Respiratory Muscle Strength in Chronic Obstructive Pulmonary Disease13 DUDLEY F. ROCHESTER, NORMA M. T. BRAUN, and NARINDER S. ARORA
T h e importance of respiratory muscle function in the pathophysiologic features of the chronic obstructive pulmonary disease (COPD) syndrome is highlighted by clinical and physiologic observations. Patients with COPD breathe in an abnormal way, with prominent use of accessory inspiratory muscles, impaired motion of the diaphragm, and, in more severely compromised patients, with asynchronous motions of the abdomen and rib cage (1, 2). Both the work and energy cost of breathing are increased, the latter out of proportion to the former, indicating that respiratory muscle efficiency is decreased (3). Electromyographic observations and analysis of intrathoracic pressure and volume changes indicate that most of the increased work of breathing falls on the inspiratory muscles (4, 5), which seem to be working at a disadvantage in COPD. One of the simplest ways to assess respiratory muscle performance is to estimate respiratory muscle strength by measuring the maximal static inspiratory and expiratory pressures (PImax and PEmax, respectively) at the mouth. Studies in normal subjects (6-8) show that PImax and PEmax vary with lung volume, such that PImax is greatest at residual volume (RV) and PEmax is greatest at total lung capacity (TLC). i From the Pulmonary Division, Department of Internal Medicine, University of Virginia Medical Center, Charlottesville, Va. 22908; the Cardiorespiratory Laboratory, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, N. Y. 10032; and the Department of Medicine, Harlem Hospital Center, New York, N. Y. 10037. 2 This work was supported by grants from the Stony Wold-Herbert Fund, Inc., and grants HL 17813, HLE 00371, and HL 22022 from the National Heart, Lung and Blood Institute.
The PImax decreases progressively from RV through functional residual capacity (FRC) toward TLC; but when corrected for respiratory system recoil, the inspiratory muscle contractile force is relatively constant around FRC at lung volumes ranging from 40 to 60 per cent of TLC. At 75 per cent of TLC, inspiratory muscle force decreases to 80 per cent of the value at FRC, and at higher lung volumes it decreases sharply to approximately 50 per cent of the FRC level at TLC (7). Thus, one would anticipate that hyperinflation of the lung consequent to COPD is a major determinant of inspiratory muscle strength. In normal subjects, the static recoil of the respiratory system (Prs) is approximately —25 to - 3 0 cm H 2 0 at RV and +30 to +35 cm H 2 0 at TLC (7). It is near zero at FRC in patients with COPD, in whom the thorax is normally compliant despite hyperinflation of the lungs (9). The FRC and the RV are close together in COPD because the expiratory reserve volume is small, so we assume that Prs at RV is also near zero, even if RV has increased 2- to 3-fold. This means that to compare values of PImax in patients with COPD with those in normal subjects, it is not necessary to correct the data obtained from the patients, but the predicted normal values of PImax must be corrected for Prs. Byrd and Hyatt (10) measured PImax at RV and PEmax at T L C in 32 patients with COPD. Recalculating their data indicated that the mean ± SD RV in these patients was 74 ± 18 per cent of their predicted TLC. When the observed values of PImax were compared to predicted normal values of PImax that were corrected for Prs, then values of PImax in COPD were distributed evenly around the line that characterized the normal relation between inspiratory
151
152
ROCHESTER, BRAUN, AND ARORA
