Reduced cardiac output accompanying exercise results in respiratory muscle ischemia. There are several strategies clinicians can employ to preserve respiratory muscle function.

Intolerance of physical activity, including activities of daily living, is a universal manifestation of many chronic disease processes, including chronic obstructive pulmonary disease (COPD), pulmonary-artery hypertension (PAH), congestive heart failure (CHF), metabolic pathologies, and myopathies. While each chronic disease process shares similar patient complaints (such as increased dyspnea, exercise intolerance, muscle weakness, and/or fatigue), the underlying pathophysiological processes are diverse and affect bodily systems in different ways. During acute exacerbations of the disease process, the body is further compromised; for some patients, this may represent a life-threatening event. Respiratory muscle weakness has been associated with increased dyspnea, exercise limitation, development of respiratory failure, increased health care utilization, and, in specific situations, increased mortality.1

The respiratory muscles continually undergo remodeling as they adapt to the ever-changing demands of respiration. Muscle remodeling attempts to compensate for a constant imbalance between energy supply and demand so as to optimize the respiratory muscles’ pump action while minimizing energy expenditure for the degree of pathology present.2 As the disease process advances, however, respiratory muscle work increases, sarcomere length-tension relationships change to a mechanically disadvantageous position, atrophy ensues (with muscle fibers destroyed), muscle cross-sectional area is decreased, bioenergetics shift toward anaerobic processes, circulatory performance (perfusion) decreases, and nervous-system activation is compromised.3,4 Further, these chronic processes give rise to remodeling elsewhere in the body, contributing to increased morbidity and mortality.

Only recently have the respiratory muscles been appreciated as something more than simple bellows that move air into and out of the lungs. During quiet breathing, the inspiratory muscles are active; the expiratory muscles are recruited for coughing and to meet increased ventilatory demand or increased load. In COPD, increased respiratory muscle load is attributed to increased airway resistance, reduced dynamic compliance, and dynamic hyperinflation or auto–positive end-expiratory pressure (PEEP).

When lung hyperinflation is present, the diaphragm is shortened and the length-tension relationship of the actin and myosin filaments is compromised, resulting in less force generation being possible at a given neural-activation level. Additional mechanisms of compromise in COPD may include malnutrition, which predisposes the diaphragm to a greater loss in muscle mass in proportion to a patient’s body-weight reduction. Corticosteroids are routinely used to combat exacerbations of the disease and to manage chronic inflammation, yet corticosteroids have negative consequences, including steroid myopathy of respiratory and skeletal muscles, even at low doses.5 Further, electrolyte imbalance and hypoxemia alter muscle function and should be corrected, when possible. These processes contribute to the reduced capacity of the respiratory muscles in COPD and translate to measurable decreases in maximal pressure generation, exhibited as lower values for maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), sniff testing, maximal voluntary ventilation (MVV), and exercise tolerance.

Premature lactic acidosis, ventilation-perfusion abnormalities, activation of the juxtacapillary receptors, altered Pco2 control of ventilation, chronic fibrotic changes, and increased work of breathing are frequently cited as contributing to the imposed exercise limitations and elevated dyspnea associated with CHF.6 A prevailing hypothesis for the dyspnea associated with CHF is that reduced cardiac output accompanying exercise results in respiratory muscle ischemia and, ultimately, respiratory muscle fatigue. Ratings of perceived dyspnea (Borg scores) are associated with indices of respiratory muscle strength, muscle oxygenation, diaphragm work, and FEV1.7 In addition, biopsies of the respiratory muscles in CHF reveal type-I fiber atrophy of the diaphragm.8 Following this line of reasoning, MIP has emerged as an independent predictor of prognosis in CHF and may yield important information regarding a candidate’s suitability for cardiac transplantation.

Exertional fatigue and dyspnea limit activities of daily living in PAH. Symptoms are typically explained by an inability of the overloaded right ventricle to perfuse the lungs and to provide systemic oxygen and nutrient delivery to meet demand.9 Exercise-testing variables and walking distance are better correlated with functional class and prognosis than with hemodynamic function.10-12 Impaired skeletal muscle function has been described in heart failure patients, giving rise to the muscle hypothesis as an explanation for dyspnea and fatigue. Recent data that extend previous observations to the respiratory muscles suggest that respiratory muscle strength is decreased in PAH.13,14

This decrease, however, appears to be unrelated to hemodynamics, blood gases, lung mechanics, exercise capacity, ventilatory efficiency, or functional class. While some of these findings contradict prior reports, indices of respiratory muscle function (such as MIP and MEP) are correlated with the severity of heart failure. These findings suggest that MIP and MEP might be generalized to skeletal muscle weakness secondary to decreased oxygen and nutrient delivery to active muscles. This would predispose the muscles to atrophy, remodeling, altered bioenergetics, and many associated biochemical and histological changes. In addition, overloading the respiratory muscles in PAH accelerates the process, yet the mechanistic processes are not completely understood. These conflicting results often lead to paradoxical conclusions; this is supported by the finding that continuous positive airway pressure (CPAP) improves respiratory muscle strength, but so does selective training of the respiratory muscles.14

Chronic disease typically predisposes patients to an imbalance of energy supply and demand. This imbalance can be amplified by eating behaviors and by the increased demand (seen in chronic disease) for energy, trace elements, and vitamins essential for normal function.15 These degenerative processes are further amplified by medication use, acid-base and electrolyte imbalances, and numerous other factors.

