Pulmonary Mechanics in Patients with Respiratory Muscle Weakness· G. J. GIBSON, N. B. PRIDE, J. NEWSOM DAVIS, and L. C. LOH
SUMMARY ________________________________________ ______________ Pulmonary mechanics and respiratory muscle pressures were studied in 7 patients with severe respiratory muscle weakness. Minimal pleural pressures were grossly abnormal and showed little variation with lung volume. Both the maximal transpulmonary pressure and static expiratory compliance were low; therefore, the pressure-volume curves of the lungs resembled those obtained after strapping the chest in normal subjects. The low compliance may result from either microatelectasis or a generalized alteration in alveolar elastic properties and is probably a major determi· nant of both the total lung capacity and the breathing pattern of patients with neuromuscular disease. Airway and gas exchange function were less abnormal than the elastic properties of the lungs.
Introduction Severe weakness of the respiratory muscles produces a restrictive ventilatory defect due to inability to inflate the lungs completely. If loss of maximal distending pressure were the only effect of muscle weakness, the pressure-volume curve of the lungs would be truncated but compliance measured over the tidal range should be normal. Measurements in patients with various neuromuscular diseases, however, have often shown low values of pulmonary compliance (1-3), although other patients have had normal values {4). Because these measurements were of dynamic compliance, low values may reflect abnormalities in airways rather than a true change in the elastic properties of the lungs. A displacement of the static pressure-volume curve, resulting in higher lung recoil pressures at a given lung volume, does, however, occur in normal subjects when maximal expansion is restricted by strapping the chest wall (5-7). To establish whether similar changes occur when lung expansion is (Received in original form June 11, 1976 and in revised form December 7, 1976) 1 From the Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London W.l2, and the Batten Unit, National Hospital for Nervous Diseases, London, W.C. l, England.
limited by chronic respiratory muscle weakness, we studied respiratory muscle pressures and the static and dynamic mechanical properties of the lungs and airways of 7 patients with neuromuscular diseases.
Materials and Methods Details of the patients are given in table I. In 6 of the 7 patients paralysis or gross weakness of the diaphragm had previously been demonstrated by measuring the change in transdiaphragmatic pressure during a maximal inspiration (8). Patient 7 had a permanent tracheostomy and was therefore excluded from dynamic measurements. None of the patients had chronic expectoration, but 2 (Patients 1 and 7) had a past history of chest infections. The chest radiograph of Patient 2 showed minor basal shadowing consistent with an area of atelectasis, but in the others the lung fields were clear. (Both Patients I and 3 had at other times been noted to have radiographic shadowing suggesting partial atelectasis of one or the other lower lobe.) The patients were seated for all the studies except sampling of arterial blood, which in Patients 1, 2, 5, 6, and 7 was performed in the standing position. Spirometric measurements of forced expiratory volume in I sec and vital capacity (VC) were made using a dry spirometer (9). Total lung capacity (TLC), residual volume (RV), and specific airway conductance (SGaw) were measured using a constantvolume body plethysmograph (10, 11).
AMERICAN REVIEW OF RESPIRATORY DISEASE, VOLUME ll5, 1977
389
390
GIBSON, PRIDE, NEWSOM DAVIS, AND LOH
Maximal expiratory flow-volume (MEFV) and pressure-volume (PV) studies were performed with the subject seated in a pressure-corrected, variablevolume plethysmograph (12). Flow was measured with a calibrated Fleisch no. 3 pneumotachygraph and displayed against change in thoracic gas volume (Vtg) on a storage oscilloscope (Tektronix, Inc., Beaverton, Ore.), from which repeatable MEFV curves were traced after the subject had been asked to perform several forced VC maneuvers. Static PV curves were obtained by the technique of Milic-Emili and associates (13) using an esophageal balloon containing 0.4 to 0.5 ml of air to estimate pleural surface pressure; transpulmonary pressure was measured by a Sanborn differential pressure transducer and recorded together with a Vtg on a Sanborn pen recorder. After a sequence of 3 full inspirations, measurements of static transpulmonary pressure (Pst [1]) were made while the subject held his or her breath at full inflation with open airway, and at several volumes during subsequent expiration as he or she relaxed for periods of 1 to 2 sec against an obstructed mouthpiece. At least 5 deflation maneuvers were performed in each subject and a line of best fit drawn by eye through the plots of Pst (I) against Vtg between TLC and functional residual capacity (FRC). In 4 patients static inspiratory PV curves were obtained during interrupted inspiration from FRC. Static compliance was measured as the slope of the PV curve over the 0.5 liter above FRC. Measurement of dynamic compliance was preceded by one full inspiration, and the subject breathed at spontaneous tidal volume and frequency; values of transpulmonary pressure and Vtg were measured at the points of zero flow at the mouth for at least 5 breaths. Maximal (expiratory) and minimal (inspiratory) pleural pressures were obtained by repeated measurements at various lung volumes while the subject attempted maximal expiratory and inspiratory efforts
against an obstruction. A conventional mouthpiece and noseclip were used, and pressmes sustained for 1 sec were recorded. The highest (expiratory) and lowest (inspiratory) values at each volume were used to construct curves of maximal and minimal pleural pressure against lung volume. The diffusing capacity for carbon monoxide (DLco) was measured by the single-breath method (14). Arterial blood was sampled while the patient breathed room air, and blood gas tensions were measured using Corning electrodes; the alveolar-arterial oxygen tension difference was estimated using the alveolar air equation, assuming a respiratory exchange ratio of 0.8. In 3 patients a single-breath nitrogen test was performed after inspiring a breath of 100 per cent 0 2 from residual volume (15). Predicted values for lung volumes and DLco are from Cotes (16). Normal ranges for the PV curves are from Turner and co-workers (17), and for MEFV curves and pressures during maximal respiratory efforts from normal subjects studied in our laboratory.
