Decreased PM10 Exposure Attenuates Age-Related Lung Function Decline: Genetic Variants in p53, p21, and CCND1 Modify This Effect

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Abstract

Background

Decreasing exposure to airborne particulates was previously associated with reduced age-related decline in lung function. However, whether the benefit from improved air quality depends on genetic background is not known. Recent evidence points to the involvement of the genes p53 and p21 and of the cell cycle control gene cyclin D1 ( CCND1) in the response of bronchial cells to air pollution.

Objective

We determined in 4,326 participants of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) whether four single-nucleotide polymorphisms in three genes [ CCND1 (rs9344 [P242P], rs667515), p53 (rs1042522 [R72P]), and p21 (rs1801270 [S31R])] modified the previously observed attenuation of the decline in the forced expiratory flow between 25% and 75% of the forced vital capacity (FEF _25–75) associated with improved air quality.

Methods

Subjects of the prospective population-based SAPALDIA cohort were assessed in 1991 and 2002 by spirometry, questionnaires, and biological sample collection for genotyping. We assigned spatially resolved concentrations of particulate matter with aerodynamic diameter ≤ 10 μm (PM ₁₀) to each participant’s residential history 12 months before the baseline and follow-up assessments.

Results

The effect of diminishing PM ₁₀ exposure on FEF _25–75 decline appeared to be modified by p53 R72P, CCND1 P242P, and CCND1 rs667515. For example, a 10-μg/m ³ decline in aver-age PM ₁₀ exposure over an 11-year period attenuated the average annual decline in FEF _25–75 by 21.33 mL/year (95% confidence interval, 10.57–32.08) among participants homozygous for the CCND1 (P242P) GG genotype, by 13.72 mL/year (5.38–22.06) among GA genotypes, and by 6.00 mL/year (−4.54 to 16.54) among AA genotypes.

Conclusions

Our results suggest that cell cycle control genes may modify the degree to which improved air quality may benefit respiratory function in adults.

Related collections

Most cited references 50

Record: found
Abstract: found
Article: not found

The European Community Respiratory Health Survey.

P. Burney, C Luczynska, S. Chinn … (1994)

The European Community Respiratory Health Survey (ECRHS) was planned to answer specific questions about the distribution of asthma and health care given for asthma in the European Community. Specifically, the survey is designed to estimate variations in the prevalence of asthma, asthma-like symptoms and airway responsiveness; to estimate variations in exposures to known or suspected risk factors for asthma, and assess to what extent these variations explain the variations in the prevalence of disease; and to estimate differences in the use of medication for asthma. The protocol provides specific instructions on the sampling strategy adopted by the survey teams, as well as providing instructions on the use of questionnaires, the tests for allergy, lung function measurements, tests of airway responsiveness, and blood and urine collection. The principal data collection sheets and questionnaires are provided in the appendices, together with information on coding and quality control. The protocol is published as a reference for those who wish to know more of the methods used in the study, and also to give other groups who wish to collect comparable data access to the detailed methodology.

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Reduced exposure to PM10 and attenuated age-related decline in lung function.

Christian Schindler, M Brutsche, Nino Künzli … (2007)

Air pollution has been associated with impaired health, including reduced lung function in adults. Moving to cleaner areas has been shown to attenuate adverse effects of air pollution on lung function in children but not in adults. We conducted a prospective study of 9651 adults (18 to 60 years of age) randomly selected from population registries in 1990 and assessed in 1991, with 8047 participants reassessed in 2002. There was complete information on lung volumes and flows (e.g., forced vital capacity [FVC], forced expiratory volume in 1 second [FEV1], FEV1 as a percentage of FVC, and forced expiratory flow between 25 and 75% of the FVC [FEF25-75]), smoking habits, and spatially resolved concentrations of particulate matter that was less than 10 microm in aerodynamic diameter (PM10) from a validated dispersion model assigned to residential addresses for 4742 participants at both the 1991 and the 2002 assessments and in the intervening years. Overall exposure to individual home outdoor PM10 declined over the 11-year follow-up period (median, -5.3 mug per cubic meter; interquartile range, -7.5 to -4.2). In mixed-model regression analyses, with adjustment for confounders, PM10 concentrations at baseline, and clustering within areas, there were significant negative associations between the decrease in PM10 and the rate of decline in FEV1 (P=0.045), FEV1 as a percentage of FVC (P=0.02), and FEF25-75 (P=0.001). The net effect of a decline of 10 microg of PM10 per cubic meter over an 11-year period was to reduce the annual rate of decline in FEV1 by 9% and of FEF25-75 by 16%. Cumulative exposure in the interval between the two examinations showed similar associations. Decreasing exposure to airborne particulates appears to attenuate the decline in lung function related to exposure to PM10. The effects are greater in tests reflecting small-airway function. Copyright 2007 Massachusetts Medical Society.

