Longitudinal Lung Function Decline Research Articles

Is Adherence to the Healthy Eating Index – 2015 Associated with Rate of Decline in Lung Function

ObjectivesWe investigated the hypothesis that a healthier dietary pattern score is associated with higher lung function with stronger associations in smokers.MethodsWe studied participants in the Health, Aging, and Body Composition study (n = 2,549) and the Respiratory Ancillary Study (n = 2,866). Three dietary pattern scores, based on Healthy Eating Index 2015 (HEI-2015), Alternate Mediterranean Diet (AMED), and Dietary Approaches to Stop Hypertension (DASH), were calculated from FFQs. Associations between the 3 diet pattern scores and lung function [forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and FEV1/FVC] were estimated using linear mixed effects regression models. Stratified analyses were explored in never vs. ever smokers. Models were run within cohort and meta-analyzed results are presented.ResultsThe cross-sectional association of dietary pattern and lung function was estimated and a 1-point higher HEI-2015, AMED, and DASH score was associated with a 2 mL, 6 mL, and 6 mL, respectively, higher FEV1 (P < 0.05) at any point in the follow-up. Among ever smokers, the associations were stronger with effect sizes of 6 mL (P = 0.002), 25 mL (P < 0.001), and 7 mL (P < 0.001), respectively. There was little to no association of dietary pattern score and the longitudinal rate of decline in lung function. The findings for FVC were similar, with evidence of cross-sectional but not longitudinal associations. There was little to no association of dietary pattern with FEV1/FVC.ConclusionsWe found a positive cross-sectional association of dietary pattern score with lung function, but little to no association of dietary pattern with longitudinal decline in lung function. The cross-sectional associations were modified by smoking status such that a healthier dietary pattern had a stronger positive association with lung function in cigarette smokers.Funding SourcesThis research was supported by R01 HL149352 (PIs: PAC and DBH).

Quantitative CT metrics are associated with longitudinal lung function decline and future asthma exacerbations: Results from SARP-3

Currently, there is limited knowledge regarding which imaging assessments of asthma are associated with accelerated longitudinal decline in lung function. We aimed to assess whether quantitative computed tomography (qCT) metrics are associated with longitudinal decline in lung function and morbidity in asthma. We analyzed 205 qCT scans of adult patients with asthma and calculated baseline markers of airway remodeling, lung density, and pointwise regional change in lung volume (Jacobian measures) for each participant. Using multivariable regression models, we then assessed the association of qCT measurements with the outcomes of future change in lung function, future exacerbation rate, and changes in validated measurements of morbidity. Greater baseline wall area percent (β= -0.15 [95% CI= -0.26 to -0.05]; P< .01), hyperinflation percent (β= -0.25 [95% CI= -0.41 to -0.09]; P < .01), and Jacobian gradient measurements (cranial-caudal β= 10.64 [95% CI= 3.79-17.49]; P< .01; posterior-anterior β= -9.14, [95% CI= -15.49 to -2.78]; P< .01) were associated with more severe future lung function decline. Additionally, greater wall area percent (rate ratio= 1.06 [95% CI= 1.01-1.10]; P= .02) and air trapping percent (rate ratio=1.01 [95% CI= 1.00-1.02]; P= .03), as well as lower decline in the Jacobian determinant mean (rate ratio= 0.58 [95% CI= 0.41-0.82]; P< .01) and Jacobian determinant standard deviation (rate ratio= 0.52 [95% CI= 0.32-0.85]; P= .01), were associated with a greater rate of future exacerbations. However, imaging metrics were not associated with clinically meaningful changes in scores on validated asthma morbidity questionnaires. Baseline qCT measures of more severe airway remodeling, more small airway disease and hyperinflation, andless pointwise regional change in lung volumes were associated with future lung function decline and asthma exacerbations.

Longitudinal Evaluation of Lung Function in Gulf War I Veterans Exposed to Depleted Uranium.

Gulf War I (GWI) Veterans exposed to depleted uranium (DU) have undergone biennial surveillance to assess for DU-related health effects. No DU-specific respiratory effects have been observed cross-sectionally, but longitudinal lung function decline has not been assessed. A dynamic cohort of 71 Veterans underwent spirometry testing between 1999 and 2019. Longitudinal rates of decline of spirometry values were compared among Veterans with high versus low uranium levels using a linear mixed model. There was no significant difference in rate of decline of spirometry values between Veterans with high versus low uranium levels. The overall rate of decline was similar to that of the general population. In 20 years of follow-up, there does not appear to be an accelerated rate of decline of lung function among veterans exposed to depleted uranium.

