Pulmonary Embolism in Idiopathic Pulmonary Fibrosis Transplant Recipients

Pulmonary Embolism in Idiopathic Pulmonary Fibrosis Transplant Recipients

carried out in other cases too, represented a rapid and safe method to recognize the neoplastic involvement of the pericardium, in spite of the scanty...

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carried out in other cases too, represented a rapid and safe method to recognize the neoplastic involvement of the pericardium, in spite of the scanty effusion. Finally, in the third case, a transbronchial approach was the only way to obtain a large amount of pericardial fluid after the failure of the conventional percutaneous approach. ACKNOWLEDGMENT: We thank Miss Elisa Ceron for the graphic arrangement and Mrs. Susan Roe for the amendment of the text.

References 1 Tsang TS, Freeman WK, Sinak LJ, et al. Echocardiographically guided pericardiocentesis: evolution and state-of-the-art technique. Mayo Clin Proc 1998; 73:647– 652 2 Tomkowski W, Szturmowicz M, Fijalkowska A, et al. New approaches to the management and treatment of malignant pericardial effusion. Support Care Cancer 1997; 5:64 – 66 3 Bastian A, Meissner A, Lins M, et al. Pericardiocentesis: differential aspects of a common procedure. Intensive Care Med 2000; 26:572–576 4 Tsang TS, El-Najdawi EK, Seward JB, et al. Percutaneous echocardiographically guided pericardiocentesis in pediatric patients: evaluation of safety and efficacy. J Am Soc Echocardiogr 1998; 11:1072–1077 5 Drummond JB, Seward JB, Tsang TS, et al. Outpatient two-dimensional echocardiography-guided pericardiocentesis. J Am Soc Echocardiogr 1998; 11:433– 435 6 Gibbs CR, Watson RD, Singh SP, et al. Management of pericardial effusion by drainage: a survey of 10 years’ experience in a city centre general hospital serving a multiracial population. Postgrad Med J 2000; 76:809 – 813 7 Uemura S, Kagoshima T, Hashimoto T, et al. Acute left ventricular failure with pulmonary edema following pericardiocentesis for cardiac tamponade: a case report. Jpn Circ J 1995; 59:55–59 8 Anguera I, Pare C, Perez-Villa F. Severe right ventricular dysfunction following pericardiocentesis for cardiac tamponade. Int J Cardiol 1997; 59:212–214 9 Hamaya Y, Dohi S, Ueda N, et al. Severe circulatory collapse immediately after pericardiocentesis in a patient with chronic cardiac tamponade. Anesth Analg 1993; 77:1278 –1281 10 Bender F. Hemoperitoneum after pericardiocentesis in a CAPD patient [letter]. Perit Dial Int 1996; 16:330 11 Taggart SC, Roberts TE, Marshall DA. Chylopericardium complicating pericardiocentesis for acute idiopathic pericardial effusion. J Thorac Cardiovasc Surg 1994; 108:388 –389 12 Cotoi S, Moldovan D, Carasca E, et al. Sinus node dysfunction occurring immediately after pericardiocentesis. Physiologie 1987; 24:63– 68 13 Calabrese P, Iliceto S, Rizzon P. Pericardiocentesis induced intrapericardial thrombus: visualization of thrombus and spontaneous internal lysis by two-dimensional echocardiography. J Clin Ultrasound 1985; 13:49 –51 14 Quecedo E, Febrer I, Martinez-Escribano JA, et al. Tumoral seeding after pericardiocentesis in a patient with a pulmonary adenocarcinoma. J Am Acad Dermatol 1994; 31:496 – 497 15 Fisher JD, Kim SG, Ferrik KJ, et al. Internal transcardiac pericardiocentesis for acute tamponade. Am J Cardiol 2000; 86:1388 –1389 16 De Divitiis M, Dialetto G, Covino FE, et al. An unusual procedure for the treatment of simultaneous pericardial and pleural effusions. G Ital Cardiol 1999; 29:796 –798 17 Verrier RL, Waxman S, Lovett EG, et al. Transatrial access to the normal pericardial space: a novel approach for diagnostic sampling, pericardiocentesis, and therapeutic interventions. 1758

