This Article Abstract Full Text (PDF) Online Data Supplement Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hart, N. Articles by Polkey, M. I. Search for Related Content PubMed PubMed Citation Articles by Hart, N. Articles by Polkey, M. I.

Effect of Severe Isolated Unilateral and Bilateral Diaphragm Weakness on Exercise Performance

Respiratory Muscle Laboratory and Lung Function Unit, Royal Brompton Hospital, London, United Kingdom; Department of Clinical Physiology, Raymond Poincaré Hospital, Garches, France; Department of Respiratory Medicine and Allergy, Guy's, King's and St. Thomas' School of Medicine, King's College Hospital, London, United Kingdom

Correspondence and requests for reprints should be addressed to Nicholas Hart, M.D., Respiratory Muscle Laboratory, Royal Brompton Hospital, Fulham Road, London SW3 6NP, UK. E-mail: drnhart{at}aol.com

	ABSTRACT

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

 
Patients with isolated diaphragm paralysis depend on recruitment of extradiaphragmatic respiratory muscles to increase ventilation, but little is known about exercise performance or the response of the inspiratory muscles to loaded breathing. By convention, unilateral diaphragm paralysis is regarded as a trivial condition whereas bilateral paralysis is considered to be potentially life-threatening. In fact, no data exist concerning exercise performance under these conditions. We studied incremental treadmill exercise performed by eight patients with bilateral diaphragm paralysis, eight patients with unilateral diaphragm paralysis, and eight age-matched control subjects. Respiratory muscle endurance (RME) was also measured by an inspiratory threshold loading method. Exercise time, compared with control subjects (671 seconds), was moderately reduced in unilateral diaphragm paralysis (512 seconds, p = 0.07) and further reduced in bilateral diaphragm paralysis (456 seconds, p = 0.02). Similarly, peak minute ventilation was lower in patients with unilateral diaphragm paralysis (84 L · min^-1, p = 0.01) and in patients with bilateral diaphragm paralysis (69 L · min^-1, p = 0.001) compared with control subjects (114 L · min^-1). However, patients with unilateral diaphragm paralysis and patients with bilateral diaphragm paralysis had increased ratios of peak oxygen consumption to peak minute ventilation compared with control subjects (p = 0.0007 and p < 0.0001, respectively). Nine patients had normal RME; exercise time was moderately increased in these patients (502 seconds) compared with seven patients with reduced RME (461 seconds). In conclusion, although exercise performance is impaired in bilateral diaphragm paralysis, these patients can sustain a reasonable exercise load, particularly if RME is preserved and compensatory mechanisms have developed. In addition, exercise tolerance is diminished in patients with unilateral diaphragm paralysis.

Key Words: diaphragm weakness • exercise • respiratory muscle endurance

	INTRODUCTION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

 
Although bilateral diaphragm paralysis was previously regarded as a serious condition that required nocturnal ventilatory support to prevent respiratory decompensation (1), unilateral diaphragm paralysis has been considered as a relatively benign disorder with no serious clinical implications. However, subsequent studies have shown that in the absence of generalized neuromuscular disease or comorbidity, isolated bilateral diaphragm paralysis is far from life-threatening (2), implying that there is compensatory recruitment of the extradiaphragmatic respiratory muscles.

Despite this, exertional dyspnea is a common symptom in patients with unilateral and bilateral diaphragm paralysis, but few studies have investigated the impact of isolated diaphragm paralysis on exercise performance (2). In addition to the clinical data that evaluating exercise performance in patients with isolated diaphragm paralysis would generate, it would also provide general data about the role of the diaphragm during exercise. This could be important to patients with other conditions, such as chronic obstructive airway disease, in which diaphragm dysfunction during exercise remains controversial; diaphragm dysfunction in chronic obstructive airway disease may be more critical if isolated diaphragm paralysis conferred substantial exercise limitation.

Finally, isolated diaphragm paralysis inevitably results in an increase in the load on the remaining inspiratory muscles. We hypothesized that the ability of the remaining inspiratory muscles to sustain an applied inspiratory load, during a test of respiratory muscle endurance (RME), would be associated with the presence of adaptive mechanisms to compensate for the loss of diaphragm function. Thus, although we would predict exercise performance to be reduced in isolated unilateral and bilateral diaphragm paralysis, the aim of the present study was to quantify the extent of this effect and, by extension, investigate the role of the diaphragm in sustaining exercise.

