scholarly journals IDENTIFICATION OF ADAMTS7 AND CEACAM19 AS CANDIDATE HEALTHY AGING ASSOCIATED GENES

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S102-S102
Author(s):  
Daniel S Evans ◽  
Steven R Cummings
Keyword(s):  
Lung Function ◽  
Cohort Studies ◽  
Multiple Testing ◽  
Healthy Aging ◽  
Forced Expiratory Volume ◽  
Healthy Human ◽  
Total N ◽  
Markers Of Inflammation ◽  
Translational Strategies ◽  
Funding Opportunities

Abstract The goals of the Longevity Genomics research group (www.longevitygenomics.org) are to develop translational strategies to promote healthy human aging based on findings from genomic studies of aging. Our investigation began with the previously reported and publicly available GWAS of the top 10% of parental lifespan in the UK Biobank, reported by Pilling et al. From five loci reported by Pilling et al., 61 candidate longevity-associated genes (LAGs) were identified using FUMA software. We then tested the 61 candidate genes for aging-related trait associations with tissue-specific predicted gene expression in cohort studies of elderly participants using PrediXcan. PrediXcan was applied to three longitudinal cohort studies of elderly individuals: Health ABC, MrOS, and SOF with a total N of 9893 participants. Aging outcomes tested for association were in the following categories: survival and lifespan, kidney function, cognitive function, physical performance tests, self-reported health and disability, diabetes-related traits, cardiovascular-related traits, lung function, and markers of inflammation. After correction for multiple testing, two genes were significantly associated with longevity-related outcomes. Predicted expression of CEACAM19 in the aorta was significantly associated with circulating C-reactive protein (CRP) levels. In addition, predicted expression of ADAMTS7 in the spleen was associated with a measure of lung function, the forced expiratory volume in the first second. Biological mechanisms for these associations are proposed, and our project provides funding opportunities for interested scientists to follow-up these results with laboratory studies (www.longevitygenomics.org/funding).

Longitudinal effects of aging on lung function at rest and exercise in healthy active fit elderly adults

1995 ◽  
Vol 78 (5) ◽  
pp. 1957-1968 ◽  
Author(s):  
S. R. McClaran ◽  
M. A. Babcock ◽  
D. F. Pegelow ◽  
W. G. Reddan ◽  
J. A. Dempsey
Keyword(s):  
Lung Function ◽  
Healthy Aging ◽  
Minute Ventilation ◽  
Forced Expiratory Volume ◽  
O2 Consumption ◽  
Expiratory Flow Limitation ◽  
Cross Sectional ◽  
Consumption Ratio ◽  
Longitudinal Effects ◽  
Effects Of Aging

We retested 18 healthy, active, and highly fit [maximal O2 consumption (VO2max) 201 +/- 12% of predicted] older adults over a 6-yr period (mean age 67-->73 yr) to determine the longitudinal effects of aging on lung function at rest and during exercise. In the 6-yr period, total lung capacity (TLC), functional residual capacity, and diffusion capacity did not change; vital capacity, forced expiratory volume in 1 s, and maximal volitional flow rates decreased; and residual volume and closing capacity/TLC increased 11-13%, all of which were greater than predicted from cross-sectional data. At maximum exercise over the 6-yr period, VO2max fell 11.2 +/- 3.4% (45.0-->40.3 ml.kg-1.min-1), six (of 18) subjects showed significant arterial hypoxemia (arterial O2 saturation < or = 92%), and maximum heart rate and minute ventilation-to-O2 consumption ratio (VF/VO2) were unchanged. At any given submaximal work rate, VE and breathing frequency were higher, the degree of expiratory flow limitation increased, and end-expiratory and end-inspiratory lung volumes were unchanged but remained significantly higher relative to young adults. We conclude that in contrast to implications from cross-sectional data, our longitudinal findings demonstrate that habitual physical activity and high aerobic capacity modify neither the normal deterioration in resting lung function nor the increased levels of ventilatory work during exercise that occur with healthy aging over the sixth and seventh decades of life.

scholarly journals Effect of TRPM8 and TRPA1 Polymorphisms on COPD Predisposition and Lung Function in COPD Patients

2021 ◽  
Vol 11 (2) ◽  
pp. 108
Author(s):  
Denis E. Naumov ◽  
Olesya O. Kotova ◽  
Dina A. Gassan ◽  
Ivana Y. Sugaylo ◽  
Evgeniya Y. Afanas’eva ◽  
...  
Keyword(s):  
Lung Function ◽  
Multiple Testing ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Bronchial Obstruction ◽  
Bronchodilator Response ◽  
Copd Patients

