Nutrition in Respiratory Diseases1
Neal M. Patel
Margaret M. Johnson
1Abbreviations: ARDS, acute respiratory distress syndrome; BMI, body mass index; CF, cystic fibrosis; CO2, carbon dioxide; COPD, chronic obstructive pulmonary disease; ICU, intensive care unit; MIP, maximum inspiratory pressure O2, oxygen; REE, resting energy expenditure; VA, alveolar minute ventilation; VE, total minute ventilation; VT, tidal volume.
Cellular respiration is essential for the functioning of all tissues. Food substrate is converted to usable energy by the formation of high-energy phosphate bonds. Oxygen (O2) fuels this process, and carbon dioxide (CO2) is produced as a byproduct. The respiratory system supplies the necessary O2 and eliminates the CO2 produced. Adequate nutrition is essential for development, growth, and function of the respiratory system. This chapter summarizes the normal structure and function of the respiratory system, the changes encountered with common diseases, and the impact of nutritional status on the epidemiology and pathophysiology of pulmonary disease.
STRUCTURE AND FUNCTION OF THE RESPIRATORY SYSTEM
Control of Breathing
Afferent signals arising from pontomedullary portion of the brainstem control resting rhythmic breathing patterns. Voluntary and involuntary input from higher cerebral centers, and changes in pH and partial pressure of arterial O2 (PaO2) and CO2 (PaCO2), can override these rhythmic impulses and alter respiratory patterns as needed to meet the changing metabolic demands of the organism.
Respiratory Muscles
Inspiration is achieved when a negative intrathoracic pressure is generated by the active contraction of the inspiratory muscles, creating a pressure gradient between the mouth, and the distal air spaces, the alveoli. Moving down this pressure gradient, air fills the lungs until the alveoli and atmospheric pressure equilibrate. Relaxation of the inspiratory muscles returns the thoracic cage to its resting position, thus reversing the pressure gradient and leading to exhalation.
The diaphragm, the primary muscle of respiration, is dome shaped at rest. With contraction, it flattens and descends, increasing both the vertical and anterior-posterior dimensions of the thoracic cage. The diaphragm does not have intrinsic automaticity properties such as cardiac muscle, and thus can fatigue when demand exceeds supply. Both fatigue (1), a reversible inability of a muscle to generate a prior attainable force, and weakness, the chronic inability to attain adequate force, may cause inadequate ventilation.
Diseases directly affecting the respiratory muscles are uncommon, but the respiratory muscles are an important compensatory mechanism in lung disease. In increased demand states such as exercise, or in the presence of muscle dysfunction from malnutrition, the compensatory capacity is overwhelmed leading to diminished functional capabilities.
Lung Parenchyma
The lungs are composed of the conducting airways, the alveoli, and the capillary beds, which form the gas-exchanging
units, the supporting interstitial structures, the pulmonary vasculature, and immune effector cells.
units, the supporting interstitial structures, the pulmonary vasculature, and immune effector cells.
Tracheobronchial Tree (Conducting Airways)
The conducting airways are a series of progressively, dichotomously branching tubular structures extending from the trachea. The trachea and proximal main airways, the bronchi, offer structural support to the airways but do not participate in gas exchange. Gas exchange occurs at the level of the distal respiratory bronchioles and the alveoli. The tracheobronchial tree is lined with ciliated columnar bronchial epithelial cells and submucosal glands that humidify, warm, and filter the inspired air and contribute to the bronchial mucus layer (2).
Smooth muscle, innervated by the parasympathetic and the nonadrenergic, noncholinergic nervous pathways, lines the tracheobronchial tree. Muscle contraction imparts rigidity to the airways and reduces the caliber of the airway lumen resulting in increased resistance to bulk gas flow. Additionally, airway edema, inflammation, and excessive mucus also narrow the airway (2), diminishing gas flow.
Terminal Respiratory Units
The terminal respiratory unit, consisting of respiratory bronchioles, alveolar ducts, and alveoli, is the gas- exchanging unit. Gas exchange occurs at the alveolar- capillary membrane, which consists of the alveolar epithelium and capillary endothelium, their basement membranes, and the contiguous interstitial space (2). Surfactant, a complex phospholipid and protein mixture that lines the alveolus, reduces its surface tension decreasing its tendency to collapse at low lung volumes.
