Age-related Decline In Lung Function Research Articles

Ever and cumulative occupational exposure and lung function decline in longitudinal population-based studies: a systematic review and meta-analysis

ObjectivesAdverse occupational exposures can accelerate age-related lung function decline. Some longitudinal population-based studies have investigated this association. This study aims to examine this association using findings reported by longitudinal population-based...

Tracking of lung function from 10 to 35 years after being born extremely preterm or with extremely low birth weight

BackgroundLifelong pulmonary consequences of being born extremely preterm or with extremely low birth weight remain unknown. We aimed to describe lung function trajectories from 10 to 35 years of age...

Lung and liver transplantation in patients with alpha-1 antitrypsin deficiency.

Alpha-1 antitrypsin (AAT) augmentation is effective in slowing the progression of emphysema due to AAT deficiency (AATD) but cannot prevent eventual progression to end-stage lung disease and complete respiratory failure, which is the leading cause of death for individuals with severe AATD. When patients develop end-stage lung disease, lung transplantation is the only treatment option available, and this can improve lung physiology and patient health status. The available data suggest that survival rates for lung transplantation are significantly higher for patients with AATD-related chronic obstructive pulmonary disease (COPD) compared with non-AATD-related COPD, but, conversely, there is a higher risk of common post-lung transplant complications in patients with AATD versus non-AATD COPD. Nevertheless, lung transplantation (single and bilateral) is favorable for patients with AATD. After respiratory failure, the second leading cause of death in patients with AATD is liver disease, for example, cirrhosis and hepatocellular carcinoma, caused by the accumulation of mutant forms of AAT retained within the liver. As with lung disease, the only treatment option for end-stage liver disease is liver transplantation. Survival rates for patients with AATD undergoing liver transplantation are also favorable, and patients, particularly pediatric patients, have benefitted from advancements in peri-/post-surgical care. As the majority of AAT is produced by the liver, the AAT phenotype of the recipient becomes that of the donor, meaning that AAT serum levels should be normalized (if the donor is AAT-replete), halting further lung and liver disease progression. However, post-liver transplant respiratory function may continue to decline in line with normal age-related lung function decline. In the most severe cases, where patients have simultaneous end-stage lung and liver disease, combined lung and liver transplantation is a treatment option with favorable outcomes. However, there is very little information available on this procedure in patients with AATD.

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.

Social integration and age-related decline in lung function.

We tested the hypothesis that social integration, measured as number of social roles, is associated with less age-related loss of lung function, an important marker of health and longevity. We also investigated possible psychological factors through which social integration might influence lung health. Data were analyzed from the Health and Retirement Study (ages 52-94, n = 4,224). Each additional social role reported at baseline was associated with less of a decline in lung function between baseline and the follow-up assessment four years later. The association withstood controls for demographics, weight, and height and was mediated by more positive and less negative affect and lower rates of cigarette smoking and more physical activity. Roles were mostly substitutable, with both high (spouse, parent, friends, relatives) and low (employee, religious service attendee, volunteer, members of other groups) intimacy roles independently contributing to less age-related decline in lung function. (PsycINFO Database Record

Supplemental Material for Social Integration and Age-Related Decline in Lung Function

Supplemental Material for Social Integration and Age-Related Decline in Lung Function

64 - Progressive loss of dual oxidase 1 (DUOX1) contributes to impaired airway epithelial wound responses in the aging lung