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Article: not found

Cigarette smoke induces cellular senescence.

G. Hunninghake, Toru Nyunoya, Jeffrey Cagley … (2006)

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States, and cigarette smoking is the major risk factor for COPD. Fibroblasts play an important role in repair and lung homeostasis. Recent studies have demonstrated a reduced growth rate for lung fibroblasts in patients with COPD. In this study we examined the effect of cigarette smoke extract (CSE) on fibroblast proliferative capacity. We found that cigarette smoke stopped proliferation of lung fibroblasts and upregulated two pathways linked to cell senescence (a biological process associated with cell longevity and an inability to replicate), p53 and p16-retinoblastoma protein pathways. We compared a single exposure of CSE to multiple exposures over an extended time course. A single exposure to CSE led to cell growth inhibition at multiple phases of the cell cycle without killing the cells. The decrease in proliferation was accompanied by increased ATM, p53, and p21 activity. However, several important senescent markers were not present in the cells at an earlier time point. When we examined multiple exposures to CSE, we found that the cells had profound growth arrest, a flat and enlarged morphology, upregulated p16, and senescence-associated beta-galactosidase activity, which is consistent with a classic senescent phenotype. These observations suggest that while a single exposure to cigarette smoke inhibits normal fibroblast proliferation (required for lung repair), multiple exposures to cigarette smoke move cells into an irreversible state of senescence. This inability to repair lung injury may be an essential feature of emphysema.

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Author and article information

Journal

Journal ID (nlm-ta): Environ Health Perspect

Title: Environmental Health Perspectives

Publisher: National Institute of Environmental Health Sciences

ISSN (Print): 0091-6765

ISSN (Electronic): 1552-9924

Publication date (Print): September 2009

Publication date (Electronic): 26 May 2009

Volume: 117

Issue: 9

Pages: 1420-1427

Affiliations

[1 ] Department of Chronic Disease Epidemiology, Institute of Social and Preventive Medicine and

[2 ] Institute of Medical Genetics, University of Zurich, Zurich, Switzerland

[3 ] Department of Environmental Health, Harvard School of Public Health, Boston, Massachussetts, USA

[4 ] Institute of Social and Preventive Medicine, University of Basel, Basel, Switzerland

[5 ] Department of Pneumology, University Hospital Zurich, Zurich, Switzerland

[6 ] Division of Pulmonary Medicine, University Hospitals Geneva, Geneva, Switzerland

Author notes

Address correspondence to N.M. Probst-Hensch, Department of Chronic Disease Epidemiology, Institute of Social and Preventive Medicine, Sumatrastrasse 30, CH-8006 Zurich, Switzerland. Telephone: 41-44-634-53-73. Fax: 41-44-634-40-09. E-mail: Nicole.Probst@ 123456ifspm.uzh.ch

The authors declare they have no competing financial interests.

Article

Publisher ID: ehp-117-1420

DOI: 10.1289/ehp.0800430

PMC ID: 2737020

PubMed ID: 19750108

SO-VID: f6dbe1a4-dbd6-414f-824b-debea64de914

Copyright © This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.

History

Date received : 27 November 2008

Date accepted : 26 May 2009

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