muscle strength and lung volume. We con- pressure is negative during less strenuous inspiclude from these data that inspiratory muscle ratory efforts (16, 17). To examine further the effect of diaphragmatstrength was normal in that group of patients, except for the effect of increased lung volume. ic resting length on inspiratory muscle strength, This conclusion is at variance with the original Braun and Rochester (14) studied 32 patients interpretation that inspiratory muscles in COPD with COPD and 8 normal subjects. Diaphragare stronger than normal. However, the original matic muscle length was determined roentgenointerpretation was based on normal values of graphically, from chest films taken at RV and PImax uncorrected for the major influence of TLC. To normalize for the sizes of the subjects, Prs at high lung volumes. In subsequent studies diaphragmatic muscle length (DML) at RV of inspiratory muscle strength in COPD, signifi- was divided by height and expressed as the incant decrease in PImax was almost always the dex, DMLI, in cm per cm of height. The patients were categorized as having moderate or severe rule (9,11-17). The strength of the inspiratory muscles con- abnormality according to the deficit in PImax. sidered together, as in measurement of PImax, The results, expressed as mean ± SD values, must be determined to a large extent by the are summarized in table 1. We conclude from weakest muscle of the group. This is because these data that the progressive shortening of the the inspiratory muscles are arranged in series diaphragm from normal to severe COPD is sigaround the thoracic cage. It is probable that the nificantly related to the parallel decreases in extradiaphragmatic inspiratory muscles function PImax. In the severe COPD group, analysis of much better than the diaphragm, as indicated by variance indicated that respiratory muscle studies of Sharp and co-workers (18). They ex- weakness (expressed by the decrease in PEmax) amined the relationship between the resting and increased work of breathing (expressed length of the inspiratory muscles at FRC and by the more severe decrease in 1-sec forced extheir contractile tension, using a roentgeno- piratory volume) also contribute to impairment graphic method to assess muscle length (19) and of inspiratory muscle function. This view is supan assumed ideal length-tension diagram. Ac- ported by the data of Marazzini and associates cording to this analysis, tension in the scalene (12), which show that the rate at which either and sternocleidomastoid muscles is slightly com- inspiratory or expiratory pressure is developed promised, and in the external intercostal mus- (dp/dt) is decreased in COPD, and cannot be cles, tension is markedly decreased by the in- explained satisfactorily by mechanical factors or crease of lung volume in COPD. The diaphragm neural control. Another determinant of respiratory muscle is so foreshortened at FRC that it can develop no active contractile tension at all. These obser- strength is the respiratory muscle mass. In COPD vations are supported by other studies of pa- this might increase consequent to the increased tients with COPD, which show that gastric work of breathing or decrease as a consequence
TABLE 1 INSPIRATORY AND EXPIRATORY MUSCLE STRENGTH, DIAPHRAGM MUSCLE LENGTH INDEX (DMLI), FORCED EXPIRATORY VOLUME IN 1 SEC (FEVx), AND ARTERIAL Pco 2 (Pa C o 2 ) , N 8 NORMAL SUBJECTS AND 32 PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) PImax
Group Normal subjects Patients with COPD M S
N 8 18 14
(cm H20) 116 ± 38 73 ± 18* 33±9+
PEmax
(cm H20)
DMLI
(cm/cm height)
194 ± 5 4
0.32 ± 0 . 0 4
164 ± 4 2 100±29f
0.27 ± 0 . 0 4 * 0.24 ± 0.03*
FEVj
(% pred.)
PaC02
(mm Hg)
105 ± 1 5 43 ± 1 6 * 24±6T
43 ± 3 54 ± 7 * *
Definitions of abbreviations: PImax = maximal inspiratory pressure at the m o u t h ; PEmax = maximal expiratory pressure at the m o u t h ; % pred. = per cent of the predicted normal value; M = moderate decrease in PImax; S = severe decrease in PImax. [Modified f r o m Braun and Rochester (14).] Significantly less than normal value (P < 0.005). "•"Significantly less than value for COPD-M (P < 0.005). **Significantly greater than value for COPD-M (P < 0.005).