Age-related chronic diseases, including chronic respiratory diseases such as COPD, are associated with organ function decline, impaired regenerative capacity, and immuno-senescence. Our recent studies indicate that such reparative processes in the lung are mediated by innate epithelial injury responses and production of reactive oxygen species (ROS) by the NADPH oxidase dual oxidase 1 (DUOX1), which were found to be associated with oxidation and activation of epithelial tyrosine kinases, such as epidermal growth factor receptor (EGFR) and the non-receptor tyrosine kinase Src, and also with epithelial secretion of alarmins such as IL-33, which promote epithelial regeneration by activating type 2 immune responses. Contrasting the common belief that aging is associated with increased ROS production, we observed that DUOX1 expression in mouse lungs markedly decreases with age. Moreover, we noticed that DUOX1-deficient mice display accelerated age-related decline in lung function and features of emphysema, as shown by airspace enlargement and increased lung compliance. We hypothesized that loss of DUOX1 may contribute to other features of lung aging, but aged-related lung changes such as increased parenchymal collagen deposition, molecular indices of senescence, or tissue levels of pro-inflammatory cytokines, were all largely unaltered in DUOX1-deficient mice. However, we observed that aged mice display markedly attenuated innate airway responses to inhaled allergens, as illustrated by diminished secretion of IL-33 and other related cytokines. Similar findings were observed in vitro using cultured mouse tracheal epithelial cells (MTEC), in which MTECs from older mice showed dramatically reduced innate responses to injury, which was associated with reduced oxidation and activation of Src and EGFR. Consistent with a potential age-related suppression of DUOX1 by epigenetic mechanisms such as promoter hypermethylation, allergen-induced IL-33 secretion in MTECs from aged mice could be rescued by treatment with the DNA methyltransferase inhibitor AzdC. Overall, these results underline the importance of DUOX1 in airway host defense and regenerative capacity, and indicate that age-related loss of DUOX1 contributes to accelerated impairment of epithelial regenerative capacity and air-space enlargement.

Lung function decline over 25 years of follow-up among black and white adults in the ARIC study cohort

BackgroundInterpretation of longitudinal information about lung function decline from middle to older age has been limited by loss to follow-up that may be correlated with baseline lung function or the rate of decline. We conducted these analyses to estimate age-related decline in lung function across groups of race, sex, and smoking status while accounting for dropout from the Atherosclerosis Risk in Communities Study. MethodsWe analyzed data from 13,896 black and white participants, aged 45–64 years at the 1987–1989 baseline clinical examination. Using spirometry data collected at baseline and two follow-up visits, we estimated annual population-averaged mean changes in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) by race, sex, and smoking status using inverse-probability-weighted independence estimating equations conditioning-on-being-alive. ResultsEstimated rates of FEV1 decline estimated using inverse-probability-weighted independence estimating equations conditioning on being alive were higher among white than black participants at age 45 years (e.g., male never smokers: black: −29.5 ml/year; white: −51.9 ml/year), but higher among black than white participants by age 75 (black: −51.2 ml/year; white: −26). Observed differences by race were more pronounced among men than among women. By smoking status, FEV1 declines were larger among current than former or never smokers at age 45 across all categories of race and sex. By age 60, FEV1 decline was larger among former and never than current smokers. Estimated annual declines generated using unweighted generalized estimating equations were smaller for current smokers at younger ages in all four groups of race and sex compared with results from weighted analyses that accounted for attrition. ConclusionsUsing methods accounting for dropout from an approximately 25-year health study, estimated rates of lung function decline varied by age, race, sex, and smoking status, with largest declines observed among current smokers at younger ages.

Dietary anthocyanin intake and age-related decline in lung function: longitudinal findings from the VA Normative Aging Study1–3

Background: It is unknown whether habitual intake of dietary flavonoids, known for their antioxidative and anti-inflammatory properties, affects longitudinal change in lung function.Objective: We investigated whether different flavonoid subclasses present in the habitual diet were associated with beneficial changes in lung function over time in the elderly.Design: This longitudinal analysis included 839 participants from the VA (Veterans Affairs) Normative Aging Study whose lung function [forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)] was measured at 2 and up to 5 visits between 1992 and 2008 (n = 2623 measurements). Yearly average intake of major flavonoid subclasses (anthocyanins, flavanones, flavan-3-ols, flavonols, flavones, and polymers) was calculated from food-frequency questionnaires at each visit. We estimated adjusted differences in annual change in lung function associated with each flavonoid subclass, categorized into quartiles, in linear mixed-effects regression models after adjustment for lifestyle and dietary confounders.Results: Strong inverse associations were found between anthocyanin intake and age-related decline in lung function. Independent of dietary and nondietary risk factors, slower rates of FEV1 and FVC decline by 23.6 (95% CI: 16.6, 30.7) and 37.3 (95% CI: 27.8, 46.8) mL/y, respectively, were observed in participants in the fourth quartile of intake compared with participants in the first quartile (P-trend < 0.0001). The protective associations observed for anthocyanin intake were present in both current/former and never smokers. Compared with no or very low intakes, an intake of ≥2 servings of anthocyanin-rich blueberries/wk was associated with slower decline in FEV1 and FVC by 22.5 (95% CI: 10.8, 34.2) and 37.9 (95% CI: 22.1, 53.7) mL/y, respectively. To a lesser extent, higher flavan-3-ol intake was also associated with slower lung function decline.Conclusions: An attenuation of age-related lung function decline was associated with higher dietary anthocyanin intake in this longitudinal sample of predominantly elderly men. Further prospective studies are needed to confirm these novel associations.

