am j clin nutr 2007 varraso 488 95 pf

7/30/2019 Am J Clin Nutr 2007 Varraso 488 95 PF

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Prospective study of dietary patterns and chronic obstructivepulmonary disease among US women13

Raphaelle Varraso, Teresa T Fung, R Graham Barr, Frank B Hu, Walter Willett, and Carlos A Camargo Jr

ABSTRACT

Background: Although many foods and nutrients are associated

with lung function or symptoms of chronic obstructive pulmonary

disease (COPD), the relation between overall diet and newly diag-

nosed COPD is not known.

Objective: We assessed the relation between dietary patterns and

newly diagnosed COPD in women.

Design: Data were collected from a large prospective cohort of US

women (Nurses Health Study). Between 1984 and 2000, 754 self-reported confirmed cases of newly diagnosedCOPD were identified

among 72 043 women. With the use of principal component analy-

sis, 2 dietary patterns were identified: a prudent pattern (fruit, veg-

etables, fish, whole-grain products) and a Western pattern (refined

grains, cured and red meats, desserts, French fries). Patterns were

categorized into quintiles, and the risk of COPD was compared

between quintiles (lowest as reference) with the use of Cox propor-

tional hazard models.

Results: After adjustmentsfor 14 potential confounders, the prudent

pattern was negatively associated with risk of newly diagnosed

COPD [relative risk (RR)for highest compared withlowest quintile:

0.75; 95% CI: 0.58, 0.98; P for trend 0.02] whereas the Western

pattern was positively associated withrisk of COPD (RR for highest

compared withlowest quintile: 1.31; 95% CI: 0.94, 1.82; P for trend

0.02). In contrast with findings for COPD, dietary patterns were

not associated with the risk of adult-onset asthma.

Conclusion: In women, a negative association was found between

a diet rich in fruit,vegetables,and fish andthe risk ofCOPD,whereas

a positive association wasfoundbetweena diet rich in refined grains,

cured and red meats, desserts, and French fries and the risk of

COPD. Am J Clin Nutr 2007;86:48895.

KEY WORDS Dietary pattern, principal component analysis,

chronic obstructive pulmonary disease, COPD, prospective cohort,

body mass index

INTRODUCTION

Increases in chronic obstructive pulmonary disease (COPD)

incidence in women are related to aging of the population and to

smoking (1). Cigarettesmokingis themainriskfactor forCOPD,

but not all smokers develop COPD (2), an observation that sug-

gests that other factors also areinvolved. Of these environmental

factors, changes in diet (particularly decreased consumption of

fresh fruit and vegetables) have been evoked to explain the large

increase in obstructive lung disease, such as asthma and COPD

(3). Most evidence about the relation between diet and COPD

comes from cross-sectional studies, which suggest benefit from

a diet rich in antioxidants and n3 fatty acids on lung function

(4 6). A few longitudinal studies have investigated the relation

between diet and the decline in forced expiratory volume in 1 s

(FEV1) or COPD symptoms (710), and they reported an appar-

ent benefit of fruit and vegetable intake.

Among patients with COPD, leanness is a majorrisk factorfor

poor prognosis (11,12). Per the hypothesis that malnutrition, and

therefore leanness, was a consequence of COPD associated witha poor prognosis, supplementation studies were conducted.

Those trials have been negative, which suggests that the associ-

ation between leanness and COPD is complex and that nutri-

tional rehabilitation per se has no significant effect (13).

The assessment of dietary patterns instead of specific foods or

nutrients has been proposed as a new approach in nutritional

epidemiology of chronic diseases (14). Dietary patterns provide

an overview of the diet. Although many foods or nutrients are

identified in relation with lung function, the relation of overall

diet to newly diagnosed COPD is not known. We examined this

issue in a prospective cohort of70 000 women.

SUBJECTS AND METHODS

Overview

The Nurses Health Study (NHS) began in 1976, when

121 700 female nurses aged 3055 y living in 11 US states

responded to a mailed health questionnaire (15). Follow-upques-

tionnaires are sent every 2 y. In 1984, participants completed a

1 From the Departments of Nutrition (RV, TTF, FBH, and WW) and

Epidemiology (FBH, WW, and CAC), Harvard School of Public Health,

Boston, MA; the Department of Nutrition, Simmons College, Boston, MA

(TTF); Channing Laboratory, Department of Medicine, Brigham and Wom-

ens Hospital, Harvard Medical School, Boston, MA (RGB, FBH, WW, and

CAC); the Division of General Medicine, Department of Medicine, andDepartment of Epidemiology, Columbia University Medical Center, New

York, NY (RGB); and the Department of Emergency Medicine, Massachu-

setts General Hospital, Harvard Medical School, Boston, MA (CAC).2 Supported by grantsCA-87969, HL-63841,HL-60712, HL-077612,HL-

075476, andAI-52338fromthe National Institutesof Health, Bethesda, MD;

grantsfromthe SocitFrancaisede Nutrition, Paris,France(to RV); andthe

Socit de Pneumologie de Langue Francaise, Paris, France (to RV).3 Reprints not available. Address correspondence to R Varraso, Depart-

mentof Nutrition,Harvard Schoolof PublicHealth, 655 HuntingtonAvenue,

Boston, MA 02115. E-mail: [email protected] March 14, 2007.

