FEV
Protein FEV (Fifth Ewing variant protein) (PC12 ETS domain-containing transcription factor 1) (PC12 ETS factor 1) (Pet-1) [PET1]
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Epigenetic aging has been found to be associated with a number of phenotypes and diseases. A few studies have investigated its effect on lung function in relatively older people. However, this effect has not been explored in the younger population. This study examines whether lung function in adolescence can be predicted with epigenetic age accelerations (AAs) using machine learning techniques. DNA methylation based AAs were estimated in 326 matched samples at two time points (at 10 years and 18 years) from the Isle of Wight Birth Cohort. Five machine learning regression models (linear, lasso, ridge, elastic net, and Bayesian ridge) were used to predict FEV (forced expiratory volume in one second) and FVC (forced vital capacity) at 18 years from feature selected predictor variables (based on mutual information) and AA changes between the two time points. The best models were ridge regression (R = 75.21% ± 7.42%; RMSE = 0.3768 ± 0.0653) and elastic net regression (R = 75.38% ± 6.98%; RMSE = 0.445 ± 0.069) for FEV and FVC, respectively. This study suggests that the application of machine learning in conjunction with tracking changes in AA over the life span can be beneficial to assess the lung health in adolescence.
Keywords
- epigenetic aging
- feature selection
- hyperparameter tuning
- lung function
- machine learning
In the IMPACT trial, single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) reduced moderate/severe exacerbation rates versus FF/VI and UMEC/VI in patients with symptomatic chronic obstructive pulmonary disease (COPD) and a history of exacerbations, with a similar safety profile. Research Question Does age have an effect on trial outcomes? IMPACT was a Phase III, double-blind, 52-week trial. Patients ≥40 years of age with symptomatic COPD and ≥1 moderate/severe exacerbation in the prior year were randomized 2:2:1 to FF/UMEC/VI 100/62.5/25 mcg, FF/VI 100/25 mcg, or UMEC/VI 62.5/25 mcg. Endpoints assessed by age included annual rate of moderate/severe exacerbations, change from baseline (CFB) in trough forced expiratory volume in 1 second (FEV ), proportion of St George's Respiratory Questionnaire (SGRQ) responders (≥4 units decrease from baseline in SGRQ total score) and safety. The intent-to-treat population comprised 10,355 patients; 4724 (46%), 4225 (41%), and 1406 (14%) were ≤64, 65-74, and ≥75 years of age, respectively. FF/UMEC/VI reduced on-treatment moderate/severe exacerbation rates versus FF/VI (% reduction [95% confidence interval (CI)], ≤64 years: 8% [-1, 16], p=0.070; 65-74 years: 22% [14, 29], p<0.001; ≥75 years 18% [3, 31], p=0.021) and versus UMEC/VI (≤64 years: 16% [7, 25], p=0.002; 65-74 years: 33% [25, 41], p<0.001; ≥75 years 24% [6, 38], p=0.012), with greatest rate reduction seen in the 65-74 and ≥75 years subgroups. Post hoc analyses of CFB in trough FEV , and proportion of SGRQ responders at Week 52 were significantly greater with FF/UMEC/VI than FF/VI or UMEC/VI in all subgroups. No new safety signals were identified. FF/UMEC/VI reduced the rate of moderate/severe exacerbations and improved lung function and health status versus FF/VI and UMEC/VI irrespective of age for most endpoints, with a similar safety profile. GSK (CTT116855/NCT02164513).
Keywords
- COPD
- aging
- exacerbations
- safety
- single-inhaler triple therapy
Maintenance of lung function is an often underappreciated, yet critical component of healthy aging. Given the unprecedented shift in the average age of Canadians over the next half century, it will be important to investigate the determinants of lung function in the elderly. In the following study, we estimated the association between lung function and a broad array of factors related to sociodemographics, lifestyle, chronic medical conditions and psychosocial factors in older adults aged 45-86 years old using cross-sectional data from the Canadian Longitudinal Study of Aging (n = 21,338). In addition to examining the entire cohort, we also performed stratified analyses within men/women, adults aged 45-64/65 , and healthy/comorbid. In multivariable regression, our explanatory factors (excluding age, sex, height and ethnicity) were able to explain 17% and 11% of the total variance in FEV and FEV /FVC, respectively. Notable and significant contributions were observed for respiratory disease, smoking, obesity, income, and physical activity, while psychosocial factors mainly exhibited non-significant associations. Generally, these associations were stronger for males than females, and adults 65 and older as compared to those aged 45-64. Our findings indicate that there are pervasive and generally under-recognized sociodemographic and lifestyle factors that exhibit significant associations with FEV and FEV /FVC in older adults. While implication of causality in these relationships is not possible due to the cross-sectional nature of the study, future work aiming to investigate determinants of lung health in older adults may choose to target these factors, given that many are modifiable.
