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Of Mycetomas and Men

2002; Elsevier BV; Volume: 121; Issue: 1 Linguagem: Inglês

10.1378/chest.121.1.5

1931-3543

Scott D. Lick, Alex Duarte,

Phytoplasmas and Hemiptera pathogens

Aspergillus is a ubiquitous fungus found in soil, water, and decaying matter. It is readily airborne and causes a variety of respiratory conditions, including allergic bronchopulmonary aspergillosis, parenchymal tissue invasion, and mycetoma. Mycetomas have long been recognized to occur in patients with preexisting pulmonary disease that results in focal destruction of lung tissue, leading to the formation of an intraparenchymal cavity. An early English postmortem report of a pulmonary mycetoma described “a soft velvety mass… firmly attached to the wall of the cavity. Under the microscope it exhibited a distinct mycelium… . ”1Doyle L Historical note: an early report of growth of an Aspergillus species on the wall of a lung cavity.Thorax. 1989; 44: 66-67Crossref Scopus (2) Google Scholar It became widely recognized that individuals with healed tuberculous cavities were at risk for development of fungus balls. As the incidence of tuberculosis declined, mycetomas were identified with greater frequency in individuals with advanced sarcoidosis, pneumonoconiosis, and bullous emphysema.2Dar MA Ahmad M Weinstein AJ et al.Thoracic aspergillosis (part I): overview and aspergilloma [review].Cleve Clin Q. 1984; 51: 615-630Crossref PubMed Scopus (13) Google Scholar With the rise of transplant medicine, Aspergillus has become a scourge, with invasive parenchymal infection afflicting 5 to 8% of solid-organ transplant recipients, and having 50 to 100% mortality. In some centers, it has been a leading cause of posttransplant death. Most Aspergillus infections after any solid-organ transplant occur in the lung, and the transplanted lung is particularly vulnerable to Aspergillus. Since the pathogen is airborne, the lung is the only transplanted organ in direct contact to Aspergillus. Moreover, the transplanted lung has a diminished cough reflex, an abnormal mucociliary clearance, and a bronchial anastomosis that is the site of local inflammation promoting Aspergillus colonization. All of these reasons predispose the post-lung transplant patient to Aspergillus infection. However, little is known about the consequences of pretransplant mycetomas (usually caused by Aspergillus), which are generally considered a strong relative contraindication to transplantation. Given the high mortality associated with invasive Aspergillus and lung transplantation, it would stand to reason that an individual with a dense, focal inoculum of Aspergillus organisms, ie, a fungus ball, might be at increased risk for posttransplant fungal disease. This month a report by the transplant group at Duke University retrospectively reviewed the clinical course of 9 of 303 lung transplant recipients found to have a mycetoma in an explanted lung. Six of nine patients were identified preoperatively as having a mycetoma on chest radiograph or CT scan. One of these, their first patient, was not treated preemptively with antifungals and died 20 days postoperatively. Another patient had Aspergillus growing from pleural fluid 3 weeks prior to transplant, and died in the operating room from sepsis. Apart from these two deaths (both, admit the authors, involving bad judgment), there was only one death in the remaining four patients with preoperatively known mycetomas, at 24 months after operation, due to noninfectious causes. Hence, patients with known contained mycetoma disease, treated preoperatively, had quite acceptable outcome. It is of interest that three of the nine mycetomas found in explanted lungs were not seen on CT scans at 2 months, 6 months, and 9 months preoperatively. Presumably, these mycetomas progressed in the intervening time or might have been difficult to detect. Given the authors' conclusions (that mycetomas should be treated as a form of septic lung disease mandating bilateral lung transplant, and that pretransplant treatment with antifungal agents is helpful), perhaps repeat CT scan(s) may be indicated while awaiting transplant, at least in the sarcoidosis population at highest risk for mycetoma development. In an era of increasing waiting times, initial CT screening may not be enough. Notably, there were only three fungal infections in the explanted lungs of the remaining 294 patients (including 69 patients with cystic fibrosis): one invasive pneumonitis and two airway colonizations. This low colonization incidence is in contrast to studies in cystic fibrosis patients, who commonly have pretransplant Aspergillus colonization (52% in one series), but are not at increased risk for posttransplant invasive Aspergillus infections, even without antifungal treatment.3Flume PA Egan TM Paradowski LJ et al.Infectious complications of lung transplantation: impact of cystic fibrosis.Am J Respir Crit Care Med. 1994; 149: 1601-1607Crossref PubMed Scopus (169) Google Scholar4Kanj SS Tapson V Davis RD et al.Infectious complications following isolated lung transplantation.Chest. 1997; 112: 924-930Abstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar5Nunley DR Ohori P Grgurich WF et al.Pulmonary aspergillosis in cystic fibrosis lung transplant recipients.Chest. 1998; 114: 1321-1329Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar However, six of nine patients with mycetomas in the Duke series suffered from sarcoidosis, a known risk factor for mycetoma. This predisposition may be due to the altered expression of natural killer inhibitory receptors on T cells of patients with sarcoidosis,6Mizuki M Eklund A Grunewald J Altered expression of natural killer inhibitory receptors (KIRs) on T cells in bronchoalveolar lavage fluid and peripheral blood of sarcoidosis patients.Sarcoidosis Vasc Diffuse Lung Dis. 2000; 17: 54-59PubMed Google Scholar considered a possible cause of the disease as well as predisposition to some infections. General conditioning may also be part of the explanation for differing outcomes: cystic fibrosis transplant recipients tend to be young and with strong cough muscles; patients with mycetomas more often are chronically debilitated. The authors point out that posttransplant survival in patients with sarcoidosis is less than for other disease states, but the survival difference is small.7Judson MA Lung transplantation for pulmonary sarcoidosis [review].Eur Respir J. 1998; 11: 738-744PubMed Google Scholar8Barbers RG Role of transplantation (lung, liver and heart) in sarcoidosis.Clin Chest Med. 1997; 18: 865-874Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar Relatively few patients have undergone lung transplantation for sarcoidosis (1 to 2% of all lung transplants), and hence it is difficult to accurately categorize risks within such a small group. Nonetheless, this study of a handful of patients is helpful to point out some caveats: beware of aspergillomas in sarcoidosis patients, transplant only contained disease, and treat with long-term antifungals.