Aspergillosis of the Lung - An Eighteen-Year Experience

Aspergillosis of the Lung - An Eighteen-Year Experience* P. A. Aslam, M.D., C. E. Eastridge, M.D., and F. A. Hughes, ]r., M.D., F.C.C.P.

We reviewed the records of Zl patients with aspergillosis seen at our institution during the past 18 years. Nine were treated by surgical resection, one by endocavitary infusion and 11 received no specific treatment. Those receiving no treatment either were not diagnosed before death or had associated severe systemic diseases. The association of aspergillosis with pulmonary infarction and ankylosing spondylitis is emphasized. The results of medical and surgical treat· ment are reviewed.

ered body defense mechanisms whether due to leukemia and lymphoma or to the use of certain therapeutic agents, such as steroids, antimetabolites, cytotoxic drugs, antibiotics, or other drugs causing depression of bone marrow function. The purpose of this report is to review our experience with 21 patients with aspergillosis and to show certain unusual features associated with this disease.

Aspergillosis of the lung generally results from saphrophytic colonization of pre-existing lung cavities, eg, due to pulmonary tuberculosis, histoplasmosis, bronchiectasis, or congenital cysts. Parenchymal involvement may occur secondarily to low•From the Veterans Administration Hospital, Thoracic Surgery Section, Surgical Service, and the University of Tennessee College of Medicine, Department of Thoracic Surgery, Memphis, Tennessee.

Table 1-Aapergilloai• Complicacins Trealmenc for Malisnancy Roentgenographic Findings

Autopsy Findings

Primary Disease

Treatment

43

Reticulum cell Sarcoma

Antibiotics Radiation

Progressive pneumonitis

Inva~ion lung parenehyma Invasion blood vesst>ls with thrombi eontaining Aspergillus

29

Acute granulocytic leukemia

Antimetabolites Antibiotics Steroids

Initially none

Aspergillus infection of hronehi and alveoli Invasion arteriPs and veins with formation of fungal thrombi

66

Chronic lymphocytic leukemia

Radioactive phosphorus Anti metabolites Antibiotics Steroids

Multiple infiltrations followed by cavitation (fungus ball)

Cavities with mye!'lial masses and blood dots

30

Hodgkin's disease

Radiation Antibiotics Steroids

Middle lobe pneumonitis

Hemorrhagic pneumonia due to Aspergillus

78

Acute leukemia

Anti metabolites Antibiotics Steroids

Bilateral infiltrates

Areas of infarction invaded by Aspergillus

Age

28

29

ASPERGILLOSIS OF THE LUNG Table 2-Surgically Treated Aspergillosis

Age

Primary Disease

59

Tuberculosis Marie-Strumpell disease

46*

Roentgenographic Findings

Operation

Complications

Results

Intracavitary fungus ball

Pneumonectomy

Empyema

Good for 10 years following modified Schede thoracoplasty

Histoplasmosis

Intracavitary fungus ball

Lobectomy

None

Good five months later

56*

Histoplasmosis

Intracavitary fungus ball

Lobectomy

None

Good 11 72 years

56*

Tuberculosis

Multiple cavities with fungus ball

Lobectomy

None

Good 12 years

38

Bronchogenic cyst

Cyst with fungus ball

Lobectomy

None

Good 9 years

32*

Tuberculosis

Intracavitary fungus ball

Segmental resection

None

Good 18 years

56

Histoplasmosis

Bronchiectasis and cavitation

Lobectomy

Residual pleural space but cleared with drainage

Died 18 months later with Leukemia

52

Histoplasmosis

Cavity

Lobectomy

None

Good 18 months later

43

Marie-Strumpell disease

Intracavitary fungus ball

Lobectomy

None

Good five months later

*Clinically suggestive but unproven by cultures. MATERIALS AND METHODS

This study represents 21 patients with aspergillosis of the lung admitted to the Veterans Administration Hospital between 1951 and 1969. Of the 21, nine were treated surgically, one medically, and 11 received no specific treatment. Surgical treatment consisted of lobectomy in seven, pneumonectomy in one, and segmental resection in one. Specific

medical treatment consisting of endocavitary infusions of amphotericin B and sodium iodide through a percutaneously placed endobronchial catheter was carried out in one instance.2 The~e patients were men ranging in age from 30 to 75 years, with the majority of their ages falling within the fifth and sixth decades. The predominance of men reflects the overwhelming majority of men patients seen at this facility.