153
RESPIRATORY MUSCLE STRENGTH IN COPD
TABLE 2 THE MASS OF T H E D I A P H R A G M IN 19 N O R M A L SUBJECTS, 3 OF WHOM WERE UNUSUALLY MUSCULAR, A N D IN 35 PATIENTS W I T H O U T T H O R A C O P U L M O N A R Y DISEASE, 11 OF WHOM WERE V E R Y POORLY NOURISHED A T T H E T I M E OF D E A T H
Nutritional Status Normal Muscular Good Poor
Observed/Predicted Diaphragm Muscle Mass
Observed/Pred icted Body Weight
(%) 101 148 103 74
±13 ±22 ±13 ±13
P Value
< 0.001 NS < 0.001
(%) 101 1 73 88 59
±17 ± 26 ±16 ±10
P Value
< 0.001 < 0.025 < 0.001
[Modified from Arora and Rochester (26). ]
of poor nutritional status (20). The supporting evidence is contradictory. Ishikawa and Hayes (21) found that the mass and thickness of the diaphragm were increased in COPD. These investigators (21), along with Scott and Hoy (22), found that the cross-sectional diameter or area of diaphragm muscle fibers was also increased in COPD; they attributed the increases in diaphragmatic dimensions to work hypertrophy. Others (23-25), in contrast, have found diaphragm mass, area, or thickness to be significantly diminished in COPD. Steele and Heard (23) attributed this to extrapulmonary factors, such as nutritional status, a view reinforced by Thurlbeck's observation that diaphragm mass was directly proportional to body weight (25). Both Butler (24) and Thurlbeck (25) found significant inverse correlations between diaphragmatic area or mass and the severity of emphysema, suggesting that the abnormally low position of the diaphragm leads to atrophy. Interpretation of these results is made difficult by lack of adequate control data. Most of the control patients were elderly and had other diseases that could affect respiratory muscle mass. To overcome this problem, and to calculate the relationship between diaphragm mass and body weight independent of disease, Arora and Rochester (26) studied 19 normal persons and 35 patients who died of a variety of systemic, infectious, and neoplastic diseases that did not involve the thorax. Patients with obesity, chronic obstructive and restrictive thoracopulmonary disorders, and edematous states were excluded. Normal subjects were defined as persons who had died suddenly of trauma or acute myocardial infarction without overt antecedent clinical illness. Three of the normal subjects were unusually muscular at the time of death.
Eleven of the patients were obviously wasted and were poorly nourished at the time of death. Because diaphragm mass and body weight underwent parallel changes, the effects of disease could not be evaluated from the ratio of diaphragm muscle mass (DMM) to body weight (BW) alone. Therefore, we predicted DMM from the product of DMM/BW in normal subjects (mean ± SD, 3.93 ± 0.43 g per kg) and ideal body weight based on height and sex. The results, with observed DMM expressed as a per cent of predicted normal, are summarized as mean ± SD values in table 2. It can be seen that the mass of the diaphragm muscle increased by more than 70 per cent in muscular persons, but decreased by approximately 40 per cent in patients who died of wasting diseases. This represents an almost 3-fold variation of DMM according to general nutritional and muscular status. In summary, respiratory muscle strength in COPD depends on several factors. Hyperinflation of the lungs places the inspiratory muscles, particularly the diaphragm, at a disadvantageous position on the length-tension curve. Because the inspiratory muscles are in series, and in COPD the diaphragm is the weakest link in the chain, PImax is significantly dependent on the resting length of the diaphragm at RV and FRC. Nonmechanical factors must also be operative. Decreases in PEmax and expiratory dp/dt cannot be explained by mechanical factors alone, and do not seem to result from alterations in neural drive. Studies of the mass of the diaphragm in COPD and other nonpulmonary illnesses suggest that COPD may have a dual effect on respiratory muscle strength: initial increases of strength and hypertrophy in response to the increased work of breathing may be succeeded
154
ROCHESTER, BRAUN, AND ARORA
by decreased strength and atrophy consequent to deteriorating nutritional and generalized muscular status. Whatever the cause, marked diminution of inspiratory muscle strength is associated with dyspnea and hypercapnic respiratory failure (13-15).