Results Values of lung volumes and SGaw are shown in table 2. The degree of lung volume restriction varied from 41 to 85 per cent of predicted TLC and 20 to 59 per cent of predicted VC. Residual volume was markedly elevated in Patient 7 and slightly elevated in 3 others, whereas FRC tended to be low. Both the ratios of RV and FRC to TLC were grossly elevated, mainly because of the loss of inspiratory capacity. MEFV curves are shown in figure l for Patients I to 6, with derived data in table 3. There was some reduction in the peak expiratory flow, which developed at a lower than normal percentage of the (restricted) VC. In relation to the
TABLE 1 DETAILS OF PATIENTS WITH RESPIRATORY MUSCLE WEAKNESS Patient No. Sex
Age (years)
Diagnosis
Smoking History
History of Chest Infections
+
M
M
33
Acid maltase deficiency
Ex-smoker
2
F
45
Acid maltase deficiency
Ex-smoker
3
F
52
Limb girdle dystrophy
Ex-smoker
4 5 6 7*
M M F M
26 38 61 43
Limb girdle dystrophy Previous poliomyelitis Myasthenic myopathy Kugelberg-Welander syndrome
None Ex-smoker None 8 cigarettes/ day
• Tracheostomy.
+
Chest Roentgenogram Lung fields clear, raised left diaphragm Minor shadowing in left costophrenic angle, raised diaphragms Lung fields clear, raised diaphragms Normal Normal Normal Normal
Diaphragm Function {8) Grossly weak Paralyzed
Paralyzed Not studied Paralyzed Grossly weak Paralyzed
391
1.9 1.8 1.3 1.8 1.4 2.3 3.7 41 56 59 66 64 81 85 20 26 41 47 58 59 46
2.9 2.5 2.2 3.9 4.1 3.9 5.8
(liter) (%pred.) (liter) (%pred.) (liter)
1.0 0.7 0.9 2.1 2.7 1.6 2.1 2 3 4 5 6 7
Definition of abbreviations: VC = vital capacity; TLC = total lung capacity; RV = residual volume; FRC = functional residual capacity; FEVI = 1-sec forced expiratory volume; SGaw = specific airway conductance.
76 74 78 80
0.30 0.56 0.34 0.52 0.26 79
80 77
65 77 59 47 34 59 64 80 86 89 95 85 72 91 55 80 81 83 76 98 106 2.3 2.0 1.7 2.95 3.05 3.05 4.65
(%) (%pred.)
(liter)
(%pred.)
(%)
(%)
RVITLC
FEVIIVC FRC RV TLC VC
Patient no.
TABLE 2
SUBDIVISIONS OF LUNG VOLUME AND SPECIFIC CONDUCTANCE
100 117 100 124 78 121 182
SGaw
FRC/TLC
(see-I. em H2O-I)
LUNG MECHANICS IN MUSCLE WEAK:NESS
absolute lung volume, however, flow rates were high in 5 of the patients, and 2 patients also had values of SGaw (table 2) above the normal up· per limit of 0.35 sec -1 • em H 2Q-1, The static expiratory PV curves are shown in figure 2 with values of compliance and of Pst (1) at TLC (Pst[IJmax) in table 3. Both Pst(l)max and static compliance were subnormal. ·Dynamic compliance during tidal breathing was only slightly less than static expiratory compliance. Maximal and minimal pleural pressures at differing lung volumes in 6 patients are shown in figure 3. As anticipated, the inspiratory muscles were grossly weak in all; the minimal (inspiratory) pleural pressure measurements showed little variation with lung volume. Expiratory pressures were also considerably reduced in Patients I, 4, 6, and 7. Results (when available) of DLco, blood gas analyses, and single-breath nitrogen test are shown in table 4. Two patients had a slightly increased alveolar-arterial oxygen tension difference; no closing volume was demonstrated in the 3 patients in whom the single-breath test was performed (2 of whom had large residual volumes), but the slope of the alveolar plateau (Phase III) was increased above normal for nonsmoking subjects in our laboratory (upper limit, 1.6 per cent nitrogen per liter). Discussion Weakness of the inspiratory muscles was confirmed in all the patients by the values of minimum pleural pressure, which were considerably less negative than normal. Most of our patients had conditions with widespread involvement of skeletal muscle, which accounts for the reduction of maximal expiratory pressures. The patient with the highest age 26-)8
age 45-61
VEIIICIII
ptcdiCUd
TLC Sl£1
~~~~~~.~0~~.00 VOLUME
0
/o predicted TLC
2~0~~~~~~~.00 VOLU~E
0
/o predicted TLC
Fig. 1. Maximal expiratory flow-volume curves for 6 patients (table 1). Flow and volume expressed in relation to predicted total lung capacity (TLC). Shaded areas represent ranges of maximal flow (VE max) below 80 per cent TLC in 16 and 12 age-matched normal subjects.
392
GIBSON, PRIDE, :-.IEWSOM DAVIS, AND LOH
TABLE 3 DATA FROM MAXIMAL EXPIRATORY FLOW-VOLUME AND PRESSURE-VOLUME STUDIES Static Expiratory Compliance• PEF Patient (/iter/ sec) no.
% VC at
(% pred.)
PEF
43 47 65 68 95 54
44 62 66 61 84 72
4.5 3.0 3.6 6.7 9.2 3.4
1 2 3 4 5 6 7
(/iter/ em H20)
Static Inspiratory Dynamic (%pred_ Compliance Compliance (/iter/ (/iter/ TLCI em H20) em H20) em H20)
0.056 0.071 0.048 0.140 0.120 0.096 0.190
0.8 1.6 1.3 2.4 1.9 2.5 2.8
VT (/iter)
Pst (I) at TLC (per min) (em H20)
r
0.057
0.048
0.47
32
0.048 0.122
0.045 0.130 0.090 0.091
0.40 0.37 0.40 0.36
23 26 23 18
18.5 12 10.5 17 9 13.5 17
0.160
Definition of abbreviations: PEF =peak expiratory flow; Pst (I) = transpulmonary pressure; VT =tidal volume; f = frequency. For definition of other abbreviations, see table 2. • Range of values in 22 normal subjects, 2.9 to 7.9 per cent of predicted TLC/cm H20.
