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Mild and Moderate-to-Severe COPD in

Nonsmokers*
Distinct Demographic Profiles
Carolyn E. Behrendt, PhD

Study objective: To investigate the risk of COPD among nonsmokers.


Design: Case-control study, logistic regression analysis.
Setting: Third National Health and Nutrition Examination Survey, from 1988 to 1994.
Participants: Community residents 18 to 80 years of age, of white, black, or Mexican-American
ethnicity. Nonsmokers included never-smokers and former smokers with a < 5 pack-year
smoking history who had never smoked cigars or pipes.
Measurements: COPD (FEV1/FVC < 70%) was classified as mild (FEV1 > 80% predicted) or
moderate to severe (FEV1 23 to 79% predicted).
Results: Among 13,995 examinees, 51.3 0.4% were female, mean age was 42.2 0.4 years,
48.7 0.9% were nonsmokers, 8.8 0.3% had mild COPD, and 4.1 0.3% had moderate-to-
severe COPD [ SE]. One fourth of mild and moderate-to-severe cases were nonsmokers. Among
7,526 nonsmokers, 4.7 0.3% had mild COPD (n 403; age, 60.9 1.3 years) and were mostly
female (82.5%), while 1.9 0.3% had moderate-to-severe COPD (n 92, age 39.3 1.3) and
were mostly male (88.1%). Few nonsmokers with COPD (12.1 2.4%) had a previous diagnosis
of chronic bronchitis or emphysema. Among nonsmokers, physician-diagnosed asthma increased
the risk of mild and especially of moderate-to-severe COPD. Independently of asthma, risk of
mild COPD in nonsmokers increased with age (doubling every 12 years), before age 60 was lower
among men than women, and was inversely associated with current exposure to tobacco smoke at
home and at work. In contrast, the risk of moderate-to-severe COPD in nonsmokers was
markedly associated with male gender, peaked in middle age, and was inversely associated with
nonwhite ethnicity. COPD risks did not vary by minimal smoking history, longest-held occupa-
tion, urban residence, income, allergies, thyroid disease, or Helicobacter pylori antibody.
Conclusions: Among nonsmokers, mild and moderate-to-severe COPD are associated with asthma
but otherwise have distinct demographic profiles, suggesting that moderate-to-severe disease is
not a mere progression of mild COPD. (CHEST 2005; 128:1239 1244)

Key words: asthma; COPD; epidemiology; nonsmoker

Abbreviations: CI confidence interval; OR odds ratio

C tis,OPDemphysema,
most commonly refers to chronic bronchi-
and the subset of asthma char-
previous epidemiologic study2 of COPD in non-
smokers, prevalence is greater among women than
acterized by irreversible or partly reversible airflow men until the age of 60 years, when prevalence
obstruction.1 Although the majority of COPD occurs ceases to differ by sex. Neither urban residence nor
in current or former smokers, the disease also occurs occupational category is associated with COPD in
in persons who have never smoked. According to the nonsmokers.2 In the general population, COPD is
independently associated with smoking, age, and
*From Epidemiology, Pfizer Global Research and Development. asthma but not with atopy alone.3,4 In addition,
This work was performed at Pfizer La Jolla Laboratories, San
Diego, CA. genetic predisposition, environmental tobacco
Financial support was provided by Pfizer, Inc. smoke, air pollution, Helicobacter pylori infection,
Manuscript received October 7, 2004; revision accepted January and autoimmune thyroid disease have been pro-
29, 2005.
Reproduction of this article is prohibited without written permission posed as risk factors for COPD.59
from the American College of Chest Physicians (www.chestjournal. The possibility that risk factors for COPD differ
org/misc/reprints.shtml). according to the severity of disease has not been
Correspondence to: Carolyn Behrendt, PhD, 3413 Paseo del
Campo, Palos Verdes Estates, CA 90274; e-mail: carolynbehrendt@ investigated to date. Using data from a national
yahoo.com health examination, the current study identifies and