Keywords
- Aging
- Determinants
- Lung function
- Sex
- Spirometry
S100 calcium-binding protein A9 (S100A9), is elevated in plasma and bronchoalveolar lavage fluid (BALF) of COPD patients and aging enhances S100A9 expression in several tissues. Currently, the direct impact of S100A9-mediated signaling on lung function and within the aging lung is unknown. Here, we observed that elevated S100A9 levels in human BALF correlated with age. Elevated lung levels of S100A9 were higher in older mice compared to young animals and coincided with pulmonary function changes. Both acute and chronic exposure to cigarette smoke enhanced S100A9 levels in age-matched mice. To examine the direct role of S100A9 on the development of COPD, S100a9 mice or inhibited activity with paquinimod, and exposed the models to chronic cigarette smoke S100A9 depletion and inhibition attenuated the loss of lung function, pressure-volume loops, airway inflammation, lung compliance, and FEV /FVC, compared to age-matched wild type or vehicle administered animals. Loss of S100a9 signaling reduced cigarette smoke-induced airspace enlargement, alveolar remodeling, lung destruction, ERK, and c-RAF phosphorylation, MMP-3, MMP-9, MCP-1, IL-6, and KC release into the airways. Paquinimod administered to non-smoked aged animals reduced age-associated loss of lung function. Since fibroblasts play a major role in the production and maintenance of extracellular matrix in emphysema, primary lung fibroblasts were treated with the ERK inhibitor, LY3214996, or the c-RAF inhibitor, GW5074, resulting in less S100A9-induced MMP-3, MMP-9, MCP-1, IL-6, and IL-8. Silencing TLR4, RAGE or EMMPRIN prevented S100A9-induced phosphorylation of ERK and c-RAF. Our data suggest that S100A9 signaling contributes to the progression of smoke and age-related COPD.
Keywords
- Cigarette smoke
- S100A9
- aging
- kinase
- pulmonary function
Several lung structural and functional abnormalities may occur associated with aging, including emphysema. In this study, we evaluated the frequency and risk factors associated with emphysema in respiratory asymptomatic individuals enrolled in our Lung Aging Program. From a cohort of 687 subjects, we found by high-resolution computed tomography (HRCT) 29 individuals (4%) with emphysematous changes that were compared with 87 controls (3:1) randomly selected from the same cohort. This was a transversal, observational, case-control study where we examined demographics and functional characteristics, as well as telomere length and serum Klotho concentration, two conditions that have been associated with aging and some aging-associated diseases including emphysema. Individuals with subclinical pulmonary emphysema were older (72 ± 9 versus 67 ± 6 years), and primarily smoker males with low body mass index. Despite that they were asymptomatic, two of them exhibited a decrease of forced expiratory volume in 1 s (FEV ), with a lower FEV /FVC suggesting airway obstruction. Cigarette smoking (OR = 5.43, CI95% 1.8-16.7), family history of lung disease (OR = 4.32, CI95% 1.0-19.0) and lower body mass index (OR 7.22, CI95% 1.2-3.5) were risk factors for the development of lung emphysematous changes. No association was found with telomere length and Klotho serum concentration. Our findings reveal that a small but important percentage of older people without respiratory symptoms, present pulmonary emphysema and indicate that smoking exposure and genetic background may contribute to etiological factors.
Keywords
- Aging
- COPD
- Klotho
- Pulmonary emphysema
- Risk factors
- Telomere length
Data are limited on the differential response to long-acting bronchodilators in older versus younger adults with asthma. To determine whether the response to tiotropium Respimat differed in older versus younger patients with asthma. Post hoc analyses of 4 randomized, double-blind, placebo-controlled studies in adults with asthma were carried out. Two studies compared tiotropium Respimat 5 μg once daily with placebo, both added to high-dose inhaled corticosteroid (ICS) plus long-acting β -agonist (ie, severe asthma). The other 2 evaluated tiotropium Respimat 2.5 or 5 μg once daily, salmeterol 50 μg twice daily, or placebo, all added to medium-dose ICS (moderate asthma). Data were analyzed in 2 pools: (1) severe and (2) moderate asthma. Efficacy end points: trough and peak FEV ; trough forced vital capacity; Asthma Control Questionnaire total score and responder percentage, all at week 24. One set of analyses was performed with age as a continuous covariate; the second was conducted in categories less than 40, 40 to 60, and more than 60 years, with treatment-by-age subgroup interaction P values obtained. Safety was analyzed in age categories. Across the age categories, treatment-by-age subgroup interaction P values for trough FEV were .13 and .77 for patients with severe and moderate asthma, respectively, not indicating significant impact of age on overall treatment effect, with this observation replicated in the 2 continuum analyses. The other end points (including safety) were also not impacted by age. Once-daily tiotropium Respimat add-on to ICS or ICS/long-acting β -agonist therapy was effective and well tolerated in patients with asthma independent of age.