Circulation 1998; 98:2331–2333 18 Wang KP. How I do it: transbronchial needle aspiration. J Bronchol 1994; 1:63– 68 19 Duvernoy O, Magnusson A. CT-guided pericardiocentesis. Acta Radiol 1996; 37:775–778 20 Witte MC, Opal SM, Gilbert JG, et al. Incidence of fever and bacteremia following transbronchial needle aspiration. Chest 1986; 89:85– 87 21 Ceron L, Cecchetto A, Manzato M, et al. L’agoaspirazione transbronchiale (T. B. N. A.) nella diagnosi della patologia ilo-mediastinica e nella stadiazione del tumore polmonare: 6 anni di esperienza. In: Ferrante G, Loizzi M, Deodato G, et al, eds. Endoscopia toracica: attualita` e prospettive. Napoli, Italy: G. De Nicola, 2001; 183–189

Pulmonary Embolism in Idiopathic Pulmonary Fibrosis Transplant Recipients* Steven D. Nathan, MD, FCCP; Scott D. Barnett, PhD; Bruce A. Urban, MD; Cynthia Nowalk, RN; Brian R. Moran, RN, BSN; and Nelson Burton, MD, FCCP

The objectives of the study were the assessment of the incidence of pulmonary embolism (PE) in lung transplant recipients. We performed a retrospective review of the medical records in a tertiary center lung transplant program. A total of 72 lung transplants were performed. There were seven symptomatic PE events diagnosed among six patients (group 1). All PE events were in the subgroup of patients with idiopathic pulmonary fibrosis (IPF) [6 of 23 patients (27%) vs 0 among all other patients (0%); p < 0.001]. All patients were out of the hospital, not receiving oxygen therapy, and were ambulatory at the time of the event. The median time to occurrence of the PE was 175 days posttransplant (range, 26 to 541 days). All patients who developed PEs were men. The group of IPF patients with no PEs was evenly split between genders (group 2; p < 0.009). PE patients required a longer posttransplant hospitalization (mean [ⴞ SD], 18.5 ⴞ 3.9 vs 13.5 ⴞ 4 days, respectively; p < 0.018). Aside from this, there was no apparent difference in patient functional status between the two groups. PEs appear to be relatively common in IPF lung transplant recipients. This should be considered in the differential diagnosis of *From the Inova Transplant Center (Drs. Nathan and Burton, Ms. Nowalk, and Mr. Moran), the Inova Heart Institute (Dr. Barnett), and the Department of Radiology (Dr. Urban), Inova Fairfax Hospital, Falls Church, VA. Manuscript received May 22, 2002; revision accepted October 9, 2002. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: [email protected]). Correspondence to: Steven D. Nathan, MD, FCCP, Inova Transplant Center, 3300 Gallows Rd, Falls Church, VA 22042; e-mail: [email protected] Selected Reports

any such patient who presents with dyspnea or hypoxia posttransplant. Patients do not appear to have been predisposed to their embolic events through lack of activity or prolonged hospital stays. (CHEST 2003; 123:1758 –1763) Key words: lung; lung diseases; obstructive; pulmonary fibrosis; respiratory function tests; thromboembolism; transplantation Abbreviations: IPF ⫽ idiopathic pulmonary fibrosis; LSLTx ⫽ left single-lung transplant; PE ⫽ pulmonary embolus; PFT ⫽ pulmonary function test; RSLTx ⫽ right single-lung transplant

are many causes of allograft dysfunction in the T here lung transplant recipient. Most of these are of paren-

chymal or airway origin. The most common complications seen are related to infection, ischemia/reperfusion, or immunologic injury. Posttransplant pulmonary vascular complications are rare, although complications from vascular anastomotic problems can occur.1,2 Pulmonary embolisms (PEs) have been reported to occur after transplant, but there have been no reports of a predilection for any particular patient group.3 Some patients with idiopathic pulmonary fibrosis (IPF) will succumb to PEs as the terminating event of their disease.4 This has been attributed mostly to inactivity in the later stages of the disease. However, to our knowledge, there have been no reports of a predisposition among IPF patients for the development of thromboembolic complications. We report a high incidence of PEs in IPF patients who received single-lung transplants.