A disease progression model of longitudinal lung function decline in idiopathic pulmonary fibrosis patients.

Pirfenidone and nintedanib are the first two FDA-approved therapies for treatment of idiopathic pulmonary fibrosis (IPF). The clinical programs for pirfenidone and nintedanib included 1132 patients in the placebo arms and 1691 patients in the treatment arms across 6 trials. We developed a disease progression model to characterize the observed variability in lung function decline, measured as percent predicted forced vital capacity (%p-FVC), and its decrease in decline after treatment. The non-linear longitudinal change in %p-FVC was best described by a Weibull function. The median decreased decline in %p-FVC after treatment was estimated to be 1.50% (95% CI [1.12, 1.79]) and 1.96% (95% CI [1.47, 2.36]) at week 26 and week 52, respectively. Smoking status, weight, %p-FVC, %p-DLco and oxygen use at baseline were identified as significant covariates affecting decline in %p-FVC. The decreased decline in %p-FVC were observed among all subgroups of interest, of which the effects were larger at 1year compared to 6months. Based on the disease progression model smoking status and oxygen use at baseline may affect the treatment effect size. At week 52, the decreased decline in %p-FVC for current smokers and patients with oxygen use at baseline were 1.56 (90% CI [1.02, 1.99]) and 2.32 (90% CI [1.74, 2.86]), respectively. These prognostic factors may be used to enrich studies with patients who are more likely to respond to treatment, by demonstrating a lesser decline in lung function, and therefore provide the potential to allow for IPF studies with smaller study populations or shorter durations.

DNA Methylation Is Predictive of Mortality in Current and Former Smokers.

Rationale: Smoking results in at least a decade lower life expectancy. Mortality among current smokers is two to three times as high as never smokers. DNA methylation is an epigenetic modification of the human genome that has been associated with both cigarette smoking and mortality.Objectives: We sought to identify DNA methylation marks in blood that are predictive of mortality in a subset of the COPDGene (Genetic Epidemiology of COPD) study, representing 101 deaths among 667 current and former smokers.Methods: We assayed genome-wide DNA methylation in non-Hispanic white smokers with and without chronic obstructive pulmonary disease (COPD) using blood samples from the COPDGene enrollment visit. We tested whether DNA methylation was associated with mortality in models adjusted for COPD status, age, sex, current smoking status, and pack-years of cigarette smoking. Replication was performed in a subset of 231 individuals from the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study.Measurements and Main Results: We identified seven CpG sites associated with mortality (false discovery rate < 20%) that replicated in the ECLIPSE cohort (P < 0.05). None of these marks were associated with longitudinal lung function decline in survivors, smoking history, or current smoking status. However, differential methylation of two replicated PIK3CD (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta) sites were associated with lung function at enrollment (P < 0.05). We also observed associations between DNA methylation and gene expression for the PIK3CD sites.Conclusions: This study is the first to identify variable DNA methylation associated with all-cause mortality in smokers with and without COPD. Evaluating predictive epigenomic marks of smokers in peripheral blood may allow for targeted risk stratification and aid in delivery of future tailored therapeutic interventions.

Association of urinary dimethylformamide metabolite with lung function decline: The potential mediating role of systematic inflammation estimated by C-reactive protein

Dimethylformamide (DMF) is a volatile organic compound listed as one of the four toxicants with the highest priority for human field study. However, the effect of DMF exposure on lung function and the underlying mechanisms remain unknown. We aimed to investigate the exposure-response relationship and possible mechanism between internal DMF exposure and lung function alteration. We studied 3701 Chinese adults from the Wuhan-Zhuhai cohort with a 3-year follow-up. The cross-sectional relationship between urinary biomarker of DMF exposure (N-Acetyl-S-(N-methylcarbamoyl)-L-cysteine, AMCC) and lung function, and the mediating role of plasma C-reactive protein (CRP) were assessed. We also convened a sub-cohort (N = 138) to assess the stability of AMCC in repeated urine samples collected for continuous 3 days and intervals of 1, 2 and 3 years. The longitudinal association between AMCC and lung function change in 3 years was further assessed. We found a dose-response relationship between AMCC and lung function reduction. Each 2-fold increase in AMCC was cross-sectionally associated with a 23.12-mL (95% CI: −36.68, −9.55) decrease in FVC and a 19.01-mL (95% CI: −31.08, −6.93) decrease in FEV1. Increased CRP significantly mediated 5.39% and 5.87% of the AMCC-associated FVC and FEV1 reductions, respectively. With 3-year follow-up, AMCC showed a fair to excellent stability (intra-class correlation coefficients were 0.88, 0.55, 0.60 and 0.50 for continuous 3 days, intervals of 1, 2 and 3 years, respectively) and was dose-dependently associated with longitudinal lung function decline. Compared with those with persistent low AMCC levels, participants with persistent high AMCC levels had a 101.09-mL/year (95% CI: −167.40, −34.77) decline in FVC and a 66.27-mL/year (95% CI: −114.14, −18.41) decline in FEV1 in the sub-cohort. Similar results were found in the full-cohort. Our findings suggest that exposure of general population to environmental DMF may impair lung function, and systematic inflammation may be an underlying mechanism.