Keywords
- Aging
- Asthma
- Long-acting muscarinic antagonist
- Long-acting β(2)-agonists
- Pharmacotherapy
Asthma is common in older adults and is confirmed by demonstration of variable expiratory air-flow limitations, typically evaluated by spirometric assessment of bronchodilator responsiveness. However, many patients with clinically suspected asthma and documented air-flow obstruction do not exhibit a post-bronchodilator response that meets or exceeds current established guidelines. We investigated if extending the time from bronchodilator administration to assessment of bronchodilator response increases the yield of spirometry for the diagnosis of asthma in older adults. This was a cross-sectional study. The subjects were non-smokers, ≥ 60 y old, and with suspected asthma. Subjects were characterized as (1) those with a positive bronchodilator response on the 30-min post-bronchodilator spirometry, (2) those with a positive bronchodilator response on the 60-min post-bronchodilator spirometry, and (3) those without a positive bronchodilator response but with a positive methacholine challenge test. Factors associated with a late response to bronchodilator were evaluated by using bivariate analysis and by multivariate analysis by using a logistic regression model. This study enrolled 165 subjects. Of these, 81 (49.1%) had a positive bronchodilator response on 30-min post-bronchodilator spirometry; 25 (15.2%) had a positive bronchodilator response on the 1-h post-bronchodilator spirometry; and 59 (35.8%) had no positive bronchodilator response but had a positive methacholine challenge test. On multivariable regression analysis, those with a higher baseline percentage of predicted FEV , higher scores on a standard asthma control test, and wheezing and/or cough after exercise were more likely to either have a late bronchodilator response or no bronchodilator response. Our study showed that a late positive response to bronchodilator use was more common than previously presumed in older subjects with suspected asthma. Pulmonary function testing laboratories should consider routinely reassessing spirometry at 1 h after bronchodilator use if the earlier assessment did not reveal a significant response.
Keywords
- aging
- albuterol
- asthma
- bronchodilator effect
- lung diseases
- older adult
- spirometry
Ageing is associated with a decrease in physical performance implying that aged manual workers may be unable to match the physical requirements of their jobs. In this cross-sectional study, 96 male manual workers aged 51-72 years were recruited. Outcomes included handgrip strength (HGS), fat-free mass (FFM), fat percentage, cardiorespiratory fitness ([Formula: see text]O max), forced vital capacity (FVC), forced expiratory volume after 1 s (FEV ), spinal flexibility, sit-to-stand test performance and static balance. Covariates included height, smoking habits, leisure-time physical activity and systemic inflammation from blood samples. Outcomes were also compared with general populations. Age was negatively related to FFM and FEV , whereas static balance (velocity of displacement) was positively associated with age. Greater HGS, but poorer [Formula: see text]O max and FEV /FEV ratio were found compared with general populations. Age was negatively related with physical performances although a large part of the variance in performance could be explained by factors other than age such as smoking and systemic inflammation. The manual workers had greater muscle strength but had poorer cardiorespiratory fitness and lung function when compared with general populations. Specific health interventions targeting specifically cardiorespiratory fitness, lung function, and balance may be needed to maintain physical performances among manual workers.
MeSH Terms
- Aged
- Aging
- Body Composition
- Body Mass Index
- Cardiorespiratory Fitness
- Cross-Sectional Studies
- Hand Strength
- Humans
- Lung
- Male
- Middle Aged
- Physical Functional Performance
Commonly used thresholds for staging FEV have not been evaluated as standalone spirometric predictors of death in older persons. Specifically, the proportion of deaths attributed to a reduced FEV , when staged by commonly used thresholds in L, percent of predicted (% pred), and Z scores, has not been previously reported. In 4,232 white persons ≥ 65 y old, sampled from the Cardiovascular Health Study, FEV was stratified as stage 1 (FEV ≥ 2.00 L, ≥80% pred, and Z score ≥-1.64), stage 2 (FEV 1.50-1.99 L, 50-79%pred, and Z score -2.55 to -1.63), and stage 3 (FEV < 1.50 L, < 50% pred, and Z score < -2.55). Notably, a Z score threshold of -1.64 defines normal-for-age lung function as the lower limit of normal (ie, 5th percentile of distribution), and accounts for differences in age, sex, height, and ethnicity. Next, adjusted odds ratios and average attributable fractions for 10-y all-cause mortality were calculated, comparing FEV stages 2 and 3 against stage 1, expressed in L, % pred, and Z scores. The average attributable fraction estimates the proportion of deaths attributed to a predictor by combining the prevalence of the predictor with the relative risk of death conferred by that predictor. FEV stage 2 and 3 in L, % pred, and Z scores yielded similar adjusted odds ratios of death: 1.40-1.51 for stage 2 and 2.35-2.66 for stage 3. Conversely, FEV stages 2 and 3 in L, % pred, and Z scores differed in prevalence: 12.8-28.6% for stage 2 and 6.4-17.5% for stage 3, and also differed in the adjusted average attributable fraction for death: 3.2-6.4% for stage 2 and 4.5-9.1% for stage 3. In older persons, the proportion of deaths attributed to a reduced FEV is best stratified by Z score staging thresholds because these yield a similar relative risk of death but a more age- and sex-appropriate prevalence of FEV stage.