Certain transient receptor potential (TRP) channels including TRPM8 and TRPA1 are widely expressed in the respiratory tract and have been shown to be the receptors of cigarette smoke and particulate matter—the main causative factors of chronic obstructive pulmonary disease (COPD). The aim of the study was to investigate the effect of TRPM8 and TRPA1 polymorphisms on COPD predisposition and lung function in COPD patients. The study enrolled 143 COPD patients and 104 smokers with post-bronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) > 70%. Lung function was measured by spirometry. TRPM8 and TRPA1 polymorphisms were genotyped by LATE-PCR. None of the polymorphisms significantly influenced COPD predisposition after correction for covariates and multiple testing. Among COPD patients, the TT genotype of TRPA1 rs7819749 was significantly associated with higher degree of bronchial obstruction. In addition, we established that carriers of the C allele of TRPM8 rs11562975 more commonly had post-bronchodilator FEV1 < 60% (OR 3.2, 95%CI (1.14–8.94), p = 0.03) and revealed the effect of TRPA1 rs959976 and TRPM8 rs17865682 on bronchodilator response in COPD. Thus, the obtained results suggest possible involvement of TRPM8 and TRPA1 in COPD pathogenesis, indicating the necessity to further investigate their functional role in this pathology.

scholarly journals Dietary antioxidants and 10-year lung function decline in adults from the ECRHS survey

2017 ◽  
Vol 50 (6) ◽  
pp. 1602286 ◽  
Author(s):  
Vanessa Garcia-Larsen ◽  
James F. Potts ◽  
Ernst Omenaas ◽  
Joachim Heinrich ◽  
Cecilie Svanes ◽  
...  
Keyword(s):  
Lung Function ◽  
Multiple Testing ◽  
Vital Capacity ◽  
Respiratory Health ◽  
Forced Expiratory Volume ◽  
Lung Function Decline ◽  
Dietary Antioxidants ◽  
Food Frequency ◽  
Multivariable Analyses ◽  
The Relationship

The relationship between lung function decline and dietary antioxidants over 10 years in adults from three European countries was investigated.In 2002, adults from three participating countries of the European Community Respiratory Health Survey (ECRHS) answered a questionnaire and underwent spirometry (forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)), which were repeated 10 years later. Dietary intake was estimated at baseline with food frequency questionnaires (FFQ). Associations between annual lung function decline (mL) and diet (tertiles) were examined with multivariable analyses. Simes’ procedure was applied to control for multiple testing.A total of 680 individuals (baseline mean age 43.8±6.6 years) were included. A per-tertile increase in apple and banana intake was associated with a 3.59 mL·year−1 (95% CI 0.40, 7.68) and 3.69 mL·year−1 (95% CI 0.25, 7.14) slower decline in FEV1 and FVC, respectively. Tomato intake was also associated with a slower decline in FVC (4.5 mL·year−1; 95% CI 1.28, 8.02). Only the association with tomato intake remained statistically significant after the Simes’ procedure was performed. Subgroup analyses showed that apple, banana and tomato intake were all associated with a slower decline in FVC in ex-smokers.Intake of fruits and tomatoes might delay lung function decline in adults, particularly in ex-smokers.

scholarly journals THE LONGEVITY CONSORTIUM VISION

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S208-S209
Author(s):  
Daniel S Evans ◽  
Daniel S Evans ◽  
Steven R Cummings ◽  
Nicholas Schork
Keyword(s):  
Healthy Aging ◽  
Human Longevity ◽  
Cooperative Research ◽  
Healthy Human ◽  
Molecular Features ◽  
Human Lifespan ◽  
Age Related ◽  
Show Evidence ◽  
Funding Opportunities ◽  
Multiple Chronic Diseases

Abstract Molecular factors and pathways promoting human longevity and healthy aging can potentially delay or prevent multiple chronic diseases and conditions, but identifying such factors that can be pharmacologically targeted requires an integrated multidisciplinary approach. We describe the design of the five research projects and three cores of the Longevity Consortium (LC) and how their cooperative research is designed to discover molecular factors and pathways that can predict healthy human aging and longevity, associate with extreme human lifespan, show relevance to chronic age-related conditions, respond to interventions to slow aging in mice, and show evidence for association with lifespan across species. A systems biology approach is undertaken to identify common molecular features across human traits and organisms, and a chemoinformatics approach to link molecular targets to candidate healthy aging interventions. The LC results are made publicly available and we provide funding opportunities to the scientific community to support pilot projects.

