Severe Hemoptysis Associated with Pulmonary Aspergilloma

Severe Hemoptysis Associated with Pulmonary Aspergilloma Percutaneous Intracavitary Treatment Marcelle] Shapiro, M.D.;* Steven M. Albelda, M.D.;t Robert L. Mayock, M.D., F.C.C.~;t and Gordon K. McLean, M.D. * Surgical therapy for massive hemoptysis associated with pulmonary aspergilloma carries a high morbidity and mortality in patients with limited pulmonary reserve. Bronchial artery embolization has proven ineffective in treating and in preventing recurrent episodes of hemoptysis in this group of patients. Over a four-and-one-half year period, we have successfully treated six episodes of acute hemoptysis in four patients using a percutaneously placed catheter and intracavitary instillation of amphotericin B,

Massive hemoptysis is the cause of death in 2 to 26 percent of patients with pulmonary aspergillorna. 1 Fatal hemorrhage from aspergilloma is the second most common cause of death in sarcoidosis. 2 Traditionally surgical resection of the involved pulmonary tissue has been advocated as the treatment of choice, although morbidity and mortality rates may run as high as 25 percent and 8 percent, respectively 1-12 The foregoing statistics apply to those patients with adequate pulmonary reserve and unilateral hemorrhage. Surgery is even more hazardous for the many patients with massive hemoptysis and pulmonary aspergilloma who have severe underlying pulmonary disease. The extremely high morbidity and mortality of surgery in this subgroup of patients has prompted a search for other forms of therapy Bronchial artery embolization has proven successful in controlling massive hemoptysis occurring with tuberculosis, bronchiectasis, and lung carcinoma. Unfortunately embolotherapy has not been effective in permanently controlling massive hemoptysis associated with pulmonary aspergilloma, probably because of the presence of a massive collateral circulation. 13,14 While aspergillomas can develop in any form of cystic lung disease, the most common underlying conditions are sarcoidosis or healed cavitary tuberculosis, often resulting in lesions in the upper lung fields. Through the associated pleural adhesions, the mycetoma cavity

wall often receives a rich extrathoracic blood supply from the axillary and subclavian arteries, in addition

*Department of Radiology

Hospital of the University of Pennsylvarna, Philadelphia, and the tCardiovascular-Pulmonary Division of the Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia. Manuscript received September 18, 1987; revision accepted March 13. Reprint requests: Dr.McLean, Hospital, University of Pennsylvania, Angio-lnteroontional Radiology, 3400 Spruce Street, Philadelphia 19104

N-acetylcysteine, and aminocaproic acid. Advantages of this method of treatment for patients with severely compromised pulmonary reserve include: (1) no further loss of lung function; (2) ease and rapidity of catheter insertion; (3) prompt response to treatment; (4) relatively short hospitalization; and (5) ability to repeat the procedure in the same or another cavity if necessary (Cheat 1988;

94:1225-31)

to the bronchial arteries.' Any embolization of this complex and extensive systemic arterial network requires a high degree of skill and complete embolization may be impossible. 13 Antifungal agents have been used in a variety of ways. Intravenous amphotericin B has been shown to be no more effective than routine pulmonary toilet. 15 Several investigators have instilled antifungal agents endobrcnchially's-'? or via a transthoracic route into the cavity l 8-21 in symptomatic, but relatively stable patients with aspergilloma. Only one of these studies, a case report;" has examined the usefulness of this technique during an acute episode of hemoptysis. Over the past four and one half years, we have successfully treated six episodes of severe hemoptysis, including three episodes of massive hemoptysis (>600 ml/24 hours), in four patients with pulmonary aspergillomas and severe underlying lung disease using a percutaneously placed catheter and instillation of a combination of amphotericin B and N-acetylcysteine (Mucomist). In one instance, instillation of aminocaproic acid (Amicar) was also employed. This article describes our technique, method of treatment, and long-term results. MATERIALS AND METHODS