Plasma Cathelicidin is Independently Associated with Reduced Lung Function in COPD: Analysis of the Subpopulations and Intermediate Outcome Measures in COPD Study Cohort.

The antimicrobial peptide cathelicidin, also known in humans as LL-37, is a defensin secreted by immune and airway epithelial cells. Deficiencies in this peptide may contribute to adverse pulmonary outcomes in chronic obstructive pulmonary disease (COPD). Using clinical and biological samples from the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS), we assessed the associations of plasma cathelicidin levels with cross-sectional and longitudinal COPD outcomes. A total of 1609 SPIROMICS participants with COPD and available plasma samples were analyzed. Cathelicidin was modeled dichotomously (lowest quartile [< 50 ng/ml] versus highest 75% [≥ 50 ng/ml]) and continuously per 10 ng/ml. Fixed-effect multilevel regression analyses were used to assess associations between cathelicidin and cross-sectional as well as longitudinal lung function. The associations between cathelicidin and participant-reported retrospective and prospective COPD exacerbations were assessed via logistic regression. Cathelicidin < 50 ng/ml (N=383) was associated with female sex, black race, and lower body mass index (BMI).At baseline,cathelicidin < 50 ng/ml was independently associated with 3.55% lower % predicted forced expiratory volume in 1 second (FEV1)(95% confidence interval [CI] -6.22% to -0.88% predicted; p=0.01), while every 10 ng/ml lower cathelicidin was independently associated with 0.65% lower % predicted FEV1 (95% CI -1.01% to -0.28% predicted; p< 0.001). No independent associations with longitudinal lung function decline or participant-reported COPD exacerbations were observed. Reduced cathelicidin is associated with lower lung function at baseline. Plasma cathelicidin may potentially identify COPD patients at increased risk for more severe lung disease.

Longitudinal decline in lung function: a community-based cohort study in Korea

Progressive decline in lung function is the hallmark of chronic obstructive pulmonary disease (COPD). We aimed to assess the rate of decline in forced expiratory volume in 1 second (FEV1) in patients from a community cohort database in Korea. 5,865 subjects aged 40–69 years from the Ansung-Ansan cohort database I–III (2001–2006) were included in this study. We assessed the annual rate of decline in FEV1 over time in relation to smoking status, patient sex, and presence or absence of pre-bronchodilator airflow limitation using a generalized additive mixed model. The mean follow-up duration was 3.8 years. The annual mean decline in FEV1 in the entire cohort was significantly more rapid for men than women (31.3 mL vs 27.0 mL, P = 0.003). Among men without pre-bronchodilator airflow limitation, annual mean declines in FEV1 were 31.5, 35.5, and 40.1 mL for never smokers, former smokers (P = 0.09 vs. never smokers), and current smokers (P < 0.001 vs. never smokers), respectively; and 23.4, 19.7, and 33.9 mL, respectively, for men with pre-bronchodilator airflow limitation. Thus, among Korean males, smoking accelerates lung function decline over time whereas smoking cessation slows the rate of FEV1 decline regardless of pre-bronchodilator airflow limitation. This underscores the importance of smoking cessation in Koreans.

Occupational exposure to solvents and lung function decline: A population based study

RationaleWhile cross-sectional studies have shown associations between certain occupational exposures and lower levels of lung function, there was little evidence from population-based studies with repeated lung function measurements.ObjectivesWe aimed to...

