Rate of Decline of FEV1 as a Biomarker of Survival?
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ABSTRACT:
SUBMITTER: Papi A
PROVIDER: S-EPMC7958510 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Rate of FEV1 decline in COPD is heterogeneous and the extent to which inhaled corticosteroids (ICS) influence the rate of decline is unclear. The majority of previous reviews have investigated specific ICS and non-ICS inhalers and have consisted of randomised control trials (RCTs), which have specific inclusion and exclusion criteria and short follow up times. We aimed to investigate the association between change in FEV1 and ICS-containing medications in COPD patients over longer follow up times.MEDLINE and EMBASE were searched and literature comparing change in FEV1 in COPD patients taking ICS-containing medications with patients taking non-ICS-containing medications were identified. Titles, abstract, and full texts were screened and information extracted using the PICO checklist. Risk of bias was assessed using the Cochrane Risk of Bias tool and a descriptive synthesis of the literature was carried out due to high heterogeneity of included studies.Seventeen studies met our inclusion criteria. We found that the difference in change in FEV1 in people using ICS and non-ICS containing medications depended on the study follow-up time. Shorter follow-up studies (1 year or less) were more likely to report an increase in FEV1 from baseline in both patients on ICS and in patients on non-ICS-containing medications, with the majority of these studies showing a greater increase in FEV1 in patients on ICS-containing medications. Longer follow-up studies (greater than 1 year) were more likely to report a decline in FEV1 from baseline in patients on ICS and in patients on non-ICS containing medications but rates of FEV1 decline were similar.Further studies are needed to better understand changes in FEV1 when ICS-containing medications are prescribed and to determine whether ICS-containing medications influence rate of decline in FEV1 in the long term. Results from inclusive trials and observational patient cohorts may provide information more generalisable to a population of COPD patients.
| S-EPMC6894275 | biostudies-literature
Project description:RationaleIdentification and validation of circulating biomarkers for lung function decline in COPD remains an unmet need.ObjectiveIdentify prognostic and dynamic plasma protein biomarkers of COPD progression.MethodsWe measured plasma proteins using SomaScan from two COPD-enriched cohorts, the Subpopulations and Intermediate Outcomes Measures in COPD Study (SPIROMICS) and Genetic Epidemiology of COPD (COPDGene), and one population-based cohort, Multi-Ethnic Study of Atherosclerosis (MESA) Lung. Using SPIROMICS as a discovery cohort, linear mixed models identified baseline proteins that predicted future change in FEV1 (prognostic model) and proteins whose expression changed with change in lung function (dynamic model). Findings were replicated in COPDGene and MESA-Lung. Using the COPD-enriched cohorts, Gene Set Enrichment Analysis (GSEA) identified proteins shared between COPDGene and SPIROMICS. Metascape identified significant associated pathways.Measurements and main resultsThe prognostic model found 7 significant proteins in common (p < 0.05) among all 3 cohorts. After applying false discovery rate (adjusted p < 0.2), leptin remained significant in all three cohorts and growth hormone receptor remained significant in the two COPD cohorts. Elevated baseline levels of leptin and growth hormone receptor were associated with slower rate of decline in FEV1. Twelve proteins were nominally but not FDR significant in the dynamic model and all were distinct from the prognostic model. Metascape identified several immune related pathways unique to prognostic and dynamic proteins.ConclusionWe identified leptin as the most reproducible COPD progression biomarker. The difference between prognostic and dynamic proteins suggests disease activity signatures may be different from prognosis signatures.
| S-EPMC11326337 | biostudies-literature
Project description:A study was undertaken to determine if quantitative CT estimates of lung parenchymal overinflation and airway dimensions in smokers with a normal forced expiratory volume in 1 s (FEV(1)) can predict the rapid decline in FEV(1) that leads to chronic obstructive pulmonary disease (COPD).Study participants (n = 143; age 45-72 years; 54% male) were part of a lung cancer screening trial, had a smoking history of >30 pack years and a normal FEV(1) and FEV(1)/forced vital capacity (FVC) at baseline (mean (SD) FEV(1) 99.4 (12.8)%, range 80.2-140.7%; mean (SD) FEV(1)/FVC 77.9 (4.4), range 70.0-88.0%). An inspiratory multislice CT scan was acquired for each subject at baseline. Custom software was used to measure airway lumen and wall dimensions; the percentage of the lung inflated beyond a predicted maximal lung inflation, the low attenuation lung area with an x ray attenuation lower than -950 HU and the size distribution of the overinflated lung areas and the low attenuation area were described using a cluster analysis. Multiple regression analysis was used to test the hypothesis that these CT measurements combined with other baseline characteristics might identify those who would develop an excessive annual decline in FEV(1).The mean (SD) annual change in FEV(1) was -2.3 (4.7)% predicted (range -23.0% to +8.3%). Multiple regression analysis revealed that the annual change in FEV(1)%predicted was significantly associated with baseline percentage overinflated lung area measured on quantitative CT, FEV(1)% predicted, FEV(1)/FVC and gender.Quantitative CT scan evidence of overinflation of the lung predicts a rapid annual decline in FEV(1) in smokers with normal FEV(1).