Four patients with aspergilloma were treated for six episodes of hemoptysis from 1983 to 1987. There were three men and one woman, with a mean age of 54 years (range 48 to 63 years), Underlying lung diseases were sarcoidosis in three and bullous lung disease in one. Patient data are summarized in Table 1. Each patient had a chest roentgenogram documenting an upper lobe intracavitary mycetoma from three months to ten years prior to admission. Serum Aspergillus precipitins were positive in each of the patients; three of the four patients had sputum or percutaneous aspirates or both from which Aspergillus species were cultured. All patients had severely compromised pulmonary function, with forced vital capacity <50 percent and resting PaOI <80 mm Hg. Each presented with recurrent, persistent hemoptysis. One patient with bilateral CHEST I 94 I 6 I DECEMBER, 1988

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aspergillomas had three episodes of massive hemoptysis (~600 ml blood expectorated/24 h), which required treatment of each cavity on separate occasions, once on the left and twice on the right. Because of continued bleeding, poor pulmonary reserve, and high surgical risk, these patients were referred to the Angiography/ Interventional Radiology section for therapy Each patient first underwent fiberoptic bronchoscopy to determine the location of bleeding. In every case, it was possible to Jocalize the site of active hemorrhage. Percutaneous treatment was considered only if a solitary mycetoma was identified on routine posteroanterior and lateral chest roentgenography in an area which corresponded to the

results of bronchoscopy Patients were examined under fluoroscopy to determine the most direct route from the skin into the cavity and the appropriate area was then prepared and draped in sterile fashion. On five occasions, an anterior approach via the first, second or third intercostal space was used while on one occasion, a posterior apical approach was required. Following local anesthesia, the cavity was punctured under fluoroscopic guidance with either an 18-gauge Seldinger needle or 20-gauge Chiba needle. A portion of the cavity contents was aspirated and sent for routine bacterial, fungal cultures, KOH, and Gram stains. The percutaneous tract was dilated, and a 10 to 12 French Ring-McLean sump catheter (Cook, Inc, Blooming-

Table I-Patients with Aspergillomas and Hemoptysis Patient No. Age/Sex

Underlying Disease

Hemoptysis Mycetoma VoV24 hr Location Site (Bronch)

Drainage Catheter Used

Total Dose Amphotericin

1a*

49/F

Sarcoidosis

LUL

600 ml, LUL

12 F Ring-McLean sump

500mg

1b

49/F

Sarcoidosis

RUL

6OOml; RULposterior seg.

12 F Ring-McLean sump

800 rng

1c

541F

Sarcoidosis

RUL

500 ml: RUL 12 F Ring-McLean sump

750 mg

Results

Long-Term Follow-up

Hemoptysis ceased Vide infra by 48 hr: mycetoma cleared @' seven days (see case report) Hemoptysis ceased Only minor hemoptywithin seven sis for 54 months, days; cavitary then had another mass/mycetoma episode of massive decreased in size hemoptysis (vide over three weeks infra) (see case report). Initial treatment with aminocaproic acid; massive hemoptysis ceased then recurred five days later; additional amino-caproic acid then amphotericin B; no further bleeding over two months

2

57/M

Sarcoidosis

RUL

100 ml, RUL 12 F Ring-McLean sump

500 mgt

3

631M

Sarcoidosis (History of asbestos exposure)

LUL

100-200 ml:

8 F Pigtail catheter

500mg

4

48/M

Bullous lung disease

LUL

50-100 ml: LUL

8.5 F Cope loop nephrostomy catheter

690mg

(see case report). Hemoptysis ceased within 48 hrs; mycetoma cleared within four weeks

Readmitted on three occasions (7/83-11/ 85) for exacerbation of asthma (associated with allergic bronchopulmonary aspergillosis); no further hemoptysis or mycetoma over 4.5 years Hemoptysis ceased .. At two years, readmitwith 24 hrs, myted with recurrent cetoma cleared hemoptysis due to within two weeks endobronchial mass; symptoms resolved in one week; lost to follow-up No hemoptysis fol- No further hemoptylowing catheter sis at 12 months placement; mycetoma decreased in size over three weeks

*a indicates admission number 1; b, admission number 2; and c, admission number 3. tMinimum dose; catheter fell out during period as outpatient.