No effect of artificial gravity on lung function with exercise training during head-down bed rest

2015 ◽  
pp. 1-7
Author(s):  
Longxiang Su ◽  
Yinghua Guo ◽  
Yajuan Wang ◽  
Delong Wang ◽  
Changting Liu
Keyword(s):  
Lung Function ◽  
Pulse Rate ◽  
Vital Capacity ◽  
Pulmonary Ventilation ◽  
Bed Rest ◽  
Forced Expiratory Volume ◽  
Observation Time ◽  
Artificial Gravity ◽  
Postural Changes ◽  
Expiratory Flow

AbstractTo explore the effectiveness of microgravity simulated by head-down bed rest (HDBR) and artificial gravity (AG) with exercise on lung function. Twenty-four volunteers were randomly divided into control and exercise countermeasure (CM) groups for 96 h of 6° HDBR. Comparisons of pulse rate, pulse oxygen saturation (SpO2) and lung function were made between these two groups at 0, 24, 48, 72, 96 h. Compared with the sitting position, inspiratory capacity and respiratory reserve volume were significantly higher than before HDBR (0° position) (P&lt; 0.05). Vital capacity, expiratory reserve volume, forced vital capacity, forced expiratory volume in 1 s, forced inspiratory vital capacity, forced inspiratory volume in 1 s, forced expiratory flow at 25, 50 and 75%, maximal mid-expiratory flow and peak expiratory flow were all significantly lower than those before HDBR (P&lt; 0.05). Neither control nor CM groups showed significant differences in the pulse rate, SpO2, pulmonary volume and pulmonary ventilation function over the HDBR observation time. Postural changes can lead to variation in lung volume and ventilation function, but a HDBR model induced no changes in pulmonary function and therefore should not be used to study AG CMs.

scholarly journals Clinical features and management of children with primary ciliary dyskinesia in England

2020 ◽  
Vol 105 (8) ◽  
pp. 724-729 ◽  
Author(s):  
Bruna Rubbo ◽  
Sunayna Best ◽  
Robert Anthony Hirst ◽  
Amelia Shoemark ◽  
Patricia Goggin ◽  
...  
Keyword(s):  
Lung Function ◽  
Hearing Impairment ◽  
Hearing Aids ◽  
Primary Ciliary Dyskinesia ◽  
Service Evaluation ◽  
Forced Expiratory Volume ◽  
Management Service ◽  
National Data ◽  
Randomised Controlled ◽  
Ciliary Dyskinesia

ObjectiveIn England, the National Health Service commissioned a National Management Service for children with primary ciliary dyskinesia (PCD). The aims of this study were to describe the health of children seen in this Service and compare lung function to children with cystic fibrosis (CF).DesignMulti-centre service evaluation of the English National Management PCD Service.SettingFour nationally commissioned PCD centres in England.Patients333 children with PCD reviewed in the Service in 2015; lung function data were also compared with 2970 children with CF.ResultsMedian age at diagnosis for PCD was 2.6 years, significantly lower in children with situs inversus (1.0 vs 6.0 years, p<0.001). Compared with national data from the CF Registry, mean (SD) %predicted forced expiratory volume in one second (FEV1) was 76.8% in PCD (n=240) and 85.0% in CF, and FEV1 was lower in children with PCD up to the age of 15 years. Approximately half of children had some hearing impairment, with 26% requiring hearing aids. Children with a lower body mass index (BMI) had lower FEV1 (p<0.001). One-third of children had positive respiratory cultures at review, 54% of these grew Haemophilus influenzae.ConclusionsWe provide evidence that children with PCD in England have worse lung function than those with CF. Nutritional status should be considered in PCD management, as those with a lower BMI have significantly lower FEV1. Hearing impairment is common but seems to improve with age. Well-designed and powered randomised controlled trials on management of PCD are needed to inform best clinical practice.

scholarly journals Poor Cognitive Function Is Associated with Obstructive Lung Diseases in Taiwanese Adults