Keywords
- aging
- average attributable fraction
- death
- relative risk
- spirometry
Prediction of future lung function will enable the identification of individuals at high risk of developing COPD, but the trajectory of lung function decline varies greatly among individuals. This study involved the development and validation of an individualized prediction model of lung function trajectory and risk of airflow limitation in the general population. Data were obtained from the Framingham Offspring Cohort, which included 4,167 participants ≥ 20 years of age and who had ≥ 2 valid spirometry assessments. The primary outcome was prebronchodilator FEV ; the secondary outcome was the risk of airflow limitation (defined as FEV /FVC less than the lower limit of normal). Mixed effects regression models were developed for individualized prediction, and a machine learning algorithm was used to determine essential predictors. The model was validated in two large, independent multicenter cohorts (N = 2,075 and 12,913, respectively). With 20 common predictors, the model explained 79% of the variation in FEV decline in the derivation cohort. In two validation datasets, the model had low error in predicting FEV decline (root mean square error range, 0.18-0.22 L) and high discriminative power in predicting risk of airflow limitation (C-statistic range, 0.86-0.87). This model was implemented in a freely accessible website-based application, which allows prediction based on flexible sets of predictors (http://resp.core.ubc.ca/ipress/FraminghamFEV1). The individualized predictor is an accurate tool to predict long-term lung function trajectories and risk of airflow limitation in the general population. This model enables identifying individuals at higher risk of COPD, who can then be targeted for preventive therapies.
MeSH Terms
- Adult
- Age Factors
- Aging
- Alcohol Drinking
- Algorithms
- Alkaline Phosphatase
- Body Height
- Bronchodilator Agents
- Cigarette Smoking
- Cohort Studies
- Cough
- Dyspnea
- Electrocardiography
- Female
- Forced Expiratory Volume
- Hematocrit
- Humans
- Leukocyte Count
- Longitudinal Studies
- Lung
- Machine Learning
- Male
- Middle Aged
- Pulmonary Disease, Chronic Obstructive
- Risk Assessment
- Serum Albumin
- Serum Globulins
- Sex Factors
- Spirometry
- Triglycerides
- Vital Capacity
Keywords
- COPD
- FEV(1)
- FEV(1)/FVC
- airflow limitation
- lung function
- predictive modeling
Telomere length is associated with poorer lung health in older adults, possibly from cumulative risk factor exposure, but data are lacking in pediatric and population-based cohorts. We examined associations of telomere length with lung function in children and mid-life adults. Data were drawn from a population-based cross-sectional study of 11 to 12 year-olds and mid-life adults. Lung function was assessed by spirometric FEV , FVC, FEV /FVC ratio, and MMEF . Telomere length was measured by quantitative polymerase chain reaction from blood and expressed as the amount of telomeric genomic DNA to the beta-globin gene (T/S ratio). Associations of telomere length with spirometric parameters were tested by linear and logistic regression models, adjusting for potential confounders of sex, age, body mass index, socioeconomic position, physical activity, inflammation, asthma, pubertal status, and smoking. Mean T/S ratio was 1.09 (n = 1206; SD 0.55) in children and 0.81 (n = 1343; SD 0.38) in adults. In adults, for every additional unit in T/S ratio, FEV /FVC and MMEF z-scores were higher (β 0.21 [95% confidence interval, CI; 0.06-0.36] and 0.23 [95% CI; 0.08-0.38], respectively), and the likelihood of being in the lowest quartile for FEV /FVC and MMEF z-scores was lower (odds ratios 0.59 [95% CI, 0.39-0.89] and 0.64 [95% CI, 0.41-0.99], respectively). No evidence of association was seen for adult FEV or FVC, or any childhood spirometric index after adjustments. Shorter telomere length showed moderate associations with poorer airflow parameters, but not vital capacity (lung volume) in mid-life adults. However, there was no convincing evidence of associations in children.