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compares risk factors for mild and moderate-to- COPD. In addition, long-term occupational exposure to airway
severe COPD among nonsmokers. irritants was considered likely for persons in the following
categories of longest held occupation: extractive or precision
production, farm or nursery work, cleaning or building services,
laborer, cook, and waiter. Income was analyzed using the poverty
index, a ratio of family income to the Census Bureau poverty
Materials and Methods threshold value for the calendar year.10

Spirometry
Statistical Analysis
In the Third National Health and Nutrition Examination Sampling weights were taken into account in all analyses
Survey (from 1988 to 1994), a representative sample of the (SUDAAN; Research Triangle Institute; Research Triangle Park,
civilian, noninstitutionalized population of the United States NC). Means and percentages were reported with their SEs.
consented to an interview (assessing demographic characteristics, Logistic regression analysis was used to identify independent risk
medical history, medication use, risk behaviors) and a medical factors. Variables found significant (p 0.05) in univariate anal-
examination (including spirometry and a battery of laboratory ysis were tested in multivariate analysis and retained if they
tests).10 Spirometry was conducted by a trained technician either improved the fit of the model. As suggested by published data2
in the mobile examination center or in the home of examinees and Figure 1, an interaction term for the effect of sex 60 years
aged 60 years who were unwilling or unable to come to the and 60 years was tested in the model of mild COPD.
center.10 Excluded from spirometry were examinees who had
undergone chest or abdominal surgery within 3 weeks or had
been hospitalized for myocardial infarction, chest pain, or con-
gestive heart failure within 6 weeks. Results
Study Sample
Study Population
Of the 16,238 examinees, aged 18 to 80 years and
Current subjects were white, black, or Mexican-American identified as white, black, or Mexican American,
examinees aged 18 to 80 years whose spirometry findings met the 95.4 0.3% underwent spirometry; of these,
reproducibility and reliability criteria of the American Thoracic 95.2 0.3% produced reproducible and reliable re-
Society11,12 and who provided data on smoking history and
height. The upper age limit for the study was chosen to accord
sults. After excluding 6 persons with acceptable
with formulas used to derive predicted values of FEV1 and spirometry who lacked data on smoking history or
FVC.13 height, eligibility criteria were met by 13,995 exam-
Most of the current analysis was restricted to nonsmokers, a inees, who represented 155.82 million adults nation-
group that included both lifelong nonsmokers of cigarettes, wide (female gender, 51.3 0.4%; mean age,
cigars, or pipe tobacco and former cigarette smokers with a 5
pack-year smoking history who had never smoked cigars or
42.2 0.4 years). Among this general sample, one
pipes.9 Pack-years of smoking were calculated taking into account half (48.7 0.9%) were nonsmokers (n 7,526),
not only the most recent level of daily smoking but also periods who represented 75.95 million adults (female gen-
of higher usage or abstinence. der, 63.2 0.8%; mean age, 40.1 0.4 years). A

Definitions

Using a modification of the Global Initiative for Chronic


Obstructive Lung Disease criteria, COPD was defined as a
FEV1/FVC 70% and categorized as mild (FEV1 80% of
predicted) or moderate to severe (FEV1 80% predicted).14,15
Respiratory symptoms (cough or phlegm on most days for 3
months per year, dyspnea on exertion, or wheezing during the
past year) and physician diagnosis of asthma, chronic bronchitis,
and/or emphysema were recorded; however, none of these was a
current criterion for COPD.
Allergies included history of allergic reaction (to insect sting,
food, allergy shot, skin test), allergy symptoms (nose, eyes) during
the past year, or physician diagnosis of hay fever. Thyroid disease
was defined as thyroid stimulating hormone level of 0.1 or
4.5 mIU/L, a physician diagnosis of goiter or other thyroid
disease, or current use of thyroid medication.16 H pylori antibody
was measured by enzyme-linked immunoassay during phase 1
(from 1988 to 1991) of the survey.17
Current exposure to environmental tobacco smoke was re-
ported separately for the home and the workplace. Exposure at
home was present if a household member smoked cigarettes in
the home. Exposure at work was present if examinees smelled
tobacco smoke at the workplace for 4 h/d; lesser daily exposure Figure 1. Prevalence of mild and moderate-to-severe COPD in
at work was currently found not to associate significantly with nonsmoking adults, by age and sex.