Pulmonary Physiology
The ultimate purpose of the respiratory system is to transfer O2 from the inspired air to the bloodstream and CO2 from the bloodstream to the exhaled air. The respiratory and cardiac systems work in conjunction to provide a continuous supply of oxygenated blood to the peripheral tissues. After circulating to the periphery where O2 is extracted, blood is returned to the right side of the heart and is pumped through the pulmonary arteries to the pulmonary capillaries. At the alveolar-capillary interface, O2 diffuses down a concentration gradient from the O2-rich alveolar gas to the pulmonary capillary blood. Most of the transferred O2 binds to hemoglobin in the red blood cells; a small percentage is dissolved in the plasma. Simultaneously, CO2 diffuses down a concentration gradient from the capillary blood to the alveolus.
O2-enriched gas is continuously replenished at the alveolar level through inspiration. Approximately 30% of each inspired breath remains in the conducting airways and thus does not participate in gas exchange; this is anatomic dead space. A small fraction of each inspired breath reaches alveoli that are not perfused, and thus, do not allow gas transfer. This volume of gas is physiologic dead space. Effective alveolar minute ventilation (VA) is the difference between the total minute ventilation (VE) and the sum of anatomic and physiologic dead space ventilation (Table 99.1).
Efficient gas exchange is contingent on the delivery of gas to perfused alveoli and adequate capillary blood flow. Inadequate gas flow causes perfused alveoli not to be ventilated. The complete absence of ventilation to perfused alveoli is called shunt. Supplying inspired air to nonperfused alveoli increases physiologic dead space, thereby decreasing the effective tidal volume (VT). This is commonly seen in emphysema as a result of capillary bed obliteration.
Increased VE initially can compensate for mismatched gas and blood flow. Ultimately, however, if metabolic demands exceed these compensatory mechanisms, gas exchange abnormalities will develop.
Additional Respiratory System Functions
In addition to gas exchange functions, the lung acts as a “filter” for the blood and also has extensive metabolic functions. The lung synthesizes surfactant and other substances, including histamine and arachidonic acid. The effects of nutrition on these functions are largely unknown.
COMMON PULMONARY PATHOPHYSIOLOGY
Various diseases can affect the respiratory system and ultimately compromise gas exchange. Bulk gas flow can be diminished by airway obstruction or restriction. In obstructive disease, the airway lumen is narrowed, creating increased resistance to flow. Prototypical obstructive diseases include asthma, emphysema, and chronic bronchitis. Decreased compliance of the respiratory system leads to restrictive disease. The loss of compliance can be result from abnormalities in the lung parenchyma, respiratory muscles, or chest wall. Pulmonary fibrosis, the prototypical restrictive disease, is characterized by a loss of compliance of the lung parenchyma as a result of interstitial fibrosis. Other diseases, such as pneumonia and pulmonary edema, decrease the lung compliance by filling the alveolar spaces. Decreased compliance increases the work required to maintain adequate bulk gas flow.
Pulmonary function tests measure exhaled gas volumes and flow rates. Abnormalities in respiratory muscle function decrease the maximum pressures attainable with inspiration and expiration. Arterial blood gas determinations, which measure the arterial pH, PaCO2, and PaO2, can evaluate the efficiency of gas exchange. Other tests, including timed walk tests or cardiopulmonary exercise tests, can more comprehensively assess the interaction of the respiratory and cardiac systems with the peripheral muscles. These tests allow one to measure the impact of various nutritional interventions on lung function.
EFFECTS OF MALNUTRITION ON DEVELOPMENT, STRUCTURE, AND FUNCTION OF THE RESPIRATORY SYSTEM
Development
Both animal and human investigations demonstrate that inadequate nutrition during fetal development is deleterious.
In animal models, fetal malnutrition results in pulmonary hypoplasia (3, 4). Inadequate protein during development diminishes collagen and elastin synthesis and causes pathologic changes similar to those in emphysema (5). The timing of nutrition insults affects their manifestations: Early malnutrition leads to small but normally proportioned animals, whereas later insults result in lung size disproportionately small for body size (6). In humans, a direct correlation exists between low birth weight and subsequent decreases in pulmonary function (7, 8).
Respiratory Muscles
Diaphragm weight correlates with body weight in animal models and both healthy and emphysematous humans (9, 10, 11). Poorly nourished patients have diminished maximal respiratory muscle strength as measured by maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) (11). The extent of muscle strength loss exceeds the loss of muscle mass, a finding suggesting coexistent myopathy of the remaining muscle (11).
The diaphragm is composed of both type I and type II fibers, and malnutrition affects these fibers differently.
In grossly underfed and protein-malnourished animals, the cross-sectional area of both types of fibers is greatly reduced, but the fast-twitch fibers (type II) are quantitatively more affected (12, 13, 14). These observations suggest that malnutrition should diminish peak pressure generation but have a more limited impact on endurance.
