scholarly journals Lung function trajectory and biomarkers in the Tasmanian longitudinal health study

2021 ◽  
pp. 00020-2021
Author(s):  
Dinh S. Bui ◽  
Alvar Agusti ◽  
Haydn Walters ◽  
Caroline Lodge ◽  
Jennifer L. Perret ◽  
...  

Background and objectiveDifferent lung function trajectories through life can lead to chronic obstructive pulmonary disease (COPD) in adulthood. This study investigates if circulating levels of biomarkers can differentiate those with accelerated (AD) from normal decline (ND) trajectories.MethodsThe Tasmanian Longitudinal Health Study (TAHS) is a general population study that measured spirometry and followed up participants from ages 7 to 53 years. Based on their FEV1 trajectories from age 7 to 53 years, this analysis included those with COPD at age 53 years (60 with AD and 94 with ND) and controls (C, n=720) defined as never smokers with an average FEV1 trajectory. Circulating levels of selected biomarkers determined at 53 and 45 years of age were compared between trajectories.ResultsResults showed that CC16 levels (an anti-inflammatory protein) were lower and CRP (a pro-inflammatory marker) higher in the AD than in the ND trajectory. Higher CC16 levels were associated with a decreased risk of belonging to the AD trajectory (OR=0.79 [0.63–0.98] per unit increase) relative to ND trajectory. Higher CRP levels were associated with an increased risk of belonging to the AD trajectory (OR=1.07 [1.00, 1.13] per unit increase). Levels of CC16 (AUC=0.69 [95%CI: 0.56–0.81], p=0.002), CRP (AUC=0.63 [0.53–0.72], p=0.01) and the combination of both (AUC=0.72 [0.60–0.83], p<0.001) were able to discriminate between the AD and ND trajectories. Other quantified biomarkers (IL4, IL5, IL6, IL10 and TNFα) were not significantly different between AD, ND and C.ConclusionsCirculating levels of CRP and CC16 measured in late adulthood identify different lung function trajectories (AD versus ND) leading to COPD at age 53 years.

Thorax ◽  
2017 ◽  
Vol 73 (8) ◽  
pp. 748-757 ◽  
Author(s):  
Camilla J Kobylecki ◽  
Signe Vedel-Krogh ◽  
Shoaib Afzal ◽  
Sune F Nielsen ◽  
Børge G Nordestgaard

BackgroundUrate is a strong antioxidant in plasma and may protect against lung function impairment. We tested the hypothesis that high plasma urate is causally associated with better lung function and low risk of respiratory symptoms and COPD.MethodsWe measured lung function and plasma urate in 114 979 individuals from the Copenhagen City Heart Study and the Copenhagen General Population Study and genotyped for SLC2A9 rs7442295 and ABCG2 rs2231142 variants, previously associated with high plasma urate, in 110 152 individuals.ResultsIn the two studies combined, multivariable-adjusted 100 µmol/L higher plasma urate was associated with −1.54% (95% CI −1.67 to −1.40) lower FEV1 % predicted and −1.57% (95% CI −1.69 to −1.44) lower FVC % predicted observationally; the corresponding estimates for genetically determined 100 µmol/L higher plasma urate were −0.46% (95% CI −1.17 to 0.25) and −0.40% (95% CI −1.03 to 0.23). High plasma urate was also associated with higher risk of respiratory symptoms; however, genetically determined high plasma urate was not associated with respiratory symptoms. Finally, we identified 14 151 individuals with COPD and found ORs of 1.08 (95% CI 1.06 to 1.11) for COPD observationally and 1.01 (95% CI 0.88 to 1.15) genetically per 100 µmol/L higher plasma urate.ConclusionHigh plasma urate was associated with worse lung function and higher risk of respiratory symptoms and COPD in observational analyses; however, genetically high plasma urate was not associated with any of these outcomes. Thus, our data do not support a direct causal relationship.


2019 ◽  
Vol 29 (2) ◽  
pp. 244-251
Author(s):  
Emilie C Risom ◽  
Katrine B Buggeskov ◽  
Ulla B Mogensen ◽  
Martin Sundskard ◽  
Jann Mortensen ◽  
...  