expiratory pressures (Patient 5, figure 3) had suffered from poliomyelitis, affecting clearly defined spinal segments but sparing the muscles of the abdominal wall; interestingly, he was also the patient with the smallest residual volume. Maximal expiratory pressures are normally generated at high lung volumes (18), and single measurements of maximal expiratory pressure unrelated to volume may, therefore, tend to overestimate the degree of expiratory muscle weakness in patients with a restricted inspiratory capacity. The FRC in our patients was, in general, below normal, and in some of the patients the recoil pressure of the lungs at FRC was also low. It is possible that gross muscle weakness alters the passive recoil of the thoracic cage, modifying the neutral position at which lung and cage recoil pressures are balanced. In addition, the normal end-tidal position of patients with diaag~
phragm weakness may lie below this neutral position; in such patients inspiration may be initiated by passive descent of the diaphragm consequent on relaxation of the abdominal muscles (8), implying an active effort at the end of the preceding expiration. Our analysis of lung compliance has concentrated on the expiratory PV curve, which is generally regarded as the best index of the over-all elastic behavior of the lungs. Because of the hysteresis of the PV curve a reduction in the Pst (I)max achieved on full inspiration will itself alter the position and slope of the expiratory curve and tend to reduce static expiratory compliance. Although this mechanism may have contributed to the reduction in expiratory compliance in our patients we do not think it played an important role because values of compliance obtained during inspiration in 4 of the patients were also re-
age 45-61 years
26- 43 years
VOLUME 100 Ofo predicted
100
100
TLC 80
/l
/ '
).
60~, 40
~·
/ 20
20
0
0
20 Pst 01
30
em t-t 2 o
0 o~--~~o~-=2o~~,~0--~40 Pst 01
em H20
Fig. 2. Static expiratory pressure-volume curves for 7 patients over volume range, total lung capacity (TLC) to functional residual capacity_ Volume expressed as percentage of predicted TLC and shaded areas represent ranges of normal subjects from Turner and associates ( 1 7)-
-so
-100
Ppl min
em H20
0
50
100 P
pi
ma~
ISO
em H,P
Fig. 3. Values of maximal and minimal static pleural pressures in 6 patients_ Measurements made during attempted expiration and inspiration against an obstruction at the mouth_ Shaded area shows range of values obtained in 6 normal subjects 27 to 44 years of age.
393
LUNG MECHANICS IN MUSCLE WEAKNESS
TABLE 4 CO DIFFUSING CAPACITY, ARTERIAL BLOOD GAS ANALYSES, AND SINGLE-BREATH N 2 TEST DLco Patient no.
2 2 3 4 5 6 7
(ml/min/ mm Hg)
23.0 21.8 14.5 23.8
(%pred.)
74 71 64 77
Paoz
Pacoz
(A-a) POz Phase Ill slope
(mm Hg)
(mm Hg)
(mm Hg)
87 78 69
44 42 55
7 18 12
95 54 73
36 63 55
9 16 7
(% Nz/liter)
Phase IV
2.0
Undetectable
2.4 2.3
Undetectable Undetectable
Definition of abbreviations: DLco =diffusing capacity for CO; Pao 2 =arterial oxygen tension; Paco 2 =arterial carbon dioxide tension, (A-a) POz =alveolar-arterial oxygen tension difference.
duced (table 3). Furthermore, in 3 normal subjects we examined the immediate effects on the expiratory PV curve of voluntarily restricting the 3 preliminary inspirations to a Pst (!)max of 15 em H 2 0; the mean reduction in static expiratory compliance at FRC was only 9 per cent of the value obtained with a full inflation volume history. In our patients the changes in compliance were much greater and resulted in more severe degrees of lung volume restriction than would occur with truncation of the PV curve alone. The cause of this reduced compliance is uncertain. The 3 patients (Patients I, 2, and 3) with diaphragm elevation on the chest radiograph had the smallest lung volumes and the lowest values of compliance; all 3 at some time had radiographic changes suggesting lower lobe atelectasis. Similar functional changes, however, were present without radiographic change, indicating a more subtle secondary alteration in elastic properties present in the lungs of all the patients. This might be either atelectasis of a more focal nature, which may not be radiographically visible (19, 20) or a generalized change in the elastic behavior of the surface film lining the alveoli. A further contributory factor to the low values of compliance might be the failure of development of a normal complement of alveoli. We think this is a very unlikely explanation for our findings because most of the patients developed symptoms and signs of disease only in adult life, and certainly it could not explain the abnormally low distensibility of the lungs of Patient 5, who acquired poliomyelitis at I 8 years of age. The abnormalities demonstrated in our patients closely resemble those produced in normal subjects by artificially restricting chest expan-
sion. Caro and associates (5) and subsequent investigators (6, 7) showed that strapping the chest produced changes in the PV curve of the lungs with a reduction in compliance, a reduction in lung recoil pressure at TLC, and increases in airway conductance and maximal expiratory flow at a given volume. The patients discussed here demonstrated all these features in varying degrees. Stubbs and Hyatt (6) set up various models that might account for the effects of chest strapping, and, of the 2 most likely alternatives, they favored a true alteration in the (surface) elastic properties of the alveoli rather than a reduction in the number of contributing lung units consequent on atelectasis. This conclusion was based mainly on the finding of "supernormal" airway function, which was predicted by their model of alveolar "stiffness" but not by their model of atelectasis; the latter suggested that airway function would remain proportionate to the number of patent alveoli and, thus, conductance and maximal flow would be appropriate for lung volume. This, however, might be an unrealistic model of atelectasis if it occurred in patchy fashion throughout the lungs. In the latter case, some generations of airways would subtend both atelectatic and patent terminal units, and the reduction of compliant units would therefore be greater than the reduction of parallel conducting airways; hence, indices of airway function such as maximal expiratory flow and total airway conductance would appear "supernormal" in relation to the absolute lung volume. Sybrecht and co-workers (7) also believed that their findings with chest strapping could be best explained by a widespread increase in the surface tension of the alveolar lining layer, but they did not discuss the possibil-
394
GIBSON, PRIDE, NEWSOM DAVIS, AND LOH