Mannose-binding lectin 2 gene polymorphism and lung damage in primary ciliary dyskinesia.

Mannose-binding lectin (MBL) plays an important role in innate immunity and has been reported to be associated with the age-related decline in lung function in cystic fibrosis. MBL polymorphisms are associated with lung function decline in Primary Ciliary Dyskinesia (PCD). We performed sputum microbiology, spirometry pre- and post-administration of salbutamol, ciliary motion analysis, ultrastructural assessment of cilia, ciliogenesis in culture, and chest high resolution computed tomography in children with a clinical history of respiratory tract infections and/or presence of bronchiectasis suggestive of PCD or secondary ciliary dyskinesia (SCD). All subjects were evaluated for single nucleotide polymorphisms in the gene encoding MBL-2. The diagnosis of PCD was established in 45 subjects, while in the remaining 53 the diagnosis was SCD. A significant bronchodilator response was observed only in PCD associated with the MBL2-3 genotype, which is known to be associated with low/undetectable MBL serum levels. Also, bronchiectasis severity was significantly greater in subjects with MBL2-3 in both PCD and SCD. No other association was found between MBL genotypes and clinical findings. MBL plays a relatively minor role as a disease modifier in PCD. A similar finding in SCD supports the likely significance of this result.

(509) - Age-Related Decline in Lung Function in Patients Without CLAD After Double Lung Transplantation

This improvement was maintained at both 1 and 3 years post-conversion (p< 0.001). In regards to pulmonary function, FEV1 decreased from the time of sirolimus initiation to 3 years post-conversion (p= 0.042), mean decrease 0.23 L (95% CI, 0.01-0.46). However, early conversion to sirolimus (< 6 months post-transplant) resulted in a trend towards improved FEV1 at 3 years (+0.017 L in the early conversion group versus -0.44 L in the late conversion group, p= 0.052). The sirolimus discontinuation rate for reasons other than death was 17.8%. Conclusion: Sirolimus is a viable immunosuppressant option after lung transplant, which successfully allows for the reduction or withdrawal of the CNI, resulting in sustained improvement in renal function. The antifibrotic properties of sirolimus may allow it to slow the progression of BOS, especially when initiated within the first 6 months of transplant.

Follow-up on genome-wide main effects: Do polymorphisms modify the air pollution effect on lung function decline in adults?

Improved air quality has been found associated with attenuated age-related decline in lung function. But whether genetic polymorphisms strongly associated with lung function play a modifying role in this attenuation process has so far not been investigated.We selected ten single nucleotide polymorphisms derived from the largest genome-wide association studies on lung function and examined whether they modified the association between the change in exposure to particulate matter ≤10μm (ΔPM10) and lung function decline. 4310 participants from the SAPALDIA cohort provided valid spirometry measurements, a detailed pulmonary health questionnaire both at baseline and 11years later as well as blood samples for genetic testing. Spatially and temporally resolved air pollution exposures were assigned on an individual level based on participants' residences.Statistically significant interactions of moderate strength with ΔPM10 were detected for rs2284746. Individuals with the CC genotype had a 21ml slower annual decline of the mid expiratory flow per 10μg/m3 PM10 reduction over an 10-year period, while the benefits of CG and GG carriers were smaller (14 and 7ml per year, respectively; Pinteraction=0.04). The attenuated annual decline in the percentage of the forced expiratory volume in one second relative to the forced vital capacity (FEV1/FVC) was also increased with the presence of each C-allele (Pinteraction=0.009). We observed further suggestive interactions of similar magnitude in never-smokers, but none of the results would remain statistically significant after correction for multiple testing.We could not find strong evidence that lung function benefits from improved air quality are modified by polymorphisms associated with lung function level in large meta-analyzed genome-wide association studies.

GENOME-WIDE INTERACTION STUDY OF CUMULATIVE PARTICULATE MATTER EXPOSURE ON AGE-RELATED LUNG FUNCTION DECLINE IN ADULTS, THE SAPALDIA COHORT.

