Discusses chronic obstructive pulmonary disease (COPD) with specific emphasis on nutrition. Includes sections: "Epidemiology and pathogenesis; Pathogenesis and natural history; Nutrition and the developing lung; Nutrition and adult lung injury; Obesity and the patient with COPD; Weight loss and the patient with COPD; Metabolic abnormalities; Nutrition for the COPD patient; Hydration; Calcium and COPD; Conclusions; [and] References". Includes 32 references. Duplicates Bates 2062775940.
- Report- Scientific
- Burke-Huber, M.
- Carter, R.
- Huber, Gary L., M.D. (Harvard University: Conducted Smoke Inhalation Studies)
Testified for industry
- Lorillard Counsel
- Named Person
- Kirchner, K. Ms.
- Air pollution
- Alcohol consumption
- Alpha-1-antiprotease deficiency
- British hypothesis
- Childhood respiratory illness
- Chronic bronchitis
- Chronic Obstructive Pulmonary Disease
- Dutch hypothesis
- Genetic factors
- Inherent airway reactivity
- Lifestyle factors
- Nutritional factors
- Occupational factors
- Pulmonary infections
- Small airways disease
- Thesaurus Term
- Adverse effects
- Human research
- industry sponsored research
- Research activity
- Socioeconomic group
- tobacco use
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NUTRITION AND COPD
Gary L. Huber, M.D., Rick Carter, Ph.D.
and Mary Burke-Huber, R.T.T.
University of Texas Health Center
Tyler, Texas 75 710
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Nutrition and COPD
Chronic obstructive pulmona .ry disease (COPD) is the term given to the disorder
that occurs in patients who have a limitation of airflo~v that persists over time.
Characteristically, the airflow obstruction is most evident on expiration, and can be
quantified easily by standard spirometry in a physician's office, at the hospital bedside,
or in a pulmonary function laboratory. The obstruction to airflow is not significantly
reversed by inhalation of a bronchodilator drug. Generally, the connotation COPD is
commonly employed to include chronic bronchitis, emphysema, bronchiectasis, and
small airways disease. Thurlbeck and others have emphasized, however, that patients
with chronic airflow obstruction cannot usually be classified readily into these precise
"subcategories," in that a wide spectrum of airway and parench,vmal pathology exists
among patients with COPD and varies from patient to pauent .
Epidemiology and Pathogenesis. COPD is a common disease. Recent national
__.~_~_~rev.a.lence data are not available, but extrapolation_of assessments derived within the
past decade estimate that there are more than 1 9 million Americans with COPD ~2~. This
is comparable, by one evaluation, to about 1 4 percent of the adult male and 8 percent
of the adult female population~31. Accurate prevalence data, however, are hard to come
by, and some would place the true magnitude of the disease at a higher level.
COPD often is a debilitating disorder. It accounts each year for an estimated 1 7
million or probably more annual office visits and over 2 million hospitalizationsTM.
COPD is the second leading cause of disability in the United States, and the fifth most
common cause of death. The duration of hospitalization of patients with exacerbations
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of COPD is approximately 50 percent longer than is the duration of hospitalization for
the general population. Patients with COPD have about twice the amount of annual
disability and restricted activity, compared to the general adult population, and the cost
to the American economy in health care and in loss of productivity is enormous. The
most important risk factors that have been reported for the development of COPD
include a history, of tobacco cigarette smoking, age, air pollution, occupational exposures,
male sex, alpha-l-antiprotease deficiency, and childhood respiratory illness. Other
potentially important contributing risk factors include socioeconomic status, inherent
airway reactivity, a history of atopy, alcohol intake, and other lifestyle behaviors.
Prevalence rates for COPD are most strongly influenced by a history of tobacco
smoking, with 15 percent to as high as 50 percent of smokers reporting ~symptoms of
"smoker's cough" or chronic bronchitis (persistent cough and sputum production),
..__._.c9..~p~ed to a much lower rate (3% to 6%) of these symptoms in the nonsmoking
populationIsz). Only about 15 percent of smokers, however, develop disabling
obstructive airflow disease15), raising questions regarding genetic predisposition, inter-
personal variations, influence of childhood exposure, and other factors.
Pathogenesis and Natural History.. Extensive research has been conducted on the
pathogenesis and natural history of COPD, giving rise to two dominant theories. One,
the "British hypothesis," is based strongly on the role of pulmonary infections and
exposures to inhaled irritants as key mediators in the development of COPD. The other,
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Nutrition and COPD
the "Dutch '., " " .
m pothes~s, focuses on the role of airxvav reactivity and hypersensitivity in
response to inhaled irritating substances in the pathogenesis of COPD.