MeSH Terms
- Aged
- Asthma
- Body Mass Index
- Child
- Cohort Studies
- Cross-Sectional Studies
- Exercise
- Female
- Forced Expiratory Volume
- Humans
- Lung
- Male
- Respiratory Function Tests
- Risk Factors
- Smoking
- Spirometry
- Telomere
- Vital Capacity
Keywords
- aging
- cell senescence
- life course
- national cohort
- spirometry
To conduct a systematic review investigating the normal age-related changes in lung function in adults without known lung disease. Systematic review. MEDLINE, Embase and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched for eligible studies from inception to February 12, 2019, supplemented by manual searches of reference lists and clinical trial registries. We planned to include prospective cohort studies and randomised controlled trials (control arms) that measured changes in lung function over time in asymptomatic adults without known respiratory disease. Two authors independently determined the eligibility of studies, extracted data and assessed the risk of bias of included studies using the modified Newcastle-Ottawa Scale. From 4385 records screened, we identified 16 cohort studies with 31 099 participants. All included studies demonstrated decline in lung function-forced expiratory volume in 1 s (FEV ), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) with age. In studies with longer follow-up (>10 years), rates of FEV decline ranged from 17.7 to 46.4 mL/year (median 22.4 mL/year). Overall, men had faster absolute rates of decline (median 43.5 mL/year) compared with women (median 30.5 mL/year). Differences in relative FEV change, however, were not observed between men and women. FEV /FVC change was reported in only one study, declining by 0.29% per year. An age-specific analysis suggested the rate of FEV function decline may accelerate with each decade of age. Lung function-FEV , FVC and PEFR-decline with age in individuals without known lung disease. The definition of chronic airway disease may need to be reconsidered to allow for normal ageing and ensure that people likely to benefit from interventions are identified rather than healthy people who may be harmed by potential overdiagnosis and overtreatment. The first step would be to apply age, sex and ethnicity-adjusted FEV /FVC thresholds to the disease definition of chronic obstructive pulmonary disease. CRD42018087066.
MeSH Terms
- Age Factors
- Aged
- Aged, 80 and over
- Aging
- Female
- Humans
- Male
- Middle Aged
- Prospective Studies
- Randomized Controlled Trials as Topic
- Reference Values
- Research Design
- Respiratory Function Tests
Keywords
- age-related decline
- ageing
- cohort studies
- lung function tests
- systematic review
Lung function is lower in people with disadvantaged socio-economic position (SEP) and is associated with hazardous health behaviours and exposures. The associations are likely to be interactive, for example, exposure to socially patterned environmental tobacco smoke (ETS) in childhood is associated with an increased effect of smoking in adulthood. We hypothesise that disadvantaged childhood SEP increases susceptibility to the effects of hazards in adulthood for lung function. We test whether disadvantaged childhood SEP moderates smoking, physical activity, obesity, occupational exposures, ETS and air pollution's associations with lung function. Data are from the Nurse Health Assessment (NHA) in waves two and three of the United Kingdom Household Longitudinal Study (UKHLS). Analysis is restricted to English residents aged at least 20 for women and 25 for men, producing a study population of 16,339. Lung function is measured with forced expiratory volume in the first second (FEV ) and standardised to the percentage of expected FEV for a healthy non-smoker of equivalent age, gender, height and ethnicity (FEV %). Using STATA 14, a mixed linear model was fitted with interaction terms between childhood SEP and health behaviours and occupational exposures. Cross level interactions tested whether childhood SEP moderated household ETS and neighbourhood air pollution's associations with FEV %. SEP, smoking, physical activity, obesity, occupational exposures and air pollution were associated with lung function. Interaction terms indicated a significantly stronger negative association between disadvantaged childhood SEP and currently smoking (coefficient -6.47 %, 95% confidence intervals (CI): 9.51 %, 3.42 %) as well as with formerly smoking and occupational exposures. Significant interactions were not found with physical activity, obesity, ETS and air pollution. The findings suggest that disadvantaged SEP in childhood may make people's lung function more susceptible to the negative effects of smoking and occupational exposures in adulthood. This is important as those most likely to encounter these exposures are at greater risk to their effects. Policy to alleviate this inequality requires intervention in health behaviours through public health campaigns and in occupational health via health and safety legislation.
MeSH Terms
- Adolescent
- Adult
- Age Factors
- Aged
- Aged, 80 and over
- Aging
- Child
- Cross-Sectional Studies
- Female
- Forced Expiratory Volume
- Humans
- Linear Models
- Longitudinal Studies
- Lung
- Male
- Middle Aged
- Occupational Exposure
- Pulmonary Disease, Chronic Obstructive
- Respiratory Function Tests
- Smoking
- Socioeconomic Factors
- Tobacco Smoke Pollution
- United Kingdom
- Young Adult
Keywords
- Cross-sectional
- Health behaviours
- Lung function
- Occupational exposures
- Socio-economic position
- UKHLS
While cross-sectional studies have shown associations between certain occupational exposures and lower levels of lung function, there was little evidence from population-based studies with repeated lung function measurements. We aimed to investigate the associations between occupational exposures and longitudinal lung function decline in the population-based Tasmanian Longitudinal Health Study. Lung function decline between ages 45 years and 50 years was assessed using data from 767 participants. Using lifetime work history calendars completed at age 45 years, exposures were assigned according to the ALOHA plus Job Exposure Matrix. Occupational exposures were defined as ever exposed and cumulative exposure -unit- years. We investigated effect modification by sex, smoking and asthma status. Compared with those without exposure, ever exposures to aromatic solvents and metals were associated with a greater decline in FEV (aromatic solvents 15.5 mL/year (95% CI -24.8 to 6.3); metals 11.3 mL/year (95% CI -21.9 to - 0.7)) and FVC (aromatic solvents 14.1 mL/year 95% CI -28.8 to - 0.7; metals 17.5 mL/year (95% CI -34.3 to - 0.8)). Cumulative exposure (unit years) to aromatic solvents was also associated with greater decline in FEV and FVC. Women had lower cumulative exposure years to aromatic solvents than men (mean (SD) 9.6 (15.5) vs 16.6 (14.6)), but greater lung function decline than men. We also found association between ever exposures to gases/fumes or mineral dust and greater decline in lung function. Exposures to aromatic solvents and metals were associated with greater lung function decline. The effect of aromatic solvents was strongest in women. Preventive strategies should be implemented to reduce these exposures in the workplace.