References 1. Ashutosh, K., Gilbert, R., Auchincloss, J. R. H., and Peppi, D.: Asynchronous breathing movements in patients with chronic obstructive pulmonary disease, Chest, 1975, 67, 553. 2. Sharp, J. T., Goldberg, N. B., Druz, W. S., Fishman, H. C , and Danon, J.: Thoracoabdominal motion in chronic obstructive pulmonary disease, Am Rev Respir Dis, 1977,115,47. 3. Fritts, H. W., Jr., Filler, J., Fishman, A. P., and Cournand, A.: The efficiency of ventilation during voluntary hyperpnea: Studies in normal subjects and in dyspneic patients with either chronic pulmonary emphysema or obesity, J Clin Invest, 1959,35,1339. 4. Campbell, E. J. M., and Friend, J.: Action of breathing exercises in pulmonary emphysema, Lancet, 1955,2,325. 5. Sukumalchantra, Y., Park, S. S., and Williams, M. H., Jr.: The effect of intermittent positive pressure breathing in acute ventilatory failure, Am Rev Respir Dis, 1965,92,885. 6. Cook, C. D., Mead, J., and Orzalesi, M. M.: Static volume-pressure characteristics of the respiratory system during maximal efforts, J Appl Physiol, 1964,19,1016. 7. Ringqvist, T.: The ventilatory capacity in healthy subjects: An analysis of causal factors with special reference to the respiratory forces, Scand J Clin Lab Invest, 1966, 18 (Supplement 88, p. 1). 8. Black, L. F., and Hyatt, R. E.: Maximal respiratory pressures: Normal values and relationship to age and sex, Am Rev Respir Dis, 1969, 99, 696. 9. Sharp, J. T., van Lith, P., vej Nuchprayoon, C , Briney, R., and Johnson, F. N.: The thorax in chronic obstructive lung disease, Am J Med, 1968,44, 39. 10. Byrd, R. B., and Hyatt, R. E.: Maximum respiratory pressures in chronic obstructive lung disease, Am Rev Respir Dis, 1968, 98, 848. 11. Clausen, J. L., O'Brien, R., and Tisi, G. M.: Maximal inspiratory pressures in patients with hyperinflation, Chem Res, 1974,22,131 A. 12. Marazzini, L., Vezzoli, F., and Rizzato, G.: Intra-
13.
14.
15.
16.
17.
18.
19.
20. 21.
22.
23.
24. 25. 26.
thoracic pressure development in chronic airways obstruction, J Appl Physiol, 1974, 37, 575. O'Connell, J. M., and Campbell, A. H.: Respiratory mechanics in airway obstruction associated with inspiratory dyspnea, Thorax, 1976, 31, 669. Braun, N. M. T., and Rochester, D. F.: Respiratory muscle strength in obstructive lung disease, Am Rev Respir Dis, 1977, 115 (No. 4, Part 2), 91. Gilbert, R., Ashutosh, K., Auchincloss, J. H., Jr., Rana, S., and Peppi, D.: Prospective study of controlled oxygen therapy: Poor prognosis of patients with asynchronous breathing, Chest, 1977,71,456. Gibson, G. J., Clark, E., and Pride, N. B;: Inspiratory muscle function in patients with severe hyperinflation, Am Rev Respir Dis, 1978, 117 (Part 2), 118. Moisan, T. C , Wicks, M. S., Druz, W. S., and Sharp, J. T.: Diaphragmatic function and body position in chronic obstructive pulmonary disease, Am Rev Respir Dis, 1978, 117 (No. 4, Part 2), 378. Sharp, J. T., Danon, J., Druz, W. S., Goldberg, N. B., Fishman, H., and Machnach, W.: Respiratory muscle function in patients with chronic obstructive pulmonary disease: Its relationship to disability and to respiratory therapy, Am Rev Respir Dis, 1974,110 (Supplement, p. 154). Danon, J., Fishman, H. C , Lin, J., Sharif, M., Druz, W. S., and Sharp, J. T.: Measurement of diaphragmatic length in normal individuals and patients with COPD (abstract), Chest, 1976, 70, 423. Sadoul, P.: Les cachexies respiratoires, Bull Physiopathol Respir (Nancy), 1969,5, 3. Ishikawa, S., and Hayes, J. A.: Functional morphometry of the diaphragm in patients with chronic obstructive lung disease, Am Rev Respir Dis, 1973,108,135. Scott, J. W. M., and Hoy, J.: The cross-sectional area of diaphragmatic muscle fibers in emphysema, measured by an automated image analysis system, J Pathol, 1976,120,121. Steele, R. H., and Heard, B. E.: Size of the diaphragm in chronic bronchitis, Thorax, 1973,25,55. Butler, C : Diaphragmatic changes in emphysema, Am Rev Respir Dis, 1976,114, 155. Thurlbeck, W. M.: Diaphragm and body weight in emphysema, Thorax, 1978,33,483. Arora, N. S., and Rochester, D. F.: Effect of general nutritional and muscular status on the human diaphragm, Am Rev Respir Dis, 1977, 115 (No. 4, Part 2), 84.
