratio (HR) 1.45, 95% CI 1.13-1.84), but not in those without a history of depression (HR 0.91, 95% CI 0.68-1.22). Conclusions: Adults with chronic cough have a disproportionate burden of depressive symptoms and an increased risk of recurrent depression. This highlights the importance of screening for depression in patients with chronic cough.

Characterization of Asthma by Age of Onset: A Multi-Database Cohort Study.

BACKGROUND: Asthma can occur at any age but the differences in patient characteristics between childhood-, adult-, and late-onset asthma are not well understood. OBJECTIVE: To investigate differences in patients' characteristics by age at asthma onset. METHODS: From 5 European electronic databases, we created a cohort encompassing adult patients with doctor-diagnosed asthma in 2008 to 2013. Patients were categorized based on their age at asthma onset: childhood-onset (age at onset < 18 y), adult-onset (age at onset 18-40 y), and late-onset asthma (age at onset ≥ 40 y). Comorbidities were assessed at study entry. For each characteristic and comorbidity, odds ratios and age- and sex-adjusted odds ratios (ORadj) comparing asthma-onset categories were estimated per database and combined in a meta-analysis using a random effect model. RESULTS: In total, 586,436 adult asthma patients were included, 81,691 had childhood-onset, 218,184 adult-onset, and 286,561 late-onset asthma. Overall, 7.3% had severe asthma. Subjects with adult-onset compared with childhood-asthma had higher risks for overweight/obesity (ORadj 1.4; 95% CI 1.1-1.8) and lower risks for atopic disorders (ORadj 0.8; 95% CI 0.7-0.95). Patients with late-onset compared with adult-onset asthma had higher risks for nasal polyposis (ORadj 1.8; 95% CI 1.2-2.6), overweight/obesity (ORadj 1.3; 95% CI 1.2-1.4), gastroesophageal reflux disease (ORadj 1.4; 95% CI 1.2-1.7), and diabetes (ORadj 2.3; 95% CI 1.8-2.9). A significant association between late-onset asthma and uncontrolled asthma was observed (ORadj 2.8; 95% CI 1.7-4.5). CONCLUSIONS: This international study demonstrates clear differences in comorbidities between childhood-, adult-, and late-onset asthma phenotypes in adults. Furthermore, patients with late-onset asthma had more frequent uncontrolled asthma.

Sarcopenia, systemic immune-inflammation index and all-cause mortality in middle-aged and older people with COPD and asthma: a population-based study.

BACKGROUND: Increasing evidence suggests that sarcopenia and a higher systemic immune-inflammation index (SII) are linked with morbidity in patients with COPD. However, whether these two conditions contribute to all-cause mortality in middle-aged and older patients with COPD or asthma is unclear. Therefore, we investigated the association between sarcopenia, SII, COPD or asthma and all-cause mortality in a large-scale population-based setting. METHODS: Between 2009 and 2014, 4482 participants (aged >55 years; 57.3% female) from the population-based Rotterdam Study were included. COPD and asthma patients were diagnosed clinically and based on spirometry. Six study groups were defined according to the presence or absence of COPD or asthma and sarcopenia. Cox regression models were used to assess all-cause mortality in the study groups, adjusted for sex, age, body mass index, SII, smoking, oral corticosteroid use and comorbidities. In addition, all participants were categorised into sex-specific quartiles of SII, and mortality in these groups was compared. RESULTS: Over a median follow-up of 6.1 years (interquartile range 5.0-7.2 years), 466 (10.4%) persons died. Independent of the presence of sarcopenia, participants with COPD had a higher risk of all-cause mortality (hazard ratio (HR) 2.13, 95% CI 1.46-3.12 and HR 1.70, 95% CI 1.32-2.18 for those with and without sarcopenia, respectively). Compared to lower SII levels, higher SII levels increased mortality risk even in people without sarcopenia, COPD or asthma. CONCLUSION: Middle-aged and older people with COPD, higher SII levels or sarcopenia had an independently increased mortality risk. Our study suggests prognostic usefulness of routinely evaluating sarcopenia and SII in older people with COPD or asthma.

Incidence and predictors of asthma exacerbations in middle-aged and older adults: the Rotterdam Study.