In COPD, one third or more of patients enter nutritional imbalance at some time. Decreases in fat-free mass and weight loss are prevalent, and these conditions are associated with reduced exercise capacity and increased dyspnea. More specifically, phosphorus 31 nuclear magnetic resonance spectroscopy results suggest that nutritional status is related to maximal muscle strength, and that muscle strength can be improved through nutritional intervention.16,17 Good nutrition, however, is only part of the solution, and recent reviews question its ability to correct specific pathophysiological processes independently.18,19

Assessing Function

MIP and MEP are used to assess respiratory muscle strength.20,21 Paying careful attention to detail and ensuring a constant lung volume are essential for accurate results. A major shortcoming for MIP and MEP measurement is the degree of patient effort required. Many measurement trials are often required; if the patient has severe limitations, testing may take a considerable amount of time. Further, the information gained from these measurements is nonspecific. One cannot distinguish among insufficient effort, muscle weakness, and neurological disease.

To address this limitation, two additional techniques have been used: electrical stimulation and magnetic stimulation of the phrenic nerves.22 Magnetic stimulation has the advantage of being pain free (in contrast to electrical stimulation), although it may provide less diaphragm stimulation. These techniques address diaphragm function only, may require esophageal and gastric balloons, and are not measures of global respiratory muscle function.

MVV has been used to assess neuromuscular and respiratory dysfunction. The MVV is compared with the estimated ventilatory capacity using the measured FEV1 times a multiplier (typically 35 to 40).23 Significant differences may indicate neuromuscular disease, abnormal respiratory mechanics, or inadequate effort.

Sniff testing is used to evaluate patients in whom diaphragm paralysis is suspected. The test is simple to perform.24 The patient is instructed to make a short, quick, strong inspiration while under continuous fluoroscopic examination. Decreased excursions or paradoxical motion of the diaphragm indicates diaphragm pathology.

Esophageal or gastric balloons (or both) may be required to assess the pressures generated by the respiratory muscles accurately. This form of measurement is not widely accepted by patients, so other methods have been sought. One compromise is the use of mouth occlusive pressures during stimulation, which might provide a reasonable estimation of the pleural pressure generated.25 While this is the case for healthy subjects, it is less than satisfactory in the presence of lung disease. As an alternative, phonomyography (measurement of the sound signal produced by the diaphragm’s contraction) has been proposed.26,27 The sound signal appears to be directly proportional to the tension developed during contraction.

Improvement Strategies

The imbalance between load and capacity appears pivotal in the genesis of dyspnea and in the development of respiratory failure. Nutritional augmentation, while not of confirmed benefit, should be considered as a means of maximizing the effectiveness of other therapeutic options. When cardiovascular hemodynamics are compromised, interventions aimed at reducing pressure overloads and improving cardiac function should be instituted. Supplemental oxygen may be warranted, especially when hypoxemia is present or oxygen delivery to the tissues is compromised. Surgery to reduce lung volume can reduce hyperinflation and unload the respiratory muscles via markedly decreased auto-PEEP.28,29 Restoration of the muscles’ length-tension relationship will evolve, with corresponding improvements in muscle strength, muscle morphology, neural drive, and energetic processes. The longevity of the positive changes has not been fully evaluated, however, especially considering the different surgical options and various degrees of pathology present. Ventilatory support is typically offered in acute care settings and is essential in severe cases.

CPAP and bilevel positive airway pressure will unload the respiratory muscles to different degrees, allow recovery from fatigue, reinstate energetics, and promote better function with less dyspnea.14,30-32 The role of long-term noninvasive ventilatory support remains uncertain, yet, in severely hypercapnic patients, a benefit does appear to exist. Regular nocturnal ventilatory support has been thought to improve inspiratory muscle strength, but the suspected benefits of this intervention have not been consistently demonstrated; alternative physiological mechanisms may be important.

For decreased respiratory muscle strength and increased fatigue, respiratory muscle training has been advocated and evaluated.33,34 Three technologies have been used: breathing against an inspiratory resistance, breathing against an inspiratory threshold, and normocapnic hyperpnea. The key is to provide a stimulus that is of sufficient intensity to elicit a training response, but that is not so intense as to promote respiratory muscle fatigue or overt failure. To date, no studies have conclusively demonstrated a uniform, predictable response in respiratory muscle training. While many factors contribute to this diversity of findings, improved techniques and isolation of muscle function will promote the understanding of respiratory muscle function and the suitability of the respiratory muscles for training.


The respiratory muscles are a complex, highly integrated system undergoing continual adaptation on the molecular, biochemical, neurological, histological, and morphological levels. Muscle plasticity is pivotal in survival, given the many types of insults presented. The imbalance between load and capacity seems to be critical to optimal function and to the development of overt muscle fatigue. Lung hyperinflation contributes significantly to diaphragm weakness, and therapeutic interventions to reduce hyperinflation are required. The basis for training the respiratory muscles needs to be analyzed critically, given the constant overload against which the respiratory muscles work. Improving circulatory dynamics, correcting hypoxemia, reducing the work of breathing, resting the respiratory muscles, and improving nutritional status may reduce morbidity and improve survival.

Rick Carter, MBA, PhD, is professor and chair, Department of Health, Exercise and Sport Sciences; James S. Williams, PhD, is associate professor, Department of Health, Exercise and Sport Sciences, and adjunct associate professor of physiology, Texas Tech University, Lubbock. For more information, contact [email protected]


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