| S-EPMC3035577 | biostudies-literature
Project description:BackgroundMany microRNAs (miRNAs) have been associated with asthma and chronic obstructive pulmonary disease (COPD). Longitudinal lung function growth trajectories of children with asthma-normal growth, reduced growth (RG), early decline (ED), and RG with an ED (RGED)-have been observed, with RG and RGED associated with adverse outcomes, including COPD.ObjectiveOur aim was to determine whether circulating miRNAs from an early age in children with asthma would be prognostic of reduced lung function growth patterns over the next 16 years.MethodsWe performed small RNA sequencing on sera from 492 children aged 5 to 12 years with mild-to-moderate asthma from the CAMP clinical trial, who were subsequently followed for 12 to 16 years. miRNAs were assessed for differential expression between previously assigned lung function growth patterns.ResultsWe had 448 samples and 259 miRNAs for differential analysis. In a comparison of the normal and the most severe group (ie, normal growth compared with RGED), we found 1 strongly dysregulated miRNA, hsa-miR-145-5p (P < 8.01E-05). This miR was downregulated in both ED groups (ie, ED and RGED). We verified that miR-145-5p was strongly associated with airway smooth muscle cell growth in vitro.ConclusionOur results showed that miR-145-5p is associated with the ED patterns of lung function growth leading to COPD in children with asthma and additionally increases airway smooth muscle cell proliferation. This represents a significant extension of our understanding of the role of miR-145-5p in COPD and suggests that reduced expression of miR-145-5p is a risk factor for ED of long-term lung function.
| S-EPMC8184594 | biostudies-literature
Project description:BackgroundThe relationship between lung function decline and eosinophils and neutrophils has important therapeutic implications among asthmatics, but it has rarely been studied in large cohort studies.ObjectiveThe aim is to study the relationship between blood eosinophils and neutrophils and FEV1 decline in a long-term follow-up of a population-based adult asthma cohort.MethodsIn 2012-2014, an adult asthma cohort was invited to a follow-up including spirometry, blood sampling, and structured interviews, and n = 892 participated (55% women, mean age 59 y, 32-92 y). Blood eosinophils, neutrophils and FEV 1 decline were analyzed both as continuous variables and divided into categories with different cut-offs. Regression models adjusted for smoking, exposure to vapors, gas, dust, or fumes (VGDF), use of inhaled and oral corticosteroids, and other possible confounders were utilized to analyze the relationship between eosinophils and neutrophils at follow-up and FEV1 decline.ResultsThe mean follow-up time was 18 years, and the mean FEV 1 decline was 27 ml/year. The annual FEV1 decline was related to higher levels of both blood eosinophils and neutrophils at follow-up, but only the association with eosinophils remained when adjusted for confounders. Further, the association between FEV1 decline and eosinophils was stronger among those using ICS. With EOS <0.3 × 109/L as reference, a more rapid decline in FEV1 was independently related to EOS ≥0.4 × 109/L in adjusted analyses.Conclusions and clinical relevanceBesides emphasizing the importance of smoking cessation and reduction of other harmful exposures, our real-world results indicate that there is an independent relationship between blood eosinophils and FEV1 decline among adults with asthma.
| S-EPMC7082214 | biostudies-literature
Project description:Model-based meta-analysis (MBMA) is an approach that integrates relevant summary level data from heterogeneously designed randomized controlled trials (RCTs). This study not only evaluated the predictability of a published MBMA for forced expiratory volume in one second (FEV1) and its link to annual exacerbation rate in patients with chronic obstructive pulmonary disease (COPD) but also included data from new RCTs. A comparative effectiveness analysis across all drugs was also performed. Aggregated level data were collected from RCTs published between July 2013 and November 2020 (n = 132 references comprising 156 studies) and combined with data used in the legacy MBMA (published RCTs up to July 2013 - n = 142). The augmented data (n = 298) were used to evaluate the predictive performance of the published MBMA using goodness-of-fit plots for assessment. Furthermore, the model was extended including drugs that were not available before July 2013, estimating a new set of parameters. The legacy MBMA model predicted the post-2013 FEV1 data well, and new estimated parameters were similar to those of drugs in the same class. However, the exacerbation model overpredicted the post-2013 mean annual exacerbation rate data. Inclusion of year when the study started on the pre-treatment placebo rate improved the model predictive performance perhaps explaining potential improvements in the disease management over time. The addition of new data to the legacy COPD MBMA enabled a more robust model with increased predictability performance for both endpoints FEV1 and mean annual exacerbation rate.