Accepted for publication April 4, 2007.

488 Am J Clin Nutr 2007;86:48895. Printed in USA. 2007 American Society for Nutrition

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116-item food-frequency questionnaire (FFQ). Similar FFQs

were sent to the women every 24 y. The institutional review

board approved the NHS protocols, and written consent was

obtained from all subjects.

Participants without a completed FFQ at baseline or partici-

pants with unreasonably high (3500 kcal/d) or low intakes

(500 kcal/d) and those who had left 70 items blank were

excluded from the analysis. Women who reported a diagnosed

asthmaor COPD at baseline in 1984 were also excluded from thepresent analysis. The final baseline population included 72 043

women. Between 1984 and 2000, 90% of this population was

followed up.

Assessment of dietary patterns

Dietary intake information was collected by an FFQ designed

to assess average food intake during the previous 12 mo. Stan-

dard portion sizes were listed with each food. Foreach food item,

participants indicated their average frequency of consumption

during the past year in terms of the specified serving size by

checking 1 of 9 frequency categories, ranging from almost

never to 6 times/d. The selected frequency category for

each food item was converted to a daily intake. For example, aresponse of 1 serving/wk was converted to 0.14 servings/d.

FFQs were administrated in 1984, 1986, 1990, 1994, and 1998.

To prepare for factor analysis, food items were grouped into 38

predefined foods groups. Food items that were similar in nutrient

profile and culinary use were grouped. This classification fol-

lows that of another study of dietary patterns in these women

(16). To assess the sensitivity of dietary patterns to use of this

specific, a priori grouping of foods, we also performed principal

component analysis by using the individual food items.

With the use of principal component analysis, dietary patterns

were identified from FFQs administrated in 1984, 1986, 1990,

1994, and1998. The factors were rotated by an orthogonal trans-

formation (Varimax rotation function in SAS; SAS Institute,Cary, NC) to achieve simpler structure with greater interpret-

ability. The number of factors to retain was determined by using

the diagram of eigenvalues, the Scree plot, and the interpretabil-

ityof thefactors, as well as thepercentage of variance explained.

Foods that loaded 0.30 were considered to be making a

contribution to the factor, although the value for meaningful

factor loading is arbitrary. The factor score for each pattern was

constructed by summing observed intakes of the component food

items weighted by factor loading. To reduce measurement errors

and to represent long-term dietary patterns, the cumulative av-

erage of pattern scores was calculated and then divided into

quintiles. For the analysis according to the level of physical

activity, the cumulative average scores for patterns were divided

into tertiles to have enough cases in each group.

Assessment of respiratory phenotypes

Self-reported COPD was defined by the affirmative response

to physician-diagnosed chronic bronchitis or emphysema and by

the report of a diagnostic testat diagnosis (ie,pulmonary function

testing, chest radiograph, or chest computed tomography).

Women also reported age at diagnosis. Between 1984 and 2000,

754 cases of newly diagnosed COPD were reported.

We previously validated this definition in a 10%random sam-

ple in this cohort (17). We were unable to obtain standardized,

reliable spirometry on this random sample because NHS partic-

ipants are geographically dispersed (they lived in 11 US statesin

1976 and now live throughout the United States) and are con-

tacted by mail. Instead, we obtained participants medical

records and a physician reviewed them in a blinded fashion. The

diagnosis of COPD was confirmed in 80% of 218 cases who

meet this case definition and 88% of cases who met this

definition and denied a physician diagnosisof asthma. Results

of pulmonary function testing were available in the medical

records of 71% of confirmed cases; the mean FEV1 in this

group was 50% of predicted.Asthma was also self-reported and was defined by a doctor

diagnosis of asthma and the use of medication for asthma within

the past 12 mo. Between 1984 and 2000, 1100 new cases of

adult-onset asthma were reported and met our epidemiologic

definition.

