Family History Is a Risk Factor for COPD

doi:10.1378/chest.10-2761

Chest

Volume 140, Issue 2, August 2011, Pages 343-350

https://doi.org/10.1378/chest.10-2761 Get rights and content

Background

Studies have shown that family history is a risk factor for COPD, but have not accounted for family history of smoking. Therefore, we sought to identify the effects of family history of smoking and family history of COPD on COPD susceptibility.

Methods

We compared 821 patients with COPD to 776 control smokers from the Genetic Epidemiology of COPD (COPDGene) Study. Questionnaires captured parental histories of smoking and COPD, as well as childhood environmental tobacco smoke (ETS) exposure. Socioeconomic status was defined by educational achievement.

Results

Parental history of smoking (85.5% case patients, 82.9% control subjects) was more common than parental history of COPD (43.0% case patients, 30.8% control subjects). In a logistic regression model, parental history of COPD (OR, 1.73; P < .0001) and educational level (OR, 0.48 for some college vs no college; P < .0001) were significant predictors of COPD, but parental history of smoking and childhood ETS exposure were not significant. The population-attributable risk from COPD family history was 18.6%. Patients with COPD with a parental history had more severe disease, with lower lung function, worse quality of life, and more frequent exacerbations. There were nonsignificant trends for more severe emphysema and airway disease on quantitative chest CT scans.

Conclusions

Family history of COPD is a strong risk factor for COPD, independent of family history of smoking, personal lifetime smoking, or childhood ETS exposure. Although further studies are required to identify genetic variants that influence COPD susceptibility, clinicians should question all smokers, especially those with known or suspected COPD, regarding COPD family history.

Section snippets

Study Subjects and Procedures

Study enrollment criteria and phenotype assessment, including chest CT scan protocols, have been described previously (www.copdgene.org).⁸ Briefly, the COPDGene Study enrolled self-identified non-Hispanic white and non-Hispanic black subjects aged 45 to 80 years with at least 10 pack-years of lifetime smoking history. Subjects were enrolled at 21 US clinical centers. Subjects with other diagnosed lung diseases except asthma and subjects with a first or second degree relative enrolled in the

Results

Among the first 2,500 subjects enrolled in the COPDGene Study, 821 COPD cases and 776 control smokers were included in the analysis. Subjects with GOLD stage I COPD (n = 212) or with unclassified patterns on spirometry (FEV₁ < 80% with FEV₁/FVC ≥ 0.7; n = 227) were excluded, because the clinical significance of these phenotypes was unclear.²³ Subjects with unknown parental history of COPD were excluded (n = 464). Among both subjects with COPD and control subjects, subjects with unknown parental

Discussion

In the COPDGene Study, a large, US, multicenter study of smokers with and without COPD, we found that subjects with a parental history of COPD had an increased risk of COPD, which was independent of parental history of smoking, personal lifetime smoking intensity, childhood ETS exposure, and in utero smoke exposure. Parental history of COPD may contribute to nearly 20% of the risk of COPD in the population. Subjects with a parental history of COPD had more severe disease, with lower lung

Conclusions

Despite these limitations, our data suggest that although there is some previously reported overlap in the genetic determinants of COPD and smoking behavior, there remain genetic influences on COPD that are independent of genetic effects on smoking. Genetic factors are also likely to affect COPD severity in terms of physiology, symptoms, and exacerbations. Plausible candidate genes for COPD and COPD-severity phenotypes have already been identified,3, 41, 42 and future work should focus on the

Acknowledgments

Author contributions: Dr Hersh takes full responsibility for the work represented in this manuscript.

Dr Hersh: contributed to the study concept and design, data collection and analysis, statistical support, and writing and editing of the manuscript.

Dr Hokanson: contributed to data collection and analysis, statistical support, and writing and editing of the manuscript.

Dr Lynch: contributed to data collection and writing and editing of the manuscript.

Dr Washko: contributed to data collection and

References (46)

CP Hersh et al.
Interobserver variability in the determination of upper lobe-predominant emphysema
Chest
(2007)
DE Niewoehner et al.
Risk indexes for exacerbations and hospitalizations due to COPD
Chest
(2007)
U Nihlén et al.
Influence of family history and smoking habits on the incidence of self-reported physician's diagnosis of COPD
Respir Med
(2004)
F Kueppers et al.
Familial prevalence of chronic obstructive pulmonary disease in a matched pair study
Am J Med
(1977)
MJ Hegewald et al.
Socioeconomic status and lung function
Chest
(2007)
DJ Berglund et al.
Respiratory symptoms and pulmonary function in an elderly nonsmoking population
Chest
(1999)
CP Hersh et al.
Chronic obstructive pulmonary disease
BD Patel et al.
Airway wall thickening and emphysema show independent familial aggregation in chronic obstructive pulmonary disease
Am J Respir Crit Care Med
(2008)
SG Pillai et al.
A genome-wide association study in chronic obstructive pulmonary disease (COPD): identification of two major susceptibility loci
PLoS Genet
(2009)
CI Amos et al.
Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1
Nat Genet
(2008)

RJ Hung et al.