2021 ◽  
Vol 18 (5) ◽  
pp. 2344
Author(s):  
Sun-Wung Hsieh ◽  
Da-Wei Wu ◽  
Chih-Wen Wang ◽  
Szu-Chia Chen ◽  
Chih-Hsing Hung ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Lung Function ◽  
Lung Diseases ◽  
Mmse Score ◽  
Multivariable Analysis ◽  
Forced Expiratory Volume ◽  
Normal Lung ◽  
Obstructive Lung Diseases ◽  
Normal Lung Function ◽  
Function Group

Previous studies have reported an association between the impairment of cognitive performance and lung diseases. However, whether obstructive or restrictive lung diseases have an impact on cognitive function is still inconclusive. We aimed to investigate the association between cognitive function and obstructive or restrictive lung diseases in Taiwanese adults using the Mini-Mental State Examination (MMSE). In this study, we used data from the Taiwan Biobank. Cognitive function was evaluated using the MMSE. Spirometry measurements of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained to assess lung function. Participants were classified into three groups according to lung function, namely, normal, restrictive, and obstructive lung function. In total, 683 patients enrolled, of whom 357 participants had normal lung function (52.3%), 95 had restrictive lung function (13.9%), and 231 had obstructive lung function (33.8%). Compared to the normal lung function group, the obstructive lung function group was associated with a higher percentage of cognitive impairment (MMSE < 24). In multivariable analysis, a low MMSE score was significantly associated with low FVC, low FEV1, and low FEV1/FVC. Furthermore, a low MMSE score was significantly associated with low FEV1 in the participants with FEV1/FVC < 70%, whereas MMSE was not significantly associated with FVC in the participants with FEV1/FVC ≥ 70%. Our results showed that a low MMSE score was associated with low FEV1, low FVC and low FEV1/FVC. Furthermore, a low MMSE score was associated with obstructive lung diseases but not with restrictive lung diseases.

scholarly journals Air Trapping Is Associated with Heterozygosity for Alpha-1 Antitrypsin Mutations in Patients with Asthma

Respiration ◽  
2021 ◽  
pp. 1-10
Author(s):  
Marina Aiello ◽  
Marianna Ghirardini ◽  
Laura Marchi ◽  
Annalisa Frizzelli ◽  
Roberta Pisi ◽  
...  
Keyword(s):  
Lung Function ◽  
Serum Concentration ◽  
Forced Expiratory Volume ◽  
Small Airway ◽  
University Hospital ◽  
Air Trapping ◽  
Asthmatic Patients ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin ◽  
Few Data

<b><i>Background:</i></b> Alpha-1 antitrypsin deficiency (AATD) is a hereditary disorder involving lungs, characterized by low serum concentration of the protein alpha-1 antitrypsin (AAT) also called proteinase inhibitor (PI). Asthma is common in AATD patients, but there are only few data on respiratory function in asthmatic patients with AATD. <b><i>Objectives:</i></b> The aim of the study was to evaluate lung function in asthmatic outpatients with mutation in the <i>SERPINA1</i> gene coding for AAT versus asthmatic subjects without mutation. <b><i>Methods:</i></b> We performed the quantitative analysis of the serum concentration of AAT in 600 outpatients affected by mild to moderate asthma from the University Hospital of Parma, Italy. Fifty-seven of them underwent the genetic analysis subsequently; they were subdivided into mutated and non-mutated subjects. All the mutated patients had a heterozygous genotype, except 1 (PI*SS). We assessed the lung function through a flow-sensing spirometer and the small airway parameters through an impulse oscillometry system. <b><i>Results:</i></b> The values of forced vital capacity (% predicted) and those of the residual volume to total lung capacity ratio (%) were, respectively, lower and higher in patients mutated versus patients without mutation, showing a significantly greater air trapping (<i>p =</i> 0.014 and <i>p =</i> 0.017, respectively). Moreover, patients with mutation in comparison to patients without mutation showed lower forced expiratory volume in 3 s (% predicted) and forced expiratory volume in 6 s (L) spirometric values, reflecting a smaller airways contribution. <b><i>Conclusions:</i></b> In asthmatic patients, heterozygosity for AAT with PI*MZ and PI*MS genotypes was associated with small airway dysfunction and with lung air trapping.

scholarly journals Prognostic and functional impact of perioperative LAMA/LABA inhaled therapy in patients with lung cancer and chronic obstructive pulmonary disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yoko Azuma ◽  
Atsushi Sano ◽  
Takashi Sakai ◽  
Satoshi Koezuka ◽  
Hajime Otsuka ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Chronic Obstructive Pulmonary Disease ◽  
Postoperative Complications ◽  
Lung Function ◽  
Retrospective Review ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Inhaled Therapy ◽  
Long Acting

