Shrinking lung syndrome as a presenting manifestation of systemic lupus erythematosus in a female Kuwaiti

The shrinking lung syndrome (SLS) is a rare manifestation in patients with established systemic lupus erythematosus (SLE). Only two cases have been reported in which this syndrome was the presenting manifestation of SLE. We describe a 21-year-old female Kuwaiti who presented with SLS. In addition to clinical and serological features of lupus, she had dyspnea, respiratory muscle dysfunction, characteristic chest radiographic findings of small lung volumes, elevated right hemidiaphragm, and basilar atelectasis. There was no pulmonary parenchymal or pulmonary vascular involvement. Nerve conduction study showed right phrenic nerve palsy. She responded well to treatment with corticosteroids.     

Shrinking lung syndrome successfully treated with rituximab and cyclophosphamide

Shrinking lung syndrome (SLS) is an uncommon feature of systemic lupus erythematosus (SLE) characterized by dyspnea, pleuritic chest pain, diaphragmatic elevation, restrictive ventilatory defect and reduced respiratory muscle strength as measured by volitional tests. We report the case of a 28-year-old woman with overlapping features of SLE and Sj?gren syndrome who developed severe SLS while receiving corticosteroids and azathioprine for severe polyarthritis. She was treated with a combination of rituximab and cyclophosphamide, which led to a dramatic improvement in her clinical condition and respiratory function tests. The increase in vital capacity was one of the highest among 35 published cases of SLS. Thus, restoring a near-normal lung function is an achievable goal in SLS, and the use of rituximab, with or without concomitant cyclophosphamide, certainly deserves further study in this setting.     

Shrinking lung syndrome in systemic lupus erythematosus patients; clinical characteristics, disease activity and damage

Aim: To detect the prevalence of shrinking lung syndrome (SLS) among systemic lupus erythematosus (SLE) patients and study their clinical, laboratory and radiological characteristics and differences in disease activity and damage. Methods: The study included 200 Egyptian SLE patients and SLS was considered in those with exertional dyspnea, restrictive pulmonary function tests (PFTs) and elevated copula of the diaphragm. Full history taking, thorough clinical examination, laboratory and relevant radiological investigations were performed for all the patients. High‐resolution computed tomography scans of the chest were performed for patients with radiological findings consistent with SLS and those with pulmonary manifestations. Results: The mean age of the patients was 29.3 ± 8.4 years, mean disease duration 5.81 ± 4.32 years and female to male ratio was 9 : 1. SLS was present in 27 patients (13.5%) with a female to male ratio of 3.5 : 1.0. The demographic features, clinical and laboratory manifestations, renal biopsy class, disease activity and damage scores, PFTs and radiological findings of the SLE patients are presented. Conclusion: Shrinking lung syndrome is not rare and presents a considerable subset of SLE patients. In SLE patients with dyspnea or chest pain, SLS should be looked for and PFTs are highly suggestive.     

Respiratory failure due to diaphragmatic dysfunction in Charcot-Marie-Tooth disease: a case report]

A 56-year-woman with type 2 respiratory failure due to diaphragmatic dysfunction in Charcot-Marie-Tooth disease (CMT) is reported. The patient, who had a 50-year history of CMT, was referred to our hospital because of nocturnal dyspnea. Arterial blood gas analysis on admission showed marked hypoxia with hypercapnia, and physical examination revealed thoracoabdominal paradoxus in the supine position. Chest radiography revealed elevation of both sides of the diaphragm. The vital capacity and arterial blood gas pressure in the sitting position were markedly higher than those in the supine position. Electrical phrenic nerve stimulation failed to produce any convincing muscle action potential in the diaphragm. These findings suggested that her respiratory failure was induced by both diaphragmatic dysfunction caused by bilateral phrenic nerve palsy due to CMT. Treatment of this patient was started at home with a pressure support ventilator, resulting in satisfactory clinical improvement. In general, respiratory muscle impairment is a rare phenomenon in a patient with CMT. However when a patient with CMT complains of dyspnea or if unexpected heart failure develops, it is important to keep in mind that CMT may be associated with phrenic nerve palsy.     