Materials and Methods We reviewed the records of all patients who had undergone transplantion at our facility between September 1996 and January 2002. The breakdown of primary disease for which the patients received transplants is shown in Table 1. Patients who developed PEs were compared and contrasted to those with similar primary diseases who did not. Specifically in this regard, we compared the pretransplant pulmonary function test (PFT) results from IPF patients who had developed PEs (group 1) to IPF patients who did not develop PEs (group 2). Comparisons also were made between the length of the posttransplant hospital stays and the results of the posttransplant PFTs between the two groups. Our program did not obtain routine perfusion scans posttransplant, and therefore there were no baseline scans for comparison in the

group of patients with PEs. The time to presentation and the clinical manifestations of the PEs also were assessed. Continuous and categoric data were assessed via t tests and ␹2 tests, where appropriate. Tests were two-tailed, and a p value of ⱕ 0.05 was considered to be statistically significant. All statistical analyses were conducted using statistical software (SAS, version 8.01; SAS Institute; Cary, NC).

Results There were a total of 72 patients who received lung transplants during the time period. All except two patients were successfully discharged from the hospital posttransplant, and only one patient died within the first month for a 1-month survival rate of 98.6%. There were seven episodes of PEs among six patients. All episodes occurred in the subpopulation of IPF transplant recipients (6 of 23 patients) for an incidence of 27%. None of the recipients with other primary diseases (0 of 49 patients; 0%) developed clinical evidence or were diagnosed with PEs (p ⬍ 0.001). Of the six patients, all (left-sided lung transplant [LSLTx], three patients; right-sided lung transplant [RSLTx], three patients) developed PEs in their transplanted lungs, while the one patient who had two embolic episodes had his first to the left native lung. Of note, this patient was not receiving coumadin therapy at the time of his second event. In terms of diagnostic procedures, one of the patients had undergone a ventilation-perfusion scan, three of the patients had undergone pulmonary angiograms, and five of the patients had undergone spiral CT scans (Fig 1, 2). The clinical characteristics of those IPF patients who developed PEs posttransplant (group 1) and those who did not (group 2) are contrasted in Table 2. There were no differences in their pretransplant or first posttransplant spirometric indexes. Similarly, there was no difference in the maximal values that the groups attained posttransplant. Based on the FEV1 value obtained in closest proximity to the subsequent PE event (mean, 15 days prior), there was no patient who qualified as having bronchiolitis obliterans syndrome at the time of the PE. Only three of the patients underwent PFTs within 3 days of their embolic event. In one of these patients, there was a 9% decrement in the FVC and FEV1 on the day of the PE. Spirometry was stable in the second patient, and in the third patient the set of PFTs that he underwent on the day prior to the PE represented his best posttransplant spirometry effort. The clinical presentations of the six patients are shown in Table 3.

Discussion Table 1—Summary of Transplant Recipients by Primary Disease Transplants Primary Disease

No.

%

COPD IPF Cystic fibrosis Connective tissue disorder Pulmonary hypertension Sarcoid Lymphagioleiomyomatosis

34 23 4 3 3 3 2

47.2 31.9 5.6 4.2 4.2 4.2 2.8

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The major causes of death in the early post-lung transplant period include primary graft failure, infection, and, rarely, acute rejection. Although there has been one prior report3 of thromboembolic complications post-lung transplant and after heart-lung transplant, there is generally a paucity of data on this potentially lethal complication in lung transplant recipients. Kroshus et al3 reported a 12.1% incidence of PE. However, there was no mention of any predilection for one patient group. In our series, we have shown a strong propensity for PEs in the IPF subpopulation of transplant recipients. Although the difference in the occurrence rate between our COPD and IPF patients appears to be quite striking, with the small CHEST / 123 / 5 / MAY, 2003

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Figure 1. Spiral CT scan of a 56-year-old man with PE. The soft-tissue window reveals large, discrete, filling defects in the main right pulmonary artery of the transplanted lung.