Table 3-Aspergillosis Auocialed with Nonmalignant Disease

Age

Primary Disease

65*

Thrombophlebitis Pulmonary embolism

61

Roentgenographic Findings

Diagnosis

Results

Cavity with fungus ball

Sputum culture Chest roentgenogram

Cleared without treatment and remains well five years

Bronchiectasis Pulmonary embolism

Initially none

Autopsy

Aspergillus found in lung parenchyma at site of infarction

41

Transverse myelitis Sacral ulcer Pulmonary embolism

Initially none

Autopsy

Lobular pneumonia Aspergillus in bronchioles with ulceration

75**

Tuberculosis

Cavity with fungus ball

Sputum cultures Chest roentgenograms

Doing well one year after endocavitary infusion

62

Tuberculosis

Multiple cavities

Autopsy

Aspergillus in cavity

63

Rheumatic mitral stenosis

Bronchopneumonia

Autopsy

Aspergillus invasion of lung parenchyma

56

Undiagnosed cavity

Cavity with fungus

Sputum cultures Chest roentgenogram

None

*See Reference 2 for details. • *See Figures 4, 5, 6, for radiographs.

CHEST, VOL. 59, NO. 1, JANUARY 1971

30

ASLAM, EASTRIDGE AND HUGHES

The criteria used in diagnosis were: ( 1) the presence of Aspergillus either in tissue sections or in cultures taken from surgical or autopsy specimens, or ( 2) the repeated isolation of Aspergillus in the sputum of patients demonstrating intracavitary "fungus balls" by chest roentgenogram. Those with disseminated Aspergillus infections or allergic aspergillosis were excluded. Two patient~ from this study have been previously reported.t.2 All patients had either chronic debilitating diseases or conditions which predisposed to infection by Aspergillus. There were five under treatment for lymphoma and leukemia who were receiving large quantities of antibiotics, steroids, and antimetabolites (Table 1 ). In 16, aspergillosis was found in association with non-malignant disease (Table 2, 3). RESULTS

In the present series of nine surgically resected patients, all have remained free of disease for periods from five months to 18 years. There was no operative death. Complications occurred in two, one with empyema following pneumonectomy, which was corrected by a modified Schede thoracoplasty, and the other a residual pleural space which responded to prolonged thoracotomy tube drainage. The only medically treated patient is doing well one year following endocavitary infusions of amphotericin B and sodium iodide. 2 Eleven patients received no specific treatment for aspergillosis. In this group only three were diagnosed before death. Five of the 11 were patients with malignant disease and four of these deteriorated rapidly. In one there was a protracted course of pneumonia characterized by the presence of migrating pneumonic infiltrates, which later cavi-

FIGURE 2 ( Case 1). Three months later, there is a typical "fungus ball" in the left upper lobe, a cavity with a nodular opacity in the right upper lobe, and a nodular density in the right lower lung field.

tated (Fig 1, 2, 3) . One with thrombophlebitis developed clinical and radiologic findings suggestive of pulmonary infarction. This infarcted area later emptied, leaving a cavity in which a typical fungus ball developed (Fig

--:-·f. t~:.;< <,::.

FIGURE 1 (Case 1 ) . Chest roentgenogram showing left upper lohe inliltnite.

FIGURE 3 (Case 1). Two weeks later, three "fungus balls" are evident.

CHEST, VOL. 59, NO. 1, JANUARY 1971

ASPERGILLOSIS OF THE LUNG

31 aspergillosis by sputum culture findings alone 7 due to the difficulty of demonstrating mycelium in sputum. 5-7 Thus, in those patients not having surgical resection or postmortem examination, reliance must be placed upon the roentgen picture of intracavitary fungus ball as well, to support the diagnosis of aspergillosis. Thus, in this group of nonsurgical patients, the diagnosis was made in only four due either to the lack of suspicion of the presence of aspergillosis or the absence of characteristic roentgenographic findings. There was one patient in the group with a malignancy which demonstrated the evolution of multiple pulmonary aspergillosis. These roentgenographic changes started as multiple pulmonary infiltrates which progressed to multiple pulmonary aspergillomas in rapid succession before death (Fig 1, 2, 3 ). The association of aspergillosis with pulmonary infarction was encountered in three patients. In two, sections through the infarcted area revealed fungus in necrotic bronchioles, alveolar spaces, and permeating thrombi within the vessels. Similar cases were reported by Hinson et al3 and by Campbell

FIGURE 4 (Case 6). Laminogram of the chest showing a "fungus ball" in the right upper lobe.

4, 5). Over a period of five years, this area healed without specific treatment ( Fig 6). DISCUSSION

Several authorities have discussed the spectrum of Aspergillus infections and have suggested classifications.={-6 We have tended to use the classification as suggested by Hinson et al ;{ in which the infections may be divided into saprophytic, allergic, and pyemic (disseminated) varieties. Our cases have belonged generally to the saprophytic group, with an occasional patient showing active lung invasion as a terminal event. The clinical findings were varied and depended upon the associated disease process. Hemoptysis was a common symptom in all except those with lymphoma or leukemia. In one, hemorrhage was so severe that pneumonectomy was required for control. In general, there were no characteristic clinical features present which enabled the physician to make a positive diagnosis without the aid of sputum cultures and roentgenographic examination. Many have stressed the danger of diagnosing CHEST, VOL. 59, NO. 1, JANUARY 1971

FIGURE 5 (Case 6). Laminogram with patient in a right lateral decubitus position demonstrating mobility of the "fungus ball."