Assessment of other variables

Information on smoking status included the categories of

never smokers, exsmokers, and current smokers. For smokers,

further information about the amount of tobacco smoke was

available by pack-years of smoking. Exposure to secondhand

tobacco smoke was also reported and defined by an exposure at

home, at work, or at both locations. Menopause and hormonal

replacement therapy (HRT) use were assessed every 2 y by self-

reported questionnaires, and menopausal status was categorized

in 5 classes (premenopause, postmenopause and never HRT use,

postmenopause and past user for HRT, postmenopause and es-

trogen replacement therapy, postmenopause and estrogen-

progesterone replacement therapy).Race-ethnicity, spouses ed-

ucational attainment, physician visits, and region were also

collected. Race-ethnicity was categorized in 2 classes (white,

nonwhite), spouses educational attainment was categorized in 3

classes (graduate school, college, high school), physician exam-

ination in previous 2 y was categorized in 3 classes (no visit,

screening, symptoms), and US region was categorized in 6

classes (New England, Mid-Atlantic, East North Central, SouthAtlantic, West South Central, Pacific). Body mass index [BMI;

calculated as weight divided by height squared (kg/m2)], phys-

ical activity, and multivitamin use were assessed every 2 y by

self-reported questionnaires. BMIwas categorized into7 classes:

20.0, 20.022.4, 22.524.9, 25.027.4, 27.529.9,30.034.9,

35.0). Women also reported physical activity, including a va-

riety of activities such as walking, bicycle, swimming, or tennis.

The validity of the questionnaire in assessing physical activity

was described elsewhere (18). Physical activity was measured in

metabolic equivalents per week, whereby 1 metabolic equivalent

was equal to the energy expended at the basal metabolic rate or

at rest and divided into quintiles. Use of vitamin and mineral

supplements was investigatedevery 2 y. Total calorie intakewasestimated through the FFQ, expressed in kilocalorie per day

(kcal/d) and categorized according to quintile.

Statistical analysis

Statistical analyses included principal component analysis,

analysis of variance, and Cox proportional hazard regression

models.Cox models wereadjustedfor age,smokingstatus,pack-

years, pack-years2, exposure to secondhand tobacco smoke,

menopausal status, race-ethnicity, spouses educational attain-

ment, physician visits, US region, BMI, physical activity, mul-

tivitamin us,and energy intake. Women werecensored at thedate

of last contact, and the date of diagnosis was calculated by using

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the date of birth and the age at diagnosis. A test for trend across

the quintiles of each pattern was calculated by treating the cate-

gories as an ordinal variable in a proportional hazards model.Residual confounding by smoking remains an important issue in

studies of respiratory diseases and diet. Because smoking is the

main risk factorfor COPD, analyses were also performedamong

exsmokers and current smokers. Analyses also were stratified

according to BMI in 3 classes ( 20, 2025, 25). Physical

activity level was categorized as low compared with high by

using the median. We formally tested the interaction between

eachdietarypatternwith smoking,BMI in 3 classes,and physical

activity. All analyses were conducted with the use of SAS soft-

ware, version 9 (SAS Institute).

RESULTS

Dietary patterns and characteristics of the population

With the use of the principal component analysis, 2 distinct

major dietary patterns were identified at baseline (Table 1). The

first pattern wasloaded by a high intake of fruit, vegetables, fish,

poultry, whole-grain products, and low-fat dairy products. The

second pattern was loaded by a high consumption of refined

grains, cured and red meats, desserts and sweets, French fries,

and high-fat dairy products. According to previous studies about

dietary patterns in this population, the first pattern was labeled

the prudent pattern and the second pattern was labeled the

Western pattern. Similar dietary patterns were identified with

the use of FFQs from 1986, 1990, 1994, and 1998. The principal

component analysis performed at baseline on the individual

foods without a priori grouping gave similar results: the first

pattern wasloaded by a high intakeof fruit (freshapples or pears;

oranges; peaches, apricots, or plums; strawberries; cantaloupes;

blueberries; grapefruits), vegetables (broccoli, eggplant, cauli-

flower, coleslaw, carrots, raw spinach, celery, string beans, ro-

maine leaf lettuce, yellow squash, cooked spinach, iceberg head

lettuce, tomatoes, mushrooms, Brussels sprouts, mixed vegeta-

bles, garlic, beans lentils,beets), poultry (chicken or turkey with-

out skin), and fish. The second pattern was loaded by a high

intake of French fries, hamburger, cured meats (processed meats,

hot dogs, bacon), sweets anddesserts(home-bakedcake, dough-

nuts, brownies, ready-made sweet rolls, home-baked pies, pan-

cakes or waffles), and refined cereals (white bread, pasta).

The characteristics of the population according to the quintile

of both prudent and Western patterns are presented in Table 2.