numbers in our study we cannot exclude the possibility that we have erroneously concluded that the occurrence rates in COPD and IPF patients differ (ie, type I error). Similarly, the incidence of this complication exclusively in male recipients is noteworthy but could also represent a type 1 error. With patients having complicated conditions such as lung transplant recipients, we also cannot exclude the possibility that other patients may have had PEs that went undiagnosed. However, it is noteworthy that in four of the episodes, these were not subtle events, with three of the patients presenting with oxygen saturations in the 60% range (one of whom had a respiratory arrest) and one patient presenting with hemodynamic compromise and right heart failure. Why patients with IPF might be more predisposed to thromboembolism is uncertain and raises a number of issues. First, are these patients sicker and hence less mobile prior to undergoing transplantation? This appears to be unlikely since, compared to patients in the COPD population, IPF patients generally have been sick for less time when listed for transplantation. Also, a prerequisite for acceptance into our transplant program is that patients have to be actively engaged in pulmonary rehabilitation. The median time to occurrence of the embolic events was 175 days, which would suggest that patients’ pretransplant functional status had a minimal impact on their predisposition for the embolic events. 1760

There appeared to be a slightly longer hospital length of stay posttransplant, which might imply that these patients had a slower recovery. However, a median in-hospital stay of 19 days is unremarkable for patients with transplanted lungs. Indeed, most of the embolic events were far removed from the patient’s initial hospitalization, with more than half of the events occurring ⬎ 4 months after transplantation. The functional status of the patient at the time of the event also does not appear to have played a significant predisposing role. All patients were oxygen-independent, ambulatory without limitation, and outpatients at the time of the events. As a further objective measure of their functional status, we found no difference between their posttransplant PFT results compared to the IPF patients who had no thromboembolic complications. The PFT results that were available prior to the PE events also attest to the patients’ otherwise stable pulmonary status at the time of their thromboembolic complication, with none of the patients qualifying as having bronchiolitis obliterans syndrome. It is interesting to speculate that there may be something inherent in the disease itself that predisposes patients to thromboembolism. Indeed, approximately 3% of patients with IPF will succumb to a thromboembolic event.4 This possibly represents an underestimation as some patients with IPF who decompensate may incorSelected Reports

Figure 2. Spiral CT scan of a 58-year-old man with PE. The soft-tissue window reveals large, discrete, filling defects in the left lower lobe pulmonary artery of the transplanted lung.

rectly have this attributed to progression of their underlying disease. Although there has been at least one case report5 of an association with antiphospholipid syndrome,

to our knowledge, there has been no systematic research into whether IPF patients have a thromboembolic predisposition. Until the advent and popularity of spiral CT scanning,

Table 2—Clinical Features of the Two Groups of IPF Patients* Parameter

Group 1 (n ⫽ 6)

Group 2 (n ⫽ 17)

p Value

Gender Male Female Age, yr Pretransplant FVC, % predicted Pretransplant FEV1, % predicted First posttransplant FVC, % predicted First posttransplant FEV1,† % predicted Maximum posttransplant FVC,‡ % predicted Maximum posttransplant FEV1, % predicted Mean time to first PFT, d Posttransplant LOS, d Time to PE,§ d

6 0 58.7 ⫾ 4.3 55.5 ⫾ 18.0 60.2 ⫾ 20.9 58.8 ⫾ 12.4 56.5 ⫾ 11.0 70.0 ⫾ 12.6 76.7 ⫾ 12.5 15.2 ⫾ 6.9 18.5 ⫾ 3.9 175.0 ⫾ 193.9

8 9 54.7 ⫾ 7.0 49.3 ⫾ 13.0 54.4 ⫾ 13.8 52.9 ⫾ 15.6 52.0 ⫾ 14.2 78.7 ⫾ 18.4 80.2 ⫾ 18.4 12.6 ⫾ 5.1 13.5 ⫾ 4.0 NA

0.009 0.220 0.381 0.460 0.398 0.500 0.306 0.673 0.356 0.018 NA

*Values given as mean ⫾ SD, unless otherwise indicated. NA ⫽ not applicable; LOS ⫽ length of stay. †First posttransplant FVC and FEV1 data are from first set of PFT results obtained posttransplant. ‡Max posttransplant FVC and FEV1 data are taken from posttransplant PFT results with highest FEV1. §Includes both PE episodes in patient 4. www.chestjournal.org