MeSH Terms
- Adult
- Aging
- Female
- Forced Expiratory Volume
- Health Surveys
- Humans
- Longitudinal Studies
- Lung
- Male
- Middle Aged
- Occupational Exposure
- Sex Factors
- Solvents
- Vital Capacity
Keywords
- FEV1
- chronic obstructive pulmonary disease
- job exposure matrix
- lung function
- occupational exposure
- solvents
Patients with chronic obstructive pulmonary disease (COPD) often suffer from multiple morbidities, which occur in clusters and are sometimes related to accelerated aging. This study aimed to assess the disease specificity of comorbidity clusters in COPD and their association with a biomarker of accelerated aging as a potential mechanistic factor. Body composition, metabolic, cardiovascular, musculoskeletal, and psychological morbidities were objectively evaluated in 208 COPD patients (age 62 ± 7 years, 58% males, FEV 50 ± 16% predicted) and 200 non-COPD controls (age 61 ± 7 years, 45% males). Based on their presence and severity, the morbidities were clustered to generate distinct clusters in COPD and controls. Telomere length in circulating leukocytes was compared across the clusters. (co)morbidities were more prevalent in COPD patients compared to controls (3.9 ± 1.7 vs. 2.4 ± 1.5, [i]p[/i] < 0.05). A "Psychologic" and "Cachectic" cluster were only present in the COPD population. "Less (co)morbidity", "Cardiovascular", and "Metabolic" clusters were also observed in controls, although with less complexity. Telomere length was reduced in COPD patients, but did not differ between the (co)morbidity clusters in both populations. Two COPD-specific comorbidity clusters, a "Cachectic" and "Psychologic" cluster, were identified and warrant further studies regarding their development. Accelerated aging was present across various multimorbidity clusters in COPD.
Keywords
- COPD
- accelerated aging
- cluster
- comorbidity
- multimorbidity
- telomere length
This study aimed to evaluate the effect of the stretch-shortening cycle (SSC) on different portions of the force-velocity (F-V) relationship in older adults with and without chronic obstructive pulmonary disease (COPD), and to assess its association with physical function. The participants were 26 older adults with COPD (79 ± 7 years old; FEV = 53 ± 36% of predicted) and 10 physically active non-COPD (77 ± 4 years old) older adults. The F-V relationship was evaluated in the leg press exercise during a purely concentric muscle action and compared with that following an eccentric muscle action at 10% intervals of maximal unloaded shortening velocity (V ). Vastus lateralis (VL) muscle thickness, pennation angle (PA), and fascicle length (FL) were assessed by ultrasound. Habitual gait speed was measured over a 4-m distance. COPD subjects exhibited lower physical function and concentric maximal muscle power (P ) values compared with the non-COPD group (both [i]p <[/i] 0.05). The SSC increased force and power values among COPD participants at 0-100 and 1-100% of V , respectively, while the same was observed among non-COPD participants only at 40-90 and 30-90% of V , respectively (all [i]p[/i] < 0.05). The SSC induced greater improvements in force, but not power, among COPD compared with non-COPD subjects between 50 and 70% of V (all [i]p[/i] < 0.05). Thus, between-group differences in muscle power were not statistically significant after the inclusion of the SSC ([i]p[/i] > 0.05). The SSC-induced potentiation at 50-100% of V was negatively associated with physical function ([i]r[/i] = -0.40-0.50), while that observed at 80-100% of V was negatively associated with VL muscle thickness and PA ([i]r[/i] = -0.43-0.52) (all [i]p[/i] < 0.05). In conclusion, older adults with COPD showed a higher SSC-induced potentiation compared with non-COPD subjects, which eliminated between-group differences in muscle power when performing SSC muscle actions. The SSC-induced potentiation was associated with lower physical function, VL muscle thickness, and VL PA values. The SSC-induced potentiation may help as a compensatory mechanism in those older subjects with a decreased ability to produce force/power during purely concentric muscle actions.