	METHODS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

 
Subjects
The protocol was approved by the Royal Brompton Hospital (London, UK) Ethics Committee. Eight patients with unilateral diaphragm paralysis, eight patients with bilateral diaphragm paralysis, and eight age-matched control subjects were included in the study. Demographic details about the patients and control subjects are shown in Table 1 and in the online data supplement, respectively. None of the control subjects participated in regular exercise. All participants were male. We excluded patients with generalized neuromuscular disease, peripheral vascular disease, cardiac dysfunction, and pulmonary disease.

Pressure Measurements
After insertion of esophageal and gastric balloon catheters, esophageal pressure (Pes), gastric pressure (Pgas), and transdiaphragmatic pressure (Pdi) were measured with differential pressure transducers (Validyne, Northridge, CA) and amplified before passing the data to a computer (Apple Computers, Cupertino, CA). Data acquisition and analysis were performed with LabVIEW4.1 (National Instruments, Austin, TX).

Twitch Transdiaphragmatic Pressure
Diaphragm paralysis was diagnosed by magnetic phrenic nerve stimulation (6, 7). Bilateral diaphragm paralysis and unilateral diaphragm paralysis were diagnosed if right and/or left twitch Pdi (Tw Pdi) were less than 3.5 cm H₂O. This cut-off level was arbitrarily chosen because cardiac contraction may cause intrathoracic pressure fluctuations of up to 2 cm H₂O.

Maximum Inspiratory Pressure
Maximum inspiratory maneuvers were performed by a standard method (8). Inspiratory efforts were made from functional residual capacity (FRC) and were repeated at least 10 times. Peak esophageal pressure (Pes_max) was measured and used as an index of global inspiratory muscle strength. Peak transdiaphragmatic pressure (Pdi_max) and changes in Pgas and Pes during resting breathing were also measured.

Dynamic Compliance
Dynamic lung compliance (Cdyn) was calculated during resting breathing by dividing tidal volume by differences in Pes at points of zero flow.

Exercise Testing
Subjects underwent incremental cardiopulmonary exercise testing to exhaustion (Bruce protocol; for further details see online data supplement). During the test, heart rate (HR) and breath-by-breath measurements of minute ventilation (_V^·E) and oxygen consumption (_V^·O₂) were recorded (Jaeger, Friedberg, Germany).

Respiratory Muscle Endurance Testing
RME testing was performed on a separate day from exercise testing, using a method developed in our laboratory (9) in which subjects breathe against a constant-level negative pressure inspiratory threshold-loading device. The target negative pressure is set at 70% of Pes_max and there is no restriction placed on the pattern of breathing. Endurance time (End TLim) is defined as the period from when the negative pressure imposed reaches 70% of Pes_max to exhaustion. Average esophageal pressure time product (PTPes) per total breath cycle was calculated and used as an indicator of inspiratory load (9). PTPes and gastric pressure time product (PTPgas) per minute were also calculated. After the test, the ratio of inspiratory load to capacity was calculated by normalizing PTPes per total breath cycle for Pes_max (PTPes/Pes_max) and this was correlated with End TLim to evaluate RME (9).

Statistical Analysis
Statistical analysis was performed with StatView 5.0 (Abacus Concepts-SAS, Cary, NC). Differences between groups were assessed by analysis of variance. RME of patients with diaphragm paralysis was determined by comparing log End TLim and PTPes/Pes_max with published normal RME values (9). The predicted value for log End TLim was calculated from the PTPes/Pes_max; log End TLim less than 85% predicted was taken as a reduction in RME. Unpaired t tests were used to evaluate differences between the preserved and reduced RME groups. A value of p < 0.05 was considered statistically significant.

	RESULTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

 
Pulmonary Function Tests
Lung function data for control subjects and patients with diaphragm paralysis are shown in Table 2 . Patients with unilateral diaphragm paralysis or bilateral diaphragm paralysis had reduced lung volumes with reduction in DL_CO. However, the carbon monoxide transfer coefficient was within the range that would be predicted for the reduction in alveolar volume (10).