Ventilatory Drive
Host Defenses
Malnutrition increases general susceptibility to infections, but it specifically alters pulmonary defense mechanisms.
Animal models of severe malnourishment have demonstrated decreased alveolar macrophage counts (18), phagocytosis, and microbial killing (19). In patients with tracheostomies, nutritional status inversely correlates with lower respiratory tract bacterial colonization (20). Malnourished patients also are predisposed to pulmonary infections because of inadequate clearance of respiratory secretions resulting from ineffective cough from muscle weakness and a greater propensity for alveolar collapse.
PROTOTYPICAL LUNG DISEASES: RELATION TO NUTRITIONAL STATUS
Critical Illness and Acute Respiratory Failure
Critically ill patients often have multisystem organ failure, commonly including the respiratory system. Respiratory dysfunction is often the result of acute respiratory distress syndrome (ARDS), a syndrome characterized by hypoxemic respiratory failure in the setting of a severe systemic critical illness or isolated pulmonary disease. This section reviews nutritional supplementation in the critically ill patient, with specific attention to ARDS.
Nutrition in Critical Illness: Metabolic Requirements
The nutritional milieu of critical illness is characterized by hypermetabolism, protein catabolism, and insulin resistance leading to impaired glucose use and hyperglycemia.
Because of the inherent complications of both underfeeding and overfeeding, proper estimation of caloric requirements is an essential but challenging task. Energy requirements can be estimated using standard populationbased regression formulas, such as the Harris-Benedict equation (21). However, predictive formulas were derived from physiologically normal subjects at rest and do not address the stress and hypercatabolism of critical illness. “Correction stress factors,” ranging from 1.2 to 1.5 times the calculated resting energy expenditure (REE) are suggested, but their correlation with indirect calorimetry measurements is often suboptimal (22, 23).
O2 consumption ([V with dot above]O2), which can be used as an estimate of caloric needs, can be calculated by the Fick equation
[V with dot above]O2 = CO ÷ (Cao2 − Cvo2)
where CO is the cardiac output and Cao2 and Cvo2 are the O2 content of arterial and mixed venous blood, respectively. This approach requires invasive monitoring with a pulmonary artery catheter, and a relatively stable patient.
Alternatively, [V with dot above]O2 can be assessed with a metabolic cart that measures exhaled gases directly. This technique is not universally available, and it requires expensive equipment, technical expertise, and a stable fraction of inspired O2. Despite these limitations, this technique offers the advantage of continuous measurements rather than intermittent snapshots of one’s caloric needs.
The [V with dot above]O2 (mL/minute) obtained by either the Fick equation or by the gas exchange method is converted to kilocalories/day by using the caloric value of O2 (4.69 to 5.05 kcal/L of O2 consumed) or the modified Weir equation if VCO2 (CO2 production) is also known (24).
Substrate Supplementation: Implications for Ventilatory Requirements
Patients with acute respiratory failure typically are in a hypercatabolic state and rely in part on proteolysis of protein
stores to meet their immediate metabolic needs. Nutritional supplementation may spare consumption of endogenous protein, although the amount of glucose required differs from that needed in normal fasting adults (25). Intravenous fat emulsions, if administered with a minimum of 500 kcal/day of carbohydrate (26), and exogenous protein supplementation also can limit proteolysis (26).
stores to meet their immediate metabolic needs. Nutritional supplementation may spare consumption of endogenous protein, although the amount of glucose required differs from that needed in normal fasting adults (25). Intravenous fat emulsions, if administered with a minimum of 500 kcal/day of carbohydrate (26), and exogenous protein supplementation also can limit proteolysis (26).
The appropriate mix of carbohydrate, fat, and protein calories must be individualized. Carbohydrates produce more CO2 during oxidation than fat or protein. For every molecule of glucose completely oxidized, six molecules of CO2 are produced, giving a respiratory quotient of 1 (Table 99.1), whereas the oxidation of fat and protein produces less CO2, with a respiratory quotient of 0.7 and 0.8, respectively. VA must be increased when CO2 production increases to maintain a normal partial pressure of arterial PaCO2. In the presence of underlying lung disease, the ability to increase VA may be limited.
TABLE 99.1 DEFINITION OF RESPIRATORY PHYSIOLOGY TERMS AND ABBREVIATIONS | ||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Timing and Route of Nutritional Support
Malnutrition at the onset of critical illness is associated with poor outcomes, and improved clinical outcomes are associated with nutritional support (27). However, the optimal composition and timing of the initiation of feedings remains uncertain (28).
