Pulmonary Aspergilloma Diagnostic and Therapeutic Considerations

Richard A. Glimp, MD, A rnold S. Bayer, MD

• Pulmonary aspergillomas usually arise from colonization EPIDEMIOLOGIC CHARACTERISTICS and proliferation of Aspergillus in preexisting parenchymal cavities. The most common symptom in this disorder is The true incidence of pulmonary aspergilloma is not hemoptysis, which may be massive and life-threatening. Al known. Varkey and Rose1 estimated one case per 6,000 ad though positive sputum cultures for Aspergillus are present in missions to their facility, while MacPherson2 found six cases more than half of patients with aspergillonrsa, this is neither a of aspergilloma in his review of chest roentgenograms from sensitive nor specific diagnostic marker. Virtually all patients a patient population of 60,000. In a population at increased with this syndrome have serum precipitating antibodies to risk for this disease, the figures become more impressive— Aspergillus antigens, and this serves as a useful confirmatory 11% to 17% of patients with tuberculous pulmonary cavities test in patients with suspected aspergilloma. The routine chest were found to have roentgenographic evidence of as roentgenograph and standard tomography remain the most pergilloma in a survey by the British Thoracic and Tuber important diagnostic procedures. The computed tomograph of culosis Association.3 the chest may be helpful in certain cases. Routine surgical Aspergillus spores are ubiquitous in nature, and occupa resection of aspergillomas is not recommended but should be tional exposure is rarely reported in patients with as reserved for patients with recurrent, severe hemoptysis who pergillomas. Aspergilloma is most frequent in older age can tolerate thoracotomy. Parenteral antifungal therapy has groups, but may occur at any age, including childhood.4 The not been effective in this disease; however, selected patients usual species of Aspergillus isolated is Aspergillus fumi- may be candidates for intracavitary antifungal therapy. gatus; however, Aspergillus niger, Aspergillus flavus, As- (Arch Intern Med 1983;143:303-308) pergillus nidulans, and others have also been reported.5 PATHOLOGIC CHARACTERISTICS Th,e sPectrum of pulmonary disease caused by the fungus Early theories of aspergilloma pathogenesis held that the Aspergillus is varied and has prompted a number of pulmonary cavity arose as a direct result of the intrabron- meal classifications. The most popular of these divides chial proliferation of the fungus, with subsequent bronchial mvamonary asPergillosis into the following three categories: dilatation. While animal models exist to support this con invasiV8’fa^er^ C bronchopulmonary, and saprophytic. The cept of a “primary aspergilloma,”6 this is probably a rare noeomVe m generally occurs in the setting of an immu- sequence of events in humans. There have been only three ^gus^f tVi'S8^ ^°S*' anc* inv°lves direct invasion by the clinical settings in which Aspergillus has been reported to lergk brnnllh___ _ pul,monary [junnonary parenchymaParenchyma and vasculat^vasculature._____ Al- initiate the cavitary process, which may then be followed by tergic bronchopulmonary aspergillosis is t0mam- the mycetoma formation: (1) invasive pulmonary aspergillosis “Station of a variety of immunologic re sapro- Presence of the fungus in the bronchia re • scussed (IPA), (2) chronic necrotizing pulmonary aspergillosis (CNPA), and (3) allergic bronchopulmonary aspergillosis Phytic form, or pulmonary aspergi^ma, . p&tho_ (ABPA). Invasive pulmonary aspergillosis is a disease of herein, with emphasis on the clinical mamf pntitv- Physiologic characteristics, and therapy for immunocompromised hosts in which the fungus causes a necrotizing pulmonary vasculitis with hemorrhagic infarc tion.7 In severe cases, IPA may lead to cavity formation and a mycetoma. This process was demonstrated roentgeno- ii ' “**1 Chp t\~ «*wuu‘tion dJuly l I9j 1982. graphically by Meyer et al8 in their series of 90 patients with SarborTirn ? ePartment of Medicine, Division of Infectious Diseases, cine. LA Medical C ~ ‘ --— ~ cancer with invasive aspergillosis; five of these patients had center, Torrance, and the UCLA School of Medi- roentgenographic evidence of an aspergilloma. It should be Ca. Harbor-nrr0 ,^)e/ ,art:ment of Medicine, Division of Infectious noted that, in some cases of aspergilloma complicating IPA, 509 ®r Bayer)! ical Center- 1000 W Carson St E-5, Torrance, roentgenographically described “fungus balls” may in fact be “lung balls,” with necrotic pulmonary tissue filling the