Keywords
- aging
- concentric
- eccentric
- muscle power
- potentiation
- resistance training
Previous studies have reported inverse associations between socioeconomic status (SES) and lung function, but less is known about whether pulmonary function is affected by SES changes. We aimed to describe the relationship of changes of SES between childhood and adulthood with pulmonary function. Cross-sectional study. The study sample included 4104 men and women, aged 45-69 years, residents of Krakow, participating in the Polish part of the Health, Alcohol and Psychosocial Factors in Eastern Europe Project. Forced expiratory volume (FEV ) and forced vital capacity (FVC) were assessed by the standardised spirometry procedure. Participants were classified into three categories of SES (low, moderate or high) based on information on parent's education, housing standard during childhood, own education, employment status, household amenities and financial status. The adjusted difference in mean FVC between persons with low and high adulthood SES was 100 mL (p=0.005) in men and 100 mL (p<0.001) in women; the differences in mean FEV were 103 mL (p<0.001) and 80 mL (p<0.001), respectively. Upward social mobility and moderate or high SES at both childhood and adulthood were related to significantly higher FEV and FVC compared with low SES at both childhood and adulthood or downward social mobility. Low SES over a life course was associated with the lowest lung function. Downward social mobility was associated with a poorer pulmonary function, while upward mobility or life course and moderate or high SES were associated with a better pulmonary function.
MeSH Terms
- Aged
- Aging
- Child
- Cross-Sectional Studies
- Female
- Forced Expiratory Volume
- Humans
- Lung
- Male
- Middle Aged
- Poland
- Risk Factors
- Social Mobility
- Spirometry
- Urban Population
- Vital Capacity
Keywords
- lung function
- ses
- social mobility
The beneficial effect of improving air quality on lung function in the elderly remains unclear. We examined associations between decline in air pollutants and lung function, and effect modifications by genetics and body mass index (BMI), in elderly German women. Data were analysed from the prospective SALIA (Study on the influence of Air pollution on Lung function, Inflammation and Aging) study (n=601). Spirometry was conducted at baseline (1985-1994; age 55 years), in 2007-2010 and in 2012-2013. Air pollution concentrations at home addresses were determined for each time-point using land-use regression models. Global Lung Initiative 2012 z-scores were calculated. Weighted genetic risk scores (GRSs) were determined from lung function-related risk alleles and used to investigate interactions with improved air quality. Multiple linear mixed models were fitted. Air pollution levels decreased substantially during the study period. Reduction of air pollution was associated with an increase in z-scores for forced expiratory volume in 1 s (FEV ) and the FEV /forced vital capacity ratio. For a decrease of 10 µg·m in nitrogen dioxide (NO ), the z-score for FEV increased by 0.14 (95% CI 0.01-0.26). However, with an increasing number of lung function-related risk alleles, the benefit from improved air quality decreased (GRS×NO interaction: p=0.029). Interactions with BMI were not significant. Reduction of air pollution is associated with a relative improvement of lung function in elderly women, but also depends on their genetic make-up.
MeSH Terms
- Aged
- Aging
- Air Pollutants
- Air Pollution
- Cohort Studies
- Female
- Forced Expiratory Volume
- Germany
- Humans
- Lung
- Middle Aged
- Nitrogen Dioxide
- Obesity
- Prospective Studies
- Vital Capacity
To determine and explain the effect of age on exhaled nitric oxide values in North African healthy subjects aged from 5 to 83 years. Prospective cross-sectional study. Volunteer children adults and elderly healthy subjects were included. A medical questionnaire was used to assess several subject characteristics. The levels of exhaled fraction of nitric oxide (FeNO) were measured by Medisoft HypAir FeNO method. Spirometry function test was done after the FeNO measurement. The following parameters were measured: forced vital capacity (FVC, L); 1st second forced expiratory volume (FEV , L); FEV /FVC ratio (absolute value); maximal mid expiratory flow (MMEF, L/s); Mid expiratory flow from 25 to 75% (MEF25%, MEF50%, and MEF75%). Statistical analyses were carried out using Statistica software with a significance set at the 0.05 level. A significant increase in FeNO is noted between groups with respective age ranges of (5, 17) and (17, 25) years with a breakpoint at 1,397,034 years. A significant decrease of FeNO is noted between groups with respective age ranges of (45, 55) and (55, 65) years with a breakpoint at 6,366,052 years. No statistical significant difference was found between females' and males' means FeNO data. Finally, SEL, obesity status, and hypertension contribute significantly in the variations of FeNO values. The development and aging of the lung touched non-respiratory functions and so modified FeNO values in healthy North African subjects.
