Exposure to ambient particulate matter is associated with accelerated functional decline in idiopathic pulmonary fibrosis

BACKGROUND: Idiopathic pulmonary fibrosis (IPF), a progressive disease with an unknown pathogenesis, may be due in part to an abnormal response to injurious stimuli by alveolar epithelial cells. Air pollution and particulate inhalation of matter evoke a wide variety of pulmonary and systemic inflammatory diseases. We therefore hypothesized that increased average ambient particulate matter (PM) concentrations would be associated with an accelerated rate of decline in FVC in IPF. METHODS: We identified a cohort of subjects seen at a single university referral center from 2007 to 2013. Average concentrations of particulate matter < 10 and < 2.5 μg/m3 (PM10 and PM2.5, respectively) were assigned to each patient based on geocoded residential addresses. A linear multivariable mixed-effects model determined the association between the rate of decline in FVC and average PM concentration, controlling for baseline FVC at first measurement and other covariates. RESULTS: One hundred thirty-five subjects were included in the final analysis after exclusion of subjects missing repeated spirometry measurements and those for whom exposure data were not available. There was a significant association between PM10 levels and the rate of decline in FVC during the study period, with each μg/m3 increase in PM10 corresponding with an additional 46 cc/y decline in FVC (P = .008). CONCLUSIONS: Ambient air pollution, as measured by average PM10 concentration, is associated with an increase in the rate of decline of FVC in IPF, suggesting a potential mechanistic role for air pollution in the progression of disease

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

Genome-wide association analysis identifies six new loci associated with forced vital capacity

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10−8) with FVC in or near EFEMP1, BMP6, MIR129-2–HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

Penetrance of variants in monogenic disease and clinical utility of common polygenic variation has not been well explored on a large-scale. Here, the authors use exome sequencing data from 77,184 individuals to generate penetrance estimates and assess the utility of polygenic variation in risk prediction of monogenic variants

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease

Serum interleukin 6 is predictive of early functional decline and mortality in interstitial lung disease associated with systemic sclerosis

16siBiomarkers of progression of interstitial lung disease (ILD) are needed to allow early therapeutic intervention in patients with scleroderma-associated disease (SSc-ILD).reservedmixedDe Lauretis, Angelo; Sestini, Piersante; Pantelidis, Panagiotis; Hoyles, Rachel; Hansell, David M; Goh, Nicole S L; Zappala, Christopher J; Visca, Dina; Maher, Toby M; Denton, Christopher P; Ong, Voon H; Abraham, David J; Kelleher, Peter; Hector, Laureen; Wells, Athol U; Renzoni, Elisabetta ADe Lauretis, Angelo; Sestini, Piersante; Pantelidis, Panagiotis; Hoyles, Rachel; Hansell, David M; Goh, Nicole S. L; Zappala, Christopher J; Visca, Dina; Maher, Toby M; Denton, Christopher P; Ong, Voon H; Abraham, David J; Kelleher, Peter; Hector, Laureen; Wells, Athol U; Renzoni, Elisabetta A

Erratum: “Baseline characteristics of idiopathic pulmonary fibrosis: Analysis from the Australian Idiopathic Pulmonary Fibrosis Registry.” Helen E. Jo, Ian Glaspole, Christopher Grainge, Nicole Goh, Peter M.A. Hopkins, Yuben Moodley, Paul N. Reynolds, Sally Chapman, E. Haydn Walters, Christopher Zappala, Heather Allan, Gregory J. Keir, Andrew Hayen, Wendy A. Cooper, Annabelle M. Mahar, Samantha Ellis, Sacha Macansh and Tamera J. Corte (European Respiratory Journal (2017) 49 (1601592) DOI: 10.1183/13993003.01592-2016)

This article from the February 2017 issue of the European Respiratory Journal was published with an error in figure 5. The legend identifying “Anti-fibrotics” and “No anti-fibrotics” in figure 5c was mistakenly transposed in production. The figure has been corrected and is reproduced below. The article has been corrected and republished online