Vol 143 ■ Feb 1983 Aspergilloma—Glimp & Bayer 303 Table 1.— Pulmonary Aspergilloma: Selected Clinical Findings

No. of Patients* Total No. of Aspergillus " Source, yr Patients Hemoptysis! Precipitinst Sputum Culture*^ Kilman et al,36 1969 20 >50% 7/10 15/20 Reddy et al,37 1970 16 13 (ND) 5/6 12/16 Solit et al,19 1971 32 23 (ND) ND 16/17 McCarthy and Pepys,5 1973 28 23 (ND) 28/28 16/28 Karas et al,38 1976 36 23 (20) ND 17/36 Varkey and Rose,' 1976 15 ND 10/10 11/14 Garvey et al,30 1977 11 9(4) 4/4 3/11 Soltanzadeh et al,34 1977 14 13(3) 1/2 4/6 Faulkner et al,33 1978 42 29(14) ND 15/42 Hargis et al,35 1980 6 4 (ND) 6/6 5/6 Total (%) 185 (100)§ 137/185 (74) 61/66 (92)|| 114/196 (58)

*ND indicates no data. fNumber in parentheses indicates number of patients with severe hemoptysis (£150 mL/day of blood). ^Number of patients with positive results/number of patients tested. §lncludes only series reporting exact figures for incidence of hemoptysis; true total is 220. IjWhen patients from study of Longbottom et al39 are included (56 of 57 had positive results), figure becomes 95%. cavity, rather than fungal hyphae.9,10 The newly described cavity, depending on local intracavitary conditions. Dead entity of CNPA is an indolent clinical variant of IPA seen in fungal elements may undergo fragmentation and liquefac!t immunocompetent hosts, which resembles chronic pulmo tion, allowing for portions of the fungal mass to be expecto nary tuberculosis or coccidioidomycosis. Binder et al,11 in rated. Calcification of an aspergilloma may also occur,” reviewing the literature for cases of CNPA, found that 48% Aspergilloma and its cavities may increase in size, r of the patients with this syndrome had roentgenographic or exist for long periods as a stable roentgenographic k evidence of mycetomas. In its chronic form, ABPA may lesion. In addition, spontaneous lysis of the mycetoma has § cause bronchiectasis,12 which in turn may lead to the been reported to occur in approximately 7% to 10% of the I development of an aspergilloma.13 The coexistence of these cases.3,29 Intercurrent bacterial infections are thought to if two pulmonary Aspergillus syndromes is not rare; McCar contribute to this lysis phenomenon.3,29,3° thy and Pepys14 found aspergilloma in 7% of their patients The most frequent complication associated with aspergil-1 with ABPA. Additionally, aspergilloma may serve as the loma is hemoptysis, and a variety of theories have been antigenic stimulus leading to the ABPA syndrome.15 proposed to explain its cause. One theory holds that the Most cases of aspergilloma are thought to arise from mechanical action and “friction” of a mobile fungus colonization and proliferation of the fungus in a preexisting causes bleeding from the hypervascular cavity wall.27 An pulmonary cavity (“secondary aspergilloma”). The factors other possibility is that toxins and/or enzymes elaborated allowing this process to become established in a patient are by the fungus lead to localized hemorrhage.31 A third not well understood. Tuberculosis is by far the most com opinion is that the provocation of a type III (antigen- mon condition associated with aspergilloma,3 with other antibody) inflammatory injury causes changes in the cavity cavitary pulmonary disorders varying in frequency be wall and resultant hemorrhage.32 Last, hemoptysis maybe tween reviews.8-13,16'26 These disorders include sarcoid,16 due to accompanying tracheitis or bronchitis in patients cavitary neoplasm,17 pulmonary fibrosis,18 lung abscess,19 with aspergilloma rather than the lesion itself.33 bronchial cyst,19 asbestosis,20 histoplasmosis,21 blastomyco CLINICAL FEATURES sis,22 ankylosing spondylitis,23 bronchiectasis,24 pneu monia,20 cyanotic heart disease,25 pulmonary infarction,26 Most patients with aspergilloma probably remain asymp allergic bronchopulmonary aspergillosis,13 and invasive as tomatic with regard to their lesions. When p re s e n t, sym? pergillosis.8 toms are varied and often difficult to ascribe to the as- The histopathologic characteristics of the aspergilloma pergilloma in the face of other underlying pulmonai? disclose an intracavitary mass of tangled mycelia (with both disease processes. The most common symptom is hemop dead and living fungal elements), fibrin, mucus, amorphous tysis, which has been reported to occur in approximate!! debris, inflammatory cells, and degenerating blood and 50% to 85% of patients with aspergilloma.25 Combining® epithelial elements. The mycelia mass may lay free within results of recent major reviews shows an overall estim ate the cavity or be attached to the cavity wall via granulation incidence of 74% (Table I ).1-5 19-30-34-38 Hemoptysis is usual? tissue. The wall of the cavity is lined with bronchial epi intermittent and scanty but in occasional cases may thelium (occasionally undergoing squamous metaplasia) or massive and life threatening. Other symptoms associate highly vascular granulation tissue. The surrounding lung with aspergilloma include cough (usually productive a > may show varying degrees of pneumonitis. Communication chronic), dyspnea, malaise, and weight loss. W heezing"1 of the cavity with a bronchus may or may not occur. been reported in some cases but is probably a m a n if e s t3®1 of Aspergillus allergy (as with ABPA) or the underlyw NATURAL HISTORY pulmonary disease process. Fever is not a usual fin®. The natural history of this disease has been poorly unless there is a concurrent bacterial infection or VeI studied, with the best descriptions coming from Pimentel27 an allergic process with a type III response. and Villar and co-workers.28 They describe a repetitive Physical examination is generally not specific, - - process of growth and death of fungal elements within the localizing signs, such as decreased air movement, bronc H,

