Original Article
Dietary n-3 Polyunsaturated Fatty Acids and Smoking-Related Chronic Obstructive Pulmonary Disease
N Engl J Med 1994; 331:228-233July 28, 1994
- Abstract
Background
Fish contain n-3 polyunsaturated fatty acids, principally eicosapentaenoic acid and docosahexaenoic acid, which are known to interfere with the body's inflammatory response and may be of benefit in chronic inflammatory conditions.
Methods
We studied the relation between the dietary intake of n-3 fatty acids and chronic obstructive pulmonary disease (COPD) in 8960 current or former smokers participating in a population-based study of atherosclerosis. Intake of fatty acids was estimated with a dietary questionnaire. The presence of COPD was assessed by a questionnaire on respiratory symptoms and by spirometry. Three case definitions of COPD were used: symptoms of chronic bronchitis (667 subjects), physician-diagnosed emphysema reported by the subject (185 subjects), and spirometrically detected COPD (197 subjects).
Results
After control for pack-years of smoking, age, sex, race, height, weight, energy intake, and educational level, the combined intake of eicosapentaenoic acid and docosahexaenoic acid was inversely related to the risk of COPD in a quantity-dependent fashion. The adjusted odds ratio for the highest quartile of intake as compared with the lowest quartile was 0.66 for chronic bronchitis (95 percent confidence interval, 0.52 to 0.85; P<0.001 for linear trend across the range of intake values), 0.31 for physician-diagnosed emphysema (95 percent confidence interval, 0.18 to 0.52; P for linear trend, 0.003), and 0.50 for spirometrically detected COPD (95 percent confidence interval, 0.32 to 0.79; P for linear trend, 0.007).
Conclusions
A high dietary intake of n-3 fatty acids may protect cigarette smokers against COPD.
Media in This Article
Table 1
Characteristics of 8960 Subjects Who Had Ever Smoked Cigarettes.Table 2
Dietary Intake of Fish and Selected n-3 Polyunsaturated Fatty Acids by 8960 Subjects Who Had Ever Smoked Cigarettes.Article Activity
- Article
Polyunsaturated fatty acids of the n-3 series, primarily eicosapentaenoic acid (C20:5) and docosahexaenoic acid (C22:6), are abundant in fish and may affect numerous health-related characteristics favorably1. Extensive research has focused on the relation of these fatty acids to coronary heart disease, but more recently it became evident that they also have antiinflammatory properties1. Dietary supplementation with eicosapentaenoic acid and docosahexaenoic acid interferes with the production of several mediators of inflammation2-5 and has clinical benefit in patients with chronic inflammatory diseases, such as rheumatoid arthritis6 and ulcerative colitis7.
Chronic bronchitis and emphysema, referred to collectively as chronic obstructive pulmonary disease (COPD), are important causes of morbidity and mortality among persons who smoke cigarettes8. The pathogenic mechanisms linking cigarette smoke to these diseases are not entirely understood, but inflammatory mediators are likely to be involved,9 including those that may be influenced by n-3 fatty acids10. We therefore hypothesized that smoking-related COPD is inversely related to dietary intake of n-3 fatty acids.
Methods
Study Subjects
The study sample was drawn from the participants in the Atherosclerosis Risk in Communities (ARIC) study,11 a prospective study of atherosclerotic disease. We used probability sampling to recruit a cohort of 15,800 men and women 45 to 64 years of age from 1986 through 1989 in four U.S. communities: Forsyth County, North Carolina; Jackson, Mississippi; the suburbs of Minneapolis; and Washington County, Maryland. Blacks were oversampled in Forsyth County and were sampled exclusively in Jackson, whereas in the other two communities the subjects were overwhelmingly white. The response rate was 46 percent in Jackson and ranged from 65 to 67 percent in the other three communities. After providing informed consent, the subjects underwent a comprehensive examination that included a dietary assessment and measurements of lung function. The study was approved by the institutional review boards of the participating universities.
Smoking-Related Measurements
The subjects were classified as current smokers, former smokers, or persons who had never smoked. The lifetime number of pack-years of cigarette smoking was computed by multiplying the average number of cigarettes smoked per day by the number of years of smoking and dividing by 20. Each subject's respiratory symptoms were elicited by a standardized interviewer-administered questionnaire adapted from the Epidemiology Standardization Project12.