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Selected Reports

3

RSLTx/R

6

30

101

541

26

339

132

56

Time Posttransplant, d

SOB; large right effusion; room air saturation, 82%; p ⫽ 106/min; BP, 106/73 mm Hg; no PFTs SOB; oxygen saturation in the 60% range; BP, 100/60 mm Hg; p ⫽ 90/min No PFTs SOB; oxygen saturation in mid-80% range; p ⫽ 80/ min; BP, 113/70 mm Hg; 9% decrease in FVC and FEV1 SOB; saturation, 94% on room air; p ⫽ 140/min; BP, 100/50 mm Hg; right heart failure; highest PFT set on the day prior

Respiratory arrest with oxygen saturations in the 60% range; p ⫽ 113/min; BP, 155/90 mm Hg

Y

SOB; room air saturation in 60% range; p ⫽ 100/min; BP, 170/100 mm Hg; home spirometry stable; no PFTs done SOB; room air saturation, 88%; P ⫽ 87/min; BP, 120/ 70 mm Hg; PFTs 3 d prior stable

Y

N

Y

Y

N

N

DVT

Clinical Presentation

˙ scan; pulmonary V˙/Q angiogram

Spiral CT scan

Spiral CT scan

Spiral CT scan

Pulmonary angiogram

Spiral CT scan Pulmonary angiogram

Spiral CT scan

Diagnosis

TPA, IV heparin

TPA, heparin, coumadin, IVC filter IV heparin, coumadin

IV heparin, coumadin

TPA, heparin, coumadin, IVC filter Mechanical thrombectomy TPA, IVC filter

IV heparin, coumadin, IVC filter

Treatment

Recovered

Recovered

Recovered

Recovered

Recovered

Recovered

Outcome

Died 16 h after presentation

˙ ⫽ ventilation-perfusion; Y ⫽ yes; N ⫽ no; IVC ⫽ inferior vena cava; TPA ⫽ tissue plasminogen activator; p ⫽ pulse. *L ⫽ left; R ⫽ right; SOB ⫽ shortness of breath; V˙/Q

RSLTx/R

5

RSLTx/R

LSLTx/L

2

Episode 2

LSLTx/L

1

RSLTx/L

LSLTx/L

Patient No.

4 Episode 1

Transplant/ PE side

Table 3—Clinical Presentation of PEs in IPF Patients*

the only definitive way to diagnose PEs in this patient population was via pulmonary angiography, since ventilation-perfusion scanning is known to be inaccurate in the IPF patient.6 Contrast-enhanced spiral CT scanning has been used increasingly to diagnose PE, and, although there are data to attest to its accuracy, the sensitivity and specificity have not as yet been fully determined.7 For the five patients in our cohort in whom PE was diagnosed by this modality, the detected PEs were large in size and central in location, and as such were diagnosed with certainty. Spiral CT scanning also helped to quantify the clot burden, which supported the clinical decision to use thrombolytic therapy in two of the patients. The clinical presentation of PE in this group of patients is well worth noting. In most the cases, the initial index of suspicion for PE was high, based on their clinical presentation. Consequently, only one patient underwent PFTs on presentation as part of his workup. Although this patient’s PFT results were reduced, there is no apparent reason to believe that PE should be added to the list of causes of reduced spirometry in lung transplant recipients. Indeed, when there is hypoxemia that is out of proportion to any spirometric or radiographic changes, then the index of suspicion for PE should be raised. It is not surprising that 86% of the embolic events (six of seven events) were on the side of the transplant, since it is well-recognized that the majority of the blood flow goes to the allograft posttransplant. All of the patients presented with shortness of breath, and none of them had associated chest pain. This is interesting from the standpoint that the patients still had their native parietal pleura. In terms of the clinical consequences of their PEs, the lack of a bronchial circulation theoretically placed them at higher risk for lung infarction. Chest imaging, including CT scans, in four of the patients at the time of their presentation did not show any evidence of this. One of the patients had a respiratory arrest requiring intubation but was stable hemodynamically throughout the event. One of the six patients presented with associated right heart failure and was the only patient to succumb to the event. The other patients appeared to tolerate their embolic events quite well from a hemodynamic standpoint, despite evidence of large clot burden in five of the remaining six episodes. This raises the notion of their right ventricles being “preconditioned” by virtue of their underlying IPF and associated pretransplant pulmonary hypertension. In summary, thromboembolic events appear to be relatively common in lung transplant recipients with IPF. This should be considered in the differential diagnosis of any such patient who presents with shortness of breath and/or hypoxia posttransplant. With their abnormal lung parenchyma, spiral CT scans can be very useful diagnostic tools. The question of whether IPF patients in general have a predilection for thromboembolic events may warrant further study.