ity of atelectasis. Their demonstration that when volume was expressed as per cent of TLC the PV curves before and after strapping were indistinguishable would, however, be compatible with a simple reduction in the complement of gascontaining alveoli; similarly, atelectasis could lead to an increase in upstream resistance (owing to functional loss of peripheral airways subtending atelectatic units) and to a reduction in closing volume as found by these investigators. The most important evidence against atelectasis is their demonstration that the distribution of a radioactive bolus was not altered by chest strapping, suggesting that there were proportionate reductions in compliance in all regions of the lung. But although this failure to demonstrate greater cl1anges at the lung bases is an important point against atelectasis, the alternative mechanism proposed (change in surface properties consequent on breathing at small lung volume) should also be most pronounced at the bases in erect subjects. Because we are not confident that atelectasis has been excluded as a cause of the reduction in compliance during strapping, we believe atelectasis also remains a possible cause for the similar changes found in our patients with muscle weakness. The elevated arterial Pco 2 in 3 patients may be specifically related to diaphragm failure (8). Otherwise, the effects of severe respiratory muscle weakness on indices of pulmonary gas exchange in our patients were relatively minor in comparison to conditions such as fibrosing alveolitis that restrict lung volume by an intrapulmonary mechanism and where the gas exchange defect is often out of proportion to the mechanical abnormality. Studies of the volume dependence of the single-breath DLco in normal subjects (21) imply that some reduction would be an inevitable consequence of the patients' inability to inflate their lungs fully. The characteristic pattern of breathing of patients with severe respiratory muscle weakness is with small tidal volume and rapid frequency (22); this is similar to that described in patients with a restrictive ventilatory defect of primary intrapulmonary origin and hence may be related to the reduced compliance of the lungs, irrespective of the mechanism by which this is produced. An important practical implication of our study is that measurement of lung compliance in a patient with small volumes will not in itself allow a distinction between primary intrapulmonary and extrapulmonary causes of restriction. A low value of Pst(l) at full inflation, as recently em-
phasized by Colp and co-workers (23), indicates extrapulmonary restriction, but its value can be surprisingly high in some patients with gross weakness of the inspiratory muscles. Muscle weakness as a contributory factor to lung volume restriction should be easily recognizable by careful measurement of pressure during maximal inspiratory efforts at several lung volumes. The detection of primary intrapulmonary disease by mechanical tests may be impossible if an extra pulmonary component is also present. References 1. Ferris, B. G., Mead, J., Whittenberger, J. L.,
and Saxton, G. A.: Pulmonary function in convalescent poliomyelitic patients. III. Compliance of the lungs and thorax, N Eng! J Med, 1952, 247,390.
2. Stone, D. J., and Keltz, H.: The effect of respiratory muscle dysfunction on pulmonary function, Am Rev Respir Dis, 1963,88,621. 3. Hapke, E. J., Meak, J. C., and Jacobs, J.: Pulmonary function in progressive muscular dystrophy, Chest, 1972, 61, 41. 4. McKinley, A. C., Auchincloss, J. H., Gilbert, R., and Nicholas, J. J.: Pulmonary function, ventilatory control and respiratory complications in quadriplegic subjects, Am Rev Respir Dis, 1969, 100,526.
5. Caro, C. G., Butler, J., and DuBois, A. B.: Some effects of restriction of chest cage expansion on pulmonary function in man: An experimental study, J Clin Invest, 1960, 39, 573. 6. Stubbs, S. E., and Hyatt, R. E.: Effect of increased lung recoil pressure on maximal expir· atory flow in normal subjects, J Appl Physiol, 1972, 32, 325.
7. Sybrecht, G. W., Garrett, L., and Anthonisen, N. R.: Effect of chest strapping on regional lung function, J Appl Physiol, 1975,39,707. 8. Newsom Davis, J., Goldman, M., Loh, L., and Casson, M.: Diaphragm function and alveolar hypoventilation, Q J Med, 1976,45, 87. 9. McDermott, M., McDermott, T. J., and Collins, M. M.: A portable bellows spirometer and timing unit for the measurement of respiratory function, Med Bioi Eng, 1968, 6, 291. 10. DuBois, A. B., Botelho, S. Y., Bedell, G. N., Marshall, R., and Comroe, J. H., Jr.: A rapid plethysmographic method for measuring thoracic gas volume: A comparison with a nitrogen washout method for measuring functional residual capacity in normal subjects, J Clin Invest, 1956,35,322. 11. DuBois, A. B., Botelho, S. Y., and Comroe, J. H.,
Jr.: A new method for measuring airway resistance in man using a body plethysmograph. Values in normal subjects and in patients with respiratory disease, J Clin Invest, 1956,35,327.
LUNG MECHANICS IN
12. Mead, J.: Volume displacement body plethysmograph for respiratory measurements in human subjects, J Appl Physiol, 1960, 15, 736. 13. Milic-Emili, J., Mead, J., Turner, J. M., and Glauser, E. M.: Improved technique for estimating pleural pressure from esophageal balloons, J Appl Physiol, 1964, 19, 207. 14. Ogilvie, C. M., Forster, R. E., Blakemore, W. S., and Morton, J. W.: A. standardized breathholding technique for the clinical measurement of the diffusing capacity of the lung for carbon monoxide, J Clin Invest, 1957,36, 1. 15. Anthonisen, N. R., Danson, J., Robertson, P. C., and Ross, W. R. D.: Airway closure as a function of age, Respir Physiol, 1969,8, 58. 16. Cotes, J. E.: Lung Function, ed. 3, Blackwell Scientific Publications, Oxford, 1975, pp. 380, 381. 17. Turner, J. M., Mead, J., and Wohl, M. E.: Elasticity of human lungs in relation to age, J App1 Physiol, 1968,25,664.
~IUSCLE
WEAKNESS
395
18. Rohrer, F.: Der Zusammenhang der Atemkrafte and ihre Abhangigkeit vom Dehnungszustand der Atmungsorgane, Pfluegers Arch, 1916, 165, 419. 19. Rahn, H., and f'arhi, L. E.: Gaseous environment and atelectasis, Fed Proc, 1963, 22, 1035. 20. Prys-Roberts, C., Nunn, J. F., Dobson, R. H., Robinson, R. H., Greenbaum, R., and Harris, R. S.: Radiologically undetectable pulmonary collapse in the supine position, Lancet, 1967, 2, 399. 21. Miller, J. M., and Johnson, R. L.: Effect of lung inflation on pulmonary diffusing capacity at rest and exercise, J Clin Invest, 1966,45,493. 22. Newsom Davis, J., Stagg, D., Loh, L., and Casson, M.: The effects of respiratory muscle weakness on some features of the breathing pattern, Clin Sci Mol Med, 1976,50, lOP. 23. Colp, C., Reichel, J., and Park, S. S.: Severe pleural restriction: The maximum static pulmonary recoil pressure as an aid to diagnosis, Chest, 1975, 67, 658.
