Clinical analysis of two patients with frequent acute exacerbations of chronic obstructive pulmonary disease, both caused by Aspergillus?_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

GU Yu ¹ , WANG Yu ² , SHEN Kunlu ³ ,  SU Xin ^1,2,3

1. Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing Medical University School, Nanjing, Jiangsu 210002, P. R. China;
2. Department of Respiratory and Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P. R. China;
3. Department of Respiratory and Critical Care Medicine, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, Jiangsu 210002, P. R. China;

Corresponding author：

SU Xin, Email: suxinjs@163.com

Keywords：

Chronic obstructive pulmonary disease; Acute exacerbations; Fungi; Aspergillus

DOI：

10.7507/1671-6205.201907034

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Objective To investigate the role of Aspergillus in the severe refractory exacerbations of chronic obstructive pulmonary disease (COPD).Methods The clinical data of two COPD patients suffering from refractory acute exacerbations were analyzed and the relevant literature were reviewed.Results Two patients were male, aging 72 and 64 years respectively. Both of them had a history of frequent acute exacerbations with severe COPD recently. Meanwhile, they received intravenous use of antibiotics repeatedly, one of them took oral corticosteroids to control wheezing, but failed. Their serum Aspergillus-specific IgG antibody was weakly positive. Besides traditional treatment, they received additional antifungal therapy, and the symptoms alleviated. There was no acute exacerbation in the half a year follow-up period after appropriate therapy.Conclusions Aspergillus colonization, sensitization, infection should be considered in patients with severe COPD. When Aspergillus-associated evidence are acquired, antifungal therapy will be unexpected helpful.

Citation： GU Yu, WANG Yu, SHEN Kunlu, SU Xin. Clinical analysis of two patients with frequent acute exacerbations of chronic obstructive pulmonary disease, both caused by Aspergillus?. Chinese Journal of Respiratory and Critical Care Medicine, 2021, 20(5): 305-309. doi: 10.7507/1671-6205.201907034 Copy