References 1 Griffith BP, Magee MJ, Gonzalez IF, et al. Anastomotic pitfalls in lung transplantation. J Thorac Cardiovasc Surg 1994; 107:743–754 2 Leibowitz DW, Smith CR, Michler RE, et al. Incidence of www.chestjournal.org

3 4 5 6 7

pulmonary vein complications after lung transplantation: a prospective transesophageal echocardiographic study. J Am Coll Cardiol 1994; 24:671– 675 Kroshus TJ, Kshettry VR, Hertz MI, et al. Deep venous thrombosis and pulmonary embolus after lung transplantation. J Thorac Cardiovasc Surg 1995; 110:540 –544 Panos RJ, Mortenson RL, Niccoli SA, et al. Clinical deterioration in patients with idiopathic pulmonary fibrosis: causes and assessment. Am J Med 1990; 88:396 – 404 Kelion AD, Cockcroft JR, Ritter JM. Antiphospholipid syndrome in a patient with rapidly progressive fibrosing alveolitis. Postgrad Med J 1995; 71:233–235 Pochis WT, Krasnow AZ, Collier BD, et al. Idiopathic pulmonary fibrosis: a rare cause of scintigraphic ventilationperfusion mismatch. Clin Nucl Med 1990; 15:321–323 Blachere H, Latrabe V, Montaudon M, et al. PEssm revealed on helical CT angiography: comparison with ventilationperfusion radionuclide lung scanning. AJR Am J Roentgenol 2000; 174:1041–1047

Chronic Eosinophilic Pneumonia* A Case Report and National Survey Catherine Wubbel, MD; Deborah Fulmer, MD; and James Sherman, MD

Few reports of chronic eosinophilic pneumonia (CEP) in the pediatric population can be found in the literature. Our patient, a 16-year-old male subject presenting with signs and symptoms of CEP, prompted a survey of pediatric pulmonary training centers in the United States to determine the prevalence of eosinophilic pneumonia. The survey showed a low prevalence of acute eosinophilic pneumonia and CEP in the pediatric population, with an overall male/female ratio of 1.6:1. (CHEST 2003; 123:1763–1766) Key words: adolescence; BAL; chronic eosinophilic pneumonia; transbronchial lung biopsy Abbreviations: ACR ⫽ American College of Rheumatology; AEP ⫽ acute eosinophilic pneumonia; CEP ⫽ chronic eosinophilic pneumonia; CSS ⫽ Churg-Strauss syndrome

pneumonia is a rare cause of lung disease E osinophilic in children and adolescents. The relatively nonspe1

cific nature of the clinical presentation of this disease *From the Department of Pediatrics (Drs. Wubbel and Sherman), University of Florida College of Medicine, Gainesville, FL; and Department of Pediatrics (Dr. Fulmer), Memorial Health University Medical Center, Mercer University, Savannah, GA. Manuscript received May 28, 2002; revision accepted September 27, 2002. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: [email protected]). Correspondence to: Catherine Wubbel, MD, Department of Pediatrics, University of Florida College of Medicine, 1600 SW Archer Rd, Gainesville, FL 32610; e-mail: [email protected] CHEST / 123 / 5 / MAY, 2003

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