MeSH Terms
- Adolescent
- Adolescent Development
- Adult
- African Continental Ancestry Group
- Age Factors
- Aged
- Aged, 80 and over
- Aging
- Biomarkers
- Child
- Child Development
- Child, Preschool
- Cross-Sectional Studies
- Exhalation
- Female
- Forced Expiratory Volume
- Humans
- Hypertension
- Lung
- Male
- Middle Aged
- Nitric Oxide
- Obesity
- Tunisia
- Vital Capacity
- Young Adult
Keywords
- Exhaled nitric oxide
- Lung aging
- Lung development
- North Africa
Menopause involves hypoestrogenism, which is associated with numerous detrimental effects, including on respiratory health. Hormone replacement therapy (HRT) is often used to improve symptoms of menopause. The effects of HRT on lung function decline, hence lung ageing, have not yet been investigated despite the recognized effects of HRT on other health outcomes. The population-based multi-centre European Community Respiratory Health Survey provided complete data for 275 oral HRT users at two time points, who were matched with 383 nonusers and analysed with a two-level linear mixed effects regression model. We studied whether HRT use was associated with the annual decline in forced vital capacity (FVC) and forced expiratory volume in one second (FEV ). Lung function of women using oral HRT for more than five years declined less rapidly than that of nonusers. The adjusted difference in FVC decline was 5.6 mL/y (95%CI: 1.8 to 9.3, p = 0.01) for women who had taken HRT for six to ten years and 8.9 mL/y (3.5 to 14.2, p = 0.003) for those who had taken it for more than ten years. The adjusted difference in FEV decline was 4.4 mL/y (0.9 to 8.0, p = 0.02) with treatment from six to ten years and 5.3 mL/y (0.4 to 10.2, p = 0.048) with treatment for over ten years. In this longitudinal population-based study, the decline in lung function was less rapid in women who used HRT, following a dose-response pattern, and consistent when adjusting for potential confounding factors. This may signify that female sex hormones are of importance for lung ageing.
MeSH Terms
- Adult
- Aging
- Estrogen Replacement Therapy
- Estrogens
- Female
- Follow-Up Studies
- Forced Expiratory Volume
- Humans
- Lung
- Menopause
- Middle Aged
- Vital Capacity
Keywords
- Hormone replacement therapy (HRT)
- Lung function
- Menopause
- Reproductive aging
- Sex hormones
DNA methylation is an epigenetic regulator of gene transcription, which has been found to be both metastable and variable within human cohort studies. Currently, few studies have been done to identify metastable DNA methylation biomarkers associated with longitudinal lung function decline in humans. The identification of such biomarkers is important for screening vulnerable populations. We hypothesized that quantifiable blood-based DNA methylation alterations would serve as metastable biomarkers of lung function decline and aging, which may help to discover new pathways and/or mechanisms related to pulmonary pathogenesis. Using linear mixed models, we performed an Epigenome Wide Association Study (EWAS) between DNA methylation at CpG dinucleotides and longitudinal lung function (FVC, FEV , FEF ) decline and aging with initial discovery in the Normative Aging Study, and replication in the Cooperative Health Research in the Region of Augsburg cohort. We identified two metastable epigenetic loci associated with either poor lung function and aging, cg05575921 (AHRR gene), or lung function independently of aging, cg06126421 (IER3 gene). These loci may inform basic mechanisms associated with pulmonary function, pathogenesis, and aging. Human epigenomic variation, may help explain features of lung function decline and related pathophysiology not attributable to DNA sequence alone, such as accelerated pulmonary decline in smokers, former smokers, and perhaps non-smokers. Our EWAS across two cohorts, therefore, will likely have implications for the human population, not just the elderly.
MeSH Terms
- Aged
- Aging
- CpG Islands
- DNA Methylation
- Epigenesis, Genetic
- Female
- Genome-Wide Association Study
- Humans
- Lung
- Lung Diseases
- Male
Keywords
- Biomarker
- DNA methylation
- lung function decline
- pulmonary function
{{medline-entry |title=Contribution of peripheral airway function to changes in FEV /FVC and RV/TLC with aging. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30138079 |abstract=Multiple breath nitrogen washout (MBNW) indices provide insight into ventilation heterogeneity globally [lung clearance index (LCI)] and within acinar (S ) and conducting (S ) airways. Normal aging leads to an accelerated deterioration of S in older adults, but little is known about the contribution of peripheral airway function to changes in pulmonary function indices reflecting expiratory airflow [forced expiratory volume in one second (FEV )/forced vital capacity (FVC)] and gas trapping [residual volume (RV)/total lung capacity (TLC)] with aging. We aimed to examine associations between MBNW and FEV /FVC as well as RV/TLC in healthy adults, and to determine if these relationships differ in older (≥50 yr) versus younger subjects (<50 yr). Seventy-nine healthy adult volunteers aged 23-89 yr with no cardiac or respiratory disease and a smoking history of <5 pack-years underwent spirometry, plethysmography, and MBNW. After adjustment for sex, height, and body mass index, the following relationships were present across the entire cohort: S was inversely related to FEV /FVC (R = 0.22, P < 0.001); S and S were positively related to RV/TLC (R = 0.53, P < 0.001); on separate analyses, the relationship between S and FEV /FVC was strongest in the older group (R = 0.20, P = 0.003) but markedly weaker in the younger group (R = 0.09, P = 0.04); and S and S were related to RV/TLC in older (R = 0.20, P = 0.003) but not younger subgroups. No relationships were observed between LCI and FEV /FVC or RV/TLC. Changes in FEV /FVC and RV/TLC are at least in part due to changes in peripheral airway function with aging. Further studies of the relationships between MBNW and standard pulmonary function indices may prove useful for their combined application and interpretation in obstructive airways disease. NEW