| S-EPMC10374752 | biostudies-literature
Project description:BackgroundThere is considerable heterogeneity in the rate of lung function decline in chronic obstructive pulmonary disease (COPD), the determinants of which are largely unknown. Observational studies in COPD indicate that low body mass index (BMI) is associated with worse outcomes, and overweight/obesity has a protective effect - the so-called "obesity paradox". We aimed to determine the relationship between BMI and the rate of FEV1 decline in data from published clinical trials in COPD.MethodsWe performed a systematic review of the literature, and identified 5 randomized controlled trials reporting the association between BMI and FEV1 decline. Four of these were included in the meta-analyses. We analyzed BMI in 4 categories: BMI-I (<?18.5 or?<? 20?kg/m2), BMI-II (18.5 or 20 to <?25?kg/m2), BMI-III (25 to <?29 or?<?30?kg/m2) and BMI-IV (?29 or???30?kg/m2). We then performed a meta-regression of all the estimates against the BMI category.ResultsThe estimated rate of FEV1 decline decreased with increasing BMI. Meta-regression of the estimates showed that BMI was significantly associated with the rate of FEV1 decline (linear trend p =?1.21?×?10-?5).ConclusionsThese novel findings support the obesity paradox in COPD: compared to normal BMI, low BMI is a risk factor for accelerated lung function decline, whilst high BMI has a protective effect. The relationship may be due to common but as-of-yet unknown causative factors; further investigation into which may reveal novel endotypes or targets for therapeutic intervention.
| S-EPMC6819522 | biostudies-literature
Project description:RationaleRescue/recovery work at the World Trade Center disaster site (WTC) caused a proximate decline in lung function in Fire Department of the City of New York firefighters. A subset of this cohort experienced an accelerated rate of lung function decline over 15 years of post-September 11, 2001 (9/11) follow-up.ObjectivesTo determine if early postexposure blood leukocyte concentrations are biomarkers for subsequent FEV1 decline and incident airflow limitation.MethodsIndividual rates of forced expiratory volume in 1 second (FEV1) change were calculated for 9,434 firefighters using 88,709 spirometric measurements taken between September 11, 2001, and September 10, 2016. We categorized FEV1 change rates into three trajectories: accelerated FEV1 decline (FEV1 loss >64 ml/yr), expected FEV1 decline (FEV1 loss between 0 and 64 ml/yr), and improved FEV1 (positive rate of change >0 ml/yr). Occurrence of FEV1/FVC less than 0.70 after 9/11 defined incident airflow limitation. Using regression models, we assessed associations of post-9/11 blood eosinophil and neutrophil concentrations with subsequent FEV1 decline and airflow limitation, adjusted for age, race, smoking, height, WTC exposure level, weight change, and baseline lung function.ResultsAccelerated FEV1 decline occurred in 12.7% of participants (1,199 of 9,434), whereas post-9/11 FEV1 improvement occurred in 8.3% (780 of 9,434). Higher blood eosinophil and neutrophil concentrations were each associated with accelerated FEV1 decline after adjustment for covariates (odds ratio [OR], 1.10 per 100 eosinophils/μl; 95% confidence interval [CI], 1.05-1.15; and OR, 1.10 per 1,000 neutrophils/μl; 95% CI, 1.05-1.15, respectively). Multivariable-adjusted linear regression models showed that a higher blood neutrophil concentration was associated with a faster rate of FEV1 decline (1.14 ml/yr decline per 1,000 neutrophils/μl; 95% CI, 0.69-1.60 ml/yr; P < 0.001). Higher blood eosinophil concentrations were associated with a faster rate of FEV1 decline in ever-smokers (1.46 ml/yr decline per 100 eosinophils/μl; 95% CI, 0.65-2.26 ml/yr; P < 0.001) but not in never-smokers (P for interaction = 0.004). Higher eosinophil concentrations were also associated with incident airflow limitation (adjusted hazard ratio, 1.10 per 100 eosinophils/μl; 95% CI, 1.04-1.15). Compared with the expected FEV1 decline group, individuals experiencing accelerated FEV1 decline were more likely to have incident airflow limitation (adjusted OR, 4.12; 95% CI, 3.30-5.14).ConclusionsHigher post-9/11 blood neutrophil and eosinophil concentrations were associated with subsequent accelerated FEV1 decline in WTC-exposed firefighters. Both higher blood eosinophil concentrations and accelerated FEV1 decline were associated with incident airflow limitation in WTC-exposed firefighters.
