Invited commentary

Abstract

Depending upon a variety of host and inoculum factors, pulmonary infection from Aspergillus species forms a spectrum from innocuous colonization of preexisting cavities through rapidly progressive, life-threatening, acute invasive aspergillosis, usually occurring in the setting of immunocompromise. Intermediate between these two extremes is the entity of chronic necrotizing pulmonary aspergillosis (CNPA). CNPA is a slowly progressive, necrotizing pneumonic process which can result in both scar and cavity formation, with cavities containing both fungus and necrotic lung. This type of infection, termed semiinvasive aspergillosis by some authors to distinguish it from the acute form of the disease, usually arises in the setting of at least mild host immunologic compromise, as with diabetes mellitus or steroid use, or of some structural abnormality to the lung parenchyma, as with chronic obstructive lung disease. As one observes the radiographic progression of the disease, the pulmonary infiltrate, usually in the upper lobes, consolidates, frequently cavitates, and is often associated with pleural reaction. In contrast to typical aspergillomas, CNPA frequently results in cavity formation, rather than developing within a preexisting cavity. Clinical differentiation of CNPA from acute invasive aspergillosis is usually made by observing a more indolent time course in the former and a more profoundly immunocompromised host in the latter. Nevertheless, it is clear that these processes represent a continuum which renders categorization of some patients quite difficult.As with almost all pulmonary infections, medical management should, in theory, be the preferred treatment strategy, with surgery reserved for specific complications. While many patients with Aspergillus infection can be managed with antifungal therapy, the limitations of these drugs, both with regard to efficacy and patient tolerance, frequently result in consideration of surgical resection as a prime component of the treatment strategy. In fact, the limitations of current antifungal therapy in the immunocompromised patient are widely acknowledged, and there is a consensus that early resection of Aspergillus infection offers a survival advantage over prolonged medical therapy. The role of resection in CNPA, however, is not as well established.This manuscript by Endo and colleagues points out the strengths and weaknesses of lung resection in the management of patients with CNPA who have failed medical management. As in many series, the most frequent and appropriate indication for surgery was hemoptysis. The strength of this surgical strategy is evident in the fact that only one of ten patients had recurrence of Aspergillus infection after resection, thus establishing the critical role of the thoracic surgeon in the management of these patients, some of whom presented with life-threatening pulmonary hemorrhage. On the other hand, the weaknesses of the surgical strategy are all too evident upon a close reading of the hospital course of these patients. While there were no operative deaths, the mean duration of these procedures was over 6.5 hours, 90% of patients required blood transfusion, bronchopleural fistula or empyema requiring additional surgical procedures was noted in 30%, and the mean hospital stay for even uncomplicated patients was over one month. While the etiology of these problems could certainly be debated, one could not argue that the surgical successes were achieved at the cost of considerable morbidity.As is often the case, this manuscript raises several important questions. Assuming that the authors have succeeded in the difficult task of identifying patients with CNPA as opposed to other forms of Aspergillus infection, one would like to know the denominator from which this group was selected. What percentage of patients under medical therapy for CNPA came to resection? Do newer lipid-complex formulations of amphotericin offer added efficacy in these patients? Answers to these questions would offer a clearer picture of the relative roles of medical and surgical therapy in dealing with this disease. In addition, the results of this study raise the question of optimal timing for surgical intervention. One could charitably ascribe much of the postoperative morbidity described in this manuscript to the fact that surgery was undertaken at an advanced stage of disease, perhaps at a point where there was extensive hilar inflammation or fibrosis and pleural involvement. Would earlier surgical intervention have permitted more technically straightforward procedures with fewer complications?While the medical community awaits much needed improvements in antifungal therapy, the thoracic surgeon remains an important contributor to the successful management of many patients with CNPA, but the role is difficult. A precipitous decision to resect prior to documentation of medical failure subjects the patient to unnecessary surgical risks, just as does a delayed decision resulting in an operation of increased complexity. Close following of these patients is critical, with the goal of early surgical resection in those patients whose infection is not promptly controlled by medical therapy. Hopefully this study will stimulate others to review their experiences with CNPA, as many important questions remain