1240 Clinical Investigations

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mortality in the United States: data from the First National 22 Sandford AJ, Silverman EK. Chronic obstructive pulmonary
Health and Nutrition Examination Survey follow up study. disease: 1. Susceptibility factors for COPD, the genotype-
Thorax 2003; 58:388 393 environment interaction. Thorax 2002; 57:736 741
20 Snyder LD, Eisner MD. Obstructive lung disease among the 23 Montnemery P, Lanke J, Lindholm LH, et al. Familial related
urban homeless. Chest 2004; 125:1719 1725 risk-factors in the development of chronic bronchitis/emphy-
21 Bakke PS. Factors affecting growth of FEV1. Monaldi Arch sema as compared to asthma assessed in a postal survey. Eur
Chest Dis 2003; 59:103107 J Epidemiol 2000; 16:10031007

1244 Clinical Investigations

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tory, current exposure to smoking in the home or income, or allergies (data not shown). Associations
workplace, urban residence, income, occupation, or between COPD and asthma (described above) did
education. not vary by age at asthma diagnosis.

Nonsmoker Risk of Mild COPD


Discussion
Univariate associations with thyroid disease, H
pylori antibody, education, and ethnicity (Table 1) According to the current study, nonsmokers ac-
became nonsignificant after adjustment for age and count for one fourth (24.9 1.4%) of COPD cases
sex. Instead, multivariate analysis (Table 2) indicated in the United States. Similar proportions of non-
that risk of mild COPD increased with asthma and smokers have been reported among COPD cases in
with age (doubling every 12 years). Risk was reduced the United Kingdom and Spain (22.9% and 23.4%,
among men before age 60 years; thereafter, risk did respectively).9,18 Few nonsmokers with COPD in the
not differ significantly by sex. Compared to persons current study had had a previous diagnosis of chronic
without COPD, mild cases were half as likely to be bronchitis or emphysema. Mild and moderate-to-
currently exposed to smoking in the home and one severe COPD were currently associated with distinct
fourth as likely to be currently exposed to smoking in demographic profiles among nonsmokers, suggesting
the workplace. that moderate-to-severe disease is not a mere pro-
gression of mild COPD.
Nonsmoker Risk of Moderate-to-Severe COPD The previous epidemiologic study of COPD
Asthma was even more strongly associated with among nonsmokers employed data from earlier Na-
moderate-to-severe COPD than with mild COPD tional Health and Nutrition Examination Surveys
(Table 2). Unlike mild COPD, the risk of moderate- (from 1971 to 1975, from 1976 to 1980, and from
to-severe COPD was markedly increased among 1982 to 1984).2 The current study differed from the
males, peaked in middle age, and was inversely previous study by defining COPD cases through
associated with nonwhite ethnicity. Also unlike mild spirometry rather than reported diagnosis of chronic
COPD, moderate-to-severe COPD was not associ- bronchitis or emphysema, by considering mild and
ated with current exposure to smoking at home or at moderate-to-severe COPD separately, by consider-
work. ing asthma and current exposure to tobacco smoke as
risk factors, and by reporting the prevalence of
respiratory symptoms among COPD cases. In addi-
Nonrisks for COPD
tion, while the previous study defined nonsmokers as
Neither mild nor moderate-to-severe COPD persons who had not smoked 100 cigarettes in their
among nonsmokers was associated with ever smok- lifetime, the current study demonstrated the appro-
ing up to 5 pack-years (Table 1), occupation involv- priateness of including among nonsmokers those
ing exposure to airway irritants, urban residence, former smokers with minimal smoking history.9

Table 2Characteristics Independently Associated with Mild and Moderate-to-Severe COPD Among Nonsmokers
Aged 18 to 80 Years

Mild COPD Moderate-to-Severe COPD


(397 Cases, 6,922 Controls*), (92 cases, 7,030 Controls*),
Characteristics OR (95% CI) OR (95% CI)