Background and Aims: Air pollution exposure accelerates age-related lung function decline. There is however evidence that i) genetic variation in individuals determines the susceptibility to ambien...

Pleiotropic Effects of Statins

Evidence is mounting that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have a number of pleiotropic effects over and above their lipid-lowering properties in patients with cardiovascular disease and heart failure. In addition to lowering low-density lipoprotein cholesterol and triglyceride levels, several studies have shown statins to improve survival and reduce the risk of major cardiovascular events in patients without established cardiovascular disease but with cardiovascular risk factors. Statins have also been shown to have beneficial effects, including a reduction in all-cause mortality, in patients with ischemic and non-ischemic congestive heart failure, and have been associated with a reduced incidence of atrial fibrillation. Furthermore, statins have been associated with improvements in renal function in patients with pre-existing renal disease or the prevention of new-onset renal dysfunction, as well as improvements in lung function in patients with chronic obstructive pulmonary disease or age-related decline in lung function. The pleiotropic effects of statins appear to result from improvements in endothelial function, a reduction in inflammatory mediators, a decline in the development of atheroma through the stabilization of atheromatous plaques, and the inhibition of cardiac hypertrophy through an antioxidant mechanism. Long-term statin use may reduce morbidity and mortality rates in a broad range of patients, and most patients at high risk of cardiovascular disease may benefit from statin treatment; however, further data are required to demonstrate conclusively whether these trends are truly independent of the lipid-lowering effects of statins.

HMOX1 and GST variants modify attenuation of FEF25-75% decline due to PM10 reduction

Reduced exposure to particulate matter with a 50% cut-off aerodynamic diameter of 10 microm (PM(10)) attenuated age-related lung function decline in our cohort, particularly in the small airways. We hypothesised that polymorphisms in glutathione S-transferase (GST) and haem oxygenase-1 (HMOX1) genes, important for oxidative stress defence, modify these beneficial effects. A population-based sample of 4,365 adults was followed up after 11 yrs, including questionnaire, spirometry and DNA blood sampling. PM(10) exposure was estimated by dispersion modelling and temporal interpolation. The main effects on annual decline in forced expiratory flow at 25-75% of forced vital capacity (FEF(25-75%)) and interactions with PM(10) reduction were investigated for polymorphisms HMOX1 rs2071746 (T/A), rs735266 (T/A) and rs5995098 (G/C), HMOX1 (GT)(n) promoter repeat, GSTM1 and GSTT1 deletions, and GSTP1 p.Ile105Val, using mixed linear regression models. HMOX1 rs5995098, HMOX1 haplotype TTG and GSTP1 showed significant genetic main effects. Interactions with PM(10) reduction were detected: a 10 microg.m(-3) reduction significantly attenuated annual FEF(25-75%) decline by 15.3 mL.s(-1) only in the absence of HMOX1 haplotype ATC. Similarly, carriers of long (GT)(n) promoter repeat alleles or the GSTP1 Val/Val genotype profited significantly more from a 10 microg.m(-3) reduction (26.5 mL.s(-1) and 27.3 mL.s(-1) respectively) than non-carriers. Benefits of a reduction in PM(10) exposure are not equally distributed across the population but are modified by the individual genetic make-up determining oxidative stress defence.

Decreased PM 10 Exposure Attenuates Age-Related Lung Function Decline: Genetic Variants in p53 , p21 , and CCND1 Modify This Effect

BackgroundDecreasing exposure to airborne particulates was previously associated with reduced age-related decline in lung function. However, whether the benefit from improved air quality depends on genetic background is not known. Recent evidence points to the involvement of the genes p53 and p21 and of the cell cycle control gene cyclin D1 (CCND1) in the response of bronchial cells to air pollution.ObjectiveWe determined in 4,326 participants of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) whether four single-nucleotide polymorphisms in three genes [CCND1 (rs9344 [P242P], rs667515), p53 (rs1042522 [R72P]), and p21 (rs1801270 [S31R])] modified the previously observed attenuation of the decline in the forced expiratory flow between 25% and 75% of the forced vital capacity (FEF25–75) associated with improved air quality.MethodsSubjects of the prospective population-based SAPALDIA cohort were assessed in 1991 and 2002 by spirometry, questionnaires, and biological sample collection for genotyping. We assigned spatially resolved concentrations of particulate matter with aerodynamic diameter ≤ 10 μm (PM10) to each participant’s residential history 12 months before the baseline and follow-up assessments.ResultsThe effect of diminishing PM10 exposure on FEF25–75 decline appeared to be modified by p53 R72P, CCND1 P242P, and CCND1 rs667515. For example, a 10-μg/m3 decline in aver-age PM10 exposure over an 11-year period attenuated the average annual decline in FEF25–75 by 21.33 mL/year (95% confidence interval, 10.57–32.08) among participants homozygous for the CCND1 (P242P) GG genotype, by 13.72 mL/year (5.38–22.06) among GA genotypes, and by 6.00 mL/year (−4.54 to 16.54) among AA genotypes.ConclusionsOur results suggest that cell cycle control genes may modify the degree to which improved air quality may benefit respiratory function in adults.