T h e importance of respiratory muscle function in the pathophysiologic features of the chronic obstructive pulmonary disease (COPD) syndrome is highlighted by clinical and physiologic observations. Patients with COPD breathe in an abnormal way, with prominent use of accessory inspiratory muscles, impaired motion of the diaphragm, and, in more severely compromised patients, with asynchronous motions of the abdomen and rib cage (1, 2). Both the work and energy cost of breathing are increased, the latter out of proportion to the former, indicating that respiratory muscle efficiency is decreased (3). Electromyographic observations and analysis of intrathoracic pressure and volume changes indicate that most of the increased work of breathing falls on the inspiratory muscles (4, 5), which seem to be working at a disadvantage in COPD. One of the simplest ways to assess respiratory muscle performance is to estimate respiratory muscle strength by measuring the maximal static inspiratory and expiratory pressures (PImax and PEmax, respectively) at the mouth. Studies in normal subjects (6-8) show that PImax and PEmax vary with lung volume, such that PImax is greatest at residual volume (RV) and PEmax is greatest at total lung capacity (TLC). i From the Pulmonary Division, Department of Internal Medicine, University of Virginia Medical Center, Charlottesville, Va. 22908; the Cardiorespiratory Laboratory, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, N. Y. 10032; and the Department of Medicine, Harlem Hospital Center, New York, N. Y. 10037. 2 This work was supported by grants from the Stony Wold-Herbert Fund, Inc., and grants HL 17813, HLE 00371, and HL 22022 from the National Heart, Lung and Blood Institute.
The PImax decreases progressively from RV through functional residual capacity (FRC) toward TLC; but when corrected for respiratory system recoil, the inspiratory muscle contractile force is relatively constant around FRC at lung volumes ranging from 40 to 60 per cent of TLC. At 75 per cent of TLC, inspiratory muscle force decreases to 80 per cent of the value at FRC, and at higher lung volumes it decreases sharply to approximately 50 per cent of the FRC level at TLC (7). Thus, one would anticipate that hyperinflation of the lung consequent to COPD is a major determinant of inspiratory muscle strength. In normal subjects, the static recoil of the respiratory system (Prs) is approximately —25 to - 3 0 cm H 2 0 at RV and +30 to +35 cm H 2 0 at TLC (7). It is near zero at FRC in patients with COPD, in whom the thorax is normally compliant despite hyperinflation of the lungs (9). The FRC and the RV are close together in COPD because the expiratory reserve volume is small, so we assume that Prs at RV is also near zero, even if RV has increased 2- to 3-fold. This means that to compare values of PImax in patients with COPD with those in normal subjects, it is not necessary to correct the data obtained from the patients, but the predicted normal values of PImax must be corrected for Prs. Byrd and Hyatt (10) measured PImax at RV and PEmax at T L C in 32 patients with COPD. Recalculating their data indicated that the mean ± SD RV in these patients was 74 ± 18 per cent of their predicted TLC. When the observed values of PImax were compared to predicted normal values of PImax that were corrected for Prs, then values of PImax in COPD were distributed evenly around the line that characterized the normal relation between inspiratory
151
152
ROCHESTER, BRAUN, AND ARORA