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severe Hemoptysis Associated with Pulmonary Aspergilloma (Shapiro st

all

ton, IN), pigtail catheter, or an 8,5 French Cope nephrostorny catheter was advanced into the cavity. The catheter was then capped and sutured to the skin , In the first two patients, the catheters were maintained on continuous low pressure suction except during installation of medication. We subsequently modified this approach, using only intermittent periods of low wall suction (40 to 60 cmH,O) as described below. On the first day of catheter placement, a test dose of amphotericin B (5 mg diluted in 20 ml D5W) was instilled slowly into the cavity with the patient in the ipsilateral decubitus position. The position of the patient which minimized coughing was determined, and the patient was monitored carefully for any untoward reactions. For the remainder of the treatment period, 40 to 50 mg of amphotericin B dissolved in 10 to 20 ml of D5W was instilled over three to five minutes each morning, The catheter was then capped. Each afternoon, approximately 8 to 12 hours following amphotericin instillation, N-acetylcysteine (Mucomist, 10 percent solution, 10 ml dissolved in 10 ml 0.9% saline) was slowly injected into the cavity. N-acetylcysteine was added to the treatment regimen to facilitate dissolution of the fungus ball and to help in clearing debris. The catheter was placed on low continuous wall suction (20 cmH,O) two hours after administration of N -acetylcysteine and maintained overnight. When necessary. the patients were premedicated with acetaminophen for fever, diphenhydramine hydrochloride (Benadryl) for urticaria, and/or codeine for excessive coughing during subsequent treatments. Because of massive, life-threatening bleeding in one patient (see case report), intracavity instillation of aminocaproic acid (5 g in 20 ml D5W) was also used in addition to amphotericin Band N-acetylcysteine. Intracavitary therapy was continued until hemoptysis had ceased and a minimum total dose of 500 mg amphotericin B had been given . Serial chest roentgenograms were obtained biweekly to check the catheter position and status of the cavity. At the conclusion of the treatment period (10 to 20 days), the catheter was removed under fluoroscopic guidance, and a sterile dressing was placed over the site . RESULTS

Six episodes of acute hemoptysis secondary to an aspergilloma were treated with percutaneous intracavitary instillation of amphotericin Band N-acetylcysteine, Table 1 contains treatment data summarized, In one case (Table 1, patient Ia), prior bronchial artery embolization was performed but was unsuccessful in controlling hemoptysis from a left upper lobe mycetoma . During another course of therapy in this patient (Table 1, patient lc), aminocaproic acid was added to the regimen to control intermittent massive hemoptysis shortly after initial catheter placement. Catheter insertion was completely uneventful in four of the six placements, and none of the patients experienced pneumothorax with cavity puncture, However, in two patients, complications developed, One patient experienced transient, severe bronchospasm following contrast injection into the cavity which was successfully treated with nasal oxygen. Following this experience, we no longer routinely inject contrast into the cavity. The other patient developed massive hemoptysis with placement of a stiff guidewire into a right upper lobe cavity. This problem was treated successfully by administering oxygen, placing the

