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A. Tamura et al. / Interactive CardioVascular and Thoracic Surgery
[8] Tochigi N, Okubo Y, Ando T, Wakayama M, Shinozaki M, Gocho K et al. Histopathological implications of Aspergillus infection in lung. Mediat Inflamm 2013;2013:809798. [9] Denning DW, Riniotis K, Dobrashian R, Sambatakou H. Chronic cavitary and fibrosing pulmonary and pleural aspergillosis: case series, proposed nomenclature change, and review. Clin Infect Dis 2003;37:S265–80. [10] Gefter WB, Weingrad TR, Epstein DM, Ochs RH, Miller WT. “Semi-invasive” pulmonary aspergillosis: a new look at the spectrum of Aspergillus infections of the lung. Radiology 1981;140:313–21. [11] Binder RE, Faling LJ, Pugatch RD, Mahasaen C, Snider GL. Chronic necrotizing pulmonary aspergillosis: a discrete clinical entity. Medicine (Baltimore) 1982;61:109–24. [12] Tashiro T, Izumikawa K, Tashiro M, Morinaga Y, Nakamura S, Imamura Y et al. A case series of chronic necrotizing pulmonary aspergillosis and a new proposal. Jpn J Infect Dis 2013;66:312–6. [13] Smith NL, Denning DW. Underlying conditions in chronic pulmonary aspergillosis including simple aspergilloma. Eur Respir J 2011;37:865–72. [14] Matsuura S, Suganuma H, Inoue Y, Itou Y, Iwashim D, Matsui K et al. Clinical case study of lung cancer accompanied by pulmonary aspergillosis. Nihon Kokyuki Gakkai Zasshi 2009;47:455–61. [15] Coviello V, Boggess M. Cumulative incidence estimation in the presence of competing risks. Stata J 2004;4:103–12. [16] Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Anal 1999;94:496–509. [17] Denning DW, Pleuvryb A, Cole DC. Global burden of chronic pulmonary aspergillosis as a sequel to pulmonary tuberculosis. Bull World Health Organ 2011;89:864–72. [18] Crabtree TD, Denlinger CE. Complications of surgery for lung cancer. In: Pass HI, Carbone DP, Johnson DH, Minna JD, Scagliotti GV, Turrisi AT III (eds). Principles & Practice of Lung Cancer. Philadelphia: Lippincott Williams & Wilkins, 2010, 531–46. [19] Tanaka H, Matsumura A, Ohta M, Ikeda N, Kitahara N, Iuchi K. Late sequelae of lobectomy for primary lung cancer: fibrobullous changes in ipsilateral residual lobes. Eur J Cardiothorac Surg 2007;32:859–62. [20] Padovani B, Ducreux D, Macario S, Maillard M, Iannessi A, Brunner P et al. Postoperative chest: normal imaging features. J Radiol 2009;90:991–1000. [21] Kumar N, Mishra M, Singhal A, Kaur J, Tripathi V. Aspergilloma coexisting with idiopathic pulmonary fibrosis: a rare occurrence. J Postgrad Med 2013;59:145–8. [22] Arakawa H, Honma K. Honeycomb lung: history and current concepts. AJR Am J Roentgenol 2011;196:773–82. [23] Godet C, Philippe B, Laurent F, Cadranel J. Chronic pulmonary aspergillosis: an update on diagnosis and treatment. Respiration 2014;88:162–74. [24] Nam HS, Jeon K, Um SW, Suh GY, Chung MP, Kim H et al. Clinical characteristics and treatment outcomes of chronic necrotizing pulmonary aspergillosis: a review of 43 cases. Int J Infect Dis 2010;14:e479–82. [25] Ohba H, Miwa S, Shirai M, Kanai M, Eifuku T, Suda T et al. Clinical characteristics and prognosis of chronic pulmonary aspergillosis. Respir Med 2012;106:724–9.