304 Arch Intern Med— Vol 143, Feb 1983 Aspergilloma— Glimp & ^ ^ h Inter Fig 1.— Top, Pulmonary aspergilloma at lung hiium (arrow) in patient with chronic pulmonary coccidioidomycosis. Bottom, Right lateral decubitus roentgenogram demonstrating positional move ment of intracavitary mycetoma (arrow).

Fig 2.— Tomographic “cut" of pulmonary aspergilloma demonstrat ing lobulated mycelial mass (arrow) within parenchymal cavity.

.his 'the

'Acs

breath sounds, and adventitial sounds were heard in 86% of represent mycetomas with nonviable fungal elements that Patients in one study.6 Standard laboratory studies are of have ceased to be a source of antigenic stimulation40 or the tie use in the diagnosis. Total WBC counts are usually patient with aspergilloma with impaired immunologic re normal. Eosinophilia is rarely seen without some evidence sponsiveness. Surgical excision of the aspergilloma gener o allergy to Aspergillus. Sputum fungal cultures are of ally leads to a diminution in the strength of the precipitin ■nor diagnostic value due to the ubiquitous presence of the reaction and eventual disappearance of these antibodies;39,40 CoP s !n such specimens, its frequent role as a laboratory persistence of serum antibody is occasionally seen postop- cavtami"ant’ atK* Possibility that communication of the eratively when other sites of antigenic stimulus are pres ttavh Wlt^ a '3ronc^us may n°t be present. The diagnosis ent. 4 sL e suggested by multiple positive sputum cultures for Immediate skin test reactivity to Aspergillus antigens are s . > however, as shown in Table 1, positive cultures has been reported in 30% to 75% of patients with as The8n m °n^ Pat’ents w'th aspergilloma. pergilloma, depending on methods of patient selection.5,39 cailnot CuUrse an<^ Pr°gnos>s of patients with aspergilloma Evidence for Type III (antigen-antibody) allergic reac c°exist t Pre^^c*-ed and depend mainly on the patient’s tions, as demonstrated through delayed intradermal and health p Pulmonary disease processes and general inhalation challenge reactions, also can be found occasion «ussed i=3ftaI hem°Ptysis can occur, but, as will be dis- ally in patients with an aspergilloma, although not as e°mPlicat tUnat y uncommon. Few other symptoms or frequently as with ABPA.5 Elevated IgE levels have been death is 10nSi a^er the overall course of the disease, and found in a small group of patients with aspergilloma.41 As Secondanfvf ascr*bed to an aspergilloma. Surprisingly, was previously mentioned, all of these tests reflect the rarely rep0 infection of aspergilloma cavities is degree of concomitant allergic response to the fungus in the lung and show great variability from patient to patient. ^ IMMUNOLOGIC FEATURES ROENTGENOGRAPHIC FEATURES tb °| We prgg^ .a^ Patients with aspergilloma can be found to Chest roentgenograms remain the single most important ■0m ^fr8erum»frp??,germJ»7rj;lug antibodiesantlt>odies to Aspergillus antigens in... method of diagnosing pulmonary aspergilloma. The as 'Table 1). The rare exceptions to this probably pergilloma typically appears as a solid, rounded mass 104 Afch t8rn Med"V o l 143, Feb 1983 Asnprnillnma— ^lim n o o n e Table 2. — Surgery for Pulmonary Aspergilloma