patient in the right lateral decubitus position, rapidly replacing blood losses and by performing nasotracheal intubation with selective catheterization of the left mainstem bronchus, After stabilization in the medical intensive care unit, intracavitary therapy was successfully completed (see case report). In three instances (Table 1, patients 1b, Ic, and 4), patients received total doses of 800 mg, 750 mg, and 690 mg of amphotericin B in an attempt to clear the mycetoma. In each case, the intracavitary mass decreased in size but did not completely resolve after three weeks. The roentgenographic appearance of these intracavitary masses has remained stable during two months to four years offollow-up. In treating three additional mycetomas (Table 1, patients Ia, 2 and 3), a total dose of 500 mg of amphotericin B was instilled with complete clearing of the cavity within one to four weeks, Although all patients manifested a transient increase in sputum production with initiation of therapy, acute hemoptysis ceased completely within two to eight days. Patient 1 required daily premedication with diphenhydramine and acetaminophen for fever during amphotericin B infusion, while patient 4 required daily codeine premedication for cough suppression, N-acetylcysteine was eliminated and Amicar was added to the treatment regimen of patient lc because of recurrent hemoptysis during her most recent course of therapy. No patient showed evidence of renal toxicity or other side-effects. Patients were followed for one to 54 months posttreatment (Table 1). Two patients required hospitalization for recurrent hemoptysis at 2, 24, and 54 months, respectively. In the first case, hemoptysis was self-limited, apparently secondary to bacterial super-

FIGl'l\E 1. Chest x-ray film (posteroanterior view, March 1983). Bilateral upper lobe cavities; mycetoma in right cavity, air-fluid level in left cavity with adjacent pleural thickening; scarring secondary to sarcoidosis.

CHEST I 94 I 6 I DECEMBER. 1988

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infection of the preexisting cavity. In the second case, bronchoscopy revealed an endobronchial mass; however, the patient declined further evaluation and was lost to followup. In the third case, the patient developed massive hemoptysis 54 months after initial intracavitary therapy of a right upper lobe mycetoma (see Case Report). The remaining two patients, followed for 12 and 48 months respectively, reported no recurrence of hemoptysis. CASE REPORT

admission showed slight enlargement of the RUL cavity and mycetoma. The LUL cavity appeared stable when compared to a film obtained two months earlier. Emergency fiberoptic bronchoscopy revealed bright red blood coming from the posterior segment bronchus of the RUL with an entirely clear left tracheobronchial tree. Intracavitary therapy was initiated in the RUL cavity following placement of a 12-French Ring-McLean sump via a posterior approach. She was treated with 40 mg of amphotericin B instilled at night and N-acetylcysteine (10 percent solution, 2 ml in 20 ml sterile saline) instilled in the morning, each solution indwelling for one hour before resuming continuous low wall suction. The hemoptysis quickly slowed and ceased within seven days, although an intracavitary mass persisted on chest x-ray film. A total dose of 800

A 49-year-old woman (Table I , patient 1 a, b, c) with biopsyproven sarcoidosis was admitted to the Hospital of the University of Pennsylvania with massive hemoptysis in March 1983. She first sought medical attention in 1972, when she complained of progressive dyspnea. After sarcoidosis was diagnosed, she started alternate day prednisone therapy. She experienced several limited episodes of scant hemoptysis during the next five years for which she did not seek medical attention. In 1977, a chest roentgenogram revealed new bilateral upper lobe cavities with possible mycetomas. She declined bronchoscopy, surgery, or any further evaluation and was lost to medical follow-up until 1983 when she presented with a oneyear history of weight loss, 4.5 kg, (ten pounds) and a three-day history of increasing hemoptysis (>200 mV24 h) Physical examination revealed blood pressure of 120170mm Hg, resting pulse of 100 without orthostatic change, a respiratory rate of 30 per minute, and clear lung fields, without dullness to percussion. Her laboratory values were remarkable for the following: HgblHct, 9.2128, and room air arterial blood gas; pH , 7.38; POt, 68; Pco., 20. A chest roentgenogram (Fig 1) showed diffuse bilateral interstitial disease with scarring and upper lobe cavities. The right upper lobe cavity showed a characteristic crescent with mycetoma, while the left upper lobe cavity had an air-8uid level which proved to be blood . Hemoptysis continued (>300 mV12 h), and she underwent emergency bronchoscopy, which showed active bleeding from the left upper lobe (LUL) bronchus. Given her limited pulmonary reserve (FVC, 44 percent of predicted), she was felt to be at great surgical risk and was referred to angiography for embolization of the left bronchial arteries. Selective left intercostal and bronchial arteriography showed the fourth and fifth intercostal arteries and the left bronchial artery to be dilated and tortuous, supplying a hypervascular cavity with multiple in8ammatory vessels (Fig 2A, B, C), Each of these arteries was selectively embolized with Gelfoam particles. No spinal artery branches were identified. The left subclavian artery also was catheterized, revealing an extensive network of small arterial branches from the costocervical trunk and lateral thoracic artery supplying the cavity wall. Because of their small size and large number, as well as the cessation of hemoptysis, these branches were not embolized, however, 12 hours later, she developed recurrent hemoptysis. A percutaneous intracavitary catheter (12-French Ring-McLean sump) was then placed to allow aspiration of the cavity and to instill amphotericin B according to a regimen proposed by Hargis et all. (Fig 3). The regimen was modified so the N-acetylcysteine (10 percent solution 2 ml diluted in 20 ml of sterile saline) solution was instilled each afternoon, approximately eight hours after the daily morning intracavitary dose of 40 mg amphotericin B. She required premedication with acetaminophen prior to each dose of amphotericin B because of fever. By 48 hours, hemoptysis had ceased, and within seven days, the cavity had cleared (Fig 4). She received a total dose ofSOO mg amphotericin B, instilled over 13 days, and was discharged in stable condition following removal of the catheter. The patient was asymptomatic for two months, when she developed recurrent massive hemoptysis. A chest roentgenogram on