Metastable DNA methylation sites associated with longitudinal lung function decline and aging in humans: an epigenome-wide study in the NAS and KORA cohorts

ABSTRACTDNA methylation is an epigenetic regulator of gene transcription, which has been found to be both metastable and variable within human cohort studies. Currently, few studies have been done to identify metastable DNA methylation biomarkers associated with longitudinal lung function decline in humans. The identification of such biomarkers is important for screening vulnerable populations. We hypothesized that quantifiable blood-based DNA methylation alterations would serve as metastable biomarkers of lung function decline and aging, which may help to discover new pathways and/or mechanisms related to pulmonary pathogenesis. Using linear mixed models, we performed an Epigenome Wide Association Study (EWAS) between DNA methylation at CpG dinucleotides and longitudinal lung function (FVC, FEV1, FEF25–75%) decline and aging with initial discovery in the Normative Aging Study, and replication in the Cooperative Health Research in the Region of Augsburg cohort. We identified two metastable epigenetic loci associated with either poor lung function and aging, cg05575921 (AHRR gene), or lung function independently of aging, cg06126421 (IER3 gene). These loci may inform basic mechanisms associated with pulmonary function, pathogenesis, and aging. Human epigenomic variation, may help explain features of lung function decline and related pathophysiology not attributable to DNA sequence alone, such as accelerated pulmonary decline in smokers, former smokers, and perhaps non-smokers. Our EWAS across two cohorts, therefore, will likely have implications for the human population, not just the elderly.

Mixed graphical models for integrative causal analysis with application to chronic lung disease diagnosis and prognosis.

Integration of data from different modalities is a necessary step for multi-scale data analysis in many fields, including biomedical research and systems biology. Directed graphical models offer an attractive tool for this problem because they can represent both the complex, multivariate probability distributions and the causal pathways influencing the system. Graphical models learned from biomedical data can be used for classification, biomarker selection and functional analysis, while revealing the underlying network structure and thus allowing for arbitrary likelihood queries over the data. In this paper, we present and test new methods for finding directed graphs over mixed data types (continuous and discrete variables). We used this new algorithm, CausalMGM, to identify variables directly linked to disease diagnosis and progression in various multi-modal datasets, including clinical datasets from chronic obstructive pulmonary disease (COPD). COPD is the third leading cause of death and a major cause of disability and thus determining the factors that cause longitudinal lung function decline is very important. Applied on a COPD dataset, mixed graphical models were able to confirm and extend previously described causal effects and provide new insights on the factors that potentially affect the longitudinal lung function decline of COPD patients. The CausalMGM package is available on http://www.causalmgm.org. Supplementary data are available at Bioinformatics online.

Declining Lung Function and Cardiovascular Risk: The ARIC Study

BackgroundPulmonary dysfunction predicts incident cardiovascular disease (CVD). ObjectivesThe purpose of this study was to evaluate whether longitudinal decline in lung function is associated with incident heart failure (HF), coronary heart disease (CHD), and stroke. MethodsAmong 10,351 participants in the ARIC (Atherosclerosis Risk In Communities) study free of CVD, rapid lung function decline was defined as the greatest quartile (n = 2,585) of decline in either forced expiratory volume in 1 s (FEV1) (>1.9% decline/year) or forced vital capacity (FVC) (>2.1% decline/year) over 2.9 ± 0.2 years. The relationship between rapid decline in FEV1 or FVC and subsequent incident HF, CHD, stroke, or a composite of these was assessed using multivariable Cox regression adjusting for the baseline spirometry value, demographics, height, body mass index, heart rate, diabetes, hypertension, low-density lipoprotein, use of lipid-lowering medication, N-terminal fragment of prohormone for B-type natriuretic peptide, and smoking. ResultsThe mean age was 54 ± 6 years, 56% were women, and 81% were white. At 17 ± 6 years of follow-up, HF occurred in 14%, CHD 11%, stroke 6%, and the composite in 24%. Rapid decline in FEV1 and in FVC were both associated with a heightened risk of incident HF (hazard ratio [HR]: 1.17; 95% confidence interval [CI]: 1.04 to 1.33; p = 0.010; and HR: 1.27; 95% CI: 1.12 to 1.44; p < 0.001; respectively), with rapid decline in FEV1 most prognostic in the first year of follow-up (HR: 4.22; 95% CI: 1.34 to 13.26; p = 0.01). Rapid decline in FEV1 was also associated with incident stroke (HR: 1.25; 95% CI: 1.04 to 1.50; p = 0.015). ConclusionsA rapid decline in lung function, assessed by serial spirometry, is associated with a higher incidence of subsequent CVD, particularly incident HF.