No. of Patients

Total No. of Undergoing Surgical Source, yr Patients Surgery Deaths Complicatim,. Kilman et al,36 1969 20 14 2 7 Reddy et al,37 1970 16 5 1 3 Solit et al,19 1971 32 13 0 5 Eastridge et al,'16 1972 22 22 0 5 Karas et al,36 1976 36 15 2 1 Varkey and Rose,1 1976 15 5 1 2 Garvey et al,30 1977 11 11 1 2 Soltanzadeh et al,34 1977 14 14 1 1 Faulkner et al,33 1978 42 11 1 1 Total (%) 208 (100) 110/208 (53) 9/110 (8.2) 27/110(24.5) within a cavity, separated from the wall of the cavity by air might have produced the initial cavity and environment (Fig 1). Cavities average 3 to 5 cm and have walls of varying supportive for the development of the mycetoma (eg, tuber thickness.42 Serial roentgenograms have shown that the culosis or sarcoidosis). walls of the preexisting cavity begin to thicken prior to the THERAPY actual appearance of the fungus ball.42 There may be evi dence of surrounding pneumonitis, and thickening of adja The optimum therapy for pulmonary aspergilloma is con cent pleura can be seen with peripheral mycetomata.43 The troversial and is the basis of most recent studies in the majority of aspergillomas are solitary lesions located in the literature. The major options available include surgical upper lung fields (owing to the high association with resection of the lesion, a number of medical therapies or tuberculosis), but can be multiple and bilateral.44 If the simple observation of the patient for a time. In reviewing fungus ball is not attached to the cavity wall, positional therapy studies, one must keep in mind the notable variety movement may be demonstrable within the cavity (Fig 1). of clinical settings and host diseases encountered in pa- Air-fluid levels are occasionally seen within the cavities, tients with aspergilloma. Often, such patients have severe especially when the fungal mass undergoes liquefaction.44 underlying pulmonary diseases that not only influence the Calcification may occur along the cavity rim, scattered choice of therapy but also influence the eventual prognosis through the fungal mass, or extensively throughout the and therapeutic response. The magnitude of this problem is lesion. emphasized by one study in which only 32 of 120 patients Although standard chest roentgenograms are often suffi with pulmonary aspergilloma were considered candidates cient to make the diagnosis of a mycetoma, occasionally the for surgical resection.46 Surgery was precluded by such lesion is obscured by local pneumonitis or the changes of problems as severe, chronic-obstructive lung disease, em chronic lung disease. In this setting, tomography is often physema, pulmonary fibrosis, and bilateral aspergilloma. helpful45 (Fig 2). Another use for tomography comes in the These patients are thus, generally, placed in “nonsurgical diagnosis of large intracavitary fungal masses that almost treatm ent” categories. Therefore, without controlling for completely fill the cavity. Computed tomographic scanning underlying illness and general patient health, comparative is also useful and may be superior to standard tomographic studies of therapies are difficult to interpret. Despite these techniques in the problematic case.11 Bronchography is obvious problems of therapeutic “preselection” and bias, rarely a useful diagnostic tool, as fungal debris frequently the general therapeutic trends in pulmonary aspergilloma prevents the contrast dye from entering the cavity.46 are discussed herein. The roentgenographic differential diagnosis of aspergil- Since the original report of Gerstl et al47 of a successful loma includes the following: (1) cavitating neoplasm, (2) surgical resection of an aspergilloma, many centers have blood clot in a pulmonary cavity following a hemorrhage, (3) reported good results with surgery in this disease. More disintegrating hydatid cyst, and (4) pulmonary abscess than 100 surgical resections have been reported. While with necrosis. A number of other fungi that have been there is little debate that surgery is the treatment of choice reported to cause mycetomas (though much less frequently in patients with severe, life-threatening hemoptysis, many than Aspergillus) include Petriellidium, Sporotrichum, reviews have advocated surgical resection as a prophylactic Torulopsis, Candida, and Streptomyces:'2"'1 therapeutic modality in all patients with aspergilloma who can tolerate this procedure.19-30,36-38’48 The arguments for this DIAGNOSIS approach are multiple: (1) hemoptysis is an unpredictable With this information, one can formulate a diagnostic and potentially fatal complication of an aspergilloma, W approach to a patient with an aspergilloma. The diagnosis is surgical resection is generally curative and one rarely seeS suggested after obtaining an abnormal chest roentgeno the relapses that can plague medical therapies, and (3)» gram, either for the symptoms mentioned or incidentally. rare complication of invasion by the fungus, sh o u ld we Chest tomographs and/or decubitus films can be obtained to patient become immunosuppressed, is avoided. . demonstrate the lesion better and perhaps show positional Table 2 shows the results of surgical resection in patie" movement of the fungus ball. Serum precipitin assays, if with aspergilloma from some major recent reviews. 1 positive, will then confirm the diagnosis. Positive sputum overall mortality rate of approximately 8% is essentia® cultures for Aspergillus are suggestive, but not diagnostic, unchanged from the approximate 7% figure cited in ear‘‘ of an aspergilloma. Once the diagnosis is made, the clinician should search for underlying pulmonary processes that * References 1, 19, 30, 33, 34, 36, 37, 38, 48.

