Phrenic Nerve Function in Patients with Diaphragmatic Weakness and Systemic Lupus Erythematosus

Phrenic Nerve Function in Patients with Diaphragmatic Weakness aod Systemic Lupus Erythematosus· Pearce G. Wilcox, M.D.;t Howard B. Stein, M.D.; Stephen D. Clarke, M.D.; Peter D. Pare, M.D.; and Richard L. Pardy, M.D., F.C.C.~

Diaphragmatic weakness has been identi6ed as one of the pulmonary manifestations of systemic lupus erythematosus. Whether this weakness results from a neuropathic or myopathic process has not been established. Thirty patients with SLE were screened for ~e presence of inspiratory muscle (1M) weakness. Detailed studies were performed in nine with 1M weakness. All nine were found to have diaplp-agmaticweakness (mean ± SD, maximal transdiaphragPhrenic nerve latencies, matic pressure 50 ± 12 c~O~ evaluated using transcutaneous stimulation, were normal in all individuals excluding a demyelinating neuropathy. Com-

pound diaphragm action potential (CDAP) with phrenic nerve stimulation was normal in six of these nine patients. Reduced CDAP in three of nine patients was consistent either with axonal degeneration of the phrenic nerve or diaphragm myopathy. Nerve conduction and electromyographic studies on peripheral nerves and muscles respectively £ailedto demonstrate an associated generalized neUropathy or myopathy. We conclude that diaphragmatic weakness in patients with sLE is both common and is very unlikely to be caused by a phrenic neuropathy.

SystemiC lupus erythematosus (SLE) has a variety of pleuropulmonary manifestations. These range from the common finding of pleurisy'" to much more unusual conditions such as pulmonary hemorrhage" or recurrent pulmonary embolism. ~ Sporadic reports of patients with SLE demonstrating a restrictive pattern on lung function tests and elevated hemidiaphragms with clear lung fields on chest radiographs, have existed in the literature since the 1950s.5-8 Initially, this "shrinking lung syndrome" was ascribed to either a process affecting the lung parenchyma'< or to restrictions in diaphragmatic movement secondary to pleural adhesions.v'?" More recently, however, Gibson et all! demonstrated that this condition could be explained on the basis of diaphragmatic weakness. The pathogenesis of the diaphragmatic weakness has not been established. It is unlikely to be due to associated pleural disease since diaphragmatic strength is only slightly reduced even in the presence of bilateral diffuse pleural thickening." Generalized neuropathic'v" and myopathic 16 processes are known: to occur in patients with SLE and either could involve the diaphragm. To date, however, the "shrinking lung syndrome" has been observed mainly in patients without obvious generalized neuromuscular disease. The objective of this study was to further evaluate the pathogenesis of

diaphragmatic weakness in patients with SLE. Specifically, we sought to determine whether this could be explained on the basis of a phrenic neuropathy.

·From the University of British Columbia Pulmonary Research Laboratory and the Department of Medicine, St. Pauls Hospital, Vancouver, Canada. . Supported by MRC Canada and British Columbia Lung Association. tCanadian Lung Association Research Fellow Manuscript received March 24; revision accepted June 16. 352

METHODS

Evaluation for AUPatients Thirty patients fulfilling the revised American Rheumatism Association criteria for the diagnosis of SLE 11 were recruited from the combined outpatient and inpatient practices of three rheumatologists. All but three patients were females. There was no attempt made to select on the basis of respiratory symptoms or the degree and severity of systemic involvement of SLE. Details of the patients' history, medication use, and disease activity were obtained from hospital and office charts, supplemented by selective reevaluation. A modified American Thoracic Society questionnaire was given to all patients to evaluate respiratory symptoms. After informed consent was obtained, patients were studied in a volume displacement body plethysmograph for measurement of expiratory flow rates and subdivisions of lung volume. Volume was measured by a linear displacement transducer (type 3OOHR, Shavitz Engineering, Pennsauken, NJ) attached to a water-filled wedge spirometer which was calibrated over its full 8-liter range with a calibration syringe. Flow was measured with a pneumotachograph (Fleish No 3) which was calibrated for air and was linear with flowsup to 10 Us. Maximalinspiratory (PImaJ and expiratory (PE....) pressures at the mouth were measured from residual volume (RV) and near total lung capacity (TLC) respectively using the technique reported by Blackand Hyatt. 18 Pressures were measured using a ± 100cmH t 9 differential pressure transducer (MP 43-3~, Validyne, Northridge, CA)and recorded on a chart recorder (Gould Instruments, Ballainvilliers, France). Values were expressed as percent predicted using the regression equations published by Black and Hyatt. 18

