© 2002 American Thoracic Society
Evaluating Respiratory Muscle AdaptationsA New ApproachUniversity of Pennsylvania Medical Center Department of Veterans Affairs Medical Center Philadelphia, Pennsylvania In this issue of AJRCCM (pp. 1491–1497), Ramírez-Sarmiento and colleagues (1) present the results of a controlled study of inspiratory muscle training that was performed in patients with severe chronic obstructive pulmonary disease (COPD). The experimental group of patients with COPD received training by breathing through an inspiratory threshold load for 30 minutes 5 days a week for 5 weeks. For each subject, the load was set at 40–50% of the maximal inspiratory pressure. This training protocol is best viewed as containing both strength and endurance components. Control subjects with COPD underwent sham therapy by breathing through the same apparatus—without the load—as the experimental group; the training schedule for the control group was identical to that of the experimental group. After training, the experimental group exhibited increases in both inspiratory muscle strength and endurance, whereas these measurements did not change in the control group. Despite these improvements in inspiratory muscle performance, exercise tolerance did not improve. This study by Ramírez-Sarmiento and coworkers (1) contains additional important data that are novel and unique. Before inspiratory muscle training and after its completion, they obtained biopsies of the external intercostal muscles from the fourth interspace in the anterior axillary line. In this location, the serratus anterior muscle fibers lie superficial to the external intercostals, and the internal intercostal fibers lie deep to the external intercostals; nonetheless, the authors present persuasive arguments that they are obtaining selective biopsies of the external intercostal. After training, the experimental group exhibited increases in the proportion of slow (type I) fibers and decreases in the proportion of fast (type II) fibers; in addition, both fiber types exhibited an increase in cross-sectional area, but only the increase in type II fibers was statistically significant. All of these measurements in the control group showed no differences between pretraining and post-training biopsy specimens. Therefore, the data indicate that the changes in the experimental group represent adaptations elicited by the training, and they are consistent with a training effect (2, 3). To the best of our knowledge, these data represent the first longitudinal (i.e., changes over time in the same subject) histochemical evidence of a human respiratory muscle training effect. These adaptations warrant comment. We hypothesize that the training-induced increase in the proportion of type I fibers resulted from an endurance training effect on "deconditioned" muscle; space constraints prevent elaboration of this concept. In contrast, the increases in fiber-type cross-sectional area are best explained as usual responses to strength-training protocols (2, 3). We have previously hypothesized that chronic endurance training accounts for the diaphragmatic adaptations noted in severe COPD. In contrast to the experimental design of Ramirez-Sarmiento and coworkers, we (4, 5) and others (6, 7) have studied adaptations of the diaphragm to severe COPD by comparing diaphragmatic features in groups of subjects with minimal or no airways obstruction—control groups—with those noted in groups of patients with severe COPD. The term "cross-sectional approach" is applied to this type of experimental design. We (4, 5) and others (6, 7) have noted that severe COPD elicits the following diaphragmatic adaptations: (1) a fast-to-slow transformation in myosin heavy chain isoforms and important myofibrillar regulatory proteins (myosin light chains, troponin subunits, and tropomyosins), (2) an increase in the proportion of type I fibers (to levels that are above any "control data" in the literature) and an accompanying decrease in the proportion of type II fibers, (3) statistically significant decreases in the cross-sectional area of slow (type I fibers) and a tendency of type II fibers to show a decrease in cross-sectional area, (4) marked increases in the diaphragmatic area fraction of type I fibers (the relative contribution of type I fibers to the cross-sectional area of the diaphragm) and an accompanying decrease in the area fraction of type II fibers, (5) increases in mitochondrial volume density, and (6) increases in the mitochondrial oxidative capacity of all fiber types. Despite this relative plethora of data on diaphragmatic remodeling exhibited by patients with severe COPD, the cross-sectional design of these studies does not allow definitive evaluation of our hypothesis that diaphragmatic training accounts for these adaptations. We compare the training effect noted by Ramírez-Sarmiento and coworkers (1) in the external intercostals with our data on diaphragmatic adaptations exhibited by patients with severe COPD. First, both the diaphragm and external intercostal show an increase in the proportion of type I fibers. The increase in the proportion of type I fibers reported by Ramírez-Sarmiento and coworkers (1), however, was not accompanied by any change in the relative contribution of type I fibers to the cross-sectional area of the external intercostal (in the region of the biopsy), whereas the increase in the proportion of type I fibers in the diaphragms of our patients with severe COPD was accompanied by marked increases in the area fraction of type I fibers. How does one explain these differences between the adaptations of the diaphragm and the external intercostal? Conceptually, our major point is that diaphragmatic myofibers are working against the increased load of COPD for 24 hours a day. We presume that this increased activity has gone on for many years, and therefore, the remodeling—that we and others have described—represents chronic adaptations (8). In contrast, based on the available data in the literature (reviewed in 9), we presume that the external intercostals—in the region biopsied by Ramírez-Sarmiento and coworkers (1)—are not active or only occasionally active during resting breathing; however, when an external respiratory load—such as that as that used by Ramírez-Sarmiento and coworkers (1)—is superimposed on the increased airway load of COPD, we hypothesize that the external intercostal myofibers in the region of the biopsies are recruited for the duration of each training interval and that this recruitment accounts for the histologic features of the training effect seen in the post-training biopsy. Therefore, after cessation of training—if the severity of the COPD and respiratory muscle recruitment pattern remain "essentially the same" in the patients of Ramírez-Sarmiento and coworkers—we hypothesize that these training effects will not persist. In conclusion, using cross-sectional comparisons, respiratory muscle biologists have learned much about the adaptations of the respiratory muscles to severe COPD. This cross-sectional approach, however, cannot provide us with information about the effect of various therapeutic interventions (training, lung volume reduction surgery, lung transplantation) on cellular and molecular adaptations in the respiratory muscles. A longitudinal experimental design—similar to that used by Ramírez-Sarmiento and coworkers (1)—would be ideal to answer these questions. However, we must be certain regarding the safety of the biopsy techniques used in this longitudinal approach. REFERENCES
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