eComment. Diagnostic and therapeutical considerations in post-lobectomy chronic pulmonary aspergillosis Author: Tomislav Mestrovic Clinical Microbiology and Parasitology Unit, Polyclinic "Dr. Zora Profozic", Zagreb, Croatia doi: 10.1093/icvts/ivv274 © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. I read with great interest the article by Tamura et al. regarding chronic pulmonary aspergillosis as an emerging complication after lobectomy for lung cancer [1]. The authors justly emphasized that, due to its high mortality, ample efforts should be
made to properly diagnose this frequent postoperative sequel and ensure adequate follow-up. Several points regarding diagnosis and treatment presented in this article should be addressed in order to reinforce this recommendation. In short, chronic pulmonary aspergillosis (CPA) represents a spectrum of disease entities typically presenting with prolonged cough, dyspnoea and weight loss, with occasional bronchial or pulmonary haemorrhage. CPA affects patients with underlying pulmonary conditions (such as COPD or mycobacteriosis) or common immunosuppressive conditions such as diabetes, but the condition is also associated with lung cancer and thoracic surgery. In this retrospective study, the authors state they fulfilled all the required criteria for the diagnosis of CPA, as proposed by Denning et al. [2]. Unfortunately, scarce details were provided on how all of them were met, possibly because they were designed for prospective clinical studies. For example, the data on which inflammatory markers were followed (C-reactive protein, erythrocyte sedimentation rate or plasma viscosity), and how other pulmonary pathogens were excluded are lacking. Considering the latter, it must be highlighted that not only tuberculosis should be taken into account, but also atypical mycobacteria and (in endemic countries) histoplasmosis and coccidioidomycosis. Furthermore, positivity for Aspergillus infection in the study was detected using either immunoprecipitation techniques (serum precipitins) or sputum cultures. As the authors do not state which method was employed for detecting Aspergillus precipitins, it should be noted that counter-immunoelectrophoresis (CIE) largely replaced immunodiffusion (agar gel double diffusion) due to the comparable, but less time-consuming performance. Nevertheless, CIE has certain limitations, such as poor sensitivity, subjective qualitative results and labour intensity [3]. In the seven patients diagnosed via sputum cultures, Aspergillus fumigatus was found in 71.4% of the cases, followed by A. niger in 28.6% of the cases. Knowing species profile in all 17 patients with CPA in this study would be valuable, as A. flavus and A. terreus (alongside two aforementioned species) can also be responsible for the condition. Of the 17 patients 15 patients in the study received itraconazole as a monotherapy, which was replaced by voriconazole early during treatment in 4 patients due to inadequate efficacy. Some of that ineffectiveness may be attributed to azole resistance which is increasingly being recognized as a problem. In regions with environmental resistance rates of more than 10%, a voriconazole-echinocandin combination or liposomal amphotericin B are favoured as initial therapy [4]. Moreover, in culture-positive cases, in vitro susceptibility testing should be performed where available. One patient in this study underwent pneumonectomy of the residual lung after lobectomy, in addition to the treatment with itraconazole. Such approach (i.e. completion pneumonectomy) has previously been reported as having a high burden of morbidity and mortality in the presence of infection, thus thoracoscopic approach in debilitated and often immunocompromised patients has been cited as a choice with better outcomes and shorter hospital stay [5]. Conflict of interest: none declared. References [1] Tamura A, Suzuki J, Fukami T, Matsui H, Akagawa S, Ohta K et al. Chronic pulmonary aspergillosis as a sequel to lobectomy for lung cancer. Interact CardioVasc Thorac Surg 2015;21:650–6. [2] Denning DW, Riniotis K, Dobrashian R, Sambatakou H. Chronic cavitary and fibrosing pulmonary and pleural aspergillosis: case series, proposed nomenclature change, and review. Clin Infect Dis 2003;37:S265–80. [3] Baxter CG, Denning DW, Jones AM, Todd A, Moore CB, Richardson MD. Performance of two Aspergillus IgG EIA assays compared with the precipitin test in chronic and allergic aspergillosis. Clin Microbiol Infect 2013;19:E197– 204. [4] Verweij PE, Ananda-Rajah M, Andes D, Arendrup MC, Bruggemann RJ, Chowdhary A et al. International expert opinion on the management of infection caused by azole-resistant Aspergillus fumigatus. Drug Resist Updat 2015; pii:S1368–7646(15)00035–7. [5] Farid S, Mohamed S, Devbhandari M, Kneale M, Richardson M, Soon SY et al. Results of surgery for chronic pulmonary Aspergillosis, optimal antifungal therapy and proposed high risk factors for recurrence–a National Centre’s experience. J Cardiothorac Surg 2013;8:180.