Evaluation ofPtltientswith P,_<65 Percent of Predicted From this initial group of3Opatients, a subgroup with evidence of inspiratory muscle weakness was selected. The criterion used was a diminished PIma, arbitrarily defined as being less than 65 percent of PhrenicNerveFunction in SLE (WIlcoxat aJ)

predicted. Eleven of 30 patients fulfilled this criterion and nine agreed to a more detailed assessment on a separate study day. Using a standard technique," balloon catheters were inserted into the esophagus and stomach and were coupled to separate ± 100cmH,O pressure transducers (MP 43-32, Validyne, Northridge, CA). The esophageal and gastric balloons were inflated with 0.5 ml and 2 ml of air respectively. Simultaneous tracings of esophageal (Pes), gastric (Pga) and transdiaphragmatic (Pdi) pressure (Pdi = Pga - Pes) were displayed on a four-ehannel chart recorder (Gould Instruments, Ballainvilliers, France). Maximal transdiaphragmatic pressure (Pdi...) was measured when patients performed maximal inspiratory efforts from functional residual capacity (FRC) against an occluded airway. A visual display of Pdi, Pes, and Pga was provided to maximize Pdi during these maneuvers. JO The best of a minimum of five attempts sustained for one second was selected as Pdim.. The maximal elastic recoil pressure (PLmaJ was also measured in these patients. The technique used was identical to that previously reported" and the regression equations published by Colebatch et alIIwere used to calculate PLa. as percent predicted. Phrenic nerve function was then studied in the supine position using transcutaneous phrenic nerve stimulation. Both right and left phrenic nerves were localized in the neck using a hand-held, felttipped bipolar stimulating electrode (13L22, Disa Electronics, Denmark) placed at the posterior border of the sternocleidomastoid muscle at the level of the thyroid cartilage. The compound diaphragmatic muscle action potential (CDAP) was recorded using surface disc electrodes with the active placed on the xiphoid process and the Indffferent over the seventh intercostal space at the costochondral junction (as suggested by Markand et al13). These were connected to an electromyogram (type 14Cll, Disa Electronics, Denmark) with a storage oscilloscope. The position of the stimulating electrode was altered and the voltage increased (60-150 ~ 0.2 ms) until a supramaximal stimulus was achieved. This was ensured by the demonstration of a maximal CDAP on the EMG storage oscilloscope. A permanent record of each supramaximal stimulation was obtained using an oscilloscope camera (C-27, Tektronix, Portland, OR). The other phrenic nerve was then studied in a similar manner. Motor latency was taken as the main measure of phrenic nerve function. This was measured as the time from stimulus artifact to the onset of diaphragmatic activity. The values used for comparison were those reported by Markand et al13 (mean conduction time 7.7 ms, with an upper limit of normal of 9.75 ms). The amplitude of the CDAP wasalso measured. This wastaken as the distance in millivolts from the baseline to the peak of the CDA~ An amplitude of greater than O.4mVhas been reported as normal using this method.f Six of the nine patients who had phrenic nerve studies were also assessed for possible generalized neuromuscular disease. Electrophysiologic studies were performed by an experienced neurologist using a Disa 1500 electromyograph (Oisa Electronics, Denmark). Motor and sensory nerve conduction studies were performed on the median, ulnar, sural and peroneal nerves in each patient. Monopolar needle ('mCA, Pleasantville, NY) EMG studies were also performed on a minimum of two of the following muscles: tibialis anterior, abductor hallucis, rectus femoris, gastrocnemius, deltoid, biceps, and the paraspinal muscles. Chest x-rayfilmswere obtained in the nine patients in group 2 and evaluated for evidence of decreased volumes, pleural changes, interstitial infiltrates and atelectasis.