View larger version (19K): [in this window] [in a new window]   Figure 1. Log endurance time (log End TLim) versus the load/capacity ratio (PTPes per total breath cycle/Pesmax) in patients with unilateral diaphragm paralysis (squares) and bilateral diaphragm paralysis (circles). The shaded area shows the log End TLim plotted against PTPes per total breath cycle/Pesmax in healthy subjects (9); a log End TLim less than 85% predicted for the PTPes/Pesmax when compared with the normal values indicates a reduced RME.

	DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

 
The main finding of this study is that although exercise performance is reduced in patients with isolated unilateral and bilateral diaphragm paralysis, this reduction is not as great as previous data would suggest for bilateral diaphragm paralysis, and greater than expected for patients with unilateral diaphragm paralysis; we actually found no difference in Ex TLim or _V^·E peak between the isolated unilateral and bilateral diaphragm paralysis groups. Furthermore, both sets of patients can still sustain a reasonable exercise load, particularly if RME is preserved. This reduction in exercise performance is associated with reduced peak minute ventilation, and thus the cause is primarily a ventilatory one.

Critique of the Method
Numerous methods have been proposed for diagnosis of diaphragm paralysis. Although magnetic phrenic nerve stimulation either unilaterally (6) or bilaterally (7) is currently the most precise technique for diagnosis of diaphragm paralysis (13, 14) or weakness (15, 16), we ensured a thorough assessment of diaphragm function was achieved by using three different methods: Pgas/Pes ratio, Pdi_max, and Tw Pdi. In our clinical practice, a Tw Pdi of less than 3.5 cm H₂O is used as evidence of severe diaphragm weakness because we observe pressure changes of up to 2 cm H₂O as a result of cardiac contraction. Thus, although the term "diaphragm paralysis" remains in common usage, we acknowledge that data in our study strictly pertain to patients with severe diaphragm weakness and that this may be of neuropathic or myopathic origin.

Comparison with previous studies.
No human studies have investigated the effect of isolated unilateral and bilateral diaphragm paralysis on exercise performance. Data from our own group (2) concerning four patients with isolated bilateral diaphragm paralysis showed that these patients do not desaturate during treadmill exercise, but this study made no comment on other aspects of the data. However, the exercise results in that study (2) were similar to the current observations, with the patients reaching a mean _V^·E of only 61.5 L · min^-1 and achieving a _V^·O₂ peak of 2.0 L · min^-1 (_V^·O₂ peak/_V^·E peak = 0.033).

Gosselin and coworkers (17) studied the effect of phrenic nerve section in rats and found that unilateral diaphragm paralysis had no effect on Ex TLim or _V^·O₂ peak but that bilateral diaphragm paralysis reduced both Ex TLim and _V^·O₂ peak. These investigators concluded that there was adequate respiratory muscle reserve in rats to compensate for loss of one but not both hemidiaphragms. However, quadruped studies are not an ideal method for investigation of the effect of diaphragm paralysis on exercise performance in humans because of the differing pulmonary mechanics during exercise between humans and quadrupeds (18).

Significance of the Findings
Our study confirms impairment of both ventilation and exercise performance in patients with isolated diaphragm paralysis. However, isolated unilateral diaphragm paralysis, a disease considered to have minimal clinical impact, produced a greater reduction in exercise performance than may have been predicted, whereas isolated bilateral diaphragm paralysis, a more severe disease, had a smaller reduction in exercise performance than might have been predicted. Thus, the extent of the reduction in exercise performance in patients with isolated diaphragm paralysis was unexpected when considering the degree of loss of respiratory muscle function. However, overall, patients with isolated diaphragm paralysis have a relatively well-preserved exercise capacity, suggesting the presence of compensatory adaptive mechanisms.