Compared with women with thelowest intakeof theprudent diet

(the lowest quintile), women with the highest intake of prudent

diet (the highest quintile) were more physically active, were less

likely to be current smokers, and were more frequent users of

multivitaminsupplements. Women with the highest intake of the

prudent diet consumed more polyunsaturated fat, more proteins,

and more carbohydrates, but less saturated fat and trans fatty

acids.

Compared with women with the lowest intake of the Western

diet, women with the highest intake of the Western diet had a

higher BMI, were less physically active, were more likely to

smoke, and took fewer multivitamin supplements. Women with

the highest intake of the Western diet consumed more saturated

fat and trans fatty acids, but less carbohydrates and proteins.

Dietary patterns and COPD

On average during the study period, among the 754 cases of

COPD, 62% were smokers and 26% were exsmokers. Consid-ering different time periods, cases occurring between 1984 and

1986 (n 103) had the highest proportion of smokers: 82% of

these cases were smokers in 1984 and 12% were exsmokers.

The prudent pattern was inversely associated with the risk of

newly diagnosed COPD in women after adjustment for 14 po-

tential confounders (Table 3). By contrast, the Western pattern

was positively and significantly associated with the risk of newly

diagnosed COPD. When the population wasrestricted to women

without cancer or cardiovascular disease at baseline (n

66 005),similar associations were found [for the prudent pattern,

relative risk (RR) for highest compared with lowest quintile:

0.73; 95% CI: 0.55, 0.97; P for trend 0.02; for the Western

pattern,RR for highest comparedwith lowest quintile: 1.22;95%CI: 0.86, 1.73; P for trend 0.08]. Lagged analyses were also

performed and similar results were found (data not shown).

The relation between dietary patterns and newly diagnosed

COPD also was investigated among exsmokers. After adjust-

ments for potential confounders, the association between the

prudent pattern and newly diagnosed COPD remained statisti-

cally significant (RR for highest compared with lowest quintile:

0.50; 95% CI: 0.31, 0.82; P for trend 0.01). The positive

association between the Western pattern and the risk of newly

diagnosed COPD also was present in exsmokers, but the trend

was borderline significant (RR for highest compared with lowest

quintile 1.59; 95% CI, 0.86, 2.94; P for trend 0.08).

TABLE 1

Factor loading matrix for the prudent and Western patterns at baseline

from principal component analysis1

Prudent pattern Western pattern

Other vegetables 0.68

Leafy vegetables 0.63

Cruciferous vegetables 0.61

Fruit 0.60

Yellow vegetables 0.60

Legumes 0.55

Fish 0.50

Tomatoes 0.45

Poultry 0.43

Whole-grain products 0.41

Low-fat dairy products 0.35

Garlic 0.35

Salad dressing 0.33

Refined grains 0.74

Desserts and sweets 0.60

Cured meats 0.52

Red meats 0.52

French fries 0.44

Condiments 0.40Potatoes 0.39

Pizza 0.36

Full-fat dairy products 0.35

Sweetened beverages 0.32

Mayonnaise 0.31

Margarine 0.30

1 Factor loadings represent the correlation between factor scores and

intake of food groups. Absolute values 0.30 were not listed forsimplicity.

Factorloadingspresentedare thosethat resulted fromthe orthogonalrotation.

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We found a significant interaction between BMI and the West-

ern pattern (Table 4). After adjustments for potential confound-

ers, the association between tertiles of the Western pattern and

the risk of newly diagnosed COPD was stronger in lean (BMI

20) than in other women (RR for highest compared with lowest

tertile for lean, normal, and overweight or obese subjects: 2.76,

1.17, and 1.50, respectively; P for interaction 0.03). We found

no significant interaction between BMI and the prudent pattern

(P 0.77).

To further address potential confounding by physical activity,

we next examined the association between the Western pattern

and newly diagnosed COPD in lean women, according to the

level of physical activity. In lean women, no significant in-

teraction was observed between the level of physical activity

and the Western pattern (P 0.32). The positive and signif-

icant association between the Western pattern and newly di-

agnosed COPD in lean women was seen both in participants

with a low level of physical activity (RR for highest compared

with lowest tertile 3.22; 95% CI: 1.20, 8.68; P for trend

0.03), andin subjects with a high level of physical activity (RR

for highest compared with lowest tertile: 4.58; 95% CI, 1.33,

15.80; P for trend 0.02).

