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The effect of HIV infection on longitudinal lung function decline among IDUs: a prospective cohort.

ABSTRACT: OBJECTIVE:As survival with HIV infection improves, HIV-infected individuals appear to be susceptible to development of chronic diseases, including restrictive and obstructive lung diseases. We sought to determine the independent association of HIV infection on lung function decline. DESIGN:Longitudinal analysis of the AIDS Linked to the Intravenous Experience study, an observational cohort of current and former IDUs. METHODS:Generalized estimating equations were used to determine the effects of markers of HIV infection on adjusted annual change in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). RESULTS:A total of 1064 participants contributed 4555 spirometry measurements over a median follow-up time of 2.75 years. The mean age of the cohort was 48 years; nearly, two-thirds were men and 85% current smokers. After adjustment, the overall annual decline of FEV1 and FVC between HIV-infected and uninfected persons did not differ. However, there was a 76?ml/year greater rate of decline in FEV1 and 86?ml/year greater rate of decline in FVC among HIV-infected participants with viral load more than 75?000?copies/ml compared with HIV-uninfected individuals (P?

SUBMITTER: Drummond MB

PROVIDER: S-EPMC3953568 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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The effect of HIV infection on longitudinal lung function decline among IDUs: a prospective cohort.

Drummond Michael Bradley MB Merlo Christian A CA Astemborski Jacquie J Kalmin Mariah M MM Kisalu Annamarie A Mcdyer John F JF Mehta Shruti H SH Brown Robert H RH Wise Robert A RA Kirk Gregory D GD

AIDS (London, England) 20130501 8

<h4>Objective</h4>As survival with HIV infection improves, HIV-infected individuals appear to be susceptible to development of chronic diseases, including restrictive and obstructive lung diseases. We sought to determine the independent association of HIV infection on lung function decline.<h4>Design</h4>Longitudinal analysis of the AIDS Linked to the Intravenous Experience study, an observational cohort of current and former IDUs.<h4>Methods</h4>Generalized estimating equations were used to det ...[more]

PMID: 23299176

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Project description:ObjectiveTo conduct a systematic review investigating the normal age-related changes in lung function in adults without known lung disease.DesignSystematic review.Data sourcesMEDLINE, 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.Eligibility criteriaWe 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.Data extraction and synthesisTwo authors independently determined the eligibility of studies, extracted data and assessed the risk of bias of included studies using the modified Newcastle-Ottawa Scale.ResultsFrom 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 (FEV1), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) with age. In studies with longer follow-up (>10 years), rates of FEV1 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 FEV1 change, however, were not observed between men and women. FEV1/FVC change was reported in only one study, declining by 0.29% per year. An age-specific analysis suggested the rate of FEV1 function decline may accelerate with each decade of age.ConclusionsLung function-FEV1, 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 FEV1/FVC thresholds to the disease definition of chronic obstructive pulmonary disease.Prospero registration numberCRD42018087066.

Project description:The Rationale: Molecular markers of disease activity that are predictive of forced vital capacity (FVC) progression in idiopathic pulmonary fibrosis are needed. Objectives: Develop a predictor using longitudinal within-patient gene expression differences (ΔGE) in peripheral blood mononuclear cells (PBMC) to predict of FVC progression. Methods: Patients in the training cohort (n=74) experiencing ≥10% relative reduction in FVC% of predicted over 12 months were categorized as progressors in contrast to the remaining stable patients. Baseline to 4-month within-patient ΔGE were correlated with FVC status. FVC-predictor genes were prioritized by two-group comparison with FDR<5%, logistic LASSO regression with p<0.05, and 10-Fold Cross-Validation with ≥50% support. Receiver operating characteristic with area under the curve (AUC) analyses were conducted in training subsets and independent validation cohorts from UChicago (n=27), UPMC (n=35), and Imperial (n=24) where different transcriptome assay platforms and varying transcriptome sampling times were used to derive ΔGE. Results: Intra-subject Compared to cross-sectional analysis of baseline GE, our longitudinal ΔGE variation approach demonstratedlargely reduced within-group sample variation and increased statistic power fin progressor and stable groups for prediction model development. A 25-gene FVC-predictor separated “progressors” from “stable” by Principal Component Analysis in the training and subsets of the training cohort. The resulting FVC-predictor consistently demonstrated high discriminatory performance independent of transcriptome assay platforms and varying sampling times in validation cohorts (AUC= 0.77-0.80). TGF beta was the highest-ranking canonical pathway by Gene Set Enrichment Analysis. Conclusions: Our novel short-term longitudinal within-patient ΔGE approach identified a FVC-predictor which may reflect disease activity and prove to be a reliable biomarker predictive of future FVC decline.

Dataset Information

The effect of HIV infection on longitudinal lung function decline among IDUs: a prospective cohort.

Publications

The effect of HIV infection on longitudinal lung function decline among IDUs: a prospective cohort.

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