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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., Competing Interests: Conflicts of interest D.A.G. is a Unilever employee and as an author had an influence on the analyses and interpretation of the results. Although no products were tested, these results could be used more generally to promote antiageing products and services that lead to financial gain for Unilever., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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 (OR adj ) 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 (OR adj 1.4; 95% CI 1.1-1.8) and lower risks for atopic disorders (OR adj 0.8; 95% CI 0.7-0.95). Patients with late-onset compared with adult-onset asthma had higher risks for nasal polyposis (OR adj 1.8; 95% CI 1.2-2.6), overweight/obesity (OR adj 1.3; 95% CI 1.2-1.4), gastroesophageal reflux disease (OR adj 1.4; 95% CI 1.2-1.7), and diabetes (OR adj 2.3; 95% CI 1.8-2.9). A significant association between late-onset asthma and uncontrolled asthma was observed (OR adj 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., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Conflict of interest: J.T. Arinze reports support for the present manuscript received from Merck Sharp and Dohme (MSD), support for attending meetings and/or travel received from Lung Foundation Netherlands (Long Fonds), outside the submitted work. G.G. Brusselle reports support for the present manuscript received from MSD, and payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events received from AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Novartis, Chiesi, Sanofi and Teva, outside the submitted work. The remaining authors have nothing to disclose., (Copyright ©The authors 2022.)

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., Competing Interests: Conflict of interest: E. Benz has nothing to disclose. Conflict of interest: S.R.A. Wijnant reports grants from GlaxoSmithKline outside the submitted work. Conflict of interest: K. Trajanoska has nothing to disclose. Conflict of interest: J.T. Arinze reports a doctoral research grant from Merck Sharp & Dohme, paid to their institution, outside the submitted work. Conflict of interest: E.W. de Roos has nothing to disclose. Conflict of interest: M. de Ridder has nothing to disclose. Conflict of interest: R. Williams has nothing to disclose. Conflict of interest: F. van Rooij has nothing to disclose. Conflict of interest: K.M.C. Verhamme reports that they work for a research department that receives or has received unconditional grants from Yamanouchi, Pfizer/Boehringer Ingelheim, Novartis, GSK, UCB, Amgen and Chiesi, none of which are related to the content of this paper. Conflict of interest: M.A. Ikram has nothing to disclose. Conflict of interest: B.H. Stricker has nothing to disclose. Conflict of interest: F. Rivadeneira has nothing to disclose. Conflict of interest: L. Lahousse reports financial support for the current manuscript from the Fund for Scientific Research Flanders (grant 3G037618), and payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Institute for Continuing Study of Pharmacists, outside the submitted work. Conflict of interest: G.G. Brusselle reports receiving fees for advisory boards or lectures from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Sanofi and Teva, outside the submitted work., (Copyright ©The authors 2022.)

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., (© 2021 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

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 β 2 -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., Competing Interests: Conflict of interest: E.W. de Roos has nothing to disclose. Conflict of interest: L. Lahousse has nothing to disclose. Conflict of interest: K.M.C. Verhamme works for a research group that received/receives unconditional research grants from Yamanouchi, Pfizer–Boehringer Ingelheim, Novartis, GSK, Chiesi and Amgen. Conflict of interest: G-J. Braunstahl reports grants from GSK, AstraZeneca, Chiesi and Teva, personal fees from Novartis and Sanofi, and grants and personal fees from ALK Abello, outside the submitted work. Conflict of interest: J.J.C.C.M. in ‘t Veen reports faculty grants from Teva, Chiesi, Boehringer Ingelheim and AstraZeneca, and speaker bureau and advisory board fees from Sanofi, outside the submitted work. Conflict of interest: B.H. Stricker has nothing to disclose. Conflict of interest: G.G.O. Brusselle reports advisory board fees from Amgen, Boehringer Ingelheim, Novartis, Sanofi and Teva, and advisory board and lecture fees from AstraZeneca, Chiesi and GlaxoSmithKline, outside the submitted work., (Copyright ©The authors 2021.)