Abstract OBJECTIVES Although reduced lung function and chronic obstructive pulmonary disease (COPD) is associated with higher risk of death following cardiac surgery, preoperative spirometry is not performed routinely. The aim of this study was to investigate the relationship between preoperative lung function and postoperative complications in all comers for cardiac surgery irrespective of smoking or COPD history. METHODS Preoperative spirometry was performed in elective adult cardiac surgery patients. Airflow obstruction was defined as the ratio of forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio below the lower limit of normal (LLN) and reduced forced ventilatory capacity defined as FEV1 <LLN. RESULTS A history of COPD was reported by 132 (19%) patients; however, only 74 (56%) had spirometry-verified airflow obstruction. Conversely, 64 (12%) of the 551 patients not reporting a history of COPD had spirometry-verified airflow obstruction. The probability of death was significantly higher in patients with airflow obstruction (8.8% vs 4.5%, P = 0.04) and in patients with a FEV1 <LLN (8.7% vs 3.7%, P = 0.007). In the multivariate analysis were age [hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.0–2.5; P = 0.04], prolonged cardiopulmonary bypass time (HR 1.2, 95% CI 1.02–1.3; P = 0.03), reduced kidney function (HR 2.5, 95% CI 1.2–5.6; P = 0.02) and FEV1 <LLN (HR 2.4, 95% CI 1.1–5.2; P = 0.03) all independently associated with an increased risk of death. CONCLUSIONS Preoperative spirometry reclassified 18% of the patients. A reduced FEV1 independently doubled the risk of death. Inclusion of preoperative spirometry in routine screening of cardiac surgical patients may improve risk prediction and identify high-risk patients. Clinical trial registration number NCT01614951 (ClinicalTrials.gov).


2012 ◽  
Vol 44 (15) ◽  
pp. 754-763 ◽  
Author(s):  
Andrew J. Sandford ◽  
Deepti Malhotra ◽  
H. Marike Boezen ◽  
Mateusz Siedlinski ◽  
Dirkje S. Postma ◽  
...  

An oxidant-antioxidant imbalance in the lung contributes to the development of chronic obstructive pulmonary disease (COPD) that is caused by a complex interaction of genetic and environmental risk factors. Nuclear erythroid 2-related factor 2 (NFE2L2 or NRF2) is a critical molecule in the lung's defense mechanism against oxidants. We investigated whether polymorphisms in the NFE2L2 pathway affected the rate of decline of lung function in smokers from the Lung Health Study (LHS)( n = 547) and in a replication set, the Vlagtwedde-Vlaardingen cohort ( n = 533). We selected polymorphisms in NFE2L2 in genes that positively or negatively regulate NFE2L2 transcriptional activity and in genes that are regulated by NFE2L2. Polymorphisms in 11 genes were significantly associated with rate of lung function decline in the LHS. One of these polymorphisms, rs11085735 in the KEAP1 gene, was previously shown to be associated with the level of lung function in the Vlagtwedde-Vlaardingen cohort but not with decline of lung function. Of the 23 associated polymorphisms in the LHS, only rs634534 in the FOSL1 gene showed a significant association in the Vlagtwedde-Vlaardingen cohort with rate of lung function decline, but the direction of the association was not consistent with that in the LHS. In summary, despite finding several nominally significant polymorphisms in the LHS, none of these associations were replicated in the Vlagtwedde-Vlaardingen cohort, indicating lack of effect of polymorphisms in the NFE2L2 pathway on the rate of decline of lung function.


2021 ◽  
pp. 1-10
Author(s):  
Tian Xiao ◽  
Sara R.A. Wijnant ◽  
Silvan Licher ◽  
Natalie Terzikhan ◽  
Lies Lahousse ◽  
...  