A. Tamura et al. / Interactive CardioVascular and Thoracic Surgery
[8] Tochigi N, Okubo Y, Ando T, Wakayama M, Shinozaki M, Gocho K et al. Histopathological implications of Aspergillus infection in lung. Mediat Inflamm 2013;2013:809798. [9] Denning DW, Riniotis K, Dobrashian R, Sambatakou H. Chronic cavitary and fibrosing pulmonary and pleural aspergillosis: case series, proposed nomenclature change, and review. Clin Infect Dis 2003;37:S265–80. [10] Gefter WB, Weingrad TR, Epstein DM, Ochs RH, Miller WT. “Semi-invasive” pulmonary aspergillosis: a new look at the spectrum of Aspergillus infections of the lung. Radiology 1981;140:313–21. [11] Binder RE, Faling LJ, Pugatch RD, Mahasaen C, Snider GL. Chronic necrotizing pulmonary aspergillosis: a discrete clinical entity. Medicine (Baltimore) 1982;61:109–24. [12] Tashiro T, Izumikawa K, Tashiro M, Morinaga Y, Nakamura S, Imamura Y et al. A case series of chronic necrotizing pulmonary aspergillosis and a new proposal. Jpn J Infect Dis 2013;66:312–6. [13] Smith NL, Denning DW. Underlying conditions in chronic pulmonary aspergillosis including simple aspergilloma. Eur Respir J 2011;37:865–72. [14] Matsuura S, Suganuma H, Inoue Y, Itou Y, Iwashim D, Matsui K et al. Clinical case study of lung cancer accompanied by pulmonary aspergillosis. Nihon Kokyuki Gakkai Zasshi 2009;47:455–61. [15] Coviello V, Boggess M. Cumulative incidence estimation in the presence of competing risks. Stata J 2004;4:103–12. [16] Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Anal 1999;94:496–509. [17] Denning DW, Pleuvryb A, Cole DC. Global burden of chronic pulmonary aspergillosis as a sequel to pulmonary tuberculosis. Bull World Health Organ 2011;89:864–72. [18] Crabtree TD, Denlinger CE. Complications of surgery for lung cancer. In: Pass HI, Carbone DP, Johnson DH, Minna JD, Scagliotti GV, Turrisi AT III (eds). Principles & Practice of Lung Cancer. Philadelphia: Lippincott Williams & Wilkins, 2010, 531–46. [19] Tanaka H, Matsumura A, Ohta M, Ikeda N, Kitahara N, Iuchi K. Late sequelae of lobectomy for primary lung cancer: fibrobullous changes in ipsilateral residual lobes. Eur J Cardiothorac Surg 2007;32:859–62. [20] Padovani B, Ducreux D, Macario S, Maillard M, Iannessi A, Brunner P et al. Postoperative chest: normal imaging features. J Radiol 2009;90:991–1000. [21] Kumar N, Mishra M, Singhal A, Kaur J, Tripathi V. Aspergilloma coexisting with idiopathic pulmonary fibrosis: a rare occurrence. J Postgrad Med 2013;59:145–8. [22] Arakawa H, Honma K. Honeycomb lung: history and current concepts. AJR Am J Roentgenol 2011;196:773–82. [23] Godet C, Philippe B, Laurent F, Cadranel J. Chronic pulmonary aspergillosis: an update on diagnosis and treatment. Respiration 2014;88:162–74. [24] Nam HS, Jeon K, Um SW, Suh GY, Chung MP, Kim H et al. Clinical characteristics and treatment outcomes of chronic necrotizing pulmonary aspergillosis: a review of 43 cases. Int J Infect Dis 2010;14:e479–82. [25] Ohba H, Miwa S, Shirai M, Kanai M, Eifuku T, Suda T et al. Clinical characteristics and prognosis of chronic pulmonary aspergillosis. Respir Med 2012;106:724–9.