At any given level of exercise, patients with diaphragm paralysis exhibited a greater oxygen uptake than control subjects despite reduced minute ventilation leading to a highly significant rise in the _V^·O₂ peak/_V^·E peak ratio. The mechanism underlying this observation is of physiological interest. It has been reported from human studies that respiratory muscle efficiency varies with the task imposed (19), and it would be predicted that the task imposed on extradiaphragmatic muscles in the presence of diaphragm paralysis is different from that imposed when diaphragm function is normal. Indeed, in animal studies, the relationship between mechanical and chemical power is not proportional with differing forces, lengths, and velocities of contraction (20, 21). Although the extradiaphragmatic muscles were not assessed in the current study, available animal data suggest the presence of extradiaphragmatic muscle recruitment in diaphragm paralysis (22–25). Sherrey and Megirian (23) reported increased activity of the intercostal muscles during inspiration and increased activity of the oblique muscles during expiration in rats with diaphragm paralysis, whereas Katagiri and coworkers (24) demonstrated in dogs that although the resting length of the intact hemidiaphragm in unilateral diaphragm paralysis is unchanged, during inspiration there is greater shortening and increased activity of the intact hemidiaphragm. The intercostal muscle compensation is thought to be due, in part, to a decrease in reflex inhibition by diaphragm receptors, via phrenic nerve afferents, on the efferent activity of the inspiratory intercostal muscles (25).

In contrast to the animal studies (17, 26, 27) that have investigated acute diaphragm paralysis, diaphragm paralysis in our patients was longstanding, with an average time from onset of symptoms to diagnosis of 13.3 ± 9.2 months. This symptom duration to diagnosis is similar to that previously described in the literature (14) and thus the development of compensatory mechanisms would be expected. We observed that patients with reduced RME had a shorter exercise time than those with preserved RME. Thus, investigation of differences between diaphragm paralysis patients with reduced RME and those with preserved RME could generate hypotheses with respect to compensatory mechanisms, particularly as the preserved RME group had diaphragm paralysis for a longer time course (17.2 ± 9.5 versus 8.3 ± 6.3 months; p = 0.05).

During the threshold loading test, the patients with preserved RME had greater activation of the abdominal muscles during expiration, reflected by the higher expiratory PTPgas, which would facilitate the following inspiration by allowing passive descent of the diaphragm as the abdominal muscles relax (28). Increased abdominal muscle recruitment during expiration, at rest and during exercise, has been reported in postpoliomyelitic patients (29), in patients with chronic obstructive airway disease (30, 31), in patients with scoliosis (32), and anecdotally by us in bilateral diaphragm paralysis (33). We observed in the present study that during loaded breathing, expiratory PTPgas was greater in those patients with a longer duration of diaphragm paralysis (p = 0.05). Thus, we speculate that abdominal muscle recruitment is a compensatory adaptation, perhaps achieved through a mechanism of cortical plasticity, a mechanism known to operate for nonrespiratory muscles under load (34).

Previous studies have reported reductions in lung and chest wall compliance in patients with chronic respiratory muscle disease (35–38). We found a reduction in Cdyn in patients with reduced RME compared with both control subjects and patients with preserved RME. This is inconsistent with observations of patients with spinal cord injury and generalized neuromuscular disease, in whom compliance of the lung and chest wall is reported to decrease with time (39), possibly because of changes in lung tissue elasticity, surface tension forces within the alveoli, and stiffening of the rib cage (35–38). However, these changes could be less marked in patients with isolated diaphragm paralysis for two reasons. First, expiratory muscle function is normal and risk of chest infection and basal atelectasis is less; second, isolated diaphragm paralysis is not a progressive disease and, as previously noted, there is a capacity for recruitment, adaptation, and training of extradiaphragmatic respiratory muscles.

The significance of the Pgas/Pes ratio has been reported previously (11, 28, 40). However, separating patients with unilateral diaphragm paralysis into those with and without abdominal paradox demonstrated that abnormal abdominal motion, and presumably differing pulmonary mechanics, has an impact on exercise performance. In this context we suggest that unilateral diaphragm paralysis with paradoxical abdominal motion is not a physiologically efficient method for driving the respiratory muscle pump, presumably because the ascending diaphragm on the affected side prevents effective inspiratory airflow. Therefore, this highlights the observation that unilateral diaphragm paralysis can have a greater than expected reduction in exercise performance. Furthermore, unilateral diaphragm paralysis patients with paradoxical motion had reduced RME, whereas three of four patients without paradoxical motion had preserved RME. Moreover, the patient without paradoxical motion but reduced RME had both a reduction in Cdyn and abdominal muscle recruitment and a disease duration of only 2 months.

Are the observed reductions in exercise performance clinically significant? Our data suggest that whereas patients with isolated bilateral diaphragm paralysis may have moderate exercise limitation in the course of daily life, patients with unilateral diaphragm paralysis are also susceptible to exercise limitation, which could be of importance during heavy exercise. In our experience this tends to be either intense recreational or occupational factors requiring extremes of performance.