306 Arch Intern Med— Vol 143, Feb 1983 Aspergilloma— Glimp & * pviews.1'36 This figure is relatively low when one considers serial examinations and chest roentgenograms. Compari the patient population at risk for aspergilloma and the son studies of observation v surgical resection have been freq u e n t instances where surgery is performed on patients reported in the literature. Faulkner et al33 reported their who are hemorrhaging severely. The morbidity of surgery experience with 42 patients with aspergilloma during a 22- for aspergiHoma, however, is considerably higher, with year period. Eleven of these patients underwent a surgical approximately 25% of patients having some postoperative procedure. Of the 31 patients who were not operated on, 24 nroblem , eg, bronchopleural fistulas, empyema, hemor had hemoptysis; however, in only 13 patients was hemop rhage, and a variety of infections. tysis severe (>150 mL/day), and in only three patients was T he'various forms of medical therapy have generally been hemoptysis recurrent. One death from hemoptysis oc re s e r v e d for those highly symptomatic patients whose curred in both the surgical and nonsurgical groups. Their underlying diseases cause them to be poor surgical can conclusion was that the risk of severe hemoptysis is over didates. When one also considers the technical problems stated in this disease and that the practice of routine associated with each type of therapy, it is not surprising resection of all aspergillomas is unwarranted. Other in that the results are often disappointing in this category of vestigators have agreed with this.1 therapeutic options. Moreover, “success” is frequently diffi The choice of therapy for a patient with pulmonary cult to attribute to a given modality in a disease in which aspergilloma remains controversial. Therapeutic decisions approximately 10% of lesions spontaneously resolve. The in this disease must be individualized to take into account major categories of medical therapy include parenteral, the patient’s overall health and the risks attendant with intracavitary, a n d endobronchial administration of antifun- each treatment modality. It is useful to note that while (f gal drugs. hemorrhage is reported as the cause of death in 2% to 26% of it Intravenous (IV) amphotericin B has been employed at patients with aspergilloma, other causes of death (usually some institutions in the treatment of patients with as other pulmonary complications) total 8% to 40% in this pergilloma, and sporadic reports of cures with this therapy group.33 Surgery, as noted, has a low mortality, but is have appeared.31 In a large comparative study, however, the frequently associated with a variety of postoperative com benefits of this modality were greatly questioned. The plications. The risk of severe, recurrent hemoptysis in Centers for Disease Control cooperative mycoses study49 patients with aspergilloma may not be as great as previ compared the outcome of 33 patients who were divided ously estimated. A reasonable recommendation for man j: according to whether or not they received amphotericin B agement of a patient with aspergilloma would be to reserve IV; no notable difference was found between the two groups surgical resection for those patients who have had severe, in terms of roentgenographic improvement, clearance of the recurrent hemoptysis and who can readily tolerate thoracic fungus from the sputum, or change in the frequency of surgery. Intracavitary antifungal therapy, if tolerated, may hemoptysis. Thus, there seems to be no benefit from using be of benefit to such symptomatic patients who are poor IV amphotericin B in this disease, most