Abstract Background Chronic obstructive pulmonary disease (COPD) is an important risk factor for postoperative complications and mortality. To determine the effects of perioperative combination therapy, using a long-acting muscarinic antagonist (LAMA) and a long-acting β2 agonist (LABA), on preoperative lung function, postoperative morbidity and mortality, and long-term outcome in COPD patients. Methods Between January 2005 and October 2019, 130 consecutive patients with newly diagnosed COPD underwent surgery for lung cancer. We conducted a retrospective review of their medical record to evaluate that LAMA/LABA might be an optimal regimen for patients with COPD undergoing surgery for lung cancer. All patients were received perioperative rehabilitation and divided into 3 groups according to the type of perioperative inhaled therapy and management: LAMA/LABA (n = 64), LAMA (n = 23) and rehabilitation only (no bronchodilator) (n = 43). We conducted a retrospective review of their medical records. Results Patients who received preoperative LAMA/LABA therapy showed significant improvement in lung function before surgery (p < 0.001 for both forced expiratory volume in 1 s (FEV1) and percentage of predicted forced expiratory volume in 1 s (FEV1%pred). Compared with patients who received preoperative LAMA therapy, patients with LAMA/LABA therapy had significantly improved lung function (ΔFEV1, LAMA/LABA 223.1 mL vs. LAMA 130.0 mL, ΔFEV1%pred, LAMA/LABA 10.8% vs. LAMA 6.8%; both p < 0.05). Postoperative complications were lower frequent in the LAMA/LABA group than in the LAMA group (p = 0.007). In patients with moderate to severe air flow limitation (n = 61), those who received LAMA/LABA therapy had significantly longer overall survival and disease-free survival compared with the LAMA (p = 0.049, p = 0.026) and rehabilitation-only groups (p = 0.001, p < 0.001). Perioperative LAMA/LABA therapy was also associated with lower recurrence rates (vs. LAMA p = 0.006, vs. rehabilitation-only p = 0.008). Conclusions We believe this treatment combination is optimal for patients with lung cancer and COPD.

scholarly journals Effect of mesenchymal stromal cell infusions on lung function in COPD patients with high CRP levels

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Daniel J. Weiss ◽  
Karen Segal ◽  
Richard Casaburi ◽  
Jack Hayes ◽  
Donald Tashkin
Keyword(s):  
Lung Function ◽  
Time Course ◽  
Inflammatory Marker ◽  
Controlled Trial ◽  
Phase 1 ◽  
Forced Expiratory Volume ◽  
Allogeneic Mscs ◽  
Copd Exacerbations ◽  
Copd Patients ◽  
Patient Reported

Abstract Background We previously reported a Phase 1/2 randomized placebo-controlled trial of systemic administration of bone marrow-derived allogeneic MSCs (remestemcel-L) in COPD. While safety profile was good, no functional efficacy was observed. However, in view of growing recognition of effects of inflammatory environments on MSC actions we conducted a post-hoc analysis with stratification by baseline levels of a circulating inflammatory marker, C-reactive protein (CRP) to determine the effects of MSC administration in COPD patients with varying circulating CRP levels. Methods Time course of lung function, exercise performance, patient reported responses, and exacerbation frequency following four monthly infusions of remestemcel-L vs. placebo were re-assessed in subgroups based on baseline circulating CRP levels. Results In COPD patients with baseline CRP ≥ 4 mg/L, compared to COPD patients receiving placebo (N = 17), those treated with remestemcel-L (N = 12), demonstrated significant improvements from baseline in forced expiratory volume in one second, forced vital capacity, and six minute walk distance at 120 days with treatment differences evident as early as 10 days after the first infusion. Significant although smaller benefits were also detected in those with CRP levels ≥ 2 or ≥ 3 mg/L. These improvements persisted variably over the 2-year observational period. No significant benefits were observed in patient reported responses or number of COPD exacerbations between treatment groups. Conclusion In an inflammatory environment, defined by elevated circulating CRP, remestemcel-L administration yielded at least transient meaningful pulmonary and functional improvements. These findings warrant further investigation of potential MSC-based therapies in COPD and other inflammatory pulmonary diseases. Trial registration: Clinicaltrials.gov NCT00683722.

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