Background: The etiology of dementia may partly be underpinned by impaired lung function via systemic inflammation and hypoxia. Objective: To prospectively examine the association between chronic obstructive pulmonary disease (COPD) and subclinical impairments in lung function and the risk of dementia. Methods: In the Rotterdam Study, we assessed the risk of incident dementia in participants with Preserved Ratio Impaired Spirometry (PRISm; FEV1/FVC≥0.7, FEV1 <  80%) and in participants with COPD (FEV1/FVC <  0.7) compared to those with normal spirometry (controls; FEV1/FVC≥0.7, FEV1≥80%). Hazard ratios (HRs) with 95%confidence intervals (CI) for dementia were adjusted for age, sex, education attainment, smoking status, systolic blood pressure, body mass index, triglycerides, comorbidities and Apolipoprotein E (APOE) genotype. Results: Of 4,765 participants, 110 (2.3%) developed dementia after 3.3 years. Compared to controls, participants with PRISm, but not COPD, had an increased risk for all-type dementia (adjusted HRPRISm 2.70; 95%CI, 1.53–4.75; adjusted HRCOPD 1.03; 95%CI, 0.61–1.74). These findings were primarily driven by men and smokers. Similarly, participants with FVC%predicted values in the lowest quartile compared to those in the highest quartile were at increased risk of all-type dementia (adjusted HR 2.28; 95%CI, 1.31–3.98), as well as Alzheimer’s disease (AD; adjusted HR 2.13; 95%CI, 1.13–4.02). Conclusion: Participants with PRISm or a low FVC%predicted lung function were at increased risk of dementia, compared to those with normal spirometry or a higher FVC%predicted, respectively. Further research is needed to elucidate whether this association is causal and how PRISm might contribute to dementia pathogenesis.


2011 ◽  
Vol 30 (5) ◽  
pp. 253-263 ◽  
Author(s):  
Ramzi Lakhdar ◽  
Sabri Denden ◽  
Jalel Knani ◽  
Nadia Leban ◽  
Houria Daimi ◽  
...  

Smoking is considered as the major causal factor of chronic obstructive pulmonary disease (COPD). Nevertheless, a minority of chronic heavy cigarette smokers develops COPD. This suggests important contribution of other factors such as genetic predisposing. Our objective was to investigate combined role of EPHX1, GSTP1, M1 and T1 gene polymorphisms in COPD risk, its phenotypes and lung function impairment. Prevalence of EPHX1, GSTP1, M1 and T1 gene polymorphisms were assessed in 234 COPD patients and 182 healthy controls from Tunisia. Genotypes of EPHX1 (Tyr113His; His139Arg) and GSTP1 (Ile105Val; Ala114Val) polymorphisms were performed by PCR-RFLP, while the deletion in GSTM1 and GSTT1 genes was determined using multiplex PCR. Analysis of combinations showed a significant association of 113His/His EPHX1/null-GSTM1 (OR = 4.07) and null-GSTM1/105Val/Val GSTP1 (OR = 3.56) genotypes with increased risk of COPD (respectively P=0.0094 and P=0.0153). The null-GSTM1/ null-GSTT1, 105Val/Val GSTP1/null GSTT1, 113His/His EPHX1/null-GSTM1 and null-GSTM1/105Val/Val GSTP1 genotypes were related to emphysema (respectively P = 0.01; P = 0.009; P = 0.008 and P = 0.001). Combination of 113His/His EPHX1/null-GSTM1 genotypes showed a significant association with the decrease of ΔFEV1 in patients (P = 0.028).In conclusion, our results suggest combined EPHX1, GSTP1, GSTM1 and GSTT1 genetic polymorphisms may play a significant role in the development of COPD, emphysema and decline of the lung function.


2015 ◽  
Vol 37 (4) ◽  
pp. 453-468 ◽  
Author(s):  
Alex Exuzides ◽  
Chris Colby ◽  
Andrew H. Briggs ◽  
David A. Lomas ◽  
Maureen P. M. H. Rutten-van Mölken ◽  
...  