FIGI:RE 2. Top, Selective injection of the left fourth intercostal artery. Note hypervascular cavity wall and shunting into pulmonary circulation. Center and bottom, injection into fifth intercostal and left bronchial arteries. Note dilated, tortuous vessels supplying cavity wall.

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severe Hemoptysis Associated with PulmonaryAspergilloma (Shapiro et 81)

Ring-Mclean sump via an anterior approach. Insertion of the guide wire into the cavity provoked an episode of acute massive hemoptysis requiring emergency nasotracheal intubation with selective catheterization of the left mainstem bronchus and transfusion of eight units of packed red blood cells. The patient was stabilized in the medical intensive care unit , but because ofcontinued heavy bleeding from the cavity over the next 12 hours (evidenced by a drop in hemoglobin of 3 g/dl), intracavitary aminocaproic acid (5 g in 20 ml D5W) was instilled via the catheter as suggested by Fernandez. 21 This was associated with a prompt cessation of bleeding and a stabilization of her hemoglobin level, allowing extubation. One day after the bleeding had stopped, the standard course of amphotericin Band N-acetylcysteine was begun . She remained stable for four days, when she had another episode of massive hemoptysis requiring intubation and transfusion. Five grams of aminocaproic acid were again instilled with rapid cessation of bleeding. One day after stabilization, she resumed standard intracavitary therapy. She had one more episode of hemoptysis (approximately 100 ml) four days later (at a total dose of amphotericin B of 500 mg). This was treated successfully with one instillation of 5 g of aminocaproic acid. She received an additional 250 mg of amphotericin B (total dose 750 mg) without further instillation of N-acetylcysteine which seemed to be inducing some coughing. After completing her course of intracavitary therapy, the catheter was pulled without complication and the patient has remained stable , without further hemoptysis for two months (Fig 5). FIGl'RE 3. Twelve-French left percutaneous sump catheter in place; communication with LUL bronchus following contrast medium injection .

DISCUSSION

mg of amphotericin B was instilled over 20 days. Although there was incomplete resolution of the RUL mycetoma, the patient was symptomatically improved , with no further hemoptysis. The catheter was removed, and she was discharged. Over the next three years, she experienced occasional bouts of coughing with blood-streaked sputum and was hospitalized once for bacterial superinfection of the LUL cavity associated with mild, self-limited hemoptysis. Fifty-four months following initial therapy of the RUL mycetoma, the patient presented again with massive hemoptysis. Emergency bronchoscopy revealed bleeding from the RUL. Intracavitary therapy was again initiated in the RUL cavity by placing a I2-French