groups for parameters of disease activity and respiratory symptoms. RESULrS

Thirty consecutive patients with SLE (27 F, 3 M; 32.2 ± 9.4 years, mean ± SD) were recruited for study. The mean duration of disease from the time of diagnosis was 6.4±5.2 years (range 0.2-20 years). All had evidence of either current or previous multisystem involvement secondary to SLE. Two patients (5, 8 in Table 2) had an acute presentation in keeping with that of the shrinking lung syndrome. Associated renal disease (biopsy proven) occurred in 21 of 30 patients and two were receiving long-term dialysis. Skin manifestations (malar rash, photosensitivity) were present in 13 patients while cardiac disease (pericarditis, myocarditis) had been diagnosed at some time in 13 patients. Thirteen had a previous history of roentgenographically documented pleural involvement. A neuropathic or myopathic disorder had been substantiated in only two (one each in group 1 and 2) and three patients (two in group 1, one in group 2) respectively. Twenty-four patients were currently receiving corticosteroid therapy (mean duration 4.6±4.2 years) with a mean daily prednisone dose over the six months prior to evaluation of 13.1 ± 11.2 mg. The antinuclear antibody (ANA) was obtained in 27 patients within two months of evaluation, with 18 demonstrating a homogeneous and nine a speckled pattern. The mean antibody titer was 1:415 (range 1:40 to 1:1280). Pulmonary function test results are presented in Table 1. Subdivisions of lung volumes (VC, TLC) were at the lower limit of normal. However, there was large intersubject variability (VC range, 40-120 percent; TLC, 49-113 percent predicted). There was no evidence of airflow obstruction since FEVb FEV/FVC and maximal Howat 50 percent ofVC (VM)) were within the normal range. Mean PIma (82.6±21.3 percent predicted) and PE mu (47 ± 13.7 percent predicted) were reduced. There was no significant correlation between these indices of inspiratory and expiratory muscle strength and any of the lung volumes. Similarly, no relationship existed between prednisone dose and PIma or PEmu for the 30 patients. Pulmonary function data, Pdi mu and, PLmu are shown in Table 2 for the nine patients with a PImu ofless Table I-Pulmonary Function DattJ in 30 Patient8 with SLE

Statistical Analysis

Correlation coefficients (one-way ANOVA) were used to assess an association between various parameters for all patients: group 1 patients (PIm.a>65 percent predicted), and group 2 patients (PI... <65 percent predicted). Differences in the mean responses for the same parameters between groups 1and 2 were evaluated using a standard Student's t test. A 2 x 2 chi square analysis was used to determine whether significant differences existed between the

Age, yrs Mean SD

32.2 9.4

FE VI %

"so %

FVC

TLC

PI_

%

%

%

PE_ %

pred

pred

pred

pred

pred

pred

88.2 18

84.2 20.5

83.7 18.6

81.4 15.9

82.6 21.3

47 13.7

"so

FEV1=forced expired volume in 1 second; = flow at 50% FVC; FVC = forced vital capacity; TLC =total lung capacity; PI,.. =maximal inspiratory pressure; PE.. = maximal expiratory pressure. CHEST I 93 I 2 I FEBRUARY. 1988

353

Table I-PulmoratJ'lI Function and BapirtJtorfl Muck Strength Data in 9 PtJIienta with lnapirtJtOfll MUick Weaknea Pt

No

1 2

3 4 5 6 7 8 9 Mean SO

TLC (If, pred)