muscle strength and lung volume. We con- pressure is negative during less strenuous inspiclude from these data that inspiratory muscle ratory efforts (16, 17). To examine further the effect of diaphragmatstrength was normal in that group of patients, except for the effect of increased lung volume. ic resting length on inspiratory muscle strength, This conclusion is at variance with the original Braun and Rochester (14) studied 32 patients interpretation that inspiratory muscles in COPD with COPD and 8 normal subjects. Diaphragare stronger than normal. However, the original matic muscle length was determined roentgenointerpretation was based on normal values of graphically, from chest films taken at RV and PImax uncorrected for the major influence of TLC. To normalize for the sizes of the subjects, Prs at high lung volumes. In subsequent studies diaphragmatic muscle length (DML) at RV of inspiratory muscle strength in COPD, signifi- was divided by height and expressed as the incant decrease in PImax was almost always the dex, DMLI, in cm per cm of height. The patients were categorized as having moderate or severe rule (9,11-17). The strength of the inspiratory muscles con- abnormality according to the deficit in PImax. sidered together, as in measurement of PImax, The results, expressed as mean ± SD values, must be determined to a large extent by the are summarized in table 1. We conclude from weakest muscle of the group. This is because these data that the progressive shortening of the the inspiratory muscles are arranged in series diaphragm from normal to severe COPD is sigaround the thoracic cage. It is probable that the nificantly related to the parallel decreases in extradiaphragmatic inspiratory muscles function PImax. In the severe COPD group, analysis of much better than the diaphragm, as indicated by variance indicated that respiratory muscle studies of Sharp and co-workers (18). They ex- weakness (expressed by the decrease in PEmax) amined the relationship between the resting and increased work of breathing (expressed length of the inspiratory muscles at FRC and by the more severe decrease in 1-sec forced extheir contractile tension, using a roentgeno- piratory volume) also contribute to impairment graphic method to assess muscle length (19) and of inspiratory muscle function. This view is supan assumed ideal length-tension diagram. Ac- ported by the data of Marazzini and associates cording to this analysis, tension in the scalene (12), which show that the rate at which either and sternocleidomastoid muscles is slightly com- inspiratory or expiratory pressure is developed promised, and in the external intercostal mus- (dp/dt) is decreased in COPD, and cannot be cles, tension is markedly decreased by the in- explained satisfactorily by mechanical factors or crease of lung volume in COPD. The diaphragm neural control. Another determinant of respiratory muscle is so foreshortened at FRC that it can develop no active contractile tension at all. These obser- strength is the respiratory muscle mass. In COPD vations are supported by other studies of pa- this might increase consequent to the increased tients with COPD, which show that gastric work of breathing or decrease as a consequence
TABLE 1 INSPIRATORY AND EXPIRATORY MUSCLE STRENGTH, DIAPHRAGM MUSCLE LENGTH INDEX (DMLI), FORCED EXPIRATORY VOLUME IN 1 SEC (FEVx), AND ARTERIAL Pco 2 (Pa C o 2 ) , N 8 NORMAL SUBJECTS AND 32 PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) PImax
Group Normal subjects Patients with COPD M S
N 8 18 14
(cm H20) 116 ± 38 73 ± 18* 33±9+
PEmax
(cm H20)
DMLI
(cm/cm height)
194 ± 5 4
0.32 ± 0 . 0 4
164 ± 4 2 100±29f
0.27 ± 0 . 0 4 * 0.24 ± 0.03*
FEVj
(% pred.)
PaC02
(mm Hg)
105 ± 1 5 43 ± 1 6 * 24±6T
43 ± 3 54 ± 7 * *
Definitions of abbreviations: PImax = maximal inspiratory pressure at the m o u t h ; PEmax = maximal expiratory pressure at the m o u t h ; % pred. = per cent of the predicted normal value; M = moderate decrease in PImax; S = severe decrease in PImax. [Modified f r o m Braun and Rochester (14).] Significantly less than normal value (P < 0.005). "•"Significantly less than value for COPD-M (P < 0.005). **Significantly greater than value for COPD-M (P < 0.005).