Although the treatment of choice for patients with symptomatic pulmonary aspergilloma is surgical resection of the involved segments, this therapy suffers from several drawbacks. The most significant of these is the very high operative morbidity and mortality which occurs in the setting of reduced pulmonary reserve and especially when diffuse underlying disease is present. 1-12,22 .23 Israel et al2 reviewed their surgical experience with aspergillomas in patients with sarcoidosis who had severely compromised pulmonary function, as defined by FVC and maximum breathing capacities below 50 percent and resting Pa0 2 <80 mm

FIGl:RE 4. Chest x-ray film (posteroanterior view, seven days postdrainage). Contents of LUL cavity have disappeared; RUL mycetoma persists .

FIGl:RE 5, Chest x-ray film (posteroanterior view, five years postdrainage), Note bilateral upper lobe cavities. Small mass persists in RUL cavity; LUL cavity remain s clear. CHEST I 94 I 6 I DECEMBER, 1988

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Hg. Each ofthe seven patients who underwent surgical resection for intractable bleeding or repeated severe hemorrhages required intensive respiratory care for weeks or months. Six patients experienced prolonged air leaks and two developed empyemas despite an attempt to reduce the frequency of these complications by performing a tailoring thoracoplasty in five of these patients. Three patients eventually died of postoperative respiratory failure. This experience is echoed in a more recent study by Tomlinson and Sahn'" who examined the outcomes of 28 patients with aspergillomas. In this study the predisposing lung disease in 14 paients was tuberculosis (with relatively "localized" disease), while the remaining 14 patients had sarcoidosis with more diffuse lung involvement. Ten of 13 tuberculosis patients had surgical resection of their aspergillomas because of persistent bleeding. Eight underwent lobectomy with satisfactory results, while two patients with planned lobectomies underwent pneumonectomy because of extensive pleural and parenchymal fibrosis. These two patients died in the postoperative period from respiratory failure demonstrating that surgery may be hazardous even with "localized" disease if the procedure has to be extended. Surgery was not offered to any of the patients with sarcoidosis despite the occurrence of massive hemoptysis in two of them. These two patients were treated with bronchial artery embolization for control of bleeding. Both died within six weeks of the procedure: one with recurrent hemoptysis and the other with progressive respiratory failure. Despite these results, the authors recommend embolization as the only option to control bleeding in patients with diffuse lung involvement. Our results suggest that intracavity therapy may be a viable therapeutic alternative to control hemoptysis in this group of high risk patients. While this study was not a controlled trial, and the natural history of hemoptysis in pulmonary aspergillomas is rather unpredictable,24.25 we were able to successfully treat all six episodes of bleeding without surgery thus avoiding the all-too-frequent postoperative complications. Each patient left the hospital within three weeks of their episode of hemoptysis without further loss of lung function or any permanent complications. There have been several reports describing the use of intracavitary therapy to treat pulmonary aspergillorna. 16-20 Amphotericin B, as well as sodium iodide, have been instilled by endobronchial catheters, repeated transthoracic puncture, and indwelling transthoracic catheters. In these reports, the most common indications for therapy have been persistent cough, weight loss, fever, progressive roentgenographic changes, and intermittent hemoptysis." A transthoracic approach for the control of acute hemoptysis has been described in only one case report. 21 In this case, 1230