TABLE 2

Age-standardized baseline characteristics by quintile (Q) of the 1984 pattern score among 72 043 women1

Prudent pattern Western pattern

Q1

(n 14 993)

Q3

(n 14 434)

Q5

(n 14 285)

P for

trend2Q1

(n 14 527)

Q3

(n 14 413)

Q5

(n 14 258)

P for

trend2

Smoking habits

Nonsmokers (%) 41 45 46 43 45 47

Ex-smokers (%) 34 40 43 0.001 44 39 35 0.001

Current smokers (%) 25 15 11 13 16 18

Smoking (pack-years)3 15.2 20.34 12.1 18.3 10.3 16.3 0.001 11.8 17.9 12.0 18.1 12.9 18.9 0.001

Exposure to secondhand smoke at work

or at home (%)

86 82 80 0.001 80 82 84 0.001

Postmenopause (%) 50 52 55 0.001 55 52 50 0.001

White race or ethnicity (%) 87 88 87 0.001 85 88 89 0.001

Spouses educational attainment

High school (%) 39 35 30 30 35 39

College (%) 19 23 24 0.001 22 23 21 0.001

Graduate school (%) 14 19 22 21 19 16

Missing (%) 28 23 24 27 23 24

No physician visits (%) 13 10 9 0.001 9 10 11 0.001

US region

New England (%) 13 14 15 14 15 14Mid-Atlantic (%) 45 43 43 41 44 46

East North Central (%) 23 20 16 0.001 16 20 22 0.001

South Atlantic (%) 6 6 6 6 6 6

West South Central (%) 5 5 4 5 5 4

Pacific (%) 8 12 16 18 10 8

BMI (kg/m2) 24.8 4.7 24.9 4.6 25.2 4.7 0.001 24.5 4.2 24.9 4.5 25.5 5.2 0.001

Physical activity (MET h/wk)5 10.1 17.1 13.8 19.1 20.0 27.6 0.001 17.8 25.2 13.8 19.5 11.8 20.0 0.001

Multivitamin use (%) 33 39 47 0.001 45 39 34 0.001

Total energy (kcal) 1436 1723 2086 0.001 1224 1684 2381 0.001

Food and nutrient consumption

Total vegetables (servings/d) 1.5 0.5 2.9 0.7 5.7 2.2 0.001 3.2 2.0 3.2 1.7 3.5 1.9 0.001

Whole-grains products (servings/d) 0.4 0.5 0.9 0.9 1.6 1.3 0.001 0.9 1.0 0.9 1.0 1.0 1.1 0.001

Fruit (servings/d) 0.7 0.5 1.3 0.8 2.4 1.4 0.001 1.5 1.2 1.4 1.0 1.4 1.0 0.001

Fish (servings/d) 0.2 0.1 0.3 0.2 0.5 0.4 0.001 0.4 0.3 0.3 0.2 0.3 0.2 0.001

Desserts and sweets (servings/d) 1.1 1.2 1.1 1.1 1.0 1.1 0.001 0.4 0.3 0.9 0.7 2.2 1.7 0.001

Cured meats (servings/d) 0.3 0.4 0.3 0.3 0.2 0.3 0.001 0.1 0.1 0.3 0.2 0.6 0.5 0.001

Red meats (servings/d) 0.6 0.4 0.7 0.4 0.6 0.4 0.001 0.3 0.2 0.6 0.3 0.9 0.5 0.001

Saturated fat (g) 24.2 5.0 22.2 4.3 19.7 4.0 0.001 19.9 4.8 22.4 4.3 23.5 4.2 0.001

Monounsaturated fat (g) 24.0 4.4 22.7 3.9 20.3 4.1 0.001 20.0 4.7 22.8 3.9 24.1 3.7 0.001

Polyunsaturated fat (g) 11.3 3.0 11.9 3.0 12.0 3.4 0.001 11.2 3.5 11.8 3.0 12.4 3.0 0.001

trans Fat (g) 3.8 1.1 3.4 1.0 2.8 1.0 0.001 2.8 1.1 3.4 1.0 3.8 1.0 0.001

Total carbohydrates (g) 183 34 184 30 191 31 0.001 193 37 184 30 181 27 0.001

Total proteins (g) 64.0 11.8 71.5 11.3 78.9 13.8 0.001 75.7 15.7 71.2 11.9 68.0 11.1 0.001

1 Quintile 1 represents the lowest dietary pattern intake and quintile 5 the highest.2 P fortrend acrosscategories of dietary pattern. Generalizedlinear modelswere usedfor continuousvariablesand chi-squaretests forcategoricalvariables.3 Determined as no. of packs smoked per day no. of years smoked among past and current smokers.4 x SD (all such values).5 MET, metabolic equivalent. MET h/wk is the sum of the average time per week spent in each activityMET value of each activity.