Longitudinal decline in lung function among older construction workers

BackgroundOccupational exposures to vapours, gasses, dusts and fumes (VGDF) and chest X-ray abnormalities by the International Labour Office (ILO) classification system are associated with reduced lung function, with the majority...

Genetic variants affecting cross-sectional lung function in adults show little or no effect on longitudinal lung function decline.

BackgroundGenome-wide association studies have identified numerous genetic regions that influence cross-sectional lung function. Longitudinal decline in lung function also includes a heritable component but the genetic determinants have yet to be defined.ObjectivesWe aimed to determine whether regions associated with cross-sectional lung function were also associated with longitudinal decline and to seek novel variants which influence decline.MethodsWe analysed genome-wide data from 4167 individuals from the Busselton Health Study cohort, who had undergone spirometry (12 695 observations across eight time points). A mixed model was fitted and weighted risk scores were calculated for the joint effect of 26 known regions on baseline and longitudinal changes in FEV1 and FEV1/FVC. Potential additional regions of interest were identified and followed up in two independent cohorts.ResultsThe 26 regions previously associated with cross-sectional lung function jointly showed a strong effect on baseline lung function (p=4.44×10−16 for FEV1/FVC) but no effect on longitudinal decline (p=0.160 for FEV1/FVC). This was replicated in an independent cohort. 39 additional regions of interest (48 variants) were identified; these associations were not replicated in two further cohorts.ConclusionsPreviously identified genetic variants jointly have a strong effect on cross-sectional lung function in adults but little or no effect on the rate of decline of lung function. It is possible that they influence COPD risk through lung development. Although no genetic variants have yet been associated with lung function decline at stringent genome-wide significance, longitudinal change in lung function is heritable suggesting that there is scope for future discoveries.

Genetics and Genomics of Longitudinal Lung Function Patterns in Individuals with Asthma.

Patterns of longitudinal lung function growth and decline in childhood asthma have been shown to be important in determining risk for future respiratory ailments including chronic airway obstruction and chronic obstructive pulmonary disease. To determine the genetic underpinnings of lung function patterns in subjects with childhood asthma. We performed a genome-wide association study of 581 non-Hispanic white individuals with asthma that were previously classified by patterns of lung function growth and decline (normal growth, normal growth with early decline, reduced growth, and reduced growth with early decline). The strongest association was also measured in two additional cohorts: a small asthma cohort and a large chronic obstructive pulmonary disease metaanalysis cohort. Interaction between the genomic region encompassing the most strongly associated single-nucleotide polymorphism and nearby genes was assessed by two chromosome conformation capture assays. An intergenic single-nucleotide polymorphism (rs4445257) on chromosome 8 was strongly associated with the normal growth with early decline pattern compared with all other pattern groups (P = 6.7 × 10-9; odds ratio, 2.8; 95% confidence interval, 2.0-4.0); replication analysis suggested this variant had opposite effects in normal growth with early decline and reduced growth with early decline pattern groups. Chromosome conformation capture experiments indicated a chromatin interaction between rs4445257 and the promoter of the distal CSMD3 gene. Early decline in lung function after normal growth is associated with a genetic polymorphism that may also protect against early decline in reduced growth groups. Clinical trial registered with www.clinicaltrials.gov (NCT00000575).

Chronic obstructive pulmonary disease secondary to household air pollution.

Approximately 3 billion people around the world cook and heat their homes using solid fuels in open fires and rudimentary stoves, resulting in household air pollution. Household air pollution secondary to indoor combustion of solid fuel is associated with multiple chronic obstructive pulmonary disease (COPD) outcomes. The exposure is associated with both chronic bronchitis and emphysema phenotypes of COPD as well as a distinct form of obstructive airway disease called bronchial anthracofibrosis. COPD from household air pollution differs from COPD from tobacco smoke with respect to its disproportionately greater bronchial involvement, lesser emphysematous change, greater impact on quality of life, and possibly greater oxygen desaturation and pulmonary hypertensive changes. Interventions that decrease exposure to biomass smoke may decrease the risk for incident COPD and attenuate the longitudinal decline in lung function, but more data on exposure-response relationships from well-designed longitudinal studies are needed.