Anthropometric and Demographic Measurements
Height was measured to the nearest centimeter with a vertical metal ruler. Weight was measured to the nearest pound and converted to kilograms; the subjects wore lightweight examination gowns and no shoes. Educational level was categorized as being below the high-school level, at the level of a high-school diploma or the equivalent, or beyond the high-school level.
Dietary Assessment
Usual dietary intake was estimated from an interviewer-administered questionnaire modified from a 61-item questionnaire developed and validated by Willett and colleagues13. The subjects were asked how often, on average, they had consumed certain foods in portions of a specified size (e.g., 85 to 113 g [3 to 4 oz] of canned tuna fish) during the preceding year. There were nine possible responses, ranging from “almost never” to “more than six times per day.” Daily intake of nutrients was calculated by multiplying the nutrient content of each food in the portion specified by the frequency of daily consumption and summing the results. The nutrient content of each food was obtained from the Harvard nutrient data base,13 for which the primary source was the Department of Agriculture handbook14.
Fish consumption, the main dietary source of n-3 fatty acids,15 was estimated by summing the reported consumption of three items: 85 to 113 g of canned tuna fish, 85 to 142 g (3 to 5 oz) of dark-meat fish (e.g., salmon, mackerel, swordfish, sardines, or bluefish), and 85 to 142 g of other fish (e.g., cod, perch, or catfish). The eicosapentaenoic acid and docosahexaenoic acid content of these foods was estimated to be 190 and 500 mg, respectively, for tuna fish, 560 and 780 mg for dark-meat fish, and 240 and 460 mg for other fish.
Spirometric Measurements
Lung function was measured according to a standard protocol based on the guidelines of the Epidemiology Standardization Project12 and the American Thoracic Society,16 using a Collins Survey II volume-displacement spirometer (Warren E. Collins, Braintree, Mass.) that was connected to an IBM PC/XT computer by the calibration and analytic programs of the Pulmo-Screen II system (S&M Instrument, Doylestown, Pa.). The computer programs were modified to accommodate the ARIC protocols for linearity and electronic storage of spirograms. The technicians were trained and certified, and their performance was closely monitored by the staff of the pulmonary-function reading center.
During at least five forced expirations, the technician attempted to obtain three acceptable spirograms at least two of which had similar results, within 5 percent, for forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). The acceptability and reproducibility of the spirograms were indicated by the computer program, confirmed by the technician observing the volume-time spirograms, and ultimately determined at the reading center. The largest FEV1 and the largest FVC on any of the acceptable tests were used16. Sex-specific predicted values for FEV1 and FVC, adjusted for age and height, were computed from Crapo's equations17. For blacks, equation-derived predictions were multiplied by 0.8818.
Definitions of COPD
Three definitions were used to identify subjects with COPD: symptoms of chronic bronchitis, emphysema diagnosed by a physician and reported by the subject, and spirometrically detected COPD. Chronic bronchitis was defined by persistent cough and production of phlegm on most days for at least three consecutive months of the year for two or more years. Emphysema was defined by a positive response to three questions: Have you ever had emphysema? Do you still have it? and Was it confirmed by a doctor? Spirometrically detected COPD was defined by a measured FEV1 value ≤ 65 percent of the predicted value in the presence of a normal FVC value ( ≥ 80 percent of the predicted value). The cutoff point chosen for an abnormal FEV1 corresponded to the fifth percentile of the distribution in the cohort, as recommended elsewhere18. A fourth, composite group comprised subjects who met any of the three case definitions.
For each of the four groups a comparison group was selected, composed of subjects in the cohort who had ever smoked. For the chronic-bronchitis group, the comparison group included subjects with no persistent cough or production of phlegm. For the emphysema group, the comparison group included subjects who responded negatively to the question “Have you ever had emphysema?” and who had normal FEV1/FVC values ( ≥ 70 percent). For the group with spirometrically detected COPD, the comparison group included subjects with measured FEV1 values ≥ 80 percent of the predicted value. Finally, for the composite group (those with COPD according to any of the three case definitions), the comparison group included subjects who were defined as not having COPD according to any of the three definitions.