likely because of candidates for thoracic surgery. inadequate penetration of the drug into Aspergillus cavi Since completion of this manuscript, a study has ap ties.16 peared from Israel et al,56 describing their experience in Some investigators have attempted to control this prob resectional surgery for aspergilloma among 38 patients lem of antifungal drug penetration into aspergilloma cav with biopsy-proved pulmonary sarcoidosis. The findings of ities through direct intracavitary instillation of antifungal these investigators serves to reemphasize the difficulties in es; agents. This is usually accomplished by repeated trans- resectional surgery in patients with aspergillomas with 1® thoracic placements of a needle into the cavity. Intracavi- severe, underlying pulmonary diseases. In most of their p tajy amphotericin B, sodium iodide, nystatin hydrochlo- patients (36/38), extensive bilateral fibrocavitary sar ,fj; nde, and natamycin alone and in combination, have been coidosis was present. All patients had detailed physiologic ati«; ?se(J with variable success.26,35,46,60 The drugs are usually diagnostic studies to define their capability to undergo i0i instilled in liquid form, though use of a paste of amphoteri- thoracotomy; ten patients were deemed as satisfactory bi*. ® B °r nystatin has been reported.46 The major drawbacks candidates, while 28 were considered unsatisfactory surgi III o this form of therapy have been poor patient tolerance to cal risks. In the “satisfactory risk” group, seven patients e antifungal agents instilled (with fever and other sys- underwent resection for moderate to severe hemoptysis and ;ssi*: f ®!c symptoms) risk of pneumothorax, and relapse of in six of seven had a favorable long-term outcome; however, i'*1'! repQ0? the cavity. Recently, however, Hargis et al35 one patient experienced postoperative invasive pulmonary ti findin stakilization or improvement in roentgenographic aspergillosis and empyema. In the “unsatisfactory risk” lorna £ an<^ symPt°ms in four of five patients with aspergil- group, seven patients underwent resection for persistent or 8 cin B in cJ'°|eratec^ intracavitary instillation of amphoteri- recurrent hemoptysis; three patients died of postoperative attribut- M ^rose in water. Their success may have been respiratory failure. In addition, immediate postoperative drug a(jV e.to relatively large total dose (500 mg) of the complication rates were high in the 14 patients undergoing thisf^^. ^stered. Such studies show some promise for resection. Twelve of 14 acquired persistent air leaks, with ot® svmnf theraPy and may offer an alternative to surgery empyema occurring in four patients. This high frequency of ictJK 1 al1Cpatients- pleural complications led these authors to advise “tailoring na. r°nchial instillation of antifungal agents has had thoracoplasty” at the time of resection to minimize the °avity withtvf„St'51W ith t h K p------ommunicationwiv, of the aspergilloma residual pleural space. These investigators also noted, as in this form of th nc^us may not exist, and relapses with other literature reports, that exsanguinating hemoptysis should be cn .^raPy may occur. Corticosteroid therapy was not encountered on the first episode and suggested |ergy or clas^nAWhen symPtom s of Aspergillus al- that, as a rule, resectional surgery should be deferred in ,3i nto ent improvpmcoexist with an aspergilloma; excel- patients with notable bilateral underlying pulmonary dis 1 an(! the risk116^ ^ symPt°ms usually follows their use,6" - ease until recurrent hemoptysis ensues and comprehensive mvasive or disseminated aspergillosis is evaluation of surgical risk is accomplished.