Asthma diagnosis 4.27 (2.597.04) 18.8 (8.640.8)


Per year of age 1.06 (1.041.08) 1.04 (1.021.07)
Per year of age 60 0.85 (0.740.97)
Male gender 18.3 (7.743.4)
Gender by age category, yr
Male, age 60 0.12 (0.050.28)
Female, age 60 0.72 (0.391.35)
Male, age 60 1.29 (0.802.10)
Female, age 60 1.00
Nonwhite ethnicity 0.58 (0.370.89)
Now exposed to smoking at home 0.56 (0.350.90)
Now exposed to smoking at work 0.26 (0.080.82)
*Controls are nonsmokers without COPD. Six cases and 109 controls were excluded from the model of mild COPD due to missing data, chiefly
on current exposure to smoking at work. The R2 values for the fit of the two models are 0.09 and 0.05, respectively.

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As the previous study reported for COPD in References
general, mild COPD was currently found more 1 Mannino DM. Chronic obstructive pulmonary disease: defi-
prevalent among women than men before age 60 nition and epidemiology. Respir Care 2003; 48:11851191
years; in contrast, moderate-to-severe COPD was 2 Whittemore AS, Perlin SA, DiCiccio Y. Chronic obstructive
currently found to affect predominantly men pulmonary disease in lifelong nonsmokers: results from
NHANES. Am J Public Health 1995; 85:702706
throughout adulthood. The current study confirmed 3 Silva GE, Sherrill DL, Guerra S, et al. Asthma as a risk factor
the finding of the previous study2 of no association for COPD in a longitudinal study. Chest 2004; 126:59 65
between COPD in nonsmokers and occupational 4 Hospers JJ, Schouten JP, Weiss ST, et al. Asthma attacks with
category or urban residence. eosinophilia predict mortality from chronic obstructive pul-
Among a prior case series of nonsmokers with monary disease in a general population sample. Am J Respir
Crit Care Med 1999; 160:1869 1874
COPD (n 22), none was currently exposed to 5 Molfino NA. Genetics of COPD. Chest 2004; 125:1929 1940
smoking in the home or workplace; however, half 6 Jaakkola MS, Jaakkola JJ. Effects of environmental tobacco
had 20- to 30-year histories of such exposure.9 In smoke on the respiratory health of adults. Scand J Work
the current study, patients with mild COPD Environ Health 2002; 28(Suppl):5270
7 Sunyer J. Urban air pollution and chronic obstructive pulmo-
tended to avoid current exposure to smoking in the nary disease: a review. Eur Respir J 2001; 17:1024 1033
home and at work, but patients with moderate-to- 8 Shiotani A. Linking Helicobacter pylori and chronic bronchi-
severe COPD did not. Information on exposure tis: fact or fancy? J Gastroenterol 2002; 37:402 403
history was unavailable. A previous survival analy- 9 Birring SS, Brightling CE, Bradding P, et al. Clinical, radio-
logic, and induced sputum features of chronic obstructive
sis19 detected no increased mortality hazard from pulmonary disease in nonsmokers: a descriptive study. Am J
moderate-to-severe COPD among nonsmokers. Respir Crit Care Med 2002; 166:1078 1083
However, current inverse associations with age 10 U.S. Department of Health and Human Services. National
60 years and nonwhite ethnicity suggest that Center for Health Statistics. Plan and Operation of the Third
National Health and Nutrition Examination Survey, 1988
moderate-to-severe COPD may indeed compro- 1994. Hyattsville, MD: Centers for Disease Control and
mise survival among specific groups of nonsmok- Prevention, 1994. Available at: http://www.cdc.gov/nchs/data/
ers. Longitudinal studies of COPD in nonsmokers series/sr_01/sr01_032.pdf. Accessed December, 23, 2004
are needed. 11 Standardization of spirometry, 1987 update: statement of the
The current study confirmed findings from earlier American Thoracic Society. Am Rev Respir Dis 1987; 136:
12851298
COPD studies not restricted to nonsmokers, specif- 12 Third National Health and Nutrition Examination Survey,
ically independent associations with increasing age spirometry procedure manual. Rockville, MD: Westat, 1988.