SUMMARY ________________________________________ ______________ Pulmonary mechanics and respiratory muscle pressures were studied in 7 patients with severe respiratory muscle weakness. Minimal pleural pressures were grossly abnormal and showed little variation with lung volume. Both the maximal transpulmonary pressure and static expiratory compliance were low; therefore, the pressure-volume curves of the lungs resembled those obtained after strapping the chest in normal subjects. The low compliance may result from either microatelectasis or a generalized alteration in alveolar elastic properties and is probably a major determi· nant of both the total lung capacity and the breathing pattern of patients with neuromuscular disease. Airway and gas exchange function were less abnormal than the elastic properties of the lungs.
Introduction Severe weakness of the respiratory muscles produces a restrictive ventilatory defect due to inability to inflate the lungs completely. If loss of maximal distending pressure were the only effect of muscle weakness, the pressure-volume curve of the lungs would be truncated but compliance measured over the tidal range should be normal. Measurements in patients with various neuromuscular diseases, however, have often shown low values of pulmonary compliance (1-3), although other patients have had normal values {4). Because these measurements were of dynamic compliance, low values may reflect abnormalities in airways rather than a true change in the elastic properties of the lungs. A displacement of the static pressure-volume curve, resulting in higher lung recoil pressures at a given lung volume, does, however, occur in normal subjects when maximal expansion is restricted by strapping the chest wall (5-7). To establish whether similar changes occur when lung expansion is (Received in original form June 11, 1976 and in revised form December 7, 1976) 1 From the Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London W.l2, and the Batten Unit, National Hospital for Nervous Diseases, London, W.C. l, England.
limited by chronic respiratory muscle weakness, we studied respiratory muscle pressures and the static and dynamic mechanical properties of the lungs and airways of 7 patients with neuromuscular diseases.
Materials and Methods Details of the patients are given in table I. In 6 of the 7 patients paralysis or gross weakness of the diaphragm had previously been demonstrated by measuring the change in transdiaphragmatic pressure during a maximal inspiration (8). Patient 7 had a permanent tracheostomy and was therefore excluded from dynamic measurements. None of the patients had chronic expectoration, but 2 (Patients 1 and 7) had a past history of chest infections. The chest radiograph of Patient 2 showed minor basal shadowing consistent with an area of atelectasis, but in the others the lung fields were clear. (Both Patients I and 3 had at other times been noted to have radiographic shadowing suggesting partial atelectasis of one or the other lower lobe.) The patients were seated for all the studies except sampling of arterial blood, which in Patients 1, 2, 5, 6, and 7 was performed in the standing position. Spirometric measurements of forced expiratory volume in I sec and vital capacity (VC) were made using a dry spirometer (9). Total lung capacity (TLC), residual volume (RV), and specific airway conductance (SGaw) were measured using a constantvolume body plethysmograph (10, 11).
AMERICAN REVIEW OF RESPIRATORY DISEASE, VOLUME ll5, 1977
389
390
GIBSON, PRIDE, NEWSOM DAVIS, AND LOH
Maximal expiratory flow-volume (MEFV) and pressure-volume (PV) studies were performed with the subject seated in a pressure-corrected, variablevolume plethysmograph (12). Flow was measured with a calibrated Fleisch no. 3 pneumotachygraph and displayed against change in thoracic gas volume (Vtg) on a storage oscilloscope (Tektronix, Inc., Beaverton, Ore.), from which repeatable MEFV curves were traced after the subject had been asked to perform several forced VC maneuvers. Static PV curves were obtained by the technique of Milic-Emili and associates (13) using an esophageal balloon containing 0.4 to 0.5 ml of air to estimate pleural surface pressure; transpulmonary pressure was measured by a Sanborn differential pressure transducer and recorded together with a Vtg on a Sanborn pen recorder. After a sequence of 3 full inspirations, measurements of static transpulmonary pressure (Pst [1]) were made while the subject held his or her breath at full inflation with open airway, and at several volumes during subsequent expiration as he or she relaxed for periods of 1 to 2 sec against an obstructed mouthpiece. At least 5 deflation maneuvers were performed in each subject and a line of best fit drawn by eye through the plots of Pst (I) against Vtg between TLC and functional residual capacity (FRC). In 4 patients static inspiratory PV curves were obtained during interrupted inspiration from FRC. Static compliance was measured as the slope of the PV curve over the 0.5 liter above FRC. Measurement of dynamic compliance was preceded by one full inspiration, and the subject breathed at spontaneous tidal volume and frequency; values of transpulmonary pressure and Vtg were measured at the points of zero flow at the mouth for at least 5 breaths. Maximal (expiratory) and minimal (inspiratory) pleural pressures were obtained by repeated measurements at various lung volumes while the subject attempted maximal expiratory and inspiratory efforts
against an obstruction. A conventional mouthpiece and noseclip were used, and pressmes sustained for 1 sec were recorded. The highest (expiratory) and lowest (inspiratory) values at each volume were used to construct curves of maximal and minimal pleural pressure against lung volume. The diffusing capacity for carbon monoxide (DLco) was measured by the single-breath method (14). Arterial blood was sampled while the patient breathed room air, and blood gas tensions were measured using Corning electrodes; the alveolar-arterial oxygen tension difference was estimated using the alveolar air equation, assuming a respiratory exchange ratio of 0.8. In 3 patients a single-breath nitrogen test was performed after inspiring a breath of 100 per cent 0 2 from residual volume (15). Predicted values for lung volumes and DLco are from Cotes (16). Normal ranges for the PV curves are from Turner and co-workers (17), and for MEFV curves and pressures during maximal respiratory efforts from normal subjects studied in our laboratory.