I 'ort*a is sitnr)]ffr Kat*Ve 'n management of an aspergil- I 0 servation of the lesion over time, with Nancy Westburg Johnson assisted in the preparation of this manuscript. ArChlnternM^ Vh|1 v°l 143, Feb 1983 Aspergilloma—Glimp & Bayer 307 References 1. Varkey B, Rose HD: Pulmonary aspergilloma: A rational approach to treatment. Am J Med 1976;61:626-631. pulmonary aspergillomas. J Thorac Cardiovasc Surg 1977;74-5^o o( 2. MacPherson P: Pulmonary aspergillosis in Argyll. Br J Dis Chest 31. Campbell MJ, Clayton YM: Bronchopulmonary aspergi]l0 j 1965;59:148-157. relation of the clinical and laboratory findings in 272 patients inv * ^ Cot- 3. British Thoracic and Tuberculosis Association: Aspergilloma and forfnr bronchopulmonaryhrnnrhnnnlmnnarv aspergillosis.asnertrillnsis. AAm. m Rev RespirRp.srtir Dis 1964-' 1 at-, .... “lgaf^ residual tuberculosis cavities: The results of a resurvey. Tubercle 1970;51: 32. Hilvering C, Stevens EAM, Orie NGM: Fever in asp'erm'vf 227-245. cetoma. Thorax 1970;25:19-24. gIlllls ®y. 4. Evans EGV, Watson DA, Matthews NR: Pulmonary aspergillomata in 33. Faulkner SL, Vernon R, Brown PP, etal: Hemoptysis and pul a child treated with clotrimazole. Br Med J 1971;4:599-600. aspergilloma: Operative versus nonoperative treatment. A n n Them„ 5. McCarthy DS, PepysJ: Pulmonary aspergilloma: Clinical immunology. 1978;25:389-392. oric3«ij Clin Allergy 1973;3:57-70. 34. Soltanzadeh H, Wychulis AR, Sadr F, et al: Surgical treat 6. Sawasaki H, Horie K, Naito Y, et al: Experimental pulmonary pulmonary aspergilloma. A nn Surg 1977;186:13-16. *eilt of aspergilloma. Mycopathologia 1967;32:265-274. 35. Hargis JL, Bone RC, Stewart J, et al: Intracavitary amphoterj' 7. Herbert PA, Bayer AS: Fungal pneumonia (pt 4): Invasive pulmonary the treatment of symptomatic pulmonary aspergillomas. A m J Med. Iter?® aspergillosis. Chest 1981;80:220-225. 389-394. 80®: 8. Meyer RD, Young LS, Armstrong D, et al: Aspergillosis complicating 36. Kilman JW, Ahn C, Andrews NC, et al: Surgery for pui._ neoplastic disease. A m J Med 1973;54:6-15. aspergillosis. J Thorac Cardiovasc Surg 1969;57:642-647. 01latJ 9. Przyjemski C, Mattii R: The formation of pulmonary mycetomata. 37. Reddy PA, Christianson CS, Brasher CA, et al: Comparis Cancer 1980;46:1701-1704. treated and untreated pulmonary aspergilloma: An analysis of 16 casei01*0* 10. Curtis MA, Smith GJW, Ravin CE: Air crescent sign of invasive Rev Respir Dis 1970;101:928-934. -4? aspergillosis. Radiology 1979;133:17-21. 38. Karas A, Hankins JR, A ttar S, et al: Pulmonary aspergillosis- 11. Binder RE, Faling LJ, Pugatch RD, et al: Chronic necrotizing analysis of 41 patients. A nn Thorac Surg 1976;22:1-7. ' pulmonary aspergillosis: A discrete clinical entity. Medicine 1982,'61:109- 39. Longbottom JL, Pepys J, Clive FT: Diagnostic precipitin test • 124. Aspergillus pulmonary mycetoma. Lancet 1964;1:588-589. 12. Glimp RA, Bayer AS: Fungal pneumonias (pt 3): Allergic bron 40. Avila R: Immunological study of pulmonary aspergilloma Tkm chopulmonary aspergillosis. Chest 1981;80:85-94. 1968;23:144-152. ® 13. Safirstein BH: Aspergilloma consequent to allergic bronchopulmon 41. Rosenberg M, Patterson R, Mintzer R: Clinical and immunolod ary aspergillosis. A m Rev Respir Dis 1973;108:940-943. criteria for the diagnosis of allergic bronchopulmonary aspergillosis £ 14. McCarthy DS, Pepys J: Allergic bronchopulmonary aspergillosis: Intern Med 1977;86:405-414. Clinical immunology: I. Clinical features. Clin Allergy 1971;1:261-286. 