Statistical Analysis
Because COPD is related to cigarette smoking, these analyses focused on the 9178 subjects who had ever smoked. To improve the validity of the dietary data, we excluded subjects from the study if their reported daily energy intake seemed implausible (below the 1st or above the 99th percentile of the sex-specific distribution in the entire cohort). After the exclusion of these subjects, there remained 8960 subjects who had ever smoked. The analyses involving spirometric measurements were limited to 7902 subjects for whom reproducible spirograms had been obtained.
The relation between dietary intake of n-3 fatty acids (the intake of eicosapentaenoic acid and docosahexaenoic acid combined) and COPD in each of the four groups of subjects with COPD was first studied according to quartiles of intake. Crude odds ratios were computed, with the lowest quartile used as the reference group. Multiple logistic-regression models were used to adjust the odds ratios for energy intake and potentially confounding variables, including pack-years of cigarette smoking, age, race, sex, height, weight, and level of education. The models for spirometrically detected COPD did not include age, race, sex, and height as covariates, because adjustment for these variables was made in computing the predicted FEV1 and FVC values17,18. The results of the center-specific analyses were generally consistent with those of the main analysis, but there were fewer subjects and therefore the estimates were less stable. Also, modeling of interaction terms between quartiles of n-3 fatty acid intake and site revealed no statistical evidence of interaction. Linear trends were examined by modeling n-3 fatty acid intake as a continuous variable. The possibility of multiplicative interactions of race and sex with fatty acid intake was examined in several models; none were detected. Finally, sex- and race-specific multiple linear regression analysis was used to evaluate the association between fatty acid intake and spirometric measurements (FEV1, FVC, and FEV1/FVC). Computations were performed with SAS software19. All reported P values are two-tailed.
Results
Of the 8960 subjects who had ever smoked (Table 1Table 1
Characteristics of 8960 Subjects Who Had Ever Smoked Cigarettes.), 55 percent were former smokers and 45 percent were current smokers. Symptoms compatible with chronic bronchitis were reported by 667 subjects (7 percent). Two percent (185 subjects) reported having been given a diagnosis of emphysema, and 2 percent (197 subjects) met the spirometry-based definition of COPD. Although the three groups of subjects with COPD overlapped only partially (e.g., 26 subjects were included in both the emphysema group and the group with spirometrically detected COPD, whereas 39 were included in both the chronic-bronchitis group and the group with spirometrically detected COPD), the subjects with chronic bronchitis and those who reported having emphysema both had evidence of airway obstruction. For example, the mean FEV1, expressed as a percentage of the predicted value, was 61 percent among the subjects with emphysema and 77 percent among the subjects with chronic bronchitis; among the 4313 subjects classified as not having COPD according to any of the three definitions, the mean FEV1 was 100 percent.The average reported consumption of any type of fish was only about two servings per week (Table 2Table 2
Dietary Intake of Fish and Selected n-3 Polyunsaturated Fatty Acids by 8960 Subjects Who Had Ever Smoked Cigarettes.). Ten percent of the subjects reported almost never consuming fish. There was a very close correlation between the intake of eicosapentaenoic acid and that of docosahexaenoic acid (Pearson correlation coefficient, 0.97) and between the combined intake of these fatty acids and fish consumption (correlation coefficient, 0.96). Intake of n-3 fatty acids correlated only weakly with indexes of lifetime smoking, such as the number of pack-years of cigarette smoking or the average number of cigarettes smoked per day (correlation coefficient, -0.06 for both).For all three case definitions, COPD was strongly and inversely related to the intake of n-3 fatty acids in a dose-response fashion (Table 3Table 3
Relation between COPD and Dietary Intake of n-3 Polyunsaturated Fatty Acids in Subjects Who Had Ever Smoked Cigarettes.). The crude odds ratios for the highest quartile of intake as compared with the lowest quartile ranged from 0.34 (95 percent confidence interval, 0.21 to 0.54) for the emphysema group to 0.59 (95 percent confidence interval, 0.47 to 0.75) for the chronic-bronchitis group. Multivariate adjustment did not alter the crude estimates materially (Table 3), nor did further adjustment for alcohol consumption (data not shown). The results of tests for linear trend using the continuous variable for intake were all statistically significant (P<0.001 for chronic bronchitis, P = 0.003 for emphysema, P = 0.007 for spirometrically detected COPD, and P<0.001 for COPD by any definition). The results were similar in analyses stratified according to current and former smoking status.Fish consumption had a similarly inverse relation to smoking-related COPD (Table 4Table 4