Diaphragmatic weakness and paralysis

Diaphragmatic weakness implies a decrease in the strength of the diaphragm. Diaphragmatic paralysis is an extreme form of diaphragmatic weakness. Diaphragmatic paralysis is an uncommon clinical problem while diaphragmatic weakness, although uncommon, is probably frequently unrecognized because appropriate tests to detect its presence are not performed. Weakness of the diaphragm can result from abnormalities at any site along its neuromuscular axis, although it most frequently arises from diseases in the phrenic nerves or from myopathies affecting the diaphragm itself. Presence of diaphragmatic weakness may be suspected from the complaint of dyspnea (particularly on exertion) or orthopnea; the presence of rapid, shallow breathing or, more importantly, paradoxical inward motion of the abdomen during inspiration on physical examination; a restrictive pattern on lung function testing; an elevated hemidiaphragm on chest radiograph; paradoxical upward movement of 1 hemidiaphragm during fluoroscopic imaging; or reductions in maximal static inspiratory pressure. The diagnosis of diaphragmatic weakness is confirmed, however, by a reduction in maximal static transdiaphragmatic pressure (Pdimax). The diagnosis of diaphragmatic paralysis is confirmed by the absence of a compound diaphragm action potential on phrenic nerve stimulation. There are many causes of diaphragmatic weakness and paralysis. In this review we outline an approach we have found useful in attempting to determine a specific cause. Most frequently the cause is either a phrenic neuropathy or diaphragmatic myopathy. Often the neuropathy or myopathy affects other nerves or muscles that can be more easily investigated to determine the specific pathologic basis, and, by association, it is presumed that the diaphragmatic weakness or paralysis is secondary to the same disease process.     

Pleural fibrosis mediates shrinking lungs syndrome in children

The etiology of restrictive lung physiology in SLS is not well‐defined, and has been hypothesized to be due to defects in lung recoil, phrenic nerve function and diaphragmatic strength. We present a case of SLS in an adolescent in whom imaging and electrophysiology studies demonstrate pleural fibrosis as the fundamental defect accounting for the restrictive lung physiology. Pediatr Pulmonol. 2009; 44:90–92. © 2008 Wiley‐Liss, Inc.     

Presentation and prognosis of the shrinking lung syndrome in systemic lupus erythematosus

BACKGROUND AND OBJECTIVES: Systemic lupus erythematosus (SLE) may affect all the components of the respiratory system, including upper airways, lung parenchyma, pulmonary vasculature, pleura, and respiratory muscles. The shrinking lung syndrome (SLS) is a rare complication of SLE. This study describes the presenting features, investigation findings, treatment measures, and outcome of 7 patients with SLE and SLS. METHODS: Five patients with SLE/SLE were chosen retrospectively by examination of patient records, and 2 patients were chosen prospectively. All patients attended St. Thomas' Hospital or the Royal London Hospital between 1984 and 2001, with a total population of 2650 patients with SLE. RESULTS: Clinical features included dyspnea and pleuritic chest pain. Chest x-ray films showed small but clear lung fields, or basal atelectasis, with diaphragmatic elevation. No evidence of major parenchymal lung or pleural disease was found on the computerized tomography scan. Lung volumes were reduced on pulmonary function testing (PFT) in a restrictive pattern. Treatment of SLS included theophylline, increase in corticosteroid dosage, and intensification of immunosuppressive medication to include methotrexate or cyclophosphamide. During follow-up, 5 of 7 patients showed objective evidence on PFT of stabilization or improvement. CONCLUSIONS: The long-term prognosis of our SLS patients was reasonable, highlighting the importance of establishing a correct diagnosis and in particular differentiating it from fibrosing lung disease. Immunosuppressive therapy was helpful in stabilizing SLS and improving respiratory symptoms and PFT in some cases. RELEVANCE: SLS represents a rare complication of SLE, and it is important to be aware of its presenting features and prognosis.     

Respiratory arrest in systemic lupus erythematosus due to phrenic nerve neuropathy

Diaphragmatic weakness in patients with systemic lupus erythematosus (SLE) is a controversial issue and is claimed to have a neuropathic, myopathic or unknown pathogenesis. In this patient a predominantly motor neuropathy with diaphragmatic paralysis due to axonal involvement of the phrenic nerve was discovered and successfully treated with immunosuppressive drugs.     

Reinforcing a medical hypothesis with a new question: is there a subgroup of shrinking lungs syndrome that is induced by pleurisy in systemic lupus erythematosus and is this subgroup marked by anti-Ro/SSA?

Shrinking lungs syndrome (SLS) is a rare entity associated with autoimmune diseases and its underlying pathogenesis is still unclear. We describe a series of seven consecutive cases of SLS in systemic lupus erythematosus, all of them with serositis and six (85.7%) with anti-Ro/SSA antibodies. Our findings reinforce the hypothesis that SLS may be, in some cases, a consequence of diaphragmatic restriction due to pleuritic pain, and we suggest anti-Ro/SSA as a marker of this subgroup of SLS.     