Results Values of lung volumes and SGaw are shown in table 2. The degree of lung volume restriction varied from 41 to 85 per cent of predicted TLC and 20 to 59 per cent of predicted VC. Residual volume was markedly elevated in Patient 7 and slightly elevated in 3 others, whereas FRC tended to be low. Both the ratios of RV and FRC to TLC were grossly elevated, mainly because of the loss of inspiratory capacity. MEFV curves are shown in figure l for Patients I to 6, with derived data in table 3. There was some reduction in the peak expiratory flow, which developed at a lower than normal percentage of the (restricted) VC. In relation to the
TABLE 1 DETAILS OF PATIENTS WITH RESPIRATORY MUSCLE WEAKNESS Patient No. Sex
Age (years)
Diagnosis
Smoking History
History of Chest Infections
+
M
M
33
Acid maltase deficiency
Ex-smoker
2
F
45
Acid maltase deficiency
Ex-smoker
3
F
52
Limb girdle dystrophy
Ex-smoker
4 5 6 7*
M M F M
26 38 61 43
Limb girdle dystrophy Previous poliomyelitis Myasthenic myopathy Kugelberg-Welander syndrome
None Ex-smoker None 8 cigarettes/ day
• Tracheostomy.
+
Chest Roentgenogram Lung fields clear, raised left diaphragm Minor shadowing in left costophrenic angle, raised diaphragms Lung fields clear, raised diaphragms Normal Normal Normal Normal
Diaphragm Function {8) Grossly weak Paralyzed
Paralyzed Not studied Paralyzed Grossly weak Paralyzed
391
1.9 1.8 1.3 1.8 1.4 2.3 3.7 41 56 59 66 64 81 85 20 26 41 47 58 59 46
2.9 2.5 2.2 3.9 4.1 3.9 5.8
(liter) (%pred.) (liter) (%pred.) (liter)
1.0 0.7 0.9 2.1 2.7 1.6 2.1 2 3 4 5 6 7
Definition of abbreviations: VC = vital capacity; TLC = total lung capacity; RV = residual volume; FRC = functional residual capacity; FEVI = 1-sec forced expiratory volume; SGaw = specific airway conductance.
76 74 78 80
0.30 0.56 0.34 0.52 0.26 79
80 77
65 77 59 47 34 59 64 80 86 89 95 85 72 91 55 80 81 83 76 98 106 2.3 2.0 1.7 2.95 3.05 3.05 4.65
(%) (%pred.)
(liter)
(%pred.)
(%)
(%)
RVITLC
FEVIIVC FRC RV TLC VC
Patient no.
TABLE 2
SUBDIVISIONS OF LUNG VOLUME AND SPECIFIC CONDUCTANCE
100 117 100 124 78 121 182
SGaw
FRC/TLC
(see-I. em H2O-I)
LUNG MECHANICS IN MUSCLE WEAK:NESS
absolute lung volume, however, flow rates were high in 5 of the patients, and 2 patients also had values of SGaw (table 2) above the normal up· per limit of 0.35 sec -1 • em H 2Q-1, The static expiratory PV curves are shown in figure 2 with values of compliance and of Pst (1) at TLC (Pst[IJmax) in table 3. Both Pst(l)max and static compliance were subnormal. ·Dynamic compliance during tidal breathing was only slightly less than static expiratory compliance. Maximal and minimal pleural pressures at differing lung volumes in 6 patients are shown in figure 3. As anticipated, the inspiratory muscles were grossly weak in all; the minimal (inspiratory) pleural pressure measurements showed little variation with lung volume. Expiratory pressures were also considerably reduced in Patients I, 4, 6, and 7. Results (when available) of DLco, blood gas analyses, and single-breath nitrogen test are shown in table 4. Two patients had a slightly increased alveolar-arterial oxygen tension difference; no closing volume was demonstrated in the 3 patients in whom the single-breath test was performed (2 of whom had large residual volumes), but the slope of the alveolar plateau (Phase III) was increased above normal for nonsmoking subjects in our laboratory (upper limit, 1.6 per cent nitrogen per liter). Discussion Weakness of the inspiratory muscles was confirmed in all the patients by the values of minimum pleural pressure, which were considerably less negative than normal. Most of our patients had conditions with widespread involvement of skeletal muscle, which accounts for the reduction of maximal expiratory pressures. The patient with the highest age 26-)8
age 45-61
VEIIICIII
ptcdiCUd
TLC Sl£1
~~~~~~.~0~~.00 VOLUME
0
/o predicted TLC
2~0~~~~~~~.00 VOLU~E
0
/o predicted TLC
Fig. 1. Maximal expiratory flow-volume curves for 6 patients (table 1). Flow and volume expressed in relation to predicted total lung capacity (TLC). Shaded areas represent ranges of maximal flow (VE max) below 80 per cent TLC in 16 and 12 age-matched normal subjects.
392
GIBSON, PRIDE, :-.IEWSOM DAVIS, AND LOH
TABLE 3 DATA FROM MAXIMAL EXPIRATORY FLOW-VOLUME AND PRESSURE-VOLUME STUDIES Static Expiratory Compliance• PEF Patient (/iter/ sec) no.
% VC at
(% pred.)
PEF
43 47 65 68 95 54
44 62 66 61 84 72
4.5 3.0 3.6 6.7 9.2 3.4
1 2 3 4 5 6 7
(/iter/ em H20)
Static Inspiratory Dynamic (%pred_ Compliance Compliance (/iter/ (/iter/ TLCI em H20) em H20) em H20)
0.056 0.071 0.048 0.140 0.120 0.096 0.190
0.8 1.6 1.3 2.4 1.9 2.5 2.8
VT (/iter)
Pst (I) at TLC (per min) (em H20)
r
0.057
0.048
0.47
32
0.048 0.122
0.045 0.130 0.090 0.091
0.40 0.37 0.40 0.36
23 26 23 18
18.5 12 10.5 17 9 13.5 17
0.160
Definition of abbreviations: PEF =peak expiratory flow; Pst (I) = transpulmonary pressure; VT =tidal volume; f = frequency. For definition of other abbreviations, see table 2. • Range of values in 22 normal subjects, 2.9 to 7.9 per cent of predicted TLC/cm H20.