| S-EPMC5802620 | biostudies-literature
Project description:BackgroundLung transplantation (LTx) is frequently considered for patients with cystic fibrosis (CF) when the FEV1 reaches < 30%. This study estimated transplant-free survival for patients with CF and an FEV1 < 30% and identified predictors of death without LTx.MethodsWe conducted a retrospective cohort study using the CF Foundation Patient Registry from January 1, 2003 to December 31, 2013. Adult patients (? 18 years) with FEV1 < 30% prior to LTx were included. We performed Kaplan-Meier survival estimates censored at LTx. Multivariable Cox proportional hazard regression identified predictors of mortality.ResultsThere were 3,340 patients with an FEV1 < 30%. Death without LTx occurred in 1,250 patients (37.4%); 951 patients (28.5%) underwent LTx; 918 patients (27.5%) remained alive without LTx at the end of follow-up; and 221 patients (6.6%) were lost to follow-up. Median transplant-free survival after FEV1 < 30% was 6.6 years (95% CI, 5.9-7.0). Adjusted predictors of death without LTx included supplemental oxygen use (hazard ratio [HR], 2.1; 95% CI, 1.7-2.6), Burkholderia cepacia infection (HR, 1.8; 95% CI, 1.3-2.6), BMI ? 18 (HR, 1.6; 95% CI, 1.3-1.9), female sex (HR, 1.6; 95% CI, 1.2-2.0), CF-related diabetes in patients receiving insulin (HR, 1.4; 95% CI, 1.2-1.8), and ? one exacerbation per year (HR, 1.7; 95% CI, 1.3-2.2 vs. 0 exacerbations).ConclusionsMedian survival was > 6.5 years for patients with CF and an FEV1 < 30%, exceeding prior survival estimates. There was substantial heterogeneity in survival, with some patients with CF dying soon after reaching this lung function threshold and others living for many years. For this reason, we conclude that FEV1 < 30% remains an important marker of disease severity for patients with CF. Patients with a supplemental oxygen requirement or frequent exacerbations should have prompt referral because of their increased risk of death.
| S-EPMC5472512 | biostudies-literature
Project description:Purpose: The purpose of this study was to train and validate machine learning models for predicting rapid decline of forced expiratory volume in 1 s (FEV1) in individuals with a smoking history at-risk-for chronic obstructive pulmonary disease (COPD), Global Initiative for Chronic Obstructive Lung Disease (GOLD 0), or with mild-to-moderate (GOLD 1-2) COPD. We trained multiple models to predict rapid FEV1 decline using demographic, clinical and radiologic biomarker data. Training and internal validation data were obtained from the COPDGene study and prediction models were validated against the SPIROMICS cohort. Methods: We used GOLD 0-2 participants (n = 3,821) from COPDGene (60.0 ± 8.8 years, 49.9% male) for variable selection and model training. Accelerated lung function decline was defined as a mean drop in FEV1% predicted of > 1.5%/year at 5-year follow-up. We built logistic regression models predicting accelerated decline based on 22 chest CT imaging biomarker, pulmonary function, symptom, and demographic features. Models were validated using n = 885 SPIROMICS subjects (63.6 ± 8.6 years, 47.8% male). Results: The most important variables for predicting FEV1 decline in GOLD 0 participants were bronchodilator responsiveness (BDR), post bronchodilator FEV1% predicted (FEV1.pp.post), and CT-derived expiratory lung volume; among GOLD 1 and 2 subjects, they were BDR, age, and PRMlower lobes fSAD. In the validation cohort, GOLD 0 and GOLD 1-2 full variable models had significant predictive performance with AUCs of 0.620 ± 0.081 (p = 0.041) and 0.640 ± 0.059 (p < 0.001). Subjects with higher model-derived risk scores had significantly greater odds of FEV1 decline than those with lower scores. Conclusion: Predicting FEV1 decline in at-risk patients remains challenging but a combination of clinical, physiologic and imaging variables provided the best performance across two COPD cohorts.
| S-EPMC10161244 | biostudies-literature