In summary, exercise performance is unexpectedly high in patients with bilateral diaphragm paralysis and unexpectedly low in patients with isolated unilateral diaphragm paralysis. Although patients with unilateral diaphragm paralysis are overall less affected than those with bilateral diaphragm paralysis, there is a subgroup of patients with unilateral diaphragm paralysis, identified clinically by the finding of paradoxical abdominal motion during resting breathing, who have reduced exercise performance and RME. Compensatory recruitment of extradiaphragmatic respiratory muscles and the abdominal muscles appears to play an important role in maintaining exercise performance.

	Acknowledgments

 
The authors would like to thank Prof. Malcolm Green for his help throughout the preparation of this manuscript.

	FOOTNOTES

 
Supported by the Dorothy Osbourne Legacy (N. H.) and the British Lung Foundation (A. H. N.).

This article has an online data supplement, which is accessible from this issue's table of contents online at www.atsjournals.org

Received in original form October 3, 2001; accepted in final form February 12, 2002

	REFERENCES

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

 

1. Newsom-Davis J, Goldman M, Loh L, Casson M. Diaphragm function and alveolar hypoventilation. Q J Med 1976;177:87–100.
2. Laroche CM, Carroll N, Moxham J, Green M. Clinical significance of severe isolated diaphragm weakness. Am J Respir Crit Care Med 1988; 138:862–866.
3. British Thoracic Society. Guidelines for the measurement of respiratory function. Respir Med 1994;88:165–194.[Medline]
4. Quanjer P, Tammeling G, Cotes J, Pedersen O, Peslin R, Yernault Y. Standardised lung function testing, lung volumes and forced ventilatory flows. Eur Respir J 1993;6:5–40.[Medline]
5. Cotes JE. Lung function: assessment and application in medicine, Vol. 5. Oxford: Blackwell Scientific Publications; 1993.
6. Mills GH, Kyroussis D, Hamnegard C-H, Wragg S, Moxham J, Green M. Unilateral magnetic stimulation of the phrenic nerve. Thorax 1995; 50:1162–1172.[Abstract]
7. Mills GH, Kyroussis D, Hamnegard CH, Polkey MI, Green M, Moxham J. Bilateral magnetic stimulation of the phrenic nerves from an anterolateral approach. Am J Respir Crit Care Med 1996;154:1099–1105.[Abstract]
8. Black LF, Hyatt RE. Maximal respiratory pressures: normal values and relationships to age and sex. Am Rev Respir Dis 1969;99:696–702.[Medline]
9. Hart N, Hawkins P, Hamnegard C-H, Green M, Moxham J, Polkey M. A novel clinical test of respiratory muscle endurance. Eur Respir J 2002; 19:232–239.[Abstract/Free Full Text]
10. Stam H, Hrachovina V, Stijnen T, Versprille A. Diffusing capacity dependent on lung volume and age in normal subjects. J Appl Physiol 1994;76:2356–2363.[Abstract/Free Full Text]
11. Hillman DR, Finucane KE. Respiratory pressure partitioning during quiet inspiration in unilateral and bilateral diaphragmatic weakness. Am Rev Respir Dis 1988;137:1401–1405.[Medline]
12. Mulvey DA, Aquilina RJ, Elliot MW, Moxham J, Green M. Diaphragmatic dysfunction in neuralgic amyotrophy: an electrophysiological evaluation of 16 patients presenting with dyspnoea. Am Rev Respir Dis 1993;147:66–71.[Medline]
13. Mills GH, Kyroussis D, Hamnegard C-H, Wragg S, Polkey MI, Moxham J, Green M. Cervical magnetic stimulation of the phrenic nerves in bilateral diaphragm paralysis. Am J Respir Crit Care Med 1997;155:1565–1569.[Abstract]
14. Hughes PD, Polkey MI, Moxham J, Green M. Long-term recovery of diaphragm strength in neuralgic amyotrophy. Eur Respir J 1999;13:379–384.[Abstract]
15. Hughes PD, Polkey MI, Harris ML, Coats AJS, Moxham J, Green M. Diaphragm strength in chronic heart failure. Am J Respir Crit Care Med 1999;160:529–534.[Abstract/Free Full Text]
16. Polkey MI, Harris ML, Hughes PD, Hamnegard C-H, Lyons D, Green M, Moxham J. The contractile properties of the elderly human diaphragm. Am J Respir Crit Care Med 1997;155:1560–1564.[Abstract]
17. Gosselin LE, Megirian D, Rodman J, Mueller D, Farkas GA. Respiratory muscle reserve in rats during heavy exercise. J Appl Physiol 1997; 83:1405–1409.[Abstract/Free Full Text]