and asthma but not with allergy alone.3,4 The mag- Available at: http://www.cdc.gov/nchs/data/nhanes/nhanes3/
nitude of the association between asthma and COPD cdrom/nchs/manuals/spiro.pdf. Accessed December 23, 2004
was currently shown to increase with the severity of 13 Hankinson JL, Odencrantz JR, Fedan KB. Spirometric refer-
ence values from a sample of the general U.S. population.
COPD. Am J Respir Crit Care Med 1999; 159:179 187
Limitations of the current study include its 14 Pauwels RA, Buist AS, Calverley PM, et al. Global strategy for
cross-sectional nature, limited numbers of non- the diagnosis, management and prevention of chronic ob-
smokers with moderate and severe COPD (pre- structive pulmonary disease: NHLBI/WHO Global Initiative
cluding separate analyses), and nonsampling of for Chronic Obstructive Lung Disease (GOLD) workshop
summary. Am J Respir Crit Care Med 2001; 163:1256 1276
nursing home residents and homeless persons.20 15 Mannino DM, Ford ES, Redd SC. Obstructive and restrictive
Also, as noted in the footnote to Table 2, current lung disease and markers of inflammation: data from the
models explained a small fraction of the risk of Third National Health and Nutrition Examination. Am J Med
mild and moderate-to-severe COPD among non- 2003; 114:758 762
smokers, indicating that important risk factors 16 Hollowell JG, Staehling NW, Flanders WD, et al. Serum
TSH, T4, and thyroid antibodies in the United States popu-
remain to be identified. Data on several proposed lation (1988 to 1994): National Health and Nutrition Exami-
risks were not available for the current study: nation Survey (NHANES III). J Clin Endocrinol Metab 2002;
gestational age, birth weight, lower respiratory 87:489 499
tract infections before age 7 years, parental smok- 17 U.S. Department of Health and Human Services. National
ing during gestation and childhood, exposure to Center for Health Statistics. Third National Health and
Nutrition Examination Survey, 1988 1994, NHANES III
environmental tobacco smoke and other airway second laboratory data file documentation (Series 11, No.
irritants throughout adulthood, genetic markers, 2A). Hyattsville, MD: Centers for Disease Control and
and family history of COPD.5,6,2123 Future spiro- Prevention, 1998. Available at: http://www.cdc.gov/nchs/data/
metric studies, especially if lifetime medical and nhanes/nhanes3/lab2-acc.pdf. Accessed December 23, 2004
exposure histories are obtained and subjects are 18 Pena VS, Miravitlles M, Gabriel R, et al. Geographic varia-
tions in prevalence and underdiagnosis of COPD: results of
followed up prospectively, will provide a means of the IBERPOC multicentre epidemiological study. Chest
testing and improving on current models of COPD 2000; 118:981989
risk among nonsmokers. 19 Mannino DM, Buist AS, Petty TL, et al. Lung function and

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Downloaded From: http://journal.publications.chestnet.org/ by a Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas User on 07/27/2015
mortality in the United States: data from the First National 22 Sandford AJ, Silverman EK. Chronic obstructive pulmonary
Health and Nutrition Examination Survey follow up study. disease: 1. Susceptibility factors for COPD, the genotype-
Thorax 2003; 58:388 393 environment interaction. Thorax 2002; 57:736 741
20 Snyder LD, Eisner MD. Obstructive lung disease among the 23 Montnemery P, Lanke J, Lindholm LH, et al. Familial related
urban homeless. Chest 2004; 125:1719 1725 risk-factors in the development of chronic bronchitis/emphy-
21 Bakke PS. Factors affecting growth of FEV1. Monaldi Arch sema as compared to asthma assessed in a postal survey. Eur
Chest Dis 2003; 59:103107 J Epidemiol 2000; 16:10031007

1244 Clinical Investigations

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