Background. To develop statistical models predicting disease progression and outcomes in chronic obstructive pulmonary disease (COPD), using data from ECLIPSE, a large, observational study of current and former smokers with COPD. Methods. Based on a conceptual model of COPD disease progression and data from 2164 patients, associations were made between baseline characteristics, COPD disease progression attributes (exacerbations, lung function, exercise capacity, and symptoms), health-related quality of life (HRQoL), and survival. Linear and nonlinear functional forms of random intercept models were used to characterize these relationships. Endogeneity was addressed by time-lagging variables in the regression models. Results. At the 5% significance level, an exacerbation history in the year before baseline was associated with increased risk of future exacerbations (moderate: +125.8%; severe: +89.2%) and decline in lung function (forced expiratory volume in 1 second [FEV1]) (–94.20 mL per year). Each 1% increase in FEV1 % predicted was associated with decreased risk of exacerbations (moderate: –1.1%; severe: –3.0%) and increased 6-minute walk test distance (6MWD) (+1.5 m). Increases in baseline exercise capacity (6MWD, per meter) were associated with slightly increased risk of moderate exacerbations (+0.04%) and increased FEV1 (+0.62 mL). Symptoms (dyspnea, cough, and/or sputum) were associated with an increased risk of moderate exacerbations (+13.4% to +31.1%), and baseline dyspnea (modified Medical Research Council score ≥2 v. <2) was associated with lower FEV1 (–112.3 mL). Conclusions. A series of linked statistical regression equations have been developed to express associations between indicators of COPD disease severity and HRQoL and survival. These can be used to represent disease progression, for example, in new economic models of COPD.


2020 ◽  
Author(s):  
Ponrathi Athilingam ◽  
Andrew Bugajski ◽  
Usha Menon

UNSTRUCTURED Chronic obstructive pulmonary disease (COPD) predominantly affects older adults, and claimed 3 million lives in 2016, making it the third leading cause of death worldwide. Over 35 million Americans aged 40 or older have lung function consistent with diagnosable COPD. COPD and cardiovascular disease (CVD) have a bidirectional relationship, in that one is a risk factor for developing the other. National and international consortiums recommend early screening of adults at risk of COPD, such as those with CVD. Recommended screening strategies include screening tools to assess symptoms, medical history, and handheld spirometry. Handheld spirometry has high diagnostic accuracy and if impaired lung function is indicated, these patients are referred for pulmonary function testing (PFT), the diagnostic gold standard for COPD. However, there is no clinical consensus for pulmonary screening in people with CVD. Current knowledge relating to the prevalence and incidence of CVD in people with COPD and the mechanisms that underlie their coexistence is key in combating the global burden of COPD.


2021 ◽  
Vol 12 ◽  
pp. 204062232110159
Author(s):  
Jung Eun Yoo ◽  
Dahye Kim ◽  
Hayoung Choi ◽  
Young Ae Kang ◽  
Kyungdo Han ◽  
...  

Background: The aim of this study was to investigate whether physical activity, sarcopenia, and anemia are associated an with increased risk of tuberculosis (TB) among the older population. Methods: We included 1,245,640 66-year-old subjects who participated in the National Screening Program for Transitional Ages for Koreans from 2009 to 2014. At baseline, we assessed common health problems in the older population, including anemia and sarcopenia. The subjects’ performance in the timed up-and-go (TUG) test was used to predict sarcopenia. The incidence of TB was determined using claims data from the National Health Insurance Service database. Results: The median follow-up duration was 6.4 years. There was a significant association between the severity of anemia and TB incidence, with an adjusted hazard ratio (aHR) of 1.28 [95% confidence interval (CI), 1.20–1.36] for mild anemia and 1.69 (95% CI, 1.51–1.88) for moderate to severe anemia. Compared with those who had normal TUG times, participants with slow TUG times (⩾15 s) had a significantly increased risk of TB (aHR 1.19, 95% CI, 1.07–1.33). On the other hand, both irregular (aHR 0.88, 95% CI 0.83–0.93) and regular (aHR 0.84, 95% CI, 0.78–0.92) physical activity reduced the risk of TB. Male sex, lower income, alcohol consumption, smoking, diabetes, and asthma/chronic obstructive pulmonary disease increased the risk of TB. Conclusion: The risk of TB among older adults increased with worsening anemia, sarcopenia, and physical inactivity. Physicians should be aware of those modifiable predictors for TB among the older population.


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