32

ASLAM, EASTRIDGE AND HUGHES

ease as seen in this series, but on occasion segmental resection may suffice. The morbidity and mortality should be low, with recurrence of the disease uncommon. Similar conclusions have been reached independently by others. 1 1 Obviously, surgical intervention is not indicated in those patients with associated systemic malignancy or when aspergillosis develops as a terminal event. Amphotericin B is the only widely employed therapeutic agent used in the medical treatment of aspergillosis, even though toxic reactions are common and the results are unpredictable. 1 2 Another therapeutic agent, natamycin, to be used as an irrigation following surgical evacuation, has been advocated in selected patients by Henderson et al. 13 Their experience with three patients treated in this manner was satisfactory. Our one experience with medical treatment in the form of endobronchial infusion or amphotericin B and sodium iodide over a three-month period, has resulted in satisfactory response. 2 This mode of treatment may be useful in properly selected patients in the future. REFERENCES

FIGURE 6 (Case 6). Chest roentgenogram five years later showing an opacity without evidence of fungus ball.

and Clayton. 7 The other patient is unique in that an aspergilloma in an area of pulmonary excavation healed without treatment over a periol of five years. This is contrary to the usual course described for aspergillomas secondary to causes other than pulmonary infarction. 8 · 9 This example raises the possibility that some patients with apparent primary aspergillosis may, in fact, represent occult cases of pulmonary infarction in which aspergillosis is superimposed. The occurrence of aspergillomas within residual cavities following tuberculosis or histoplasmosis, or within a cyst of the lung, has been pointed out repeatedly.a-;;.s.ll Less well known is the association of ankylosing spondylitis ( Marie-Strumpell disease) with aspergillomas. This association was seen in two patients in the surgically resected group. Krohn et al 1 0 commented upon this feature and reported this occurrence in three of five patients with ankylosing spondylitis. Whether this suggests that the debility associated with chronic disease or whether an uneven ventilation-perfusion ratio resulting from a restriction of the thoracic cage may predispose one to Aspergillus infection is not known. Surgical resection appears to be the treatment of choice for aspergillomas of the lung. Lobectomy is usually necessary to eradicate completely the dis-

2 3 4 5 6 7

8 9 10 11 12 13

Hughes FA Jr, Courley RD, Burwell JR: Primary pulmonary aspergillosis: Report of an unusual case successfully treated by lobectomy. Ann Surg 144:138, 1956 Aslam PA, Larkin J, Eastridge CE, et al: Endocavitary infusion through percutaneous endobronchial catheter. Chest 57:94, 1970 Hinson KFW, Moon AJ, Plummer NS: Bronchopulmonary aspergillosis. Thorax 7:317, 1952 Finegold SM, Drake W, Murray JF: Aspergillosis. A review and report of twelve cases. Amer J Med 27:463, 1959 Orie NGM, Devries GA, Kikstra A: Growth of Aspergillus in the human being: Aspergilloma and aspergillosis. Amer Rev Resp Dis 82:649, 1960 Carbone PP, Savesin SM, Sidransky H, et al: Secondary aspergillosis. Ann Int Med 60:556, 1964 Campbell MJ, Clayton YM: Bronchopulmonary aspergillosis. A correlation of clinical and laboratory findings in 272 patients investigated for bronchopulmonary aspergillosis. Amer Rev Resp Dis 89:186, 1964 Golberg B: Radiological appearances in pulmonary aspergillosis. Clin Radiol13: 106, 1962 Levin EJ: Pulmonary intracavitary fungus ball. Radiology 66:9, 1956 Krohn J: Aspergilloma of the lung in ankylosing spondylitis. Scand J Resp Dis Supplement 63:131, 1968 Kilman JW, Ahn C, Andrews NC, et al: Surgery for pulmonary aspergillosis. J Thorac and Cardiovas Surg 57:642, 1969 Rifkind D, Marchioro TL, Schenck SA, et al: Systemic fungal infections complicating renal transplantation and immunosuppression therapy. Amer J Med 43:28, 1969 Henderson AH, Pearson JEG: Treatment of bronchopulmonary aspergillosis with observations on the use of Natamycin. Thorax 23:519, 1968

Reprint requests: Dr. Eastridge, VA Hospital, 1030 Jefferson Avenue, Memphis 38104

CHEST, VOL. 59, NO. 1, JANUARY 1971