A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25

Nature

(2008)

TE Thorgeirsson et al.

A variant associated with nicotine dependence, lung cancer and peripheral arterial disease

Nature

(2008)

N Caporaso et al.

Genome-wide and candidate gene association study of cigarette smoking behaviors

PLoS ONE

(2009)

EA Regan et al.

Genetic epidemiology of COPD (COPDGene) study design

COPD

(2010)

BG Ferris

Epidemiology Standardization Project (American Thoracic Society)

Am Rev Respir Dis

(1978)

PW Jones et al.

A self-complete measure of health status for chronic airflow limitation. The St. George's Respiratory Questionnaire

Am Rev Respir Dis

(1992)

American Thoracic Society

Standardization of spirometry, 1994 update

Am J Respir Crit Care Med

(1995)

DA Redelmeier et al.

Interpreting small differences in functional status: the six minute walk test in chronic lung disease patients

Am J Respir Crit Care Med

(1997)

RS Estépar et al.

Accurate airway wall estimation using phase congruency

Med Image Comput Comput Assist Interv

(2006)

EA Hoffman et al.

VIDA: an environment for multidimensional image display and analysis

Proc SPIE

(1992)

KF Rabe et al.

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary

Am J Respir Crit Care Med

(2007)

P Liberatos et al.

The measurement of social class in epidemiology

Epidemiol Rev

(1988)

JL Hankinson et al.

Spirometric reference values from a sample of the general U.S. population

Am J Respir Crit Care Med

(1999)

Cited by (43)

Early life exposures contributing to accelerated lung function decline in adulthood – a follow-up study of 11,000 adults from the general population
2023, eClinicalMedicine
We aimed to assess whether exposure to risk factors in early life from conception to puberty continue to contribute to lung function decline later in life by using a pooled cohort comprising approx. 11,000 adults followed for more than 20 years and with up to three lung function measurements.
Participants (20–68 years) in the ECRHS and NFBC1966 cohort studies followed in the periods 1991–2013 and 1997–2013, respectively, were included. Mean annual decline in maximum forced expired volume in 1 s (FEV₁) and forced vital capacity (FVC) were main outcomes. Associations between early life risk factors and change in lung function were estimated using mixed effects linear models adjusted for sex, age, FEV₁, FVC and height at baseline, accounting for personal smoking.
Decline in lung function was accelerated in participants with mothers that smoked during pregnancy (FEV₁ 2.3 ml/year; 95% CI: 0.7, 3.8) (FVC 2.2 ml/year; 0.2, 4.2), with asthmatic mothers (FEV₁ 2.6 ml/year; 0.9, 4.4) (FEV₁/FVC 0.04 per year; 0.04, 0.7) and asthmatic fathers (FVC 2.7 ml/year; 0.5, 5.0), and in women with early menarche (FVC 2.4 ml/year; 0.4, 4.4). Personal smoking of 10 pack-years contributed to a decline of 2.1 ml/year for FEV₁ (1.8, 2.4) and 1.7 ml/year for FVC (1.3, 2.1). Severe respiratory infections in early childhood were associated with accelerated decline among ever-smokers. No effect-modification by personal smoking, asthma symptoms, sex or cohort was found.
Mothers’ smoking during pregnancy, parental asthma and early menarche may contribute to a decline of FEV₁ and FVC later in life comparable to smoking 10 pack-years.
European Union's Horizon 2020; Research Council of Norway; Academy of Finland; University Hospital Oulu; European Regional Development Fund; Spanish Ministry of Science and Innovation; Generalitat de Catalunya.
Using a computer-tailored COPD screening assessment to promote advice-seeking behaviors
2021, World Allergy Organization Journal
Citation Excerpt :
However, adults with a family history of COPD reported expectations to speak with a healthcare provider but not to seek advice from other online resources. There is a genetic component to COPD (ie, alpha-1 antitrypsin deficiency) and having a family history is associated with more severe symptoms and breathing exacerbations.42 Also, the relationship between asthma and COPD is complex, as asthma is both a common misdiagnosis of COPD and a comorbid condition of COPD.43
Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and mortality, despite evidence there is a high proportion of underdiagnosis. Online screening assessments are low-cost solutions to identify high-risk adults who may benefit from confirmatory screening (ie, spirometry test). Little evidence exists to support whether high-risk adults seek advice after completing COPD screening assessments and from whom. The purpose of this study is to examine how the perceived quality of an online screening assessment influences high-risk adults to seek advice from a healthcare provider or other online resources.
Adults without a prior COPD diagnosis (N = 199) completed an online survey that included a computer-tailored assessment programmed with the clinically validated COPD Population Screener (COPD-PS).
An elevated COPD risk score was associated with expectations to talk with a healthcare provider (P < 0.05) or go on the Internet (P < 0.05) to get advice, controlling for statistically significant covariates. Positive perceptions about the quality of the risk score was associated with strengthened expectations to speak with a healthcare provider, but only among high-risk adults (P < 0.01).
Results of this study support the use of computer-tailored screening assessments as a scalable solution to encourage high-risk adults to learn more about COPD. Strengthened perceptions about the quality of an online COPD screening assessment increased the likelihood that high-risk adults will speak with their healthcare provider about the condition. Implications are discussed for leveraging telehealth solutions, such as conversational agents (ie, chatbots), to disseminate COPD screening assessments and alleviate its underdiagnosis.
not applicable
Hereditary pulmonary emphysema
2019, Emery and Rimoin's Principles and Practice of Medical Genetics and Genomics: Cardiovascular, Respiratory, and Gastrointestinal Disorders
Emphysema is included in the syndrome of chronic obstructive pulmonary disease (COPD). Alpha 1-antitrypsin (AAT) deficiency is a proven genetic determinant of COPD. However, only a small percentage of patients with COPD inherit severe AAT deficiency, and additional genetic factors likely influence the development of COPD. Further efforts in linkage analysis, association studies, and animal models may lead to the identification of such factors. Identification of genetic factors influencing the development of COPD and characterization of the interactions between genetic determinants and environmental factors could lead to new therapeutic interventions for COPD.
Analysis of influencing factors and a predictive model of small airway dysfunction in adults
2023, BMC Pulmonary Medicine
Lung Function Trajectories and Associated Mortality among Adults with and without Airway Obstruction
2023, American Journal of Respiratory and Critical Care Medicine
Lung volumes differentiate the predominance of emphysema versus airway disease phenotype in early COPD: an observational study of the COPDGene cohort
2023, ERJ Open Research