FEV 1 (If, pred)

FVC (If, pred)

75

83 III 77 77

72 101 76

93 77

76 49 57 98 75 72 75 15

49

60

106

83 73

80 20

65

47 52 107 90 70 76 21

Pima cmH.O (If, pred)

PE_ cmH.O (% pred)

45 (52)

42 (28)

Pdi... cmH.O

76 (SO)

52 (60)

49 (56) 30 (39) 31 (36) 56 (52) 54 (62) 37 (43) 40 (45) 44 (49) 10 (9)

46 66 47 88 61 40

66

24 (68)

59 50 38 64

38 18 32 18 16

54

(30) (46) (31) (62) (40) (26)

18 (54) 22 (63) 25 9

50 50 12

59 (40) 17 (12)

(118) (52) (103) (56) (57)

36 (100)

36 36

68 (45)

PLm. cmHIO (% pred)

Numbers in parentheses are percentages. Abbreviations: See Table 1; Pdt.. =maximal transdiaphragmatic pressure; Pt... =maximal elastic recoil pressure of the lungs.

than 65 percent predicted who completed these tests. Both the mean value of Pdimu and the highest value of Pdi.... obtained were well below values that would be expected for normal individuals of this age. This therefore confirms the presence of diaphragmatic weakness. There was a relationship between the absolute values for Pdimu and PIma (r = 0.86, p
(r = O. 73, p<0.05). A similar trend was noted for the right CDAP; however; the correlation did not reach significance (r=O.62, p=O.07). A comparison of disease characteristics, medication use and lung function parameters was made between those individuals with PIma greater than 65 percent predicted (group 1, and PIma less than 65 percent predicted (group 2). There was no difference in disease duration or in overall duration of prednisone therapy between the two groups (Table 4). However; those in group 2 had been on a higher mean dose of prednisone during the six months prior to evaluation (p
Left Phrenic Nerve

Patient Number

Latency (ms)

Amplitude COAP (mv)

Latency (ms)

1 2 3 4 5 6 7

7.5 7.5 9.2 7.1 8.0 7.5 6.9 7.6 7.2 7.6 0.7

0.55 0.63 0.60 0.30 0.40 0.70 0.34 0.42 0.53 0.50 0.14

7.3 7.5 9.0 7.1 8.0 7.5 7.3 7.6 7.2 7.6 0.6

8

9 Mean SO

Amplitude CDAP (mv) 0.50 0.60 0.60 0.41 0.55 0.67

0.30 0.38 0.55 0.51 0.12

COAP =Compound diaphragm action potential. Phrenic NeNe Function in SLE (WIlcox sf aI)

Table 4-CUnictJl Featura and DettJilB of Pmlniaone Therapy in Two Grou", ofSLE PtJtients Group 1 (PIma >65% pred) n=19 Duration of lupus (yrs) Dose of prednisone a) daily (mg) b) duration (yrs) Immunosuppresive use Systemic involvement Joints Renal (glomerulonephritis) Cardiac pericarditis myocarditis Vasculitis Respiratory (pleuritis) Myopathy Neuropathy

5.4±4 10±10 4±3.9 11 (58) 16 (84) 13 (68) 6 2 5 5 2 1

(31) (10) (26) (26) (26) (5)

Group 2 (PIma <65% pred) n=11 8.1±6.7 18.4±11.7· 5.5±4.7

5 (45)

10 (90) 8 (73) 3 (27) 2 (18) 4 (36) 8 (82)· 1 (9) 1 (9)

*p
All values are mean ± SD.

Numbers in parentheses are percentages.