eComment. Diagnostic and therapeutical considerations in post-lobectomy chronic pulmonary aspergillosis Author: Tomislav Mestrovic Clinical Microbiology and Parasitology Unit, Polyclinic "Dr. Zora Profozic", Zagreb, Croatia doi: 10.1093/icvts/ivv274 © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. I read with great interest the article by Tamura et al. regarding chronic pulmonary aspergillosis as an emerging complication after lobectomy for lung cancer [1]. The authors justly emphasized that, due to its high mortality, ample efforts should be
made to properly diagnose this frequent postoperative sequel and ensure adequate follow-up. Several points regarding diagnosis and treatment presented in this article should be addressed in order to reinforce this recommendation. In short, chronic pulmonary aspergillosis (CPA) represents a spectrum of disease entities typically presenting with prolonged cough, dyspnoea and weight loss, with occasional bronchial or pulmonary haemorrhage. CPA affects patients with underlying pulmonary conditions (such as COPD or mycobacteriosis) or common immunosuppressive conditions such as diabetes, but the condition is also associated with lung cancer and thoracic surgery. In this retrospective study, the authors state they fulfilled all the required criteria for the diagnosis of CPA, as proposed by Denning et al. [2]. Unfortunately, scarce details were provided on how all of them were met, possibly because they were designed for prospective clinical studies. For example, the data on which inflammatory markers were followed (C-reactive protein, erythrocyte sedimentation rate or plasma viscosity), and how other pulmonary pathogens were excluded are lacking. Considering the latter, it must be highlighted that not only tuberculosis should be taken into account, but also atypical mycobacteria and (in endemic countries) histoplasmosis and coccidioidomycosis. Furthermore, positivity for Aspergillus infection in the study was detected using either immunoprecipitation techniques (serum precipitins) or sputum cultures. As the authors do not state which method was employed for detecting Aspergillus precipitins, it should be noted that counter-immunoelectrophoresis (CIE) largely replaced immunodiffusion (agar gel double diffusion) due to the comparable, but less time-consuming performance. Nevertheless, CIE has certain limitations, such as poor sensitivity, subjective qualitative results and labour intensity [3]. In the seven patients diagnosed via sputum cultures, Aspergillus fumigatus was found in 71.4% of the cases, followed by A. niger in 28.6% of the cases. Knowing species profile in all 17 patients with CPA in this study would be valuable, as A. flavus and A. terreus (alongside two aforementioned species) can also be responsible for the condition. Of the 17 patients 15 patients in the study received itraconazole as a monotherapy, which was replaced by voriconazole early during treatment in 4 patients due to inadequate efficacy. Some of that ineffectiveness may be attributed to azole resistance which is increasingly being recognized as a problem. In regions with environmental resistance rates of more than 10%, a voriconazole-echinocandin combination or liposomal amphotericin B are favoured as initial therapy [4]. Moreover, in culture-positive cases, in vitro susceptibility testing should be performed where available. One patient in this study underwent pneumonectomy of the residual lung after lobectomy, in addition to the treatment with itraconazole. Such approach (i.e. completion pneumonectomy) has previously been reported as having a high burden of morbidity and mortality in the presence of infection, thus thoracoscopic approach in debilitated and often immunocompromised patients has been cited as a choice with better outcomes and shorter hospital stay [5]. Conflict of interest: none declared. References [1] Tamura A, Suzuki J, Fukami T, Matsui H, Akagawa S, Ohta K et al. Chronic pulmonary aspergillosis as a sequel to lobectomy for lung cancer. Interact CardioVasc Thorac Surg 2015;21:650–6. [2] Denning DW, Riniotis K, Dobrashian R, Sambatakou H. Chronic cavitary and fibrosing pulmonary and pleural aspergillosis: case series, proposed nomenclature change, and review. Clin Infect Dis 2003;37:S265–80. [3] Baxter CG, Denning DW, Jones AM, Todd A, Moore CB, Richardson MD. Performance of two Aspergillus IgG EIA assays compared with the precipitin test in chronic and allergic aspergillosis. Clin Microbiol Infect 2013;19:E197– 204. [4] Verweij PE, Ananda-Rajah M, Andes D, Arendrup MC, Bruggemann RJ, Chowdhary A et al. International expert opinion on the management of infection caused by azole-resistant Aspergillus fumigatus. Drug Resist Updat 2015; pii:S1368–7646(15)00035–7. [5] Farid S, Mohamed S, Devbhandari M, Kneale M, Richardson M, Soon SY et al. Results of surgery for chronic pulmonary Aspergillosis, optimal antifungal therapy and proposed high risk factors for recurrence–a National Centre’s experience. J Cardiothorac Surg 2013;8:180.