AIM: The aim of this study was to investigate occurrence and determinants of asthma exacerbations in an ageing general population. METHODS: Subjects aged 45 years or above with physician-diagnosed asthma in the Rotterdam Study, a population-based prospective cohort from January 1991 to May 2018, were assessed for asthma exacerbations. Exacerbations were defined as acute episodes of worsening asthma treated with oral corticosteroids. Cox proportional hazards analysis was used to investigate risk factors for a future exacerbation. RESULTS: Out of 763 participants with asthma (mean age 61.3 years, 69.2% female), 427 (56.0%) experienced at least one exacerbation, in a mean follow-up time of 13.9 years. The mean annual exacerbation rate was 0.22. Most exacerbations occurred during winter months. Risk factors for exacerbations were a history of previous exacerbations (HR 4.25; 95% CI 3.07-5.90, p<0.001)), respiratory complaints (HR 2.18; 95% CI 1.48-3.21, p<0.001), airflow obstruction (HR 1.52; 95% CI 1.07-2.15, p=0.019), obesity (HR 1.38; 95% CI 1.01-1.87, p=0.040) and depressive symptoms (HR 1.55; 95% CI 1.05-2.29, p=0.027). Compared to those not using respiratory medication, we observed higher hazard ratios for those on short-acting ß2-agonists (SABA, i.e. rescue medication) only (HR 3.08, 95% CI 1.61-5.90, p=0.001) than those on controller medication (HR 2.50, 95% CI 1.59-3.92, p<0.001). CONCLUSION: Many older adults with asthma suffer from at least one severe exacerbation. Previous exacerbations, use of SABA without concomitant controller medication, respiratory complaints, obesity, airway obstruction and depression are independent risk factors for exacerbations.

Sarcopenia in older people with chronic airway diseases: the Rotterdam study.

Sarcopenia is a heterogeneous skeletal muscle disorder involving the loss of muscle mass and function. However, the prevalence of sarcopenia based on the most recent definition remains to be determined in older people with chronic airway diseases. The aim was to evaluate sarcopenia prevalence and association with chronic airway diseases and its lung function in an older population, using the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. We performed a cross-sectional analysis in 5082 participants (mean age 69.0±8.8 years, 56% females) from the Rotterdam Study. Participants with interpretable spirometry and an available assessment of sarcopenia were included. The appendicular skeletal muscle mass index (ASMI) and handgrip strength (HGS) were assessed using dual-energy X-ray absorptiometry (DXA) and a hydraulic hand dynamometer, respectively. We analysed the association between sarcopenia and chronic airway diseases by using regression models adjusted for age, sex, smoking status, total fat percentage and other relevant confounders. Participants with chronic airway diseases had higher prevalence of probable sarcopenia (12.0%, 95% CI 10.2-13.8) and confirmed sarcopenia (3.0%, 95% CI 2.1-3.9) than without. Chronic airway diseases were associated with "probable sarcopenia" (OR 1.28, 95% CI 1.02-1.60), "confirmed sarcopenia" (OR 2.13, 95% CI 1.33-3.43), reduced HGS (ß -0.51 (-0.90--0.11)) and reduced ASMI (ß -0.19 (-0.25--0.14)). Forced expiratory volume in 1 s <80% was associated with lower HGS (ß -1.03 (-1.75--0.31)) and lower ASMI (ß -0.25 (-0.36--0.15)) than forced expiratory volume in 1 s ≥80%. Sarcopenia was prevalent and associated with chronic airway diseases among older population. These results suggest the need for early diagnosis of sarcopenia in older people with chronic airway diseases by applying EWGSOP2 recommendations.

Prevalence and incidence of, and risk factors for chronic cough in the adult population: the Rotterdam Study.

Chronic cough is a common complaint in the general population but there are no precise data on the incidence of, and prospectively examined risk factors for chronic cough in a population-based setting. Therefore, we investigated the period prevalence, incidence and risk factors for chronic cough in adult subjects. In a prospective population-based cohort study among subjects aged ≥45 years, data on chronic cough were collected on two separate occasions using a standardised questionnaire. Chronic cough was defined as daily coughing for at least 3 months duration during the preceding 2 years. Potential risk factors were gathered by interview, physical examination and several investigations. Of the 9824 participants in this study, 1073 (10.9%) subjects had chronic cough at baseline. The prevalence of chronic cough increased with age and peaked in the eighth decade. In subjects aged <70 years, chronic cough was more common in women. During an average follow-up of 6 years, 439 incident cases of chronic cough occurred with an overall incidence rate of 11.6 per 1000 person-years (95% CI 10.6-12.8). In current smokers, the incidence of chronic cough was higher in men. In the multivariable analysis, current smoking, gastro-oesophageal reflux disease (GORD), asthma and COPD were identified as risk factors for chronic cough. Chronic cough is common among adults and highly prevalent in the older population. Current smoking, GORD, asthma and COPD are independent risk factors for chronic cough. Individuals at risk of developing chronic cough may benefit from smoking cessation and control of the underlying disease.