Association of Occupational Pesticide Exposure With Accelerated Longitudinal Decline in Lung Function

Cross-sectional studies have shown that occupational exposure to vapors, gases, dusts, and fumes (VGDF) and pesticides is associated with a lower level of lung function. These associations seem to be stronger in ever smokers. In the current study, we aimed to assess whether occupational exposure to VGDF and pesticides is associated with longitudinal decline in lung function. We used 12,772 observations from 2,527 participants in the Vlagtwedde-Vlaardingen Study, a general-population-based cohort study that followed subjects for 25 years, from 1965 to the last survey in 1989/1990. Job-specific exposure was estimated with the ALOHA+ job exposure matrix. Associations between exposures and annual changes in forced expiratory volume in 1 second (FEV1) and FEV1 as a percentage of inspiratory vital capacity (FEV1%VC) were assessed with linear mixed-effect models including sex, age, and level of lung function at the first measurement and pack-years of smoking at the last measurement. We tested for interaction between smoking and occupational exposure and assessed associations separately for never smokers and ever smokers. Exposure to VGDF was not associated with accelerated lung function decline after adjustment for co-exposure to pesticides. Exposure to pesticides, both in the last-held job and as a cumulative measure, was associated with accelerated decline in FEV1 and FEV1%VC, especially among ever smokers, where we found an excess change in FEV1 of -6.9 mL/year (95% confidence interval: -10.2, -3.7) associated with high pesticide exposure.

Increased rate of lung function decline in Australian adolescents with cystic fibrosis

Though baseline lung function as measured by spirometry in children with cystic fibrosis (CF) has improved, the annual rate of decline has not changed significantly during the critical period of adolescence. The aim of this study was to describe factors associated with longitudinal decline in lung function in a contemporary cohort of children with CF. Best annual lung function data from children attending the CF service of the Royal Children's Hospital Melbourne were reviewed to determine rate of decline in FEV(1) up until time of transfer to an adult center. Mixed models were used to determine the influence of age, sex, genotype, newborn screening, respiratory hospitalization, CF related diabetes mellitus (CFRD), pancreatic insufficiency, Pseudomonas aeruginosa (PsA) infection, and body mass index (BMI) on lung function decline. Longitudinal lung function data (range 5-20 years) were obtained for 98 patients with CF (55 male). Overall, the annual rate of decline in FEV(1) % predicted for the entire cohort was 1.4% per annum though the greatest rate of FEV1 decline was seen during adolescence (2.6%). Increasing age, homozygous ΔF508 genotype, CFRD, mucoid PsA infection, pancreatic insufficiency and respiratory hospitalizations were all significant predictors of FEV1 decline. FEV(1) declines at its sharpest rate during adolescence even in the presence of newborn screening. Genotype, increasing age, CFRD, PsA infection, pancreatic insufficiency and a greater number of respiratory hospitalizations are all associated with an increased rate of lung function decline in Australian children and adolescents with cystic fibrosis.

Longitudinal lung function decline among workers in a nitrate fertilizer production plant

This study examines the possible effect of exposure to aerosols and gases on lung function in a fertilizer plant in Norway. Dynamic lung volumes (FVC and FEV1) of 383 workers were measured in 2007 and 2010. During the follow-up period, most workers performed tasks with low exposure levels of acid aerosols and inorganic gases. The overall median inhalable and thoracic aerosol exposure levels were 1·1 and 0·21 mg/m(3), respectively. A questionnaire on respiratory symptoms was provided. During the follow-up period, there was an adjusted decrease of FEV1 of 18 ml/year (P<0·001). The respiratory symptoms score was low during follow-up. Work in this fertilizer industry may lead to an excessive lung function decline. We have, however, not been able to find any plausible exposure related explanation for the overall lung function decline.

The effect of HIV infection on longitudinal lung function decline among IDUs

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. Longitudinal analysis of the AIDS Linked to the Intravenous Experience study, an observational cohort of current and former IDUs. 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). 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 < 0.01). Similarly, HIV-infected individuals with CD4 cell count less than 100 cells/μl had a 57 ml/year more rapid decline in FEV1 and 86 ml/year more rapid decline in FVC than HIV-uninfected participants (P = 0.018 and P = 0.001, respectively). Markers of poorly controlled HIV disease are independently associated with accelerated annual lung function decline, with decrements in both FEV1 and FVC. These findings highlight the need for optimized HIV antiretroviral therapy in addition to smoking cessation among HIV-infected individuals with tobacco dependence.