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 (β -0.51 (-0.90--0.11)) and reduced ASMI (β -0.19 (-0.25--0.14)). Forced expiratory volume in 1 s <80% was associated with lower HGS (β -1.03 (-1.75--0.31)) and lower ASMI (β -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., Competing Interests: Conflict of interest: E. Benz has nothing to disclose. Conflict of interest: K. Trajanoska has nothing to disclose. Conflict of interest: J.D. Schoufour has nothing to disclose. Conflict of interest: L. Lahousse reports awards sponsored by AstraZeneca and Chiesi, and expert consultation for Boehringer Ingelheim GmbH and Novartis, outside the submitted work. Conflict of interest: E.W. de Roos has nothing to disclose. Conflict of interest: N. Terzikhan has nothing to disclose. Conflict of interest: C. Medina-Gomez has nothing to disclose. Conflict of interest: K. Verhamme works for a research group that received/receives research grants from Yamanouchi, Pfizer/BI, Novartis and GSK, none of which are related to the content of this work. Conflict of interest: R. Williams has nothing to disclose. Conflict of interest: B.H. Stricker has nothing to disclose. Conflict of interest: O.H. Franco has nothing to disclose. Conflict of interest: M.A. Ikram has nothing to disclose. Conflict of interest: F. Rivadeneira has nothing to disclose. Conflict of interest: G. Brusselle has nothing to disclose., (Copyright ©ERS 2021.)

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., Competing Interests: Conflict of interest: J.T. Arinze has nothing to disclose. Conflict of interest: E.W. de Roos has nothing to disclose. Conflict of interest: L. Karimi has nothing to disclose. Conflict of interest: K.M.C. Verhamme works for a research group that, in the past, received unconditional grants from Yamanouchi, Pfizer/Boehringer Ingelheim, Novartis and GSK, none of which relate to the content of this work. Conflict of interest: B.H. Stricker has nothing to disclose. Conflict of interest: G.G. Brusselle reports advisory boards and speaker's fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis and Teva; and advisory board fees from Sanofi, outside the submitted work., (Copyright ©ERS 2020.)

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., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: LL has received unrestricted research awards/grants from AstraZeneca and Chiesi, and provided expert consultation for Boehringer Ingelheim GmbH and Novartis, outside of the submitted work. MJGL reports grants from Prins Bernhard Cultuurfonds 2014; grants from De Drie Lichten Foundation 2014; grants from Erasmus University Trustfonds 2014; personal fees from American Heart Association (AHA) 2014; personal fees from Netherlands Epidemiology Society (VvE) 2014; personal fees from European Society of Cardiology (ESC) 2013; personal fees from Dutch Heart Foundation (DHF) 2016; personal fees from Capri Cardiac Rehabilitation Foundation Rotterdam 2016; grants from Albert Schweitzer Hospital Research Fund 2018; grants from Oncology Research Albert Schweitzer (ORAS) Foundation 2018; grants from Promoting Advanced Cardiology through Education (PACE) Foundation 2018; all outside of the submitted work.

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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Severe asthma in the elderly places a high burden on affected individuals and society. Emerging therapies target specific phenotypes of the asthma disease spectrum, and can be beneficial for older asthmatics, albeit their response might be altered due to age-related characteristics. Paradoxically, these characteristics are often ground for exclusion from clinical trials. The question thus arises how the senior asthmatic population can successfully enter the era of targeted therapy. Therefore, we highlight characteristics of this population relevant to effective treatment, and review the evidence for targeted therapy in elderly patients. For targeted therapy it is important to account for aging, as this affects the distribution of phenotypes (e.g. late-onset asthma, non-eosinophilic asthma) and may alter biomarkers and drug metabolism. Elderly asthmatics suffer from age-related comorbidities and subsequent polypharmacy. A systematic search into targeted asthma therapy yielded no randomized clinical trials dedicated to older asthmatics. Post hoc analyses of the anti-immunoglobulin E agent omalizumab indicate similar efficacy in both younger and older adults. Conference abstracts on anti-interleukin-5 and anti-interleukin-13 therapy suggest even more pronounced effects of targeted treatments in late-onset disease and in asthmatic patients 65 years or older, but full reports are lacking. For non-eosinophilic asthma in the elderly, there is not yet high-level evidence for targeted therapy, but macrolides may offer a viable option. In conclusion, there is a gap in knowledge regarding the effect of older age on the safety and efficacy of targeted asthma therapy. Further investigations in the elderly are needed, with special emphasis on both late-onset asthma and therapeutics for non-eosinophilic asthma.