With ageing, the normal lung of nonsmokers progressively loses structure and
function, the latter at the rate of about 20 to 40 ml/year of the forced expiratory volume
at one minute (FEV~) in nonsmoking males, from age B0 to 5c~6); the rate of decline
diminishes . Smokers,
accelerates after about age 45, but in older age the rate of decline _ (7)
in general, lose lung function at a somewhat greater rate (44 to 55 ml/yr of FEV~) and
a susceptible minority of smokers have a more accelerated rate of decline (70 to 120
ml/yr of FEV~). Furthermore, it appears that the pulmonary function of individuals
"tracks over time," meaning that those who have low levels of function in childhood
usually will have lower levels over the further course of their life, and those who lose lung
function more rapidly in their earlier years may be susceptible to an accelerated decline
..... ~vith ageingIs'9).
Some studies indicate that these changes in lung function "plateau," or remain
stable, through a certain period of early and middle-aged adulthood~°). The duration of
this plateau may infl.uence, or even determine, the susceptibility of an individual to the
later development of clinically significant COPD. For instance, a susceptible smoker may
have a shorter plateau, and thus an earlier and greater decline in lung function, than a
less susceptible smokert~t). For the susceptible smoker, the rate of decline in lung
function bears a relationship to duration and amount of smoking (pack-years), with ~
loss of about 7 ml to 8 ml of FEVt per pack-year of cigarette consumption~21.
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Nutrition and the Developing Lung. Nutrition (especially undernutrition and/or
malnutrition) has been a topic of developmental concern. The lungs of the patient ~4th
COPD can be viewed in a continuum, starting with their earliest prenatal development
through the very end stages of the disease. In this continuum, the integrity of the human
lung is dependent on good nutrition from the beginning to the end1'31. In its earliest
development, lung growth and the ultimate number of lung cells that eventually develop
are reduced when nutrient intake is diminished, either in vitro or in early life. This
reduction in cellular number, quantified by DNA and RNA analyses, may be permanent,
and it is not yet clear whether later "catch-up" lung growth can occur. The role that any
nutritionally-induced developmental abnormalities, and the associated nutritionallv-
influenced genetic imprinting for ultimate susceptibility, might play in rendering the
adult lung ultimately vulnerable to the development of COPD is, at this time,
conjectural. If, however,, lung structure and function do indeed fu]iy "track" over time 18.9~
and if the adult "plateau" in pulmonary structure and function are determined, in part,
by nutritional factors in early development/L°l, the susceptibility of the adult lung to
destruction by tobacco smoke and other factors may be to some degree preprogrammed
early in life by a relationship of genetic propensity interacting with nutritional and other
Protein-calorie malnutrition, as well as vitamin-mineral micronutrient
malnutrition, do at any stage of life significantly adversely effect the various components
of connective tissue in the lung~'3'~4). Collagen, proteoglycans, fibronectin, laminin, and
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Nutrition and COPD
chondronectin are important for normal cellular growth, adhesion, migration and
morphology in the developing lung. Malnutrition reduces the synthesis of key proteins
inherently necessary to these processes. In experimentally induced protein-calorie
malnutrition, there is a net decrease in alveolar number and total internal surface area,
with an increase in alveolar size(15'16), constituting morphologic changes consistent with
the definition of emphysema~17~.
The micronutrients copper, zinc, pyridoxine, ascorbic acid, vitamin E and vitamin
A are all important to the integrity of the lungs(~3). Copper deficiency induces
morphologic lesions with abnormally diluted terminal air spaces and a fragmented,
greatly altered elastin meshwork; these lesions appear to be due to impaired collagen and
elastin maturation and development. Pyridoxine deficiency is associated with similar,
but usually less severe, results. Ascorbic acid, vitamin E, and vitamin A (primarily as its
precursor, beta-carotene) are integrally important to the antioxidant defenses against
lung injury at all stages of life.
Nutrition and Adult Lung Injury. A recent symposium was convened, and a
subsequent monograph published, to address the influence of nutrition on tobacco-
associated health risks, including COPD~). Tobacco smoke exposure is the strongest
risk factor associated with the development of small airways disease, chronic bronchitis,
and emphysema. Pathophysiologic mechanisms employed to explain this relationship
are multifactorial, but the more prominent emerging theories have focused on the role
of oxidant injury to the airways and lung parenchyma. The potential oxidant injury
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associated with smoking has at least two maior theoretical components. First, the
fleshly-generated mainstream tobacco smoke that the consumer of cigarettes inhales is
initially rich in free radicals and a number of oxidant species. These oxidants are very.
unstable, and whether or not they reach the distal lung parenchyma is as yet unknown.
It is assumed, however, that inhalation of tobacco smoke may provide the lung with a
large burden of oxidant molecules potentially capable of inducing injury over time.