Assessment of correlates of hand hygiene compliance among final year medical students: a cross-sectional study in the Netherlands.

OBJECTIVES: To identify the factors that influence the hand hygiene compliance of final year medical students, using a theoretical behavioural framework. DESIGN: Cross-sectional survey assessing self-reported compliance and its behavioural correlates. SETTING: Internships of medical students in the Netherlands. PARTICIPANTS: 322 medical students of the Erasmus Medical Center were recruited over a period of 12 months during the Public Health internship, which is the final compulsory internship after an 18-month rotation schedule in all major specialities. PRIMARY AND SECONDARY OUTCOME MEASURES: Behavioural factors influencing compliance to hand hygiene guidelines were measured by means of a questionnaire based on the Theory of Planned Behaviour and Social Ecological Models. Multiple linear regression analysis was used to identify the effect of including attitudes, social norms, self-efficacy, knowledge, risk perception and habit on hand hygiene compliance. RESULTS: We included 313 students in the analysis (response rate 97%). The behavioural model explained 40% of the variance in self-reported compliance (adjusted R2=0.40). Hand hygiene compliance was strongly influenced by attitudes (perceived outcomes of preventive actions), self-efficacy (perception of the ability to perform hand hygiene at the clinical ward) and habit, but was not associated with knowledge and risk perception. CONCLUSIONS: Targeting medical students' behaviour should focus on the empowerment of these juniors and provide them with evidence on the health benefits of prevention, rather than increasing their factual knowledge of procedures. Clinical teaching environments could help them form good patient safety habits during this vital phase of their career.

Sarcopenia in COPD: a systematic review and meta-analysis.

COPD is associated with a progressive loss of muscle mass and function. However, there is an unmet need to define and standardise methods to estimate the prevalence of sarcopenia in COPD patients.We performed a systematic review and meta-analysis of the prevalence of this extrapulmonary manifestation in COPD patients. We searched Embase, Medline (Ovid), CINAHL (EBSCO), Web of Science, Scopus and Google Scholar for studies published up to January 17, 2019, assessing sarcopenia in COPD patients based on low muscle mass and decreased muscle function. Interventional studies, in vitro experiments, protocols or reviews and meta-analyses were excluded. We estimated heterogeneity (I2) and assessed significance (Q) using a Chi-squared test for estimates obtained from random-effects models.4465 articles were initially identified. After removing the duplicates and applying the selection criteria, we reviewed 62 full-text articles. Finally, 10 articles (n=2565 COPD patients) were included in this systematic review and meta-analyses. Overall, the prevalence of sarcopenia in patients with COPD was 21.6% (95% CI 14.6-30.9%, I2=94%), ranging from 8% in population-based to 21% in clinic-based studies, and 63% in COPD patients residing in nursing homes.Sarcopenia is frequently observed in COPD patients, with varying prevalence across population settings. Sarcopenia in COPD should be assessed using standardised tests and cut-off points from sarcopenia consensus criteria for clinical practice and international comparisons.

Asthma and its comorbidities in middle-aged and older adults; the Rotterdam Study.

BACKGROUND: Little is known on the prevalence and characteristics of asthma in middle-aged and older adults, since previous studies mainly focused on children and young adults. Therefore, the aim was to investigate the prevalence of physician-diagnosed asthma and its comorbidities, in a population-based cohort of adults 45 years of age and over. METHODS: We identified participants with physician-diagnosed asthma in the Rotterdam Study; a prospective population-based cohort in the Netherlands. Pulmonary function measurements and comorbidities of the asthma cases were assessed at baseline and compared to those of the general population. RESULTS: Out of 14,621 participants (mean age 65.5 years; 59% women), 524 subjects (31.5%males) had physician-diagnosed asthma at study entry, implicating an asthma prevalence of 3.6% [95% Confidence Interval (CI) 3.3%-3.9%] (2.8% in males and 4.2% in females). Asthmatic subjects had a significantly higher prevalence of obesity and depressive symptoms (Odds Ratio [OR]: 2,02 [95% CI 1,66-2,47] and [OR]: 2,01 [95% CI 1,52-2,66] respectively). Longer duration of asthma and current smoking were associated with lower lung function in asthmatic subjects. CONCLUSION: Four percent of middle-aged and older adults have physician-diagnosed asthma. These adult asthmatics suffer more frequently from obesity and depression than subjects without obstructive lung disease.