153
RESPIRATORY MUSCLE STRENGTH IN COPD
TABLE 2 THE MASS OF T H E D I A P H R A G M IN 19 N O R M A L SUBJECTS, 3 OF WHOM WERE UNUSUALLY MUSCULAR, A N D IN 35 PATIENTS W I T H O U T T H O R A C O P U L M O N A R Y DISEASE, 11 OF WHOM WERE V E R Y POORLY NOURISHED A T T H E T I M E OF D E A T H
Nutritional Status Normal Muscular Good Poor
Observed/Predicted Diaphragm Muscle Mass
Observed/Pred icted Body Weight
(%) 101 148 103 74
±13 ±22 ±13 ±13
P Value
< 0.001 NS < 0.001
(%) 101 1 73 88 59
±17 ± 26 ±16 ±10
P Value
< 0.001 < 0.025 < 0.001
[Modified from Arora and Rochester (26). ]
of poor nutritional status (20). The supporting evidence is contradictory. Ishikawa and Hayes (21) found that the mass and thickness of the diaphragm were increased in COPD. These investigators (21), along with Scott and Hoy (22), found that the cross-sectional diameter or area of diaphragm muscle fibers was also increased in COPD; they attributed the increases in diaphragmatic dimensions to work hypertrophy. Others (23-25), in contrast, have found diaphragm mass, area, or thickness to be significantly diminished in COPD. Steele and Heard (23) attributed this to extrapulmonary factors, such as nutritional status, a view reinforced by Thurlbeck's observation that diaphragm mass was directly proportional to body weight (25). Both Butler (24) and Thurlbeck (25) found significant inverse correlations between diaphragmatic area or mass and the severity of emphysema, suggesting that the abnormally low position of the diaphragm leads to atrophy. Interpretation of these results is made difficult by lack of adequate control data. Most of the control patients were elderly and had other diseases that could affect respiratory muscle mass. To overcome this problem, and to calculate the relationship between diaphragm mass and body weight independent of disease, Arora and Rochester (26) studied 19 normal persons and 35 patients who died of a variety of systemic, infectious, and neoplastic diseases that did not involve the thorax. Patients with obesity, chronic obstructive and restrictive thoracopulmonary disorders, and edematous states were excluded. Normal subjects were defined as persons who had died suddenly of trauma or acute myocardial infarction without overt antecedent clinical illness. Three of the normal subjects were unusually muscular at the time of death.
Eleven of the patients were obviously wasted and were poorly nourished at the time of death. Because diaphragm mass and body weight underwent parallel changes, the effects of disease could not be evaluated from the ratio of diaphragm muscle mass (DMM) to body weight (BW) alone. Therefore, we predicted DMM from the product of DMM/BW in normal subjects (mean ± SD, 3.93 ± 0.43 g per kg) and ideal body weight based on height and sex. The results, with observed DMM expressed as a per cent of predicted normal, are summarized as mean ± SD values in table 2. It can be seen that the mass of the diaphragm muscle increased by more than 70 per cent in muscular persons, but decreased by approximately 40 per cent in patients who died of wasting diseases. This represents an almost 3-fold variation of DMM according to general nutritional and muscular status. In summary, respiratory muscle strength in COPD depends on several factors. Hyperinflation of the lungs places the inspiratory muscles, particularly the diaphragm, at a disadvantageous position on the length-tension curve. Because the inspiratory muscles are in series, and in COPD the diaphragm is the weakest link in the chain, PImax is significantly dependent on the resting length of the diaphragm at RV and FRC. Nonmechanical factors must also be operative. Decreases in PEmax and expiratory dp/dt cannot be explained by mechanical factors alone, and do not seem to result from alterations in neural drive. Studies of the mass of the diaphragm in COPD and other nonpulmonary illnesses suggest that COPD may have a dual effect on respiratory muscle strength: initial increases of strength and hypertrophy in response to the increased work of breathing may be succeeded
154
ROCHESTER, BRAUN, AND ARORA
by decreased strength and atrophy consequent to deteriorating nutritional and generalized muscular status. Whatever the cause, marked diminution of inspiratory muscle strength is associated with dyspnea and hypercapnic respiratory failure (13-15).