expiratory pressures (Patient 5, figure 3) had suffered from poliomyelitis, affecting clearly defined spinal segments but sparing the muscles of the abdominal wall; interestingly, he was also the patient with the smallest residual volume. Maximal expiratory pressures are normally generated at high lung volumes (18), and single measurements of maximal expiratory pressure unrelated to volume may, therefore, tend to overestimate the degree of expiratory muscle weakness in patients with a restricted inspiratory capacity. The FRC in our patients was, in general, below normal, and in some of the patients the recoil pressure of the lungs at FRC was also low. It is possible that gross muscle weakness alters the passive recoil of the thoracic cage, modifying the neutral position at which lung and cage recoil pressures are balanced. In addition, the normal end-tidal position of patients with diaag~
phragm weakness may lie below this neutral position; in such patients inspiration may be initiated by passive descent of the diaphragm consequent on relaxation of the abdominal muscles (8), implying an active effort at the end of the preceding expiration. Our analysis of lung compliance has concentrated on the expiratory PV curve, which is generally regarded as the best index of the over-all elastic behavior of the lungs. Because of the hysteresis of the PV curve a reduction in the Pst (I)max achieved on full inspiration will itself alter the position and slope of the expiratory curve and tend to reduce static expiratory compliance. Although this mechanism may have contributed to the reduction in expiratory compliance in our patients we do not think it played an important role because values of compliance obtained during inspiration in 4 of the patients were also re-
age 45-61 years
26- 43 years
VOLUME 100 Ofo predicted
100
100
TLC 80
/l
/ '
).
60~, 40
~·
/ 20
20
0
0
20 Pst 01
30
em t-t 2 o
0 o~--~~o~-=2o~~,~0--~40 Pst 01
em H20
Fig. 2. Static expiratory pressure-volume curves for 7 patients over volume range, total lung capacity (TLC) to functional residual capacity_ Volume expressed as percentage of predicted TLC and shaded areas represent ranges of normal subjects from Turner and associates ( 1 7)-
-so
-100
Ppl min
em H20
0
50
100 P
pi
ma~
ISO
em H,P
Fig. 3. Values of maximal and minimal static pleural pressures in 6 patients_ Measurements made during attempted expiration and inspiration against an obstruction at the mouth_ Shaded area shows range of values obtained in 6 normal subjects 27 to 44 years of age.
393
LUNG MECHANICS IN MUSCLE WEAKNESS
TABLE 4 CO DIFFUSING CAPACITY, ARTERIAL BLOOD GAS ANALYSES, AND SINGLE-BREATH N 2 TEST DLco Patient no.
2 2 3 4 5 6 7
(ml/min/ mm Hg)
23.0 21.8 14.5 23.8
(%pred.)
74 71 64 77
Paoz
Pacoz
(A-a) POz Phase Ill slope
(mm Hg)
(mm Hg)
(mm Hg)
87 78 69
44 42 55
7 18 12
95 54 73
36 63 55
9 16 7
(% Nz/liter)
Phase IV
2.0
Undetectable
2.4 2.3
Undetectable Undetectable
Definition of abbreviations: DLco =diffusing capacity for CO; Pao 2 =arterial oxygen tension; Paco 2 =arterial carbon dioxide tension, (A-a) POz =alveolar-arterial oxygen tension difference.
duced (table 3). Furthermore, in 3 normal subjects we examined the immediate effects on the expiratory PV curve of voluntarily restricting the 3 preliminary inspirations to a Pst (!)max of 15 em H 2 0; the mean reduction in static expiratory compliance at FRC was only 9 per cent of the value obtained with a full inflation volume history. In our patients the changes in compliance were much greater and resulted in more severe degrees of lung volume restriction than would occur with truncation of the PV curve alone. The cause of this reduced compliance is uncertain. The 3 patients (Patients I, 2, and 3) with diaphragm elevation on the chest radiograph had the smallest lung volumes and the lowest values of compliance; all 3 at some time had radiographic changes suggesting lower lobe atelectasis. Similar functional changes, however, were present without radiographic change, indicating a more subtle secondary alteration in elastic properties present in the lungs of all the patients. This might be either atelectasis of a more focal nature, which may not be radiographically visible (19, 20) or a generalized change in the elastic behavior of the surface film lining the alveoli. A further contributory factor to the low values of compliance might be the failure of development of a normal complement of alveoli. We think this is a very unlikely explanation for our findings because most of the patients developed symptoms and signs of disease only in adult life, and certainly it could not explain the abnormally low distensibility of the lungs of Patient 5, who acquired poliomyelitis at I 8 years of age. The abnormalities demonstrated in our patients closely resemble those produced in normal subjects by artificially restricting chest expan-
sion. Caro and associates (5) and subsequent investigators (6, 7) showed that strapping the chest produced changes in the PV curve of the lungs with a reduction in compliance, a reduction in lung recoil pressure at TLC, and increases in airway conductance and maximal expiratory flow at a given volume. The patients discussed here demonstrated all these features in varying degrees. Stubbs and Hyatt (6) set up various models that might account for the effects of chest strapping, and, of the 2 most likely alternatives, they favored a true alteration in the (surface) elastic properties of the alveoli rather than a reduction in the number of contributing lung units consequent on atelectasis. This conclusion was based mainly on the finding of "supernormal" airway function, which was predicted by their model of alveolar "stiffness" but not by their model of atelectasis; the latter suggested that airway function would remain proportionate to the number of patent alveoli and, thus, conductance and maximal flow would be appropriate for lung volume. This, however, might be an unrealistic model of atelectasis if it occurred in patchy fashion throughout the lungs. In the latter case, some generations of airways would subtend both atelectatic and patent terminal units, and the reduction of compliant units would therefore be greater than the reduction of parallel conducting airways; hence, indices of airway function such as maximal expiratory flow and total airway conductance would appear "supernormal" in relation to the absolute lung volume. Sybrecht and co-workers (7) also believed that their findings with chest strapping could be best explained by a widespread increase in the surface tension of the alveolar lining layer, but they did not discuss the possibil-
394
GIBSON, PRIDE, NEWSOM DAVIS, AND LOH