Diaphragmatic weakness and paralysis

Diaphragmatic weakness implies a decrease in the strength of the diaphragm. Diaphragmatic paralysis is an extreme form of diaphragmatic weakness. Diaphragmatic paralysis is an uncommon clinical problem while diaphragmatic weakness, although uncommon, is probably frequently unrecognized because appropriate tests to detect its presence are not performed. Weakness of the diaphragm can result from abnormalities at any site along its neuromuscular axis, although it most frequently arises from diseases in the phrenic nerves or from myopathies affecting the diaphragm itself. Presence of diaphragmatic weakness may be suspected from the complaint of dyspnea (particularly on exertion) or orthopnea; the presence of rapid, shallow breathing or, more importantly, paradoxical inward motion of the abdomen during inspiration on physical examination; a restrictive pattern on lung function testing; an elevated hemidiaphragm on chest radiograph; paradoxical upward movement of 1 hemidiaphragm during fluoroscopic imaging; or reductions in maximal static inspiratory pressure. The diagnosis of diaphragmatic weakness is confirmed, however, by a reduction in maximal static transdiaphragmatic pressure (Pdimax). The diagnosis of diaphragmatic paralysis is confirmed by the absence of a compound diaphragm action potential on phrenic nerve stimulation. There are many causes of diaphragmatic weakness and paralysis. In this review we outline an approach we have found useful in attempting to determine a specific cause. Most frequently the cause is either a phrenic neuropathy or diaphragmatic myopathy. Often the neuropathy or myopathy affects other nerves or muscles that can be more easily investigated to determine the specific pathologic basis, and, by association, it is presumed that the diaphragmatic weakness or paralysis is secondary to the same disease process.     

Shrinking lung syndrome masked by pleuropericarditis: a case report and review of the literature

The purpose of this article is to present an unusual case of shrinking lung syndrome (SLS) masked by pleuropericarditis with a review of the literature. We report a case of SLS in a 44-year-old woman in which the diagnosis was initially confounded by concurrent pleuropericarditis. The English medical literature was comprehensively reviewed for SLS for its presentation, clinical findings, diagnosis, treatment, with specific focus on its pathogenesis. SLS is a rare respiratory complication associated with systemic lupus erythematosus (SLE). The main manifestation of the disease is unexplained dyspnea, chest pain, and orthopnea. Lung volume reduction without parenchymal abnormalities along with restrictive ventilatory defect on pulmonary function test (PFT) is the hallmarks of this condition. Pathogenesis, treatment, and prognosis of SLS are not well described due to the small number of reported cases. The diagnosis of SLS in our patient was made based on imaging, PFT, and the exclusion of other respiratory diseases associated with SLE. Treatment with corticosteroid and intravenous cyclophosphamide was initiated due to simultaneously diagnosed renal involvement. Our case demonstrates the salient features of SLS. It emphasizes that although SLS is a rare disease limited to small subset of patients with SLE, it should be considered in patients with SLE with unexplained dyspnea. Moreover, symptoms of pleuropericarditis can mask and delay the diagnosis of SLS. Prompt diagnosis and treatment can lead to a decrease in morbidity and stabilization of pulmonary function test abnormalities.     

Diaphragmatic eventration : an uncommon presentation of a phrenic nerve schwannoma

We describe a patient who presented with a left lower lobe lung lesion suspicious for cancer with possible hilar involvement. Intraoperatively, we found a primary left phrenic nerve tumor, diaphragmatic eventration, and left lower lobe atelectasis. He was successfully treated with total excision of the tumor and plication of the diaphragm. Histopathology was consistent with schwannoma of the phrenic nerve. Diaphragmatic eventration is an uncommon presentation of a phrenic nerve schwannoma, which is itself a rarely occurring tumor. Surgical resection of the tumor and diaphragmatic plication is the primary modality of management in these patients.     

Shrinking lungs, diaphragmatic dysfunction, and systemic lupus erythematosus

One of the more unusual respiratory manifestations of systemic lupus erythematosus is "shrinking lungs." We report a patient with this syndrome and provide evidence for this being due to diaphragm dysfunction. Significant improvement occurred after albuterol therapy, providing new possibilities in the treatment of this syndrome. This is the first report in humans supporting animal work demonstrating that beta-agonists can improve diaphragmatic performance.     