unanswered. Depending upon a variety of host and inoculum factors, pulmonary infection from Aspergillus species forms a spectrum from innocuous colonization of preexisting cavities through rapidly progressive, life-threatening, acute invasive aspergillosis, usually occurring in the setting of immunocompromise. Intermediate between these two extremes is the entity of chronic necrotizing pulmonary aspergillosis (CNPA). CNPA is a slowly progressive, necrotizing pneumonic process which can result in both scar and cavity formation, with cavities containing both fungus and necrotic lung. This type of infection, termed semiinvasive aspergillosis by some authors to distinguish it from the acute form of the disease, usually arises in the setting of at least mild host immunologic compromise, as with diabetes mellitus or steroid use, or of some structural abnormality to the lung parenchyma, as with chronic obstructive lung disease. As one observes the radiographic progression of the disease, the pulmonary infiltrate, usually in the upper lobes, consolidates, frequently cavitates, and is often associated with pleural reaction. In contrast to typical aspergillomas, CNPA frequently results in cavity formation, rather than developing within a preexisting cavity. Clinical differentiation of CNPA from acute invasive aspergillosis is usually made by observing a more indolent time course in the former and a more profoundly immunocompromised host in the latter. Nevertheless, it is clear that these processes represent a continuum which renders categorization of some patients quite difficult. As with almost all pulmonary infections, medical management should, in theory, be the preferred treatment strategy, with surgery reserved for specific complications. While many patients with Aspergillus infection can be managed with antifungal therapy, the limitations of these drugs, both with regard to efficacy and patient tolerance, frequently result in consideration of surgical resection as a prime component of the treatment strategy. In fact, the limitations of current antifungal therapy in the immunocompromised patient are widely acknowledged, and there is a consensus that early resection of Aspergillus infection offers a survival advantage over prolonged medical therapy. The role of resection in CNPA, however, is not as well established. This manuscript by Endo and colleagues points out the strengths and weaknesses of lung resection in the management of patients with CNPA who have failed medical management. As in many series, the most frequent and appropriate indication for surgery was hemoptysis. The strength of this surgical strategy is evident in the fact that only one of ten patients had recurrence of Aspergillus infection after resection, thus establishing the critical role of the thoracic surgeon in the management of these patients, some of whom presented with life-threatening pulmonary hemorrhage. On the other hand, the weaknesses of the surgical strategy are all too evident upon a close reading of the hospital course of these patients. While there were no operative deaths, the mean duration of these procedures was over 6.5 hours, 90% of patients required blood transfusion, bronchopleural fistula or empyema requiring additional surgical procedures was noted in 30%, and the mean hospital stay for even uncomplicated patients was over one month. While the etiology of these problems could certainly be debated, one could not argue that the surgical successes were achieved at the cost of considerable morbidity. As is often the case, this manuscript raises several important questions. Assuming that the authors have succeeded in the difficult task of identifying patients with CNPA as opposed to other forms of Aspergillus infection, one would like to know the denominator from which this group was selected. What percentage of patients under medical therapy for CNPA came to resection? Do newer lipid-complex formulations of amphotericin offer added efficacy in these patients? Answers to these questions would offer a clearer picture of the relative roles of medical and surgical therapy in dealing with this disease. In addition, the results of this study raise the question of optimal timing for surgical intervention. One could charitably ascribe much of the postoperative morbidity described in this manuscript to the fact that surgery was undertaken at an advanced stage of disease, perhaps at a point where there was extensive hilar inflammation or fibrosis and pleural involvement. Would earlier surgical intervention have permitted more technically straightforward procedures with fewer complications? While the medical community awaits much needed improvements in antifungal therapy, the thoracic surgeon remains an important contributor to the successful management of many patients with CNPA, but the role is difficult. A precipitous decision to resect prior to documentation of medical failure subjects the patient to unnecessary surgical risks, just as does a delayed decision resulting in an operation of increased complexity. Close following of these patients is critical, with the goal of early surgical resection in those patients whose infection is not promptly controlled by medical therapy. Hopefully this study will stimulate others to review their experiences with CNPA, as many important questions remain unanswered.