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Dietary patterns and asthma

Although the primary outcome of this study was newly

diagnosed COPD, we also examined the relation of dietary

patterns with adult-onset asthma in this cohort of women,

because of the potential overlap between the diagnoses of

COPD and asthma. In contrast with the risk of newly diag-

nosed COPD, no association was found between the Western

pattern and the risk of adult-onset asthma (RR for highest

compared with lowest quintile: 0.90; 95%CI: 0.69, 1.18; P for

trend 0.24). Before adjustment for potential confounders, a

positive association was found between the prudent pattern

and the risk of adult-onset asthma (RR for highest compared

with lowest quintile: 1.52; 95% CI: 1.26, 1.84; P for trend

0.001). Adjustment for the same 14 potential confounders

used in earlier analyses led to a borderline significant positive

association between the prudent pattern and the risk of adult-

onset asthma (RR for highest compared with lowest quintile:

1.23; 95% CI: 0.99, 1.53; P for trend 0.07).

TABLE 3

Association between quintile (Q) of the cumulative average patterns and newly diagnosed chronic obstructive pulmonary disease (COPD) (19842000) 1

Intake

P for trend2Q1 Q2 Q3 Q4 Q5

Prudent pattern

Cases (n) 203 169 140 120 122

Person-years 110 949 111 674 111 772 112 261 110 435

Age-adjusted RR (95% CI) 1.00 0.69 (0.56, 0.84) 0.57 (0.46, 0.70) 0.48 (0.39, 0.60) 0.39 (0.31, 0.49) 0.001

Multivariate RR (95% CI)3 1.00 0.88 (0.72, 1.08) 0.82 (0.66, 1.01) 0.77 (0.61, 0.96) 0.70 (0.55, 0.89) 0.001


Western pattern

Cases (n) 112 145 167 164 166

Person-years 112 223 111 449 111 352 111 407 110 660

Age-adjusted RR (95% CI) 1.00 1.26 (0.98, 1.62) 1.68 (1.32, 2.14) 2.09 (1.65, 2.64) 2.12 (1.67, 2.70) 0.001



1 RR, relative risk. The reference category is based on the lowest category of intake.2 Based on each intake category and modeled as continuous variables in a Cox proportional hazard model.3 Cox proportional hazard models adjusted for age, smoking status, pack-years, pack-years2, and exposure to secondhand tobacco smoke.4 Cox proportional hazard models adjusted for age, smoking status, pack-years, pack-years2, exposure to secondhand tobacco smoke, menopausal status,

race-ethnicity, spouses educational attainment, physician visits, US region, physical activity, multivitamin use, and energy intake.

TABLE 4

Association between tertile (T) of the cumulative average of the Western pattern and newly diagnosed chronic obstructive pulmonary disease (COPD)according to BMI (3 classes)1

Western pattern

Intake

P for trend2T1 T2 T3

Lean subjects (BMI 20)

Cases (n) 16 54 51

Person-years 10 758 10 168 10 278

Age-adjusted RR (95% CI) 1.00 3.48 (2.00, 6.07) 4.87 (2.83, 8.40) 0.001

Multivariate RR (95% CI)3 1.00 2.42 (1.38, 4.25) 2.70 (1.55, 4.70) 0.001


Normal-weight subjects (BMI: 2025)

Cases (n) 100 120 117

Person-years 79 489 78 945 74 534

Age-adjusted RR (95% CI) 1.00 1.34 (1.03, 1.75) 1.63 (1.24, 2.12) 0.001Multivariate RR (95% CI)3 1.00 1.17 (0.90, 1.53) 1.24 (0.95, 1.62) 0.12


Overweight and obese subjects (BMI 25)

Cases (n) 75 78 91

Person-years 79 403 81 555 84 928

Age-adjusted RR (95% CI) 1.00 1.37 (0.99, 1.91) 1.70 (1.24, 2.34) 0.001


Multivariate RR4 (95% CI)4 1.00 1.30 (0.91, 1.88) 1.50 (0.95, 2.35) 0.08

1 RR, relative risk. The reference category is based on the lowest category of intake. The Western pattern BMI interaction was significant, P 0.03.2 Based on each intake category and modeled as continuous variables in a Cox proportional hazard model.3 Cox proportional hazard models adjusted for age, smoking status, pack-years, pack-years2, and exposure to secondhand tobacco smoke.4 Cox proportional hazard models adjusted for age, smoking status, pack-years, pack-years2, exposure to secondhand tobacco smoke, menopausal status,

race-ethnicity, spouses educational attainment, physician visits, US region, physical activity, multivitamin use, and energy intake.