Adjusted Odds Ratios for COPD in Subjects Who Had Ever Smoked Cigarettes, According to Quartile of Fish Consumption.). The highest quartile, in which the subjects had a median intake of four servings of fish per week, had an adjusted odds ratio of COPD about half that of the lowest quartile, whichever definition of COPD was used (all P<0.005 for linear trend).Since COPD reflects the most severe impairment of lung function, we evaluated further the relation of n-3 fatty acid intake and fish consumption to continuous measurements of lung function. Among the 6228 white subjects who had ever smoked and had reproducible spirograms, higher intake of n-3 fatty acids and fish predicted better lung function in both men and women (Table 5Table 5
Differences in Lung Function Predicted among White Subjects in Association with Specified Increments in Intake of n-3 Polyunsaturated Fatty Acids or Fish.). For the 1674 black subjects who had ever smoked, the associations were not consistently positive, and none were statistically significant (data not shown).There were too few cases of COPD to evaluate among the 6546 subjects who had never smoked. Only 13 of these subjects reported a diagnosis of emphysema, and only 20 met the definition of spirometrically detected COPD. The predictions from linear regression models for those of either race who had never smoked were, for the most part, not statistically significant. The results derived from linear models for the 4179 white subjects who had never smoked are shown in Table 5.
Discussion
Although this study does not establish that the dietary intake of n-3 fatty acids or fish protects against smoking-related COPD, that hypothesis is biologically plausible. The pathogenesis of chronic bronchitis, emphysema, and deterioration of lung function in smokers is likely to involve inflammatory processes9,10,20. Cigarette smoking is associated with an accumulation of neutrophils in the lung,21 increased leukocyte production of leukotriene B4,22 a potent inflammatory metabolite of arachidonic acid, and enhanced release of reactive oxygen metabolites (e.g., superoxide anions) by alveolar macrophages23. Both leukotriene B4 and reactive oxygen metabolites may stimulate mucus secretion in the airways,10 and the latter have also been implicated in the proteinase-antiproteinase theory of emphysema24.
Supplementing the diet with n-3 fatty acids interferes with all these pathogenic mechanisms, because n-3 fatty acids reduce the chemotactic responsiveness of neutrophils, inhibit the production of leukotriene B4 from arachidonic acid in leukocytes, and decrease the production of superoxide anions in leukocytes2,3. These fatty acids also decrease the production of other putative mediators of pulmonary inflammation, including platelet-activating factor, interleukin-1, and tumor necrosis factor4,5. Although most of the antiinflammatory effects of n-3 fatty acids have been demonstrated with dietary supplements that provide doses much higher than the average intake in this study, very small increments in intake may have health benefits, possibly the result of a cumulative effect1.
Little information is available about a potential protective effect of dietary n-3 fatty acids or fish consumption against COPD. Data from the Second National Health and Nutrition Examination Survey suggested an inverse relation between fish consumption and current bronchitis25. In a study of telephone workers in the United States and Japan, societies with low and high fish consumption, respectively,26 the Japanese workers had less evidence of chronic bronchitis and somewhat higher mean FEV1 values than their American counterparts with equivalent levels of cigarette smoking27. Mortality from COPD is low in Japan despite a high prevalence of cigarette smoking28. Of course, numerous factors other than fish consumption could account for these findings.
We are uncertain why n-3 fatty acid intake was not associated with continuous measurements of lung function in the black subjects we studied who had ever smoked. Since the number of blacks was smaller, the statistical power of our study to detect a weak association was limited. Another explanation may be the somewhat lower reproducibility of the dietary data among the black subjects in the study (unpublished data). In the logistic-regression models, however, there was no statistical evidence of a differential effect according to race.