a thoracotomy was performed for a symptomatic left upper lobe aspergilloma. Lung resection could not be accomplished due to extensive radiation fibrosis and scarring. A Foley catheter was placed in the cavity during surgical exploration. Intracavitary and systemic amphotericin B were initially given; however, the patient developed massive bleeding from the cavity which was eventually controlled with instillation of 5 g of aminocaproic acid. Each of our patients was referred for percutaneous placement of an indwelling intracavitary catheter because of persistent or massive hemoptysis superimposed upon severe, diffuse underlying lung disease. The risk of surgical therapy was believed to be excessive and, as illustrated in the case report, bronchial artery embolization had proven to be ineffective in controlling acute hemoptysis. We instilled amphotericin B in larger doses than previously reported.!? Moreover, we combined this with instillation of N-acetylcysteine in an attempt to clear the mass of fungus, fibrin, mucus, and blood which comprise the fungus ball. In one case, aminocaproic acid was added to the regimen to control acute massive hemoptysis. Three of five mycetomas showed complete resolution, and there was a decrease in size of the remaining two. Regardless of the status of the mycetoma, acute hemoptysis resolved in each case over two to eight days. Even episodes of massive lifethreatening hemoptysis could be treated with intracavitary therapy in nonsurgical candidates. Fluoroscopically guided percutaneous placement of the intracavitary catheters was not accompanied by the development of a pneumothorax in any case, probably because of extensive pleural adhesions. We experienced two complications during catheter insertion. In one patient, transient bronchospasm developed after instillation of contrast media into the cavity, a procedure we now avoid. More worrisome was our most recent patient, who developed an episode of massive hemoptysis during guidewire placement. This bleeding was of such magnitude that it necessitated emergency nasotracheal intubation and selective placement of the endotracheal tube in the contralateral mainstem bronchus. In view of this recent experience, we now recommend close respiratory and hemodynamic monitoring during the procedure, with oxygen, suction, and equipment for nasotracheal intubation readily available. An anesthesiologist and/or a pulmonary physician capable of providing immediate ventilatory support is also suggested. In most patients, the daily instillations of amphotericin Band N-acetylcysteine were well tolerated. Codeine, diphenhydramine, or acetaminophen premedication were occasionally used for control of minor symptoms, In all patients, the percutaneous tract closed within one week of removal of the catheter, severe HemoptysisAssociated with PulmonaryAspergilloma (Shapiro at

all

with no evidence of bronchopIeural-cutaneous fistulae. The reasons for the rapid effectiveness of this therapy are not entirely clear. The initial rapid response to amphotericin B instillation may be related to its irritative properties and sclerosing ability rather than its antifungal action. It is believed that the bleeding associated with aspergilloma is due to extensive capillary oozing, rather than large vessel disruption.' It seems most likely that the combination of amphotericin Band N -acetylcysteine acts by first sclerosing the rich capillary lining of the cavity, and then "dissolving" the fungus ball (allowing its removal by suction). By sterilizing the cavity of its fungal elements, the source of capillary irritation may be eliminated. The mechanism of action of aminocaproic acid in this setting is unclear. It is known that amino caproic acid inhibits fibrinolysis principally via inhibition of plasminogen activating substances. It has been postulated that extravascular clots which have formed in vivo and have incorporated aminocaproic acid may not undergo spontaneous lysis." The optimal approach to the patient with mycetoma and pulmonary hemorrhage is unclear. Spontaneous lysis of mycetoma has been reported in up to 10 percent of patients. 25 However, the incidence of spontaneous lysis or recurrence of bleeding once an episode of significant hemoptysis has occurred is unknown. With persistent, progressively increasing frequency and amount of hemoptysis, intervention must be considered. In patients with adequate pulmonary reserve and hemoptysis associated with an aspergillorna, surgical resection remains the definitive therapy. However, in patients with severe, chronic respiratory insufficiency and limited pulmonary reserve with diffuse or localized underlying lung disease, intracavitary therapy with amphotericin B, N-acetylcysteine ± aminocaproic acid offers an alternative for the treatment of hemoptysis. The approach offers a number of advantages. There is no loss of lung function. Rapid evacuation of intracavitary blood and fungal debris is possible through the catheter. The technique can be performed quickly, and in our experience, was associated with minimal morbidity and no mortality. Hemoptysis was controlled in all episodes, including episodes of intermittent massive hemoptysis occurring shortly after initial catheter placement. Most importantly, this approach offers another therapeutic option for a group of patients with an otherwise poor prognosis. ACKNOWLEDGMENTS: We would like to thank Dr. Howard Eisen (Hospital of the University of Pennsylvania) for his assistance in this study and Mr. Henry Way for his skillful preparation of the manuscript.

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