The skeletal muscle—respiratory and peripheral—in chronic airway diseases is the subject of intense research. You can now submit research specifically to the respiratory and skeletal muscle categories for presentation at the annual meeting of the American Thoracic Society. But what's the point of all this research on skeletal muscles? After all, as it was once cleverly pointed out to me, “The essential problem in chronic airflow obstruction remains the lung disease.”

Given that a cure for diseases such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis is years away, there are many reasons to pay attention to the respiratory and peripheral muscles in these diseases. Better medical care has allowed patients with COPD and cystic fibrosis to enjoy a longer life. But prolonged survival also means more time to experience the adverse systemic consequences of a disease. The impairment in respiratory and peripheral muscle function has a major impact on the clinical outcome in patients with COPD and cystic fibrosis. These patients commonly die of hypercapnic respiratory failure, a terminal consequence of respiratory muscle fatigue. Peripheral muscle wasting is also a strong predictor of survival in COPD (1) and cystic fibrosis (2) and it is associated with poor exercise tolerance and quality of life.

Most of the work done on the skeletal muscles in chronic respiratory diseases has been performed in patients with COPD. COPD has a totally different impact on the diaphragm than on the vastus lateralis muscle (3, 4). Whereas adaptation of the diaphragm resembles that associated with endurance training (and should provide greater protection against fatigue), adaptation of the vastus lateralis is characterized by atrophy, switch of fiber type toward more fatigable fibers, and overall reduction in aerobic potential.

The function of the respiratory and peripheral muscles has been much less studied in cystic fibrosis than in COPD, a reflection of the former's lower prevalence. In a typical patient with cystic fibrosis, the strength of the respiratory muscle is preserved while the quadriceps is weakened (5). Preferential impairment of the peripheral muscles is seen in both COPD and cystic fibrosis. This observation is consistent with the diaphragm benefiting from a continuous training stimulus secondary to increased inspiratory impedance in the two conditions.

Intriguingly, diaphragmatic adaptation in cystic fibrosis may go beyond that usually observed in COPD where maximal diaphragmatic strength is lower than in normal individuals (6). In theory, hyperinflation should also impair the force generation of the diaphragm in cystic fibrosis, but normal inspiratory muscle strength is often found in this condition (5).

In this issue of the Journal (pp. 989–994), Pinet and coauthors (7) ingeniously used modern technology to explore respiratory and peripheral muscle function in a noninvasive fashion, and provide a potential explanation for the preservation of diaphragmatic strength in cystic fibrosis. Based on CT scan and echography, the authors show that diaphragmatic mass was preserved in patients with cystic fibrosis despite decreased lean body mass and quadriceps atrophy. Diaphragmatic hypertrophy was even found in some patients. The maintenance or increase in diaphragmatic mass may help counterbalance the adverse consequences of hyperinflation on the force generation. This finding is clearly at variance with patients with COPD in whom diaphragmatic atrophy is usual (3, 8, 9).

This hypertrophic response, however, is neither universal nor always sufficient to fully restore diaphragmatic force production in all patients with cystic fibrosis; Pinet and colleagues (7) found, on average, a reduced diaphragmatic force in their patients. Based on the preservation of diaphragmatic muscle bulk, the authors implicitly suggest that diaphragmatic weakness in their patients is consequent to the diaphragm operating at a disadvantageous position (secondary to hyperinflation) and not to muscle atrophy. Measurements of diaphragmatic strength at the same operational lung volumes in cystic fibrosis and control subjects would have been informative to confirm this hypothesis. A three-dimension plot of lung volume, diaphragmatic mass, and transdiaphragmatic pressure could have shed light on the interplay among these variables.

Although less likely, there are other potential explanations for the presence of diaphragmatic weakness despite normal or even increased muscle mass. A hypertrophic response does not necessarily imply a better capacity to produce force, as dramatically exemplified in Duchenne muscular dystrophy (10). Increased diaphragmatic mass inferred from imaging techniques may not be the result of muscle fiber hypertrophy but rather the expression of adipose and connective tissue deposition. In such a situation, a bigger muscle is not necessarily stronger. Morphological and histological explorations of the diaphragm will be necessary to address this concern. Lung transplantation might make the diaphragm accessible for such studies.

A prevailing concept is that skeletal muscle wasting in cystic fibrosis and COPD may be related to a low-grade chronic systemic inflammation (11). If this were the case, the respiratory and peripheral muscles would be expected to show similar degrees of atrophy. The data provided by Pinet and coworkers (7) are not consistent with the possibility that muscle wasting is entirely due to systemic factors. Either the systemic factors are irrelevant to muscle wasting or their impact is modulated by the level of muscle activation. I favor the latter explanation based on the observation that physical exercise may protect the muscle against the steroid myopathic effects (12).

The study of Pinet and coauthors (7) raises some interesting questions. Why did some patients with cystic fibrosis fail to show diaphragmatic hypertrophy? Why don't we see diaphragmatic hypertrophy in patients with COPD? Differences in age, duration of the disease, sex, degree of hyperinflation, nutritional status, and exposure to systemic corticosteroids may all help explain the variability in diaphragmatic adaptation across patients or diseases. I hope that Pinet and colleagues will pursue their work in a larger group of patients. This should allow useful comparisons between patients with and without diaphragmatic hypertrophy and provide useful clues on the mechanisms of skeletal muscle impairment in chronic airflow obstruction. This line of research is relevant, not only to patients with lung diseases, but also to patients suffering from the many other chronic diseases associated with muscle wasting.

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