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DISCUSSION

With the use of principal component analysis, 2 distinct di-

etary patterns were identified in this large prospective cohort of

US women. The prudent pattern was associated with a signifi-

cantly decreased risk of newly diagnosed COPD, whereas the

Western diet was associated with an increased risk of COPD.

These associations were more clearly seen in exsmokers than in

current smokers, although the interaction between smoking andeach dietary pattern was not statistically significant. The associ-

ation between the Western diet and the risk of COPD was stron-

ger among lean women (BMI 20) than among normal, over-

weight, and obese women.

Although nutritional epidemiologyoften focuses on the intake

of specific nutrients, persons do not eat isolated nutrients but

instead meals consisting of a variety of foods with complex

combinations of nutrients that may interact (19). In this context,

it was proposed to investigate dietary patterns to address an

overview of diet (14). Dietary patterns were investigated in re-

lation to several diseases such as breast cancer (16, 20), cardio-

vascular diseases (21), or diabetes (22), but prior studies on the

relation between dietary patterns and respiratory diseases are

sparse.

The finding of the prudent pattern (loaded by fruit and vege-

tables) being associated with a decrease risk of newly diagnosed

COPD is consistent with prior epidemiologic literature that sug-

gests a beneficial effect of antioxidants, particularly vitamin C,

and to a lesser extent vitamin E on COPD or FEV1 values. Most

of that epidemiologic literature comes from cross-sectional stud-

ies (2327), but the few longitudinal studies have also reported a

negative association between intake of fruit, vegetables, and

vitamin C with the decline of FEV1 (710). In 793 men from the

Netherlands, the consumption of solid fruit was inversely related

to the 25-y incidence of chronic lung disease (7). The prudent

pattern also was loaded by a high intake of fish, one of the main

sources of n3 polyunsaturated fatty acids. Results are still in-

consistent across studies (4), but the only published prospective

study observed no relationbetween n3 intakeand theincidence

of chronic lung disease (7). A few clinical trials, not designed for

respiratory diseases, have provided data on respiratory pheno-

types (28, 29), and only one recent trial was designed for em-

physema (30). Data from the -tocopherol and -carotene Can-

cerPreventionStudy in Finland (28) andfromthe-carotene and

Retinol Efficacy Trial in the United States (29) showed no re-

duction in COPD symptoms in men receiving -tocopherol or

-carotene (28) and no effect of vitamin A supplementation on

the rate of decline of FEV1 (29). Preliminary results from the

Feasibility of Retinoids in the Treatment of Emphysema, a mul-

ticenter clinical trial in the United States that includes 150patients with emphysema, showed no change in respiratory

symptoms, lung function testing, and lung density on computed

tomographic scanning after supplementation with retinoic acid

(30). The effect of any individual nutrient in reducing the risk of

COPD may be too small to detect as suggested by these negative

results, but, when several nutrients are consumed together, the

cumulative effect may be sufficient for detection. Indeed, con-

sidering diet by an overall approach rather than by specific foods

or nutrients may suggest a more comprehensive approach to

disease prevention.

The positive association between the Western pattern and

newly diagnosed COPD is a novel finding for a US population.

Recently, Butler et al (31) reported that the meat-dim sum

pattern,loadedby a high intakeof red meat,preservedfoods, rice,

noodles, and deep-fried foods, was associated with an increase

risk of incident cough with phlegm in 52 325 adult Chinese

Singaporeans. Although the diet and lifestyle of Chinese Singa-

poreans are different from those in US women, the findings are

consistent and suggested a deleterious effect of a diet rich in

meat, starchy foods,and high-fatdairy products on COPD. It was

previously reported in this cohort of women that the Westernpattern was positively correlated with concentrations of

C-reactive protein and interleukin-6, 2 markers of systemic in-

flammation (32). The association between COPD and the sys-

temic inflammation remains unclear; whereas some studies have

reported that systemic inflammation is a consequence of COPD,

causation alsoremainspossible (33,34). Morestudiesare needed

to better understand the association between the Western pattern,

COPD, and inflammation.

An interesting finding was the significant interaction between

BMI and the Western diet on newly diagnosed COPD. The as-

sociation between the Western diet and newly diagnosed COPD

was higher among lean women and was borderline significant

among overweight or obese women. Leanness is associated withpoor prognosis among patients with COPD, yet it remains un-

clear whether leanness is simply a consequence of established

disease, a risk factor, or a marker of a risk factor. One conse-

quence of systemic inflammation is to decrease fat-free mass,

and studies suggest a key role of fat-free mass in COPD (3537).