Central fatigue of the rabbit diaphragm

This study evaluates the importance of central fatigue of the diaphragm in rabbits subjected to inspiratory muscle resistive loading (IRL). Ten rabbits were subjected to constant IRL while unanesthetized and breathing supplemental oxygen. During 10-20 minutes of spontaneous breathing against IRL, there were no significant changes in arterial oxygen saturation or in diaphragm contractility, measured by the quasi-static transdiaphragmatic pressure response to a 0.3-sec train of 100 Hz supramaximal phrenic nerve stimuli. After an initial decrease due to application of the load, the minute ventilation decreased further, by an average of 15%, while arterial pCO2 increased to an average of 59 mmHg (p less than 0.05). The normalized diaphragm pressure-time index initially increased from 0.02 to 0.18 during IRL, then decreased an average of 29% (p less than 0.05). These results show that severe IRL causes a decrease in the level of diaphragmatic effort over time despite increased chemical drive and despite a preserved ability of the muscle to respond to phrenic nerve stimuli. This adaptation may help to prevent peripheral diaphragm fatigue.     

Shrinking lung syndrome in systemic lupus erythematosus patients with dyspnea

Aim of the workTo identify the frequency of shrinking lung syndrome (SLS) in systemic lupus erythematosus (SLE) with dyspnea and study the clinical characteristics and differences in disease activity and damage.Patients and methodsThe study included 47 SLE patients complaining of dyspnea. SLS was considered in those with exertional dyspnea, restrictive pulmonary function tests (PFTs) and elevated copula of the diaphragm. Full history taking, thorough clinical examination, laboratory and relevant radiological investigations were performed for all the patients. Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics (SLICC) indices were compared. High resolution CT chest was performed for patients with radiological findings consistent with SLS.ResultsThe mean age of the patients was 29.43 ± 7.45 years, mean disease duration 5.18 ± 3.62 years. The SLS was present in 8 patients (17.02%). There was bilateral elevation of the diaphragm copulae in 25% of SLS patients and two had associated basal atelectatic bands. The serum uric acid was significantly higher in those with SLS while the 24 h urine protein was significantly lower and C4 normalized. The levels of SLEDAI and SLICC tended to be lower in those with SLS, yet there was no significant difference from those without. The demographic features, clinical and laboratory manifestations, disease activity and damage scores, PFTs and radiological findings of the SLE patients are presented.ConclusionIn SLE patients with dyspnea, SLS should be looked for as it is present in a high proportion of cases.     

Phrenic afferents and ventilatory control

It has been understood since the late 1800s that the diaphragm has significant sensory innervation. The role of phrenic afferents in the control of breathing, however, has been obscure. The phrenic nerve has been shown to contain a full array of afferent fibers. However, proprioceptive (group 1 fibers) afferents are few compared to postural muscles or the intercostals. The diaphragm, unlike the inspiratory intercostal muscles, has a small complement of spindle afferents and not all of these spindles are supplied with fusorial fibers. Reduced spindle afferents under gamma control help to explain previous studies of the diaphragm that have failed to reveal autogenic facilitation, that is, a reflex-mediated increase in drive during inspiratory loading. Nevertheless, some clinical studies have revealed increased activation of the diaphragm when its length is reduced. Group 1 fibers, which are predominantly tendon organ afferents in the diaphragm, have been shown to have a phasic inhibitory function. A reduction in this inhibition brought about by a reduction in diaphragmatic length during lung inflation may explain the increased diaphragmatic activation reported in clinical studies. Phrenic afferents have been shown to have multiple spinal and supraspinal projections. Recent studies have explored the ventilatory effects of thin fiber afferents (group III and IV fibers) in the phrenic nerve. Stimulation of these afferents has been shown both to inhibit and excite ventilation. These afferents arise from polymodal receptors that respond to both mechanical and chemical stimulation. Activation of these receptors may occur in a variety of conditions and the ventilatory response may be determined by the specific receptor activated.     

Phrenic afferents and ventilatory control

It has been understood since the late 1800s that the diaphragm has significant sensory innervation. The role of phrenic afferents in the control of breathing, however, has been obscure. The phrenic nerve has been shown to contain a full array of afferent fibers. However, proprioceptive (group 1 fibers) afferents are few compared to postural muscles or the intercostals. The diaphragm, unlike the inspiratory intercostal muscles, has a small complement of spindle afferents and not all of these spindles are supplied with fusorial fibers. Reduced spindle afferents under gamma control help to explain previous studies of the diaphragm that have failed to reveal autogenic facilitation, that is, a reflex-mediated increase in drive during inspiratory loading. Nevertheless, some clinical studies have revealed increased activation of the diaphragm when its length is reduced. Group 1 fibers, which are predominantly tendon organ afferents in the diaphragm, have been shown to have a phasic inhibitory function. A reduction in this inhibition brought about by a reduction in diaphragmatic length during lung inflation may explain the increased diaphragmatic activation reported in clinical studies. Phrenic afferents have been shown to have multiple spinal and supraspinal projections. Recent studies have explored the ventilatory effects of thin fiber afferents (group III and IV fibers) in the phrenic nerve. Stimulation of these afferents has been shown both to inhibit and excite ventilation. These afferents arise from polymodal receptors that respond to both mechanical and chemical stimulation. Activation of these receptors may occur in a variety of conditions and the ventilatory response may be determined by the specific receptor activated.     