Several limitations of this cross-sectional analysis should be noted. First, fish consumption may be a surrogate for some other protective factor against COPD among the subjects who have ever smoked, or COPD may have changed their dietary habits and reduced their fish consumption. Spurious cross-sectional associations may also have been observed if the relation of fish consumption to COPD was different among the study subjects as compared with either nonparticipants who smoked or those who died of COPD at a young age. Second, dietary intake is hard to measure accurately, although estimates of n-3 fatty acid intake based on similar questionnaires correlate with concentrations of these fatty acids in plasma phospholipids and adipose tissue29,30. Finally, confounding by cigarette smoking or other variables may not have been eliminated through statistical modeling.
The findings reported here suggest a role for dietary intake of n-3 fatty acids and fish consumption as protective factors against COPD and deterioration of lung function among cigarette smokers.
Presented in part at a meeting of the Society for Epidemiologic Research, Minneapolis, June 10-12, 1992.
Supported under contracts (NO1-HC-55015, NO1-HC-55016, NO1-HC-55018, NO1-HC-55019, NO1-HC-55020, NO1-HC-55021, and NO1-HC-55022) with the National Heart, Lung, and Blood Institute.
We are indebted to Donna Neal and Patricia Smith, of the ARIC Project Office; to Kay Paton, Jeannette Bensen, Delilah Posey, Amy Haire, Carol Summers, Catherine Burke, Deanna Horwitz, and Carmen Woody, of the Forsyth County Field Center; to Bobbie Alliston, Jane Johnson, Clinton Smith, and Robert Smith, of the Jackson Field Center; to Elizabeth Justiniano, John O'Brien, Leone Reed, and Shirley Van Pilsum, of the Minneapolis Field Center; to Carol Christman, Sonny Harrell, Joel Hill, and Joan Nelling, of the Washington County Field Center; to Valerie Stinson, Pam Pfile, Hoang Pham, and Teri Trevino, of the Central Hemostasis Laboratory; to Louis Wijnberg, of the Collaborative Studies Coordinating Center; and to Laura Kemmis and Mike Wickersheimer for assistance in the preparation of the manuscript.
Source Information
From the Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis (E.S., A.R.F., S.L.M.); the Johns Hopkins School of Hygiene and Public Health, Baltimore (M.S.T., G.W.C., M.S.); the Environmental Epidemiology Service, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy (V.G.); the Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, Md. (M.W.H., P.D.S.); and the Collaborative Studies Coordinating Center, University of North Carolina, Chapel Hill (W.-J.K.).
Address reprint requests to Dr. Shahar at the Division of Epidemiology, School of Public Health, University of Minnesota, 1300 S. Second St., Suite 300, Minneapolis, MN 55454-1015.
- References
References
1
Simopoulos AP . Omega-3 fatty acids in health and disease and in growth and development. Am J Clin Nutr 1991;54:438-463
Web of Science | Medline2
Lee TH ,Hoover RL ,Williams JD , et al. Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotriene generation and neutrophil function. N Engl J Med 1985;312:1217-1224
Full Text | Web of Science | Medline3
Fisher M ,Levine PH . Effects of dietary omega3 fatty acid supplementation on leukocyte free radical production. World Rev Nutr Diet 1991;66:245-249
Medline4
Sperling RI ,Robin J-L ,Kylander KA ,Lee TH ,Lewis RA ,Austen KF . The effects of N-3 polyunsaturated fatty acids on the generation of platelet-activating factor-acether by human monocytes. J Immunol 1987;139:4186-4191
Web of Science | Medline5
Endres S ,Ghorbani R ,Kelley VE , et al. The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med 1989;320:265-271
Full Text | Web of Science | Medline6
Kremer JM ,Jubiz W ,Michalek A , et al. Fish-oil fatty acid supplementation in active rheumatoid arthritis: a double-blinded, controlled, crossover study. Ann Intern Med 1987;106:497-503
Web of Science | Medline7
Stenson WF ,Cort D ,Rodgers J , et al. Dietary supplementation with fish oil in ulcerative colitis. Ann Intern Med 1992;116:609-614
Web of Science | Medline8
Tockman MS, Khoury MJ, Cohen BH. The epidemiology of COPD. In: Petty TL, ed. Chronic obstructive pulmonary disease. 2nd ed. rev. New York: Marcel Dekker, 1985:43-92.