42. Fraser RG, PareJAP: Infectious diseases ofthe lungs, inDiagmsut/ 15. Ein ME, Wallace RJ, Williams TW: Allergic bronchopulmonary Diseases of the Chest. Philadelphia, WB Saunders Co, 1978, vol 2 1 aspergillosis-like syndrome consequent to aspergilloma. Am Rev Respir Dis 806-808. ’ f 1979;119:811-820. 43. Libshitz HI, Atkinson GW, Israel HL: Pleural thickening as i 16. Israel HL, Ostrow A: Sarcoidosis and aspergilloma. A m J Med manifestation of Aspergillus superinfection. A m J Radiol 1974;120:883-886 1969;47:243-250. 44. Goldberg B: Radiological appearances in pulmonary aspergillosis 17. Torpoco JO, Yousuffuddin M, Pate JW: Aspergilloma within a malig Clin Radiol 1962;13:106-114. nant pulmonary cavity. Chest 1976;69:561-563. 45. Irwin A: Radiology of the aspergilloma. Clin Radiol 1966;18:432-438, 18. Davies D, Somner AR: Pulmonary aspergillomas treated with 46. Krakowka P, Traczyk K, Walczak J, et al: Local treatment of corticosteroids. Thorax 1972;27:156-162. aspergilloma of the lung with a paste containing nystatin or amphotericinB 19. Solit RW, McKeown JJ, Smullens S: The surgical implications of Tubercle 1970;51:184-191. intracavitary mycetomas (fungus balls). J Thorac Cardiovasc Surg 1971 ;62: 47. Gerstl B, Weidman WH, Newmann AV: Pulmonary aspergillosis: 411-422. Report of two cases. A nn Intern Med 1948;28:662-665. 20. Joynson DHM: Pulmonary aspergilloma. BrJ CUnPract 1977;31:207- 48. Eastridge CE, Young JM, Cole F, et al: Pulmonary aspergillosis. An 216. Thorac Surg 1972;13:397-403. 21. Schwartz J, Baum GL, Straub M: Cavitary histoplasmosis compli 49. Hammerman KJ, Sarosi GA, Tosh FE: Amphotericin B in the cated by fungus ball. A m J Med 1961;31:692-700. treatment of saprophytic forms of pulmonary aspergillosis. Am Rev Respit 22. Sarosi GA, Silberfarb PM, Saliba NA, et al: Aspergillomas occurring Dis 1974;109:57-62. in blastomycotic cavities. Am Rev Respir Dis 1971;104:581-584. 50. Adelson HT, Malcolm JA: Endocavitary treatment of pulmonarj 23. Krohn J, Halvorsen JH: Aspergilloma of the lung in ankylosing mycetomas. A m Rev Respir Dis 1968;98:87-90. spondylitis. Scand J Resp Dis 1968;63(suppl):131-134. 51. Henderson AH, Pearson JEG: Treatment of bronchopulmonary as 24. Bruce RA: A case of pulmonary aspergillosis. Tubercle 1957:38: pergillosis with observations on the use of natamycin. Thorax 1968;23:519- 203-205. 523. 25. Flye MW, Sealy WC: Pulmonary aspergilloma: A report of its 52. Ramirez RJ: Pulmonary aspergilloma: Endobronchial treatment.)?. occurrence in two patients with cyanotic heart disease. Ann Thorac Surg Engl J Med 1964;271:1281-1285. 1975;20:196-203. 53. Davies D, Somner AR: Pulmonary aspergillomas treated with corti 26. Aslam PA, Eastridge CE, Hughes FA: Aspergillosis of the lung: An costeroids. Thorax 1972;27:156-162. 18-year experience. Chest 1971;59:28-32. 54. Safirstein BH, D’Souza M, Simon G, et al: Five-year follow-up» 27. Pimentel JC: Pulmonary calcification in the tumor-like form of allergic bronchopulmonary aspergillosis. Am Rev Respir Dis 1973;108:4W pulmonary aspergillosis: Pulmonary aspergilloma. Am Rev Respir Dis 459. 1966;94:208-216. 55. Anderson CJ, Craig S, Bardana EJ: Allergic bronchopulmonaij 28. Villar TG, Pimentel JC, Avila R: Some aspects of pulmonary as aspergillosis and bilateral fungus balls terminating in disseminated as pergilloma in Portugal. Dis Chest 1967;51:402-405. pergillosis. J Allergy Clin Immunol 1980;65:83-86. 29. Hammerman KJ, Christianson CS, Huntington I, et al: Spontaneous 56. Israel HL, Lenchner GS, Atkinson GW: Sarcoidosis and asptf lysis of aspergillomata. Chest 1973;64:697-699. gilloma: Role of surgery. Chest 1982;82:430-432.

308 Arch Intern Med— Vol 143, Feb 1983 Aspergilloma—Glimp & ^J ^