View all citing articles on Scopus

Funding/Support: This work was supported by the National Institutes of Health [Grants U01HL089856 (E. K. S.), U01HL089897 (J. D. C.), K08HL080242 (C. P. H.), R01HL094635 (C. P. H.)]; and a grant from the Alpha-1 Foundation (C. P. H.).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

^*: A complete list of the COPDGene Investigators can be found in e-Appendix 1.

View full text

Chest

Original ResearchCOPDFamily History Is a Risk Factor for COPD

Background

Methods

Results

Conclusions

Section snippets

Study Subjects and Procedures

Results

Discussion

Conclusions

Acknowledgments

Chest

Chest

Respir Med

Am J Med

Chest

Chest

Chronic obstructive pulmonary disease

Airway wall thickening and emphysema show independent familial aggregation in chronic obstructive pulmonary disease

Am J Respir Crit Care Med

A genome-wide association study in chronic obstructive pulmonary disease (COPD): identification of two major susceptibility loci

PLoS Genet

Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1

Nat Genet

A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25

Nature

A variant associated with nicotine dependence, lung cancer and peripheral arterial disease

Nature

Genome-wide and candidate gene association study of cigarette smoking behaviors

PLoS ONE

Genetic epidemiology of COPD (COPDGene) study design

COPD

Epidemiology Standardization Project (American Thoracic Society)

Am Rev Respir Dis

A self-complete measure of health status for chronic airflow limitation. The St. George's Respiratory Questionnaire

Am Rev Respir Dis

Standardization of spirometry, 1994 update

Am J Respir Crit Care Med

Interpreting small differences in functional status: the six minute walk test in chronic lung disease patients

Am J Respir Crit Care Med

Accurate airway wall estimation using phase congruency

Med Image Comput Comput Assist Interv

VIDA: an environment for multidimensional image display and analysis

Proc SPIE

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary

Am J Respir Crit Care Med

The measurement of social class in epidemiology

Epidemiol Rev

Spirometric reference values from a sample of the general U.S. population

Am J Respir Crit Care Med

Original Research
COPD
Family History Is a Risk Factor for COPD