18. Bramble D, Jenkins F. Mammalian locomotor–respiratory integration: implications for diaphragmatic and pulmonary design. Science 1993; 262:235–240.[Abstract/Free Full Text]
19. McCool F, Tzelepis G, Leith D, Hoppin F. Oxygen cost of breathing during fatiguing inspiratory loads. J Appl Physiol 1989;66:245–1989.[Abstract/Free Full Text]
20. Stainsby W, Barclay J. Effect of initial length on relations between oxygen uptake and load in dog muscle. Am J Physiol 1976;230:1008–1012.
21. Stainsby WN, Lambert CR. Determinants of oxygen uptake in skeletal muscle. Exerc Sport Sci Rev 1979;7:125–151.[Medline]
22. Ninane V, Farkas G, Baer R, DeTroyer A. Mechanism of ribcage inspiratory muscle recruitment in diaphragmatic paralysis. Am Rev Respir Dis 1989;139:146–149.[Medline]
23. Sherrey J, Megirian D. After phrenectomy the rat alters the output of the remaining respiratory muscles without changing its sleep–waking pattern. Respir Physiol 1990;81:213–226.[Medline]
24. Katagiri M, Young RN, Platt RS, Kieser TM, Easton PA. Respiratory muscle compensation for unilateral or bilateral hemidiaphragm paralysis in awake canines. J Appl Physiol 1994;77:1972–1982.[Abstract/Free Full Text]
25. De Troyer A. The canine phrenic-to-intercostal reflex. J Physiol 1998;508: 919–927.[Abstract/Free Full Text]
26. Stradling J, Kozar L, Dark J, Kirby T, Andrey S, Philipson E. Effect of acute diaphragm paralysis on ventilation in awake and sleeping canines. Am Rev Respir Dis 1987;136:633–637.[Medline]
27. Mickell J, Aubier M, Engel L. Effects of inspiratory loading on respiratory muscle activity during expiration. Am Rev Respir Dis 1982;125: 352–358.[Medline]
28. Newsom-Davis J, Goldman M, Loh L, Casson M. The effects of respiratory muscle weakness on some features of breathing pattern. Clin Sci 1976;50:10P–11P.
29. Weinberg J, Borg J, Bevegard S, Sinderby C. Respiratory response to exercise in post polio patients with severe inspiratory muscle dysfunction. Arch Phys Med Rehab 1999;80:1095–1100.[CrossRef][Medline]
30. Polkey MI, Kyroussis D, Hamnegard C-H, Mills GH, Hughes PD, Green M, Moxham J. Diaphragm performance during maximal voluntary ventilation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997;155:642–648.[Abstract]
31. Ninane V, Rypens F, Yernault J, De Troyer A. Abdominal muscle use during breathing in patients with chronic airflow obstruction. Am Rev Respir Dis 1992;141:16–21.
32. Estenne M, Derom E, De Troyer A. Neck and abdominal muscle activity in patients with severe thoracic scoliosis. Am J Respir Crit Care Med 1998;158:452–457.[Abstract/Free Full Text]
33. Polkey M, Lyall R, Moxham J, Leigh P. Respiratory aspects of neurological disease. J Neurol Neurosurg Psychiatry 1999;66:5–15.[Free Full Text]
34. Boroojerdi B, Ziemann U, Chen R, Butefisch CM, Cohen LG. Mechanisms underlying human motor system plasticity. Muscle Nerve 2001;24:602–613.[CrossRef][Medline]
35. Gibson G, Pride N, Newsom-Davis J, Loh L. Pulmonary mechanics in patients with respiratory muscle weakness. Am Rev Respir Dis 1977;115: 389–395.[Medline]
36. Estenne M, Gevenois PA, Kinnear W, Soudon P, Heilporn A, De Troyer A. Lung volume restriction in patients with chronic respiratory muscle weakness: the role of microatelectasis. Thorax 1993;48:698–701.[Abstract]
37. Estenne M, Heilporn A, Delhez L, Yernault Y-C, De Troyer A. Chest wall stiffness in patients with chronic respiratory muscle weakness. Am Rev Respir Dis 1983;128:1002–1007.[Medline]
38. DeTroyer A, Borenstein S, Cordier R. Analysis of volume restriction in patients with respiratory muscle weakness. Thorax 1980;35:603–610.[Abstract]
39. Smith P, Calverly P, Edwards R, Evans G, Campbell E. Practical problems in the respiratory care of patients with muscular dystrophy. N Engl J Med 1987;316:1197–1205.[Medline]
40. Lisboa C, Pare PD, Perutze J, Contreras G, Moreno R, Guillemi S, Cruz E. Inspiratory muscle function in unilateral diaphragmatic paralysis. Am Rev Respir Dis 1986;134:488–492.[Medline]