ity of atelectasis. Their demonstration that when volume was expressed as per cent of TLC the PV curves before and after strapping were indistinguishable would, however, be compatible with a simple reduction in the complement of gascontaining alveoli; similarly, atelectasis could lead to an increase in upstream resistance (owing to functional loss of peripheral airways subtending atelectatic units) and to a reduction in closing volume as found by these investigators. The most important evidence against atelectasis is their demonstration that the distribution of a radioactive bolus was not altered by chest strapping, suggesting that there were proportionate reductions in compliance in all regions of the lung. But although this failure to demonstrate greater cl1anges at the lung bases is an important point against atelectasis, the alternative mechanism proposed (change in surface properties consequent on breathing at small lung volume) should also be most pronounced at the bases in erect subjects. Because we are not confident that atelectasis has been excluded as a cause of the reduction in compliance during strapping, we believe atelectasis also remains a possible cause for the similar changes found in our patients with muscle weakness. The elevated arterial Pco 2 in 3 patients may be specifically related to diaphragm failure (8). Otherwise, the effects of severe respiratory muscle weakness on indices of pulmonary gas exchange in our patients were relatively minor in comparison to conditions such as fibrosing alveolitis that restrict lung volume by an intrapulmonary mechanism and where the gas exchange defect is often out of proportion to the mechanical abnormality. Studies of the volume dependence of the single-breath DLco in normal subjects (21) imply that some reduction would be an inevitable consequence of the patients' inability to inflate their lungs fully. The characteristic pattern of breathing of patients with severe respiratory muscle weakness is with small tidal volume and rapid frequency (22); this is similar to that described in patients with a restrictive ventilatory defect of primary intrapulmonary origin and hence may be related to the reduced compliance of the lungs, irrespective of the mechanism by which this is produced. An important practical implication of our study is that measurement of lung compliance in a patient with small volumes will not in itself allow a distinction between primary intrapulmonary and extrapulmonary causes of restriction. A low value of Pst(l) at full inflation, as recently em-
phasized by Colp and co-workers (23), indicates extrapulmonary restriction, but its value can be surprisingly high in some patients with gross weakness of the inspiratory muscles. Muscle weakness as a contributory factor to lung volume restriction should be easily recognizable by careful measurement of pressure during maximal inspiratory efforts at several lung volumes. The detection of primary intrapulmonary disease by mechanical tests may be impossible if an extra pulmonary component is also present. References 1. Ferris, B. G., Mead, J., Whittenberger, J. L.,
and Saxton, G. A.: Pulmonary function in convalescent poliomyelitic patients. III. Compliance of the lungs and thorax, N Eng! J Med, 1952, 247,390.
2. Stone, D. J., and Keltz, H.: The effect of respiratory muscle dysfunction on pulmonary function, Am Rev Respir Dis, 1963,88,621. 3. Hapke, E. J., Meak, J. C., and Jacobs, J.: Pulmonary function in progressive muscular dystrophy, Chest, 1972, 61, 41. 4. McKinley, A. C., Auchincloss, J. H., Gilbert, R., and Nicholas, J. J.: Pulmonary function, ventilatory control and respiratory complications in quadriplegic subjects, Am Rev Respir Dis, 1969, 100,526.
5. Caro, C. G., Butler, J., and DuBois, A. B.: Some effects of restriction of chest cage expansion on pulmonary function in man: An experimental study, J Clin Invest, 1960, 39, 573. 6. Stubbs, S. E., and Hyatt, R. E.: Effect of increased lung recoil pressure on maximal expir· atory flow in normal subjects, J Appl Physiol, 1972, 32, 325.
7. Sybrecht, G. W., Garrett, L., and Anthonisen, N. R.: Effect of chest strapping on regional lung function, J Appl Physiol, 1975,39,707. 8. Newsom Davis, J., Goldman, M., Loh, L., and Casson, M.: Diaphragm function and alveolar hypoventilation, Q J Med, 1976,45, 87. 9. McDermott, M., McDermott, T. J., and Collins, M. M.: A portable bellows spirometer and timing unit for the measurement of respiratory function, Med Bioi Eng, 1968, 6, 291. 10. DuBois, A. B., Botelho, S. Y., Bedell, G. N., Marshall, R., and Comroe, J. H., Jr.: A rapid plethysmographic method for measuring thoracic gas volume: A comparison with a nitrogen washout method for measuring functional residual capacity in normal subjects, J Clin Invest, 1956,35,322. 11. DuBois, A. B., Botelho, S. Y., and Comroe, J. H.,
Jr.: A new method for measuring airway resistance in man using a body plethysmograph. Values in normal subjects and in patients with respiratory disease, J Clin Invest, 1956,35,327.
LUNG MECHANICS IN
12. Mead, J.: Volume displacement body plethysmograph for respiratory measurements in human subjects, J Appl Physiol, 1960, 15, 736. 13. Milic-Emili, J., Mead, J., Turner, J. M., and Glauser, E. M.: Improved technique for estimating pleural pressure from esophageal balloons, J Appl Physiol, 1964, 19, 207. 14. Ogilvie, C. M., Forster, R. E., Blakemore, W. S., and Morton, J. W.: A. standardized breathholding technique for the clinical measurement of the diffusing capacity of the lung for carbon monoxide, J Clin Invest, 1957,36, 1. 15. Anthonisen, N. R., Danson, J., Robertson, P. C., and Ross, W. R. D.: Airway closure as a function of age, Respir Physiol, 1969,8, 58. 16. Cotes, J. E.: Lung Function, ed. 3, Blackwell Scientific Publications, Oxford, 1975, pp. 380, 381. 17. Turner, J. M., Mead, J., and Wohl, M. E.: Elasticity of human lungs in relation to age, J App1 Physiol, 1968,25,664.
~IUSCLE
WEAKNESS
395
18. Rohrer, F.: Der Zusammenhang der Atemkrafte and ihre Abhangigkeit vom Dehnungszustand der Atmungsorgane, Pfluegers Arch, 1916, 165, 419. 19. Rahn, H., and f'arhi, L. E.: Gaseous environment and atelectasis, Fed Proc, 1963, 22, 1035. 20. Prys-Roberts, C., Nunn, J. F., Dobson, R. H., Robinson, R. H., Greenbaum, R., and Harris, R. S.: Radiologically undetectable pulmonary collapse in the supine position, Lancet, 1967, 2, 399. 21. Miller, J. M., and Johnson, R. L.: Effect of lung inflation on pulmonary diffusing capacity at rest and exercise, J Clin Invest, 1966,45,493. 22. Newsom Davis, J., Stagg, D., Loh, L., and Casson, M.: The effects of respiratory muscle weakness on some features of the breathing pattern, Clin Sci Mol Med, 1976,50, lOP. 23. Colp, C., Reichel, J., and Park, S. S.: Severe pleural restriction: The maximum static pulmonary recoil pressure as an aid to diagnosis, Chest, 1975, 67, 658.