Surgery for diaphragmatic palsy

Diaphragmatic palsy leads to a permanent ascension of one or both hemi-diaphragms with highly variable functional impact. The underlying mechanisms can be divided into two main categories: neurological or muscular disorder leading to peripheral dysfunction; defective or non-transmitted central command causing central dysfunction. A complete morphological and functional work-up is required to determine the circumstances leading to diaphragmatic palsy and the uni- or bilateral nature of the paralysis. The entire phreno-diaphragmatic transmission chain from the cranium to the diaphragmatic muscle must be analyzed to search for a local cause. Function tests are used to examine central command and transmission, function of the phrenic nerve, and the capacity of the diaphragmatic muscle to generate sufficient pressure for efficacious ventilation. Once indirect causes of diaphragmatic ascension (independent of the phreno-diaphragmatic system) have been ruled out, surgery may be proposed for symptomatic, permanent and irreversible diaphragmatic paralysis. A tension procedure may be sufficient in the event of eventration with or without phrenic palsy. For well-selected patients with central paralysis due to supraspinal lesions with intact nerves and muscles, implantation of a phrenic pacemaker may be helpful to eliminate positive pressure mechanical ventilation and restore more physiological respiration.     

Phrenic Nerve Conduction Abnormalities Correlate with Diaphragmatic Descent in Chronic Obstructive Pulmonary Disease

Diaphragmatic weakness in chronic obstructive pulmonary disease (COPD) is ascribed to hyperinflation-induced diaphragm shortening as well as impairment in cellular and subcellular structures. Although phrenic neuropathy is known to cause diaphragmatic weakness, phrenic neuropathy is rarely considered in COPD. This work aimed at assessing phrenic nerve conduction in COPD and its relation to radiographic hyperinflation and pulmonary function. Patients and methods: Forty COPD patients were evaluated. Radiographic parameters of lung hyperinflation were measured on postero-anterior and lateral chest x-ray films. Flow volume loop parameters were obtained from all patients. Motor conduction study of the phrenic nerves was performed and potentials were recorded over the xiphoid process and the ipsilateral 7th intercostal space. Twenty-seven healthy subjects were enrolled as controls. Results: Parameters of phrenic nerve conduction differed significantly in patients compared to controls. Phrenic nerve abnormalities were detected in 17 patients (42.5%). Electrophysiological measures correlated with diaphragmatic angle of depression on lateral view films and with lung height on postero-anterior films. They did not correlate with the flow volume loop data or disease severity score. Conclusion: Phrenic nerve conduction abnormality is an appreciated finding in COPD. Nerve stretching associated with diaphragmatic descent can be a suggested mechanism for nerve lesion. The presence of phrenic neuropathy may be an additional contributing factor to diaphragmatic dysfunction in COPD patients.     

Reflex inhibition of crural diaphragmatic activity by esophageal distention in cats

Distention of the esophagus has been shown to result in selective inhibition of phasic inspiratory activity in the crural portion of the diaphragm, with no effect on costal diaphragmatic activity. The purpose of this study was to determine rigourously the afferent pathways that mediate this response. Bipolar EMG electrodes were placed in the costal and crural portions of the diaphragm in decerebrate, spontaneously breathing cats. Distention of the esophagus by inflation of a Foley catheter balloon with 20 ml of air resulted in a selective inhibition of crural hiatal EMG activity, while costal EMG activity was maintained at predistention levels. The distention was accompanied by a reduction in respiratory frequency. Transection of the spinal cord at the C8-T1 level did not obliterate the crural inhibition produced by inflation. Section of the C4-C8 dorsal roots also failed to abolish the response. However, after bilateral cervical vagotomy, esophageal distention no longer influenced diaphragmatic EMG activity. These results indicate that the crural inhibition observed with esophageal distention is vagally mediated and is not influenced importantly by intercostal or phrenic afferents. Records of activity of the phrenic nerve branch innervating the crural portion of the diaphragm showed a similar response pattern, confirming that the inhibition is central in origin and that the crural fibers inhibited by distention are only a fraction of the total population of crural phrenic motoneurons.