The impact of diabetes and age on pulmonary function: Data from the National Health and Nutrition Examination Survey

Using data from NHANES III, we evaluated the effect of diabetes on the age-related decline in lung function. The Diabetes group ( n = 471) had significantly lower mean FEV 1 and FVC values than the No Diabetes group ( n = 4317), but pulmonary function declined with increasing age at a similar rate for both groups.

Telling smokers their “lung age” promoted successful smoking cessation

G Parkes Dr G Parkes, The Limes Surgery, Hoddesdon, Hertfordshire, UK; parkesko@hotmail.co.uk Does describing to patients how smoking has accelerated their age-related decline in lung function (“lung age”) increase smoking...

Reduced Exposure to PM10and Attenuated Age-Related Decline in Lung Function

Air pollution has been associated with impaired health, including reduced lung function in adults. Moving to cleaner areas has been shown to attenuate adverse effects of air pollution on lung function in children but not in adults. We conducted a prospective study of 9651 adults (18 to 60 years of age) randomly selected from population registries in 1990 and assessed in 1991, with 8047 participants reassessed in 2002. There was complete information on lung volumes and flows (e.g., forced vital capacity [FVC], forced expiratory volume in 1 second [FEV1], FEV1 as a percentage of FVC, and forced expiratory flow between 25 and 75% of the FVC [FEF25-75]), smoking habits, and spatially resolved concentrations of particulate matter that was less than 10 microm in aerodynamic diameter (PM10) from a validated dispersion model assigned to residential addresses for 4742 participants at both the 1991 and the 2002 assessments and in the intervening years. Overall exposure to individual home outdoor PM10 declined over the 11-year follow-up period (median, -5.3 mug per cubic meter; interquartile range, -7.5 to -4.2). In mixed-model regression analyses, with adjustment for confounders, PM10 concentrations at baseline, and clustering within areas, there were significant negative associations between the decrease in PM10 and the rate of decline in FEV1 (P=0.045), FEV1 as a percentage of FVC (P=0.02), and FEF25-75 (P=0.001). The net effect of a decline of 10 microg of PM10 per cubic meter over an 11-year period was to reduce the annual rate of decline in FEV1 by 9% and of FEF25-75 by 16%. Cumulative exposure in the interval between the two examinations showed similar associations. Decreasing exposure to airborne particulates appears to attenuate the decline in lung function related to exposure to PM10. The effects are greater in tests reflecting small-airway function.

Association between mannan-binding lectin and impaired lung function in cystic fibrosis may be age-dependent

An association between mannan-binding lectin (MBL) status and severity of lung function impairment in cystic fibrosis (CF) has been found in several studies, but not in others. To explore the possible basis for discrepancies in the literature, we related both MBL and L-ficolin concentrations to lung function and examined the results in relation to the age of the patients. For patients under 15 years of age, those with MBL < 200 ng/ml had better lung function than those with MBL > 200 ng/ml [median forced expiratory volume in 1 s (FEV(1)), 99% versus 83%; P = 0.05]. For patients over 15 years of age, those with MBL < 200 ng/ml had poorer lung function than those with MBL > 200 ng/ml (median FEV(1), 44% versus 55%; P = 0.1). Also, for the over 15-year-olds, the proportion of patients with FEV(1) values below the median was greater in the MBL-insufficient subgroup (P < 0.04). In other words, relative deficiency of MBL appears to accelerate the age-related decline in lung function in CF patients. No corresponding relationships could be found between L-ficolin concentration and lung function. These findings and interpretation lend support to the potential value of MBL replacement therapy in a small minority of cystic fibrosis patients.