Enteral Feeding and Pulmonary Issues.
Enteral feeding is most commonly accomplished through a nasogastric tube or nasoduodenal tube. Potential mechanical risks are associated with enteric feeding tubes, including misplacement in the tracheobronchial tree or pleural space; thus, radiographic confirmation of proper placement is mandatory before initiation of feeding. It is uncertain if the risk of aspiration differs between gastric and duodenal feedings (29, 30). Postpyloric feedings should be considered in those with significant gastroesophageal reflux disease, high risk for aspiration, on high doses of sedatives/paralytics, or intolerance to gastric feeding. Maintaining patients in a semirecumbent position, rather than supine, decreases the risk of aspiration (31).
Parenteral Nutrition and Pulmonary Issues.
Parenteral nutrition is delivered through a central or peripheral vein. Central vein infusions allow for the delivery of more concentrated solutions; thus, it minimizes obligate fluid requirements. In patients with ARDS, limited fluid intake shortens the duration of mechanical ventilation (32). The addition of heparin (33), sterile line placement, and restriction of catheter use exclusively to alimentation (34) may limit catheter-associated complications such as thrombosis and infection. Infusion of lipid emulsions decrease diffusing capacity and oxygen saturation by causing ventilation and perfusion mismatch; thus, its use is typically avoided if possible.
Acute Respiratory Distress Syndrome and Acute Lung Injury
Optimal nutritional support in ARDS has been investigated. Patients with ARDS have lower levels of dietary antioxidants, including vitamin E, vitamin C, retinol, and β-carotene, than healthy controls (35). Decreased plasma concentrations of tocopherol and vitamin E and elevated lipoperoxides indicative of oxidative damage commonly are seen in patients with ARDS (36); findings prompting speculation that antioxidant supplementation may be beneficial. Although a prospective randomized trial examining the efficacy of supplementation with α-tocopherol and vitamin C did not decrease pulmonary mortality or the development of ARDS, the intervention group did have a significantly lower incidence of multisystem organ failure, shorter duration of intensive care unit (ICU) stay, and mechanical ventilation (37).
The specific dietary lipid alters the profile of eicosanoids produced by inflammatory cells, which may have clinical relevance. Linoleic acid, an n-6 fatty acid, is converted to arachidonic acid, which is the precursor of many proinflammatory prostaglandins and leukotrienes (38). Alternatively, linolenic acid, an n-3 fatty acid, is converted
to eicosapentaenoic acid, which produces eicosanoids with much less inflammatory potential (38).
to eicosapentaenoic acid, which produces eicosanoids with much less inflammatory potential (38).
Gadek et al prospectively assessed the effects of enteral feedings enriched with eicosapentaenoic acid (and fish oil), γ-linolenic acid, and antioxidants in 98 patients with ARDS. Compared with controls, the treatment group had more ventilator-free and ICU-free days, earlier improvements in oxygenation, less new organ failure development, and a nonsignificant trend toward decreased mortality (16% versus 25%; p = .31) (39).
Currently, the ARDS network is performing a prospective, randomized trial of initial trophic enteral feeding followed by advancement to full-calorie enteral feeding versus early advancement to full-calorie enteral feeding. This trial will be conducted simultaneously with a one comparing omega-3 fatty acid, γ-linolenic acid, and antioxidant supplementation with a comparator.
Chronic Lung Diseases
Chronic lung disease generally is classified as obstructive or restrictive, based on the primary physiologic abnormality, as discussed. Obstructive lung diseases include asthma, chronic bronchitis, emphysema, cystic fibrosis (CF), and bronchiectasis. Emphysema and chronic bronchitis are most commonly the result of tobacco abuse and are collectively labeled chronic obstructive pulmonary disease (COPD).
Restrictive diseases include infiltrative or fibrotic diseases of the lung parenchyma as well as extrapulmonary processes such as muscular weakness, thoracic cage abnormalities, and neurologic diseases that result in similar physiologic impairments. Investigations of the interrelationships between nutrition and chronic pulmonary disease have focused on COPD, asthma, and CF.
Obstructive Lung Disease
COPD causes substantial and increasing morbidity and mortality in the United States and worldwide. An imbalance of proteases and antiproteases resulting in destruction of the elastin and collagen lung matrix causes emphysema. Tobacco use greatly contributes to this imbalance. Tobacco smoke causes neutrophils to migrate into the lung and release elastase and other proteases. Oxidants inhaled from tobacco smoke and released from activated inflammatory cells recruited into the airways impair endogenous antiproteases.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