9
Niewoehner DE . Cigarette smoking, lung inflammation, and the development of emphysema. J Lab Clin Med 1988;111:15-27
Medline10
Hoogsteden HC, van Hal PTW. Mediators of the induction of nonallergic pulmonary inflammation. In: Bray MA, Anderson WH, eds. Mediators of pulmonary inflammation. New York: Marcel Dekker, 1991:185-277.
11
The ARIC Investigators
Web of Science | Medline12
Ferris BG . Epidemiology Standardization Project (American Thoracic Society). Am Rev Respir Dis 1978;118:Suppl:1-120
Web of Science | Medline13
Willett WC ,Sampson L ,Stampfer MJ , et al. Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol 1985;122:51-65
Web of Science | Medline14
Consumer and Food Economics Institute. Composition of foods: raw, processed, prepared. Agriculture handbook no. 8 series. Washington, D.C.: Agricultural Research Service, Department of Agriculture, 1976-1989.
15
Hepburn FN ,Exler J ,Weihrauch JL . Provisional tables on the content of omega-3 fatty acids and other fat components of selected foods. J Am Diet Assoc 1986;86:788-793
Web of Science | Medline16
American Thoracic Society
Web of Science | Medline17
Crapo RO ,Morris AH ,Gardner RM . Reference spirometric values using techniques and equipment that meet ATS recommendations. Am Rev Respir Dis 1981;123:659-664
Web of Science | Medline18
American Thoracic Society
CrossRef | Web of Science | Medline19
SAS/STAT user's guide: version 6. 4th ed. Cary, N.C.: SAS Institute, 1990.
20
McGowan SE ,Hunninghake GW . Neutrophils and emphysema. N Engl J Med 1989;321:968-970
Full Text | Web of Science | Medline21
MacNee W ,Wiggs B ,Belzberg AS ,Hogg JC . The effect of cigarette smoking on neutrophil kinetics in human lungs. N Engl J Med 1989;321:924-928
Full Text | Web of Science | Medline22
Zakrzewski JT ,Barnes NC ,Piper PJ ,Costello JF . The detection of 5-lipoxygenase and cyclo-oxygenase products in sputum of patients with chronic bronchitis and bronchiectasis. Prostaglandins 1987;33:663-674
CrossRef | Web of Science | Medline23
Hoidal JR ,Fox RB ,LeMarbe PA ,Perri R ,Repine JE . Altered oxidative metabolic responses in vitro of alveolar macrophages from asymptomatic cigarette smokers. Am Rev Respir Dis 1981;123:85-89
Web of Science | Medline24
Janoff A . Biochemical links between cigarette smoking and pulmonary emphysema. J Appl Physiol 1983;55:285-293
Web of Science | Medline25
Schwartz J ,Weiss ST . Dietary factors and their relation to respiratory symptoms: the Second National Health and Nutrition Examination Survey. Am J Epidemiol 1990;132:67-76
Web of Science | Medline26
Organisation for Economic Co-operation and Development. Food consumption statistics: 1964-1978. Paris: OECD, 1981.