Body composition is influenced by diet choice, physical activity,

and genetic factors. In our study, the association between the

Western diet and the risk of newly diagnosed COPD in lean

participants was found both in lean women with high and low

physical activity. Results should be interpreted with caution, but

lean persons with a Western diet might have a higher grade of

systemic inflammation than do normal or overweight persons

eating a Western diet if the leanness reflects a loss of fat-freemass. The mechanism for the observed interaction requires fur-

ther study.

Although our primary focus was on newly diagnosed COPD,

the relation between dietary pattern and adult-onset asthma also

was investigated because of the potential overlap between COPD

and asthma and the potential misdiagnosis of COPD. In contrast

with newly diagnosed COPD, no association was found between

the Western pattern and adult-onset asthma, a result in agreement

with Butler et al (31) who reported no association between the

meat-dim sum pattern and incident asthma in Chinese Singa-

poreans. We reported a borderline significant positive associa-

tion between the prudent pattern and adult-onset asthma. The

only published longitudinal study on the relation between diet

and adult-onset asthma was performed in this cohort (38) and

showed no association between vitamin C intake and the risk of

adult-onset asthma. Although other groups have suggested that

foods and nutrients associated with a prudent dietary pattern may

be beneficial (3942), these associations are reported mostly in

children, and evidence is growing that adult-onset asthma is

different from childhood asthma (43).

Our study has several potential limitations. First, newly diag-

nosed COPD was defined by a self-reported physician-diagnosis

of COPD and lung function results were not available. Never-

theless the questionnaire-based definition of newly diagnosed

COPD was validated in a subset of this unique population of

registered nurses (17). The main source of misclassification



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probably is a misdiagnosis with asthma, and our findings for

asthma diagnosis were null. Moreover, cigarette smoking is the

main risk factor for COPD, and only 11% of cases were non-

smokers, which provides additional support for our epidemio-

logic definition of COPD. Although we acknowledge the poten-

tial for some misclassification, these data allowed us to

investigate the relations between diet and COPD in a large pop-

ulation, with repeated assessments both of diet and newly diag-

nosed COPD.We also acknowledge that the association between

dietary patterns and COPD may be due, in part, to a residual

confounding by cigarette smoking, which is a powerful risk fac-

tor. Smokers tend to eat unhealthy diets (44), and there is a risk

of saying that an association between unhealthy diet and COPD

risk wasdue to diet when, in fact, it wasdue to thesmokingalone.

To minimize this possibility, multivariate models were ad-

justed with multiple measures of tobacco exposu re (smoking

habits, pack-years, pack-years2, and exposure to secondhand

tobacco smoke), as we have done in prior analyses (17). Our

second approach to this important issue was to assess the

relation between diet and COPD in exsmokers, who would

tend to have a better diet than current smokers (44). Analysesperformed in exsmokers yielded comparable results, but it

should be noted that the P for trend is driven by the difference

between the low and high quintiles. Finally, we acknowledge

that principal component analysis to derive dietary patterns

involves several arbitrary decisions (19). Nevertheless, we

found good reproducibility and validity over time of dietary

patterns defined by factor analysis with data from an FFQ in

a parallel cohort of men (45). We also performed a principal

component analysis with individual foods, without grouping

them a priori, and this sensitivity analysis was highly consis-

tent with the primary results.

In summary, we report prospective data on the association of

dietary patterns with the risk of newly diagnosed COPD. Weidentified the prudent and the Western patterns and found that

both are associated, in different directions, with risk of COPD.

Confirmation of these findings in other populations, particularly

among men, is warranted. These data provide additional evi-

dence about the beneficial effect of a diet rich in fruit and veg-

etables and suggest a deleterious effect of a more traditional

Western diet. The mostimportant public health message remains

smoking cessation, but these data suggest that diet might also

affect COPD risk. Guidance for nutritional education and inter-

vention might be easier to translate for dietary patterns than

guidance in term of specific nutrients.

We thank Gary Chase and Karen Corsano for invaluable assistance withthe implementation of thestudy.We alsothankRong Chen and RuiJiang for

their help with the data set.

The authors responsibilitieswere as followsRV: study conceptionand

planning, statistical programming and data analysis, data interpretation, pri-

mary manuscript preparation, and funding; TTF: data collection, refinement

of dietary pattern exposures, and data analysis; RGB: study conception and

planning, creation of supplementalquestionnaire data set, and funding; FBH:

statistical expertise and data interpretation; WW: data collection, statistical

expertise, and funding; CAC: study conception and planning, creation of

supplemental questionnaire data set, data analysis, data interpretation, and

funding. Allauthorscontributed to thedraftingof thereport andapprovedthe

final version. None of the authors had a personal or financial conflict of

interest.

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