Nutritional countermeasures, coupled with other good health habits, should be implemented when COPD is diagnosed. First a of two-part article.
Chronic obstructive pulmonary disease (COPD) is a significant worldwide cause of morbidity, health care utilization, and mortality. COPD is the fourth leading cause of death in the United States and affects roughly 10% of the population.1 Approximately 80% to 90% of COPD cases result from long-term exposure to tobacco smoke (direct or passive).2 A genetic form of COPD results from a lack of a1-antitrypsin (AAT), causing emphysematous changes in the lung.3 The resulting protease-antiprotease imbalance promotes early degradation of lung tissue, interruption of normal gas exchange, and ongoing shortness of breath with nutritional depletion. Alveolar destruction, air trapping, and formation of bullae characterize emphysema. Pulmonary function studies demonstrate airway obstruction, increased lung volume, and decreased diffusion capacity for carbon monoxide.
Chronic bronchitis is an inflammatory process promoting mucus secretion and bronchial narrowing. It is estimated that about 23.6 million individuals or 13.9% of the adult United States population have some degree of COPD while an estimated 2.4 million adults or 1.4% have moderate to severe disease.4 Symptoms include chronic cough, sputum production, frequent clearing of the throat, and shortness of breath. This group tends to be somewhat overweight, with a reduction in lean muscle mass.
Bronchiectasis, another chronic disease process of the lung not directly associated with tobacco smoke exposure, disproportionately affects females.5,6 While its underlying causes are yet to be identified, chronic colonization by respiratory pathogens is ongoing, promoting destruction of the bronchial wall, chronic inflammation, increased sputum production, dyspnea, and weight loss.6
Emphysema results from inflammation of the airways and alveolar spaces that promotes alveolar destruction and hyperinflation. The primary culprit is cigarette smokeinduced inflammation that eventually attacks the alveolar cells, destroying elastin. Through elastin degradation, the lung becomes less compliant and hyperinflated through air trapping. The work of breathing increases, gas transfer is impaired, and dyspnea increases. Further, smoking accelerates the destruction of lung tissue when AAT deficiency exists. There are now several replacement AAT products on the market, but replacements are expensive, and their long-term efficacy is unknown.
It is estimated that approximately a third of patients with COPD experience some degree of malnutrition in the later stages of disease. It is, therefore, reasonable to assume that many additional patients initiate (or have habitual) eating patterns early in the disease process that eventually contribute to a nutritional imbalance, but this has not been well studied.
Early studies7 suggested that diet-induced thermogenesis might be operative in patients with COPD, increasing the caloric expenditure associated with the disease process. These early observations have not prevailed; recent evidence7-9 indicates that there is minor thermogenesis associated with food consumption. The increase in caloric expenditure is small, however, and should not significantly affect the overall nutritional status of the COPD patient. Other causes of hypermetabolism (such as moderate hyperthyroidism) are not commonly associated with wasting, as patients are generally able to increase their food intake appropriately. If these patients also have COPD, their consumption of food may be curtailed due to increased shortness of breath experienced while eating.
There is evidence suggesting that adequate tissue oxygenation must exist for proper nutrition to be achieved. Recent data from the transtracheal-oxygen trials10,11 have demonstrated that patients with transtracheal oxygen gain weight and feel better overall. It is not known whether oxygenation itself is responsible for improved nutrient utilization from foods, or if total caloric intake is greater. Transtracheal-oxygen administration shifts pulmonary mechanics to an improved functional position, reduces the work of breathing, and lessens dyspnea.12 Further, appetite may improve due to decreased dyspnea or because the taste of food improves.13
Medications may predispose patients to increased risk for malnutrition. Specific respiratory medications are associated with gastrointestinal irritation, poor appetite, and a hypermetabolic state. For example, bronchodilators, such as b2-agonists and theophyllines, have stimulant effects on resting energy expenditure and total daily energy expenditure. Corticosteroids are used sparingly to counter inflammatory insults not well managed using other pharmacological options; they promote muscle proteolysis (perhaps through the ubiquitin-proteasome pathway), inhibit protein synthesis, inhibit the transport of amino acids into the muscle, decrease bone mineralization, and promote fluid retention, among other effects.
The quality of lung development and health depends on optimal nutrient intake throughout life. Lung growth and lung-cell populations are reduced when nutrient intake is diminished, either in vitro or in early life. The observed decrease in cell number, quantified by DNA and RNA analysis, may be permanent. While the association of nutrition and lung growth is known, the role nutrition plays in genetic imprinting for susceptibility is speculative. Conversely, if lung structure and function track over time, and if the adult plateau in pulmonary structure and function is regulated, in part, by nutritional factors in early life, then susceptibility to pulmonary irritants such as tobacco smoke may, in some degree, be programmed by genetic and nutritional interdependencies.
Protein-calorie and vitamin-mineral micronutrient imbalances may adversely affect various connective-tissue components of the lung.14 Collagen, proteoglycans, fibronectin, laminin, and chondronectin are essential for normal cellular growth, adhesion, migration, and morphology in the developing lung. Malnutrition reduces the synthesis of these key proteins. In experimentally induced protein-calorie malnutrition, alveolar number is decreased, total internal surface area is diminished, and alveolar size is increased.14,15 These morphological changes are consistent with the definition of emphysema.