References 1. Ashutosh, K., Gilbert, R., Auchincloss, J. R. H., and Peppi, D.: Asynchronous breathing movements in patients with chronic obstructive pulmonary disease, Chest, 1975, 67, 553. 2. Sharp, J. T., Goldberg, N. B., Druz, W. S., Fishman, H. C , and Danon, J.: Thoracoabdominal motion in chronic obstructive pulmonary disease, Am Rev Respir Dis, 1977,115,47. 3. Fritts, H. W., Jr., Filler, J., Fishman, A. P., and Cournand, A.: The efficiency of ventilation during voluntary hyperpnea: Studies in normal subjects and in dyspneic patients with either chronic pulmonary emphysema or obesity, J Clin Invest, 1959,35,1339. 4. Campbell, E. J. M., and Friend, J.: Action of breathing exercises in pulmonary emphysema, Lancet, 1955,2,325. 5. Sukumalchantra, Y., Park, S. S., and Williams, M. H., Jr.: The effect of intermittent positive pressure breathing in acute ventilatory failure, Am Rev Respir Dis, 1965,92,885. 6. Cook, C. D., Mead, J., and Orzalesi, M. M.: Static volume-pressure characteristics of the respiratory system during maximal efforts, J Appl Physiol, 1964,19,1016. 7. Ringqvist, T.: The ventilatory capacity in healthy subjects: An analysis of causal factors with special reference to the respiratory forces, Scand J Clin Lab Invest, 1966, 18 (Supplement 88, p. 1). 8. Black, L. F., and Hyatt, R. E.: Maximal respiratory pressures: Normal values and relationship to age and sex, Am Rev Respir Dis, 1969, 99, 696. 9. Sharp, J. T., van Lith, P., vej Nuchprayoon, C , Briney, R., and Johnson, F. N.: The thorax in chronic obstructive lung disease, Am J Med, 1968,44, 39. 10. Byrd, R. B., and Hyatt, R. E.: Maximum respiratory pressures in chronic obstructive lung disease, Am Rev Respir Dis, 1968, 98, 848. 11. Clausen, J. L., O'Brien, R., and Tisi, G. M.: Maximal inspiratory pressures in patients with hyperinflation, Chem Res, 1974,22,131 A. 12. Marazzini, L., Vezzoli, F., and Rizzato, G.: Intra-
13.
14.
15.
16.
17.
18.
19.
20. 21.
22.
23.
24. 25. 26.
thoracic pressure development in chronic airways obstruction, J Appl Physiol, 1974, 37, 575. O'Connell, J. M., and Campbell, A. H.: Respiratory mechanics in airway obstruction associated with inspiratory dyspnea, Thorax, 1976, 31, 669. Braun, N. M. T., and Rochester, D. F.: Respiratory muscle strength in obstructive lung disease, Am Rev Respir Dis, 1977, 115 (No. 4, Part 2), 91. Gilbert, R., Ashutosh, K., Auchincloss, J. H., Jr., Rana, S., and Peppi, D.: Prospective study of controlled oxygen therapy: Poor prognosis of patients with asynchronous breathing, Chest, 1977,71,456. Gibson, G. J., Clark, E., and Pride, N. B;: Inspiratory muscle function in patients with severe hyperinflation, Am Rev Respir Dis, 1978, 117 (Part 2), 118. Moisan, T. C , Wicks, M. S., Druz, W. S., and Sharp, J. T.: Diaphragmatic function and body position in chronic obstructive pulmonary disease, Am Rev Respir Dis, 1978, 117 (No. 4, Part 2), 378. Sharp, J. T., Danon, J., Druz, W. S., Goldberg, N. B., Fishman, H., and Machnach, W.: Respiratory muscle function in patients with chronic obstructive pulmonary disease: Its relationship to disability and to respiratory therapy, Am Rev Respir Dis, 1974,110 (Supplement, p. 154). Danon, J., Fishman, H. C , Lin, J., Sharif, M., Druz, W. S., and Sharp, J. T.: Measurement of diaphragmatic length in normal individuals and patients with COPD (abstract), Chest, 1976, 70, 423. Sadoul, P.: Les cachexies respiratoires, Bull Physiopathol Respir (Nancy), 1969,5, 3. Ishikawa, S., and Hayes, J. A.: Functional morphometry of the diaphragm in patients with chronic obstructive lung disease, Am Rev Respir Dis, 1973,108,135. Scott, J. W. M., and Hoy, J.: The cross-sectional area of diaphragmatic muscle fibers in emphysema, measured by an automated image analysis system, J Pathol, 1976,120,121. Steele, R. H., and Heard, B. E.: Size of the diaphragm in chronic bronchitis, Thorax, 1973,25,55. Butler, C : Diaphragmatic changes in emphysema, Am Rev Respir Dis, 1976,114, 155. Thurlbeck, W. M.: Diaphragm and body weight in emphysema, Thorax, 1978,33,483. Arora, N. S., and Rochester, D. F.: Effect of general nutritional and muscular status on the human diaphragm, Am Rev Respir Dis, 1977, 115 (No. 4, Part 2), 84.