27
Comstock GW ,Stone RW ,Sakai Y ,Matsuya T ,Tonascia JA . Respiratory findings and urban living. Arch Environ Health 1973;27:143-150
Medline28
Aoki M . Epidemiology of chronic airways diseases in Japan. Chest 1989;96:Suppl:343S-349S
Web of Science | Medline29
Silverman DI ,Reis GJ ,Sacks FM ,Boucher TM ,Pasternak RC . Usefulness of plasma phospholipid N-3 fatty acid levels in predicting dietary fish intake in patients with coronary artery disease. Am J Cardiol 1990;66:860-862
CrossRef | Web of Science | Medline30
London SJ ,Sacks FM ,Caesar J ,Stampfer MJ ,Siguel E ,Willett WC . Fatty acid composition of subcutaneous adipose tissue and diet in postmenopausal US women. Am J Clin Nutr 1991;54:340-345
Web of Science | Medline
- Citing Articles (34)
Citing Articles
1
Abdelkader Ali-Nehari, Seon-Bong Kim, Yang-Bong Lee, Hye-youn Lee, Byung-Soo Chun. (2011) Characterization of oil including astaxanthin extracted from krill (Euphausia superba) using supercritical carbon dioxide and organic solvent as comparative method. Korean Journal of Chemical Engineering
CrossRef2
R di Giuseppe, A Arcari, M Serafini, A Di Castelnuovo, F Zito, A De Curtis, S Sieri, V Krogh, N Pellegrini, H J Schünemann, M B Donati, G de Gaetano, L Iacoviello. (2011) Total dietary antioxidant capacity and lung function in an Italian population: a favorable role in premenopausal/never smoker women. European Journal of Clinical Nutrition
CrossRef3
Sonia Moorthy, Ning Cheung, Ronald Klein, Eyal Shahar, Tien Y. Wong. (2011) Are Lung Disease and Function Related to Age-Related Macular Degeneration?. American Journal of Ophthalmology 151:2, 375-379
CrossRef4
Barbara A Forey, Alison J Thornton, Peter N Lee. (2011) Systematic review with meta-analysis of the epidemiological evidence relating smoking to COPD, chronic bronchitis and emphysema. BMC Pulmonary Medicine 11:1, 36
CrossRef5
Fumi Hirayama, Andy H. Lee, Colin W. Binns, Naoko Hiramatsu, Mitsuru Mori, Koichi Nishimura. (2010) Dietary intake of isoflavones and polyunsaturated fatty acids associated with lung function, breathlessness and the prevalence of chronic obstructive pulmonary disease: Possible protective effect of traditional Japanese diet. Molecular Nutrition & Food Research 54:7, 909-917
CrossRef6
Bakhtiar Tartibian, Behzad Hajizadeh Maleki, Asghar Abbasi. (2010) The effects of omega-3 supplementation on pulmonary function of young wrestlers during intensive training. Journal of Science and Medicine in Sport 13:2, 281-286
CrossRef7
J. A. Nettleton, J. L. Follis, M. B. Schabath. (2009) Coffee Intake, Smoking, and Pulmonary Function in the Atherosclerosis Risk in Communities Study. American Journal of Epidemiology 169:12, 1445-1453
CrossRef8
F. Sahena, I.S.M. Zaidul, S. Jinap, N. Saari, H.A. Jahurul, K.A. Abbas, N.A. Norulaini. (2009) PUFAs in Fish: Extraction, Fractionation, Importance in Health. Comprehensive Reviews in Food Science and Food Safety 8:2, 59-74
CrossRef9
Manal S. Tawfik. (2009) Proximate Composition and Fatty Acids Profiles in Most Common Available Fish Species in Saudi Market. Asian Journal of Clinical Nutrition 1:1, 50-57
CrossRef10
J. M. Samet. (2008) Commentary: George W. Comstock's Contributions to Respiratory Disease Epidemiology. American Journal of Epidemiology 168:7, 794-795
CrossRef11
(2008) Honors and Awards * Bibliography of Peer-Reviewed Journal Articles. American Journal of Epidemiology 168:7, 845-854
CrossRef12
Rick Carter, Brian L Tiep, Rebecca E Tiep. (2008) The Emerging Chronic Obstructive Pulmonary Disease Epidemic. Disease Management & Health Outcomes 16:5, 275-284
CrossRef13
A.R. Rahbar ., I. Nabipour ., Z. Amiri .. (2007) Effects of Omega-3 Fatty Acids on Serum Lipids and High Sensitivity C Reactive Protein in Cigarette Smokers. Journal of Biological Sciences 7:8, 1368-1374