(p<0.05) (Table5). There was no difference in smoking prevalence or symptoms ofcough and sputum between the two groups (Table 5). Overall lung volumes were decreased in group 2 as compared to group 1; however, this difference did not reach significance (VC percent predicted, p = 0.06). Similarly, expiratory Hows did not differ between the two groups. Maximal expiratory pressures were found to be lower in individuals in group 2 (40.4±11.8 vs 52.3 ± 11.8 percent predicted) paralleling the differences in Pimu. Electrophysiologic assessment of peripheral nerves and muscles was performed in six of the nine patients with diaphragmatic weakness. Motor and sensory nerve conduction and EMG studies showed no evidence of generalized nerve or muscle disease. Mild focal abnormalities in the compound muscle action potential amplitude in three patients were found and Table 5-Frequency ofBreatlaleunea, Cough and Sputum and Smoldng HiatorrI in noo Groups ofsa Patienta Group 1 (PI.. >65% pred) n=19 Breathlessness 1) Up slight hill 2) Walk slower than others 3) Stop on level Cough and sputum Smokers

11 (58) 4 (21) 1(5) 6 (31) 7 (37)

*p
Group 2 (PI.. <65% pred) n=11 9 6 4 3

(82) (54)· (36)· (27) 2 (18)

felt clinically to be due to local factors including pressure or prior surgery and trauma. On radiologic assessment, a symmetric decrease in lung volumes was present in five of nine (patients 3,4,5,6,9) with coexistent bibasilar subsegmental atelectasis in three (patients 4,6,9). Mild interstitial changes were present in only one patient (patient 4). Pleural changes in the form of pleural thickening were found in four patients (patients 3,4,5,8), but was minimal in all. Small bilateral pleural effusions were present in one individual (patient 8). The Pdi.u for patients with pleural changes (46± 11cmH 20 ) was not different from Pdima for patients without pleural changes (54±12 cmH 20). DISCUSSION

Recent work has suggested that the restrictive lung volume changes in SLE may be secondary to inspiratory muscle weakness." This study confirms a high prevalence of inspiratory muscle weakness in a nonselected group of patients with SLE. We selected a subgroup of nine of those patients with the most marked weakness to study the pathogenesis of this condition. Allwere found to have diaphragmatic weakness, evidenced by a decrease in Pdimax • Electrophysiologic studies of the phrenic nerve excluded the presence of a demyelinating neuropathy and provided strong evidence against axonal degeneration as the cause of the weakness. Concomitant involvement of the expiratory muscles suggests a myopathic disorder, although no evidence of a generalized myopathy was discovered using clinical and electromyographic studies. A decrease in lung volumes may result because of either pulmonary or extrapulmonary disorders. Interstitial fibrosis occurs uncommonly in patients with SLE.IO A modest reduction in Pdi.u has been demonstrated in patients with this disorder in comparison to normal control subjects." Inspiratory muscle strength is probably normal when corrections are made for the increased elastic recoil of this disease. J4 The fact that only one of nine patients in group 2 had chest roentgenographic or pulmonary function evidence of an interstitial process make it an unlikely explanation for the diaphragmatic weakness. Other studies confirm a low prevalence of interstitial fibrosis in SLE patients with inspiratory muscle weakness. a. 15•• It is probable, therefore, that these changes occur secondary to an extrapulmonary disorder: Pleural effusions and thickening occur commonly in patients with SLE2.7.11•• and could be an explanation for restrictive changes on lung function testing. Indeed, the elevation of the hemidiaphragms in the eeshrinking lung syndrome" was originally attributed to pleural adhesions.801O•11 In this series, a higher incidence of previous pleural disease was noted in those patients CHEST I 93 I 2 I FEBRUARY. 1988