The second potential pathogenic mechanism for inducing lung injury by cigarette
consumption involves the activation of intrapulmonary defense cells, particularly the
pulmonary alveolar macrophage and polymorphonuciear leukocytes that are recruited
from the_cir~culation to the lung parenchyma and alveolar spaces following exposure to
tobacco smoke. These inflammatory cells become activated, presumably in response to
the physical or chemical particulate load delivered to the lung by smoking. During the
process of ingesting, or phagocytizing, foreign particles, these inflaimmatory cells release
additional reactive oxidant molecules. The body normally has adequate levels of anti-
oxidant compounds on board to neutralize these reactive species. However, with a long-
term, chronic process, especially when undemutrition is present, the anti-oxidant defense
mechanisms are compromised. This may be especially true when recurring acute
exacerbations of COPD are present. When the reactive oxidants generated by these
intrapulmonary defense cells interact with the lung parenchyma and airways, tissue
damage can ensue.
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There is now extensive literature reporting that the dietary, patterns of smokers,
as a general group, are unhealthy, compared to nonsmokers; these studies have been
summarized recently"91. Some of these studies reveal consistent trends -- the more an
individual smokes, the worse, in general, is his/her dietary intake1~9221. Of significant
note, smokers tend to be most deficient in their dietary intake of those nutrients they
perhaps need the most - the anti-oxidants beta-carotene (and vitamin A), ascorbic acid,
vitamin E, folate, pyridoxine, and other related micronutrients, including zinc and
copper. Smokers generally do not consume adequate amounts of the natural fruits and
vegetables which supply many of the important vitamins and trace elements.
Furthermore, smokers have. higher intakes of alcohol, cholesterol and other fats, and
coffee. The importance of these observations to the identification of those individuals
most susceptible to developing significant COPD remains to be determined, but it is
clear that understanding the biology of micronutrients will be key-to clarification of the
genetic expression of disease susceptibility.
Obesity. and the Patient with COPD. One most commonly thinks of weight loss
and malnutrition when the nutritional status of COPD patients is considered. It must
not be forgotten, however, that there is a group of COPD patients that are at the other
end of the spectrum. Excess body weight (excess fat) and obesity are a problem for some
patients with COPD. With excess body weight and a resultant limitation in ventilation,
dyspnea is increased, predisposing the obese COPD patient to deconditioning and
additional weight (fat) gain. Excess body weight in the abdomen displaces the
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diaphragm upxvard and increases the work of breathing. These patients often consume
high caloric foods with little nutritional value, and as a result may additionally experience
trace element malnutrition.
Patients with COPD, who have excess body fat, should be counseled regarding
weight reduction, improved eating habits, and exercise. With weight loss, the work of
breathing will be reduced and dyspnea will lessen. With improved eating habits, trace
element deficits may be restored. Exercise training will assist the patient with control of
body weight and foster better eating habits. Exercise training will also improve muscle
function, lessen dyspnea, and promote increased activities of daily living.
Weight Loss and the Patient with COPD. COPD often becomes a severely
debilitating disease. An association between weight loss, undernutrition/malnutrition
and advanced stages of COPD has been recognized for over three decades. In the
absence of edema or dehydration, body weight provides one-reasonable index of
nutritional status. Body weights of less than 90 percent of predicted ideal body weight
indicate undernutrition/malnutrition1231. By this criterion, up to 40 percent of patients
(and in some evaluations up to 70 percent of patients!) with COPD are
undernourished/malnourished at some point in their disease~241.
A better indicator of body mass depletion is the measurement of free-fat mass.
Free-fat mass can be accurately estimated using skinfolds and appropriate formulas,
bioimpedence, or the "gold standard" hydrostatic weighing. However, hydrostatic
weighing is not practical in a COPD clinical population. The reasons for this degree of
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malnutrition await further elucidation. Unfortunately, most existing data do not
adequately define the components of body weight loss, and no study has yet defined even
total caloric expenditure in COPD patients under free living conditions.
Muscle wasting with COPD (especially in patients with emphysema) appears to
be due to decreased protein synthesis1~3~, as well as probably other factors. There also is
a marked shift in muscle fiber types from the highly fatigue resistant to those which are
fatigue susceptible. Muscle weakness is generalized, and includes the diaphragm and
intercostal muscles, leading to sometimes severe respiratory muscle weakness and, in the
extreme, respiratory, failure. The greater the weight loss, the greater apparently is the
muscle weakness in most patients. Multiple studies have revealed numerous metabolic
abnormalities in the muscles of these patients, the scope of which is beyond this review.
In general, however, there are low intracellular levels of ATP and energy-controlling
phosphagens, leading to intracellular acidosis.
Malnutrition in COPD is associated with increased morbidity and increased
mortality, a greater susceptibility to infection, reduced exercise capadty, a predisposition
to acute and chronic respiratory failure, and cor pulmonaleml. Hypoxemia worsens and
carbon dioxide retention becomes more severe when malnutrition is present. Large
dietary carbohydrate loads may increase the respiratory quotient and CO~ production
in some patients. Recurrent respiratory tract infections, which are common to these
patients, exacerbate protein wasting, further weakening muscle strength. This, then,