CrossRef14
G. Perretti, A. Motori, E. Bravi, F. Favati, L. Montanari, P. Fantozzi. (2007) Supercritical carbon dioxide fractionation of fish oil fatty acid ethyl esters. The Journal of Supercritical Fluids 40:3, 349-353
CrossRef15
S. Tricon, S. Willers, H. A. Smit, P. G. Burney, G. Devereux, A. J. Frew, S. Halken, A. Host, M. Nelson, S. Shaheen, J. O. Warner, P. C. Calder. (2006) Nutrition and allergic disease. Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy Reviews 6:5, 117-188
CrossRef16
Se-Kwon Kim, Eresha Mendis. (2006) Bioactive compounds from marine processing byproducts – A review. Food Research International 39:4, 383-393
CrossRef17
L. Forli. (2005) Inhaled corticosteroids and risk of osteoporosis in asthma - reply. Journal of Internal Medicine 258:3, 295-295
CrossRef18
M. Decramer, O. Selroos. (2005) Asthma and COPD: differences and similarities. International Journal of Clinical Practice 59:4, 385-398
CrossRef19
Irfan Rahman. (2005) The Role of Oxidative Stress in the Pathogenesis??of COPD. Treatments in Respiratory Medicine 4:3, 175-200
CrossRef20
Esther Granot, Ron Kohen. (2004) Oxidative stress in childhood—in health and disease states. Clinical Nutrition 23:1, 3-11
CrossRef21
Artemis P Simopoulos. (2002) Omega-3 fatty acids in wild plants, nuts and seeds. Asia Pacific Journal of Clinical Nutrition 11:s6, S163-S173
CrossRef22
N.M. SIAFAKAS, E.G. TZORTZAKI. (2002) Few smokers develop COPD. Why?. Respiratory Medicine 96:8, 615-624
CrossRef23
O.O. Smith, P.J. Helms. (2001) Genetic/environmental determinants of adult chronic obstructive pulmonary disease and possible links with childhood wheezing. Paediatric Respiratory Reviews 2:2, 178-183
CrossRef24
C. Tabak, H. A. Smit, D. Heederik, M. C. Ocke, D. Kromhout. (2001) Diet and chronic obstructive pulmonary disease: independent beneficial effects of fruits, whole grains, and alcohol (the MORGEN study). Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy 31:5, 747-755
CrossRef25
Fogarty, Britton. (2000) The role of diet in the aetiology of asthma. Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy 30:5, 615-627
CrossRef26
Erik B Schmidt, Helle A Skou, Jeppe H Christensen, Jørn Dyerberg. (2000) n-3 fatty acids from fish and coronary artery disease: implications for public health. Public Health Nutrition 3:01,
CrossRef27
Pierre Broun, Sharmeen Gettner, Chris Somerville. (1999) GENETIC ENGINEERING OF PLANT LIPIDS. Annual Review of Nutrition 19:1, 197-216
CrossRef28
Mangalam K. Sridhar. (1999) Nutrition and lung health. Proceedings of the Nutrition Society 58:02, 303-308
CrossRef29
Henriette A. Smit, Linda Grievink, Cora Tabak. (1999) Dietary influences on chronic obstructive lung disease and asthma: a review of the epidemiological evidence. Proceedings of the Nutrition Society 58:02, 309-319
CrossRef30
Magnussen, Richter, Taube. (1998) Original Article. Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy 28:Suppl. 5, 187-194
CrossRef31
Stephen L. Archer. (1996) Fish oil as a therapy for lung disease. Nutrition 12:5, 372-374
CrossRef32
C.V. Oddis, O.H. Mayer, M.S. Finkel. (1996) Inotropic, chronotropic, and radioligand binding characteristics of leukotriene B4 in cardiac myocyte, papillary muscle, and membrane preparations. Prostaglandins, Leukotrienes and Essential Fatty Acids 54:3, 223-228
CrossRef33
D.F. Horrobin. (1995) Abnormal membrane concentrations of 20 and 22-carbon essential fatty acids: A common link between risk factors and coronary and peripheral vascular disease?. Prostaglandins, Leukotrienes and Essential Fatty Acids 53:6, 385-396
CrossRef34
S. ENDRES, R. DE CATERINA, E. B. SCHMIDT, S. D. KRISTENSENJ. (1995) n-3 Polyunsaturated fatty acids: update 1995. European Journal of Clinical Investigation 25:9, 629-638
CrossRef