3S5

with the greatest decreases in inspiratory muscle strength. Chest radiography, an insensitive means of detection of pleural disease," showedpleural thickening in fourof nine patients. Nevertheless, it is unlikely that pleural disease is the cause of the inspiratory muscle weakness in SLE for several reasons. First, patients with signiRcant pleural thickening characteristically have an increased PLmu. 13 In this study, PLmu was increased in onlyone individual. Second, maximal inspiratory pressures, performed against an occluded airway, are predominantly isometric contractions and therefore not dependent on large excursions of the diaphragm. Third, it has been shown that Pdimu isonly slightly reduced even in the presence of bilateral diffuse pleural thickening. 13 In a subgroup of five, selected from 30 consecutive SLE patients because of their small lung volumes, Gibson et alll found values for Pdimu that were grossly decreased in fOu~ Subsequently, diaphragmatic weakness was confirmed in seven patients reported by Martenset alII usingsimilarselectioncriteria forstudy. More recently, these findings were extended to patients not selected on the basis of lung function test abnormalities by Jacobelli et al.- Although these authors demonstrated an overall correlation of vital capacity with Pdimu in the 16 patients evaluated, several individuals with normal lung volumes had evidence of diaphragmatic weakness. Impairment in diaphragmatic function, therefore, is an important mechanism in the pathogenesis oflung volume restriction in patients with SLE. In this study, a subpopulation of patients with SLE demonstratingsignificant inspiratorymuscleweakness were evaluated. The criterion for selection was an arbitrary level of decline in maximal static inspiratory pressure (PIma). This pressure is determined predominantly by diaphragmatic contraction and to a variable degree by the other inspiratorymuscles. 1b speCifically assess the diaphragm, we measured the Pdtm.. in this subgroup. The maximal force that the diaphragm is able to generate has been shown to be achieved by a simultaneous combination oftnspiratory and expulsive maneuvers with visual feedback. IO•30 We utilized this technique in our study. Values considerably higher than those obtained would be expected in individuals of this age range (mean Pdimu for the visual feedback method ISO ± 14 cmH.OIO). We, therefore, feel confident in concluding that the values obtained in the present series are indicative of diaphragmatic weakness. The question then is what caused the diaphragmatic weakness. Was it caused by neuropathy, a disorder affecting neuromuscularjunction, or a myopathy? Although a variety of neuropathicdisorders occur in SLE patients,":" little information exists on phrenic nerve function in patients with diaphragmatic weak-

ness and SLE. Normal innervation was found in one case where the phrenic nerves were evaluated. 1 Six of our patients with diaphragmatic weakness were examined clinically and with peripheral nerve conduction studies. One patient had clinical features of meralgia parestheticaand another a possible leftsciatic neuropathy due to a left hip hemarthrosis and subsequent surgery. No patient had clinical or electrophysiologic features of generalized neuropathy. To assess the possibility of isolatedphrenic nerve involvement, phrenic nerve stimulation was done bilaterally in nine patients with evidence of diaphragmatic weakness. The latencyof conduction was normalin all nine patientsexamined. MultifOcal demyelinating neuropathy has been described" in patients with SLE. This would be expected to produce a prolonged phrenic nerve conduction time and possibly a dispersed CDA~ Normal phrenic nerve latenciesin our patients role out a demyelinating dtsorden Normal latencies of conduction cannot exclude the presenceofan axonal degeneration neuropathysuch as that found with mononeuritis multiplex. In this condition, a decrement in amplitude of the CDAP would be expected, reSecting fewer excitable neurons. Values for this measurement have not been well standardized because oflargeintersubject variability. Usingthe data reported by Markand et al, L1 however; six of the nine patients had CDAP amplitudes within the normal range. A neuropathyis therefore excluded as the cause of diaphragmatic weakness in these individuals. The decrement in CDAP amplitude found in the other three patients could reSect a mild bilateral phrenic axonal neuropathy. The excellentcorrelation between right and left CDAP amplitude rules out a disorder affecting predominantly one or the other phrenic nerves, such as a mononeuritis multiplex. An alternative explanation for the low values could be methodologic differences between this and the earlier study. Finally, a decrease in elicited muscle action potential amplitude may also be found in myopathic disorders. This condition will be discussed in more detail subsequently. Disorders involving the neuromuscular junction could alsoresult in diaphragmatic weakness. With the range of autoantibodies produced in these patients, it is possible that a myasthenia-like syndrome could be present. Although none of our patients had clinical features ofmyasthenia, this possibility was notformally evaluated in our patients and thus cannot be excluded as an etiologic factot In a previous case report of a patient demonstrating diaphragmatic weakness, both edrophonium chloride testing and the acetylcholine receptor antibody titer were negative, thus arguing against this diagnosis. 31 This leaves the possibility that diaphragmatic weakness in our patients was due to a myopathic process. PhNnlc NIM Funotton InSLE (Moo. It II)