The micronutrients copper, zinc, pyridoxine, ascorbic acid, vitamin E, and vitamin A are important for maintaining the integrity of the lung.14 Copper deficiency induces morphological lesions characterized by abnormally dilated terminal airspaces and a greatly altered elastin matrix. This alteration appears to result from impaired collagen and elastin maturation and development. Pyridoxine deficiency appears similar morphologically and is typically less severe. Ascorbic acid, vitamin E, vitamin A (especially its precursor b-carotene), and cofactors of antioxidant enzymes such as selenium are antioxidants that may exert protective effects throughout life. Non-nutritive compounds present in the diet such as flavonoids are also known for their antioxidant capacities. Thus, the nutritional possibilities for improving lung function and decreasing morbidity and mortality are numerous. Additional studies are required to fully elucidate the overall benefits of increasing foods rich in antioxidants and/or providing antioxidants as supplements.
Adult Lung Injury
Tobacco-smoke exposure remains the strongest risk factor for the development of small-airway disease, bronchitis, and emphysema. While the mechanism for pathophysiological lung processes is multifactorial, several theories have been put forth and are supported by ongoing research. These include the role of oxidant injury16 to the airways and lung parenchyma and the activation of intrapulmonary defense cells (macrophages and polymorphonuclear leukocytes) that are recruited from the circulation to the lung parenchyma and alveolar spaces.17
Oxidant injury can be initiated through inhalation of freshly generated tobacco smoke rich in free radicals and a number of oxidant species. Because these oxidant species are highly unstable, their ability to affect the distal lung parenchyma and initiate cellular destruction is unclear. Nonetheless, it is assumed that the oxidant burden is sufficiently large and that, over time, these oxidant molecules are capable of overwhelming the protective antioxidants and promoting lung injury. Thus, the process involves a constant oxidant load that erodes the antioxidant capacity of the system, eventually heightening inflammatory processes with superimposed, direct oxygen-radicalmediated injury.
The second proposed mechanism involves the recruitment, activation, degranulation, and digestion of parenchymal cells.18 Macrophages and polymorphonuclear leukocytes are activated, presumably in response to the physiochemical particulate load delivered to the lung by smoking. These activated inflammatory cells are attracted chemotactically to the site, where they degranulate and initiate phagocytosis of both foreign particles and altered normal cell lines in the target area, with a corresponding release of additional oxygen free radicals in the process. This process magnifies the digestive process with ongoing parenchymal cell destruction.
Under normal conditions, the body maintains an adequate level of antioxidant compounds to neutralize reactive oxidant species, but ongoing disease processes siphon off the protective species, compromising the antioxidant defense mechanism. This is especially true when malnutrition is present. Further, acute exacerbations of the disease process amplify the degradative capacities of oxidants and cell-mediated phagocytosis, placing an increasing demand on nutrient replacement. Because smokers tend to be deficient in the macronutrients and micronutrients associated with lung injury, their replacement is paramount. It is established that smokers do not consume adequate amounts of fruits and vegetables rich in antioxidants b-carotene (and vitamin A), ascorbic acid, vitamin E, foliate, pyridoxine, and other related micronutrients, including zinc and copper. Further, smokers consume more alcohol, cholesterol and other fats, and coffee.19
Overweight and Obesity in COPD
Obesity in the United States has reached epidemic proportions.20 Some patients with COPD experience excess body fat and reduced lean muscle mass. Excess fat can be a problem for some COPD patients, especially if abdominal fat is excessive. Excess abdominal fat pushes the diaphragm upward and limits respiratory muscle excursions, shifting respiratory mechanics to a more disadvantageous position. Dyspnea is increased, limiting physical activity and promoting deconditioning, a reduction in lean muscle mass, and greater fat stores. This process confounds the preexisting airway obstruction and amplifies the work of breathing. Thus, for some individuals, caloric restriction and rehabilitation are warranted. Restoration of normal lean body mass with some fat stores may reduce symptoms, morbidity, and mortality.
In the later stages of the disease, COPD becomes disabling. The association between weight loss and malnutrition has been recognized for decades. Several studies have shown that low body weight, expressed as body mass index (BMI) or percentage of ideal body weight, is associated with increased overall mortality, independent of the severity of airway obstruction present.7 Unlike starvation, however, in which the predominant body compartment for weight loss is fat, the weight loss from COPD preferentially involves the loss of muscle mass. This pattern is recognized in other chronic disease processes, as well. Therefore, decreases in body weight should be identified early, with interventions initiated to counter the imbalance at both macronutrient and micronutrient levels.
To the degree that body weight reflects lean muscle mass, it is useful as a surrogate indicator. Under conditions in which body weight does not accurately reflect lean muscle mass (such as obesity), its discriminating power is compromised. Therefore, other indices have been sought. The measurement of fat-free mass (muscle mass or lean body weight) has become practical, and results have strengthened predictive accuracy. Recently, CT scanning of the midthigh has demonstrated muscle wasting in the presence of normal body weight. Multivariate regression has identified midthigh-muscle cross-sectional area and forced expiratory volume in one second as significant predictors of mortality. Thus, for individuals receiving nutritional support, the ultimate aim should be the replenishment of muscle mass; rehabilitation may be warranted to stimulate muscle hypertrophy through facilitated protein synthesis. Others have shown that the lowest risk occurs in normal-weight to overweight subjects, whereas, in severe COPD, mortality continued to decrease with an increasing BMI. For selected patients, high body weight may be protective, yet these studies21 focused only on mortality and did not address quality of life during end-stage COPD. Future trials are needed to determine whether variables other than mortality are affected and to what degree.
Editors note: Part Two of this article appears in the June 2004 issue of RT.
Padmini Shankar, PhD, RD, is associate professor of nutrition and dietetics and Jim McMillan, EdD, is associate professor of nutrition and health sciences at the Jiann-Ping Hsu School of Public Health, Georgia Southern University, Statesboro, Ga. Rick Carter, PhD, MBA, is professor and chair of the Jiann-Ping Hsu School of Public Health.
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