This article has been cited by other articles:

				L. M. Romer and M. I. Polkey Exercise-induced respiratory muscle fatigue: implications for performance J Appl Physiol, March 1, 2008; 104(3): 879 - 888. [Abstract] [Full Text] [PDF]

				E. M. Summerhill, Y. A. El-Sameed, T. J. Glidden, and F. D. McCool Monitoring Recovery From Diaphragm Paralysis With Ultrasound Chest, March 1, 2008; 133(3): 737 - 743. [Abstract] [Full Text] [PDF]

				M. Shihata and J. C. Mullen Bilateral Diaphragmatic Plication in the Setting of Bilateral Sequential Lung Transplantation Ann. Thorac. Surg., March 1, 2007; 83(3): 1201 - 1203. [Abstract] [Full Text] [PDF]

				G P Whyte, M Harries, J Dickinson, and M I Polkey Breathless in the bath Br. J. Sports Med., June 1, 2006; 40(6): 554 - 555. [Abstract] [Full Text] [PDF]

				S. Jonville, L. Jutand, T. Similowski, A. Denjean, and N. Delpech Putative protective effect of inspiratory threshold loading against exercise-induced supraspinal diaphragm fatigue J Appl Physiol, March 1, 2005; 98(3): 991 - 998. [Abstract] [Full Text] [PDF]

				N. Hart, J. Moxham, and M.I. Polkey From the authors: Eur. Respir. J., September 1, 2004; 24(3): 511 - 511. [Full Text] [PDF]

				N Hart, M T Kearney, N B Pride, M Green, F Lofaso, A M Shah, J Moxham, and M I Polkey Inspiratory muscle load and capacity in chronic heart failure Thorax, June 1, 2004; 59(6): 477 - 482. [Abstract] [Full Text] [PDF]

				J. R. Bennett, H. M.A. Dunroy, D. R. Corfield, N. Hart, A. K. Simonds, M. I. Polkey, and M. J. Morrell Respiratory muscle activity during REM sleep in patients with diaphragm paralysis Neurology, January 13, 2004; 62(1): 134 - 137. [Abstract] [Full Text] [PDF]

				F. Laghi and M. J. Tobin Disorders of the Respiratory Muscles Am. J. Respir. Crit. Care Med., July 1, 2003; 168(1): 10 - 48. [Abstract] [Full Text] [PDF]

				M. J. Tobin Sleep-Disordered Breathing, Control of Breathing, Respiratory Muscles, and Pulmonary Function Testing in AJRCCM 2002 Am. J. Respir. Crit. Care Med., February 1, 2003; 167(3): 306 - 318. [Full Text] [PDF]

				F. Laghi, S. E. Cattapan, A. Jubran, S. Parthasarathy, P. Warshawsky, Y.-S. A. Choi, and M. J. Tobin Is Weaning Failure Caused by Low-Frequency Fatigue of the Diaphragm? Am. J. Respir. Crit. Care Med., January 15, 2003; 167(2): 120 - 127. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Online Data Supplement Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hart, N. Articles by Polkey, M. I. Search for Related Content PubMed PubMed Citation Articles by Hart, N. Articles by Polkey, M. I.