The invariable reduction OfPEmu suggests concomitant involvement of the expiratory muscles. Although clinical examination failed to elicit evidence of weakness of other muscle groups, it is possible that clinical evaluation is insensitive in comparison to the quantitative studies of respiratory muscle strength. In this study we sought to implicate a myopathy of the diaphragm by looking for electromyographic evidence of a systemic muscle disorder. No evidence of a myopathy was found in the five patients examined. These findings corroborate those of earlier reports. In two case reports, EMG studies of several skeletal muscles and biopsy of the intercostal muscles failed to demonstrate any evidence of a myositis.':" The possibility remains that our findings could be explained by a muscle disorder where routine EMG studies may be normal. One example is a myopathy related to corticosteroid use. 33•34 In the present series, there was a correlation between the average daily dose of prednisone and the degree of respiratory muscle weakness. However, several observations suggest that a steroid myopathy cannot be the sole explanation for diaphragmatic weakness. In two of our patients and in several reported in the literature, 27 the clinical presen . tation of this condition occurred prior to the initiation ofcorticosteroids. Similarly, improvement in both lung volumes and measures of respiratory muscle strength has also been noted with high-dose steroid therapy. Evidence for a myopathic process has been sought in selected individuals with SLE and diaphragmatic weakness. In three series, generalized myopathies were reported in nine patients out of a total of 30. l2.25.26 More recently, an improvement in lung volumes and How rates occurred in a patient with SLE with marked inspiratory muscle weakness following nebulized p-agonist therapy. 32 In the absence of any documented airflow obstruction it was proposed that this was secondary to an increased contractility of the diaphragm. Pathologic studies of the diaphragm have been reported in a single case of a patient with shrinking lung syndrome." At autopsy there was marked thinning of the diaphragm found with diffuse fibrosis on histologic assessment. Clinically apparent diaphragmatic weakness occurs in a significant proportion of patients with SLE. In this study we have provided evidence that a neuropathy of the phrenic nerve would be an unlikely explanation. We were unable to find evidence of a generalized myopathic disorder in our patients with respiratory muscle weakness. Further studies specifically directed to the respiratory muscles will be required before it can be concluded that a myopathy is the cause of the restrictive disorder in patients with SLE. Diaphragmatic biopsy, specific EMG studies of the diaphragm, and more sophisticated tests such as phosphorous-31 nuclear magnetic resonance are several

such possibilities. ACKNOWLEDGMENTS: The authors express their thanks to Drs. S. Huang and A. Chalmers, Mr. B. Wiggs and Mrs. C. Coppin, for their assistance in this study, and to Dr. D. Bates for his review of the manuscript REFERENCES

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second International Meeting on Respiratory Allergy The Department of Pulmonary Diseases, Cardarelli Hospital, Naples, will present this second international meeting April 22 and 23 in Sorrento at the Sorrento Palace Congress Center, For information, contact the organizing secretariat: Jean Gilder, Casella Postale Aperta, NapoliVomero, 80128 Naples, Italy

Hemodynamic Monitoring/Patient Care and Pulmonary Artery catheterization The Johns Hopkins Medical Institutions will present this program March 19-20at the Turner Building in Baltimore. Sponsors are the Department of Anesthesiology and Critical Care Medicine. For information, contact the Program Coordinator, Officeof Continuing Education, The Johns Hopkins Medical Institutions, 720 Rutland Avenue, Thrner 22, Baltimore 21205 (301:055-6046).

Phrenic Nerve function In SLE (Mcox et 8/)