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2.	Wang C, Xu J, Yang L, et al. Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national cross-sectional study. Lancet, 2018, 391(10131): 1706-1717.
3.	慢性阻塞性肺疾病急性加重(AECOPD)诊治专家组. 慢性阻塞性肺疾病急性加重(AECOPD)诊治中国专家共识(2017 年更新版). 国际呼吸杂志, 2017, 37(14): 17.
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5.	Kosmidis C, Denning DW. The clinical spectrum of pulmonary aspergillosis. Thorax, 2015, 70(3): 270-277.
6.	Bulpa P, Dive A, Sibille Y. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. Eur Respir J, 2007, 30(4): 782-800.
7.	Leav BA, Fanburg B, Hadley S. Invasive pulmonary aspergillosis associated with high-dose inhaled fluticasone. N Engl J Med, 2000, 343(8): 586.
8.	Guinea J, Torres-Narbona M, Gijon P, et al. Pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: incidence, risk factors, and outcome. Clin Microbiol Infect, 2010, 16(7): 870-877.
9.	Everaerts S, Lagrou K, Dubbeldam A, et al. Sensitization to Aspergillus fumigatus as a risk factor for bronchiectasis in COPD. Int J Chron Obstruct Pulmon Dis, 2017, 12: 2629-2638.
10.	Jin JM, Liu XF, Sun YC. The prevalence of increased serum IgE and Aspergillus sensitization in patients with COPD and their association with symptoms and lung function. Respir Res, 2014, 15: 130.
11.	Bafadhel M, Mckenna S, Agbetile J, et al. Aspergillus fumigatus during stable state and exacerbations of COPD. Eur Respir J, 2014, 43(1): 64-71.
12.	American Thoracic Society. Proceedings of the ATS workshop on refractory asthma: current understanding, recommendations, and unanswered questions. Am J Respir Crit Care Med, 2000, 162(6): 2341-2351.
13.	Zureik M, Neukirch C, Leynaert B, et al. Sensitisation to airborne moulds and severity of asthma: cross sectional study from European community respiratory health survey. BMJ, 2002, 325(7361): 411-414.
14.	Leung JM, Tiew PY, Mac Aogain M, et al. The role of acute and chronic respiratory colonization and infections in the pathogenesis of COPD. Respirology, 2017, 22(4): 634-650.
15.	Peng L, Xu ZP, Huo ZY, et al. New insights into the clinical characteristics and prognostic factors of pulmonary fungal infections from a retrospective study in Southwestern China. Infect Drug Resist, 2018, 11: 307-315.
16.	Mohedano Del Pozo RB, Rubio Alonso M, Cuetara Garcia MS. Diagnosis of invasive fungal disease in hospitalized patients with chronic obstructive pulmonary disease. Rev Iberoam Micol, 2018, 35(3): 117-122.
17.	Gago S, Denning DW, Bowyer P. Pathophysiological aspects of Aspergillus colonization in disease. Med Mycol, 2019, 57(Supplement_2): S219-S227.
18.	Kontoyiannis DP, Marr KA, Park BJ, et al. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001-2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis, 2010, 50(8): 1091-1100.
19.	Soubani AO, Chandrasekar PH. The clinical spectrum of pulmonary aspergillosis. Chest, 2002, 121(6): 1988-1999.
20.	Pashley CH, Fairs A, Morley JP, et al. Routine processing procedures for isolating filamentous fungi from respiratory sputum samples may underestimate fungal prevalence. Med Mycol, 2012, 50(4): 433-438.
21.	Tong X, Cheng A, Xu H, et al. Aspergillus fumigatus during COPD exacerbation: a pair-matched retrospective study. BMC Pulm Med, 2018, 18(1): 55.
22.	Salzer HJF, Prattes J, Hoenigl M. Editorial: Diagnostic approaches for aspergillus infections. Front Microbiol, 2019, 10: 446.
23.	Singh M, Paul N, Singh S, et al. Asthma and fungus: role in allergic bronchopulmonary aspergillosis (ABPA) and other conditions. Indian J Pediatr, 2018, 85(10): 899-904.
24.	Barberan J, Garcia-Perez FJ, Villena V, et al. Development of Aspergillosis in a cohort of non-neutropenic, non-transplant patients colonised by Aspergillus spp. BMC Infect Dis, 2017, 17(1): 34.
25.	Denning DW, Cadranel J, Beigelman-Aubry C, et al. Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management. Eur Respir J, 2016, 47(1): 45-68.
26.	Guo Y, Bai Y, Yang C, et al. Evaluation of Aspergillus IgG, IgM antibody for diagnosing in chronic pulmonary aspergillosis: a prospective study from a single center in China. Medicine (Baltimore), 2019, 98(16): e15021.
27.	中华医学会呼吸病学分会哮喘学组. 变应性支气管肺曲霉病诊治专家共识. 中华医学杂志, 2017, 97(34): 2650-2656.
28.	Pasqualotto AC, Powell G, Niven R, et al. The effects of antifungal therapy on severe asthma with fungal sensitization and allergic bronchopulmonary aspergillosis. Respirology, 2009, 14(8): 1121-1127.
29.	Agarwal R, Dua D, Choudhary H, et al. Role of Aspergillus fumigatus-specific IgG in diagnosis and monitoring treatment response in allergic bronchopulmonary aspergillosis. Mycoses, 2017, 60(1): 33-39.
30.	Sehgal IS, Dhooria S, Choudhary H, et al. Monitoring treatment response in chronic pulmonary aspergillosis: role of clinical, spirometric and immunological markers. Clin Microbiol Infect, 2019, 25(9): 1157 e1-1157 e7.

1. Lopez-Campos JL, Tan W, Soriano JB. Global burden of COPD. Respirology, 2016, 21(1): 14-23.
2. Wang C, Xu J, Yang L, et al. Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national cross-sectional study. Lancet, 2018, 391(10131): 1706-1717.
3. 慢性阻塞性肺疾病急性加重(AECOPD)诊治专家组. 慢性阻塞性肺疾病急性加重(AECOPD)诊治中国专家共识(2017 年更新版). 国际呼吸杂志, 2017, 37(14): 17.
4. Denning DW, O'driscoll BR, Powell G, et al. Randomized controlled trial of oral antifungal treatment for severe asthma with fungal sensitization: The Fungal Asthma Sensitization Trial (FAST) study. Am J Respir Crit Care Med, 2009, 179(1): 11-18.
5. Kosmidis C, Denning DW. The clinical spectrum of pulmonary aspergillosis. Thorax, 2015, 70(3): 270-277.
6. Bulpa P, Dive A, Sibille Y. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. Eur Respir J, 2007, 30(4): 782-800.
7. Leav BA, Fanburg B, Hadley S. Invasive pulmonary aspergillosis associated with high-dose inhaled fluticasone. N Engl J Med, 2000, 343(8): 586.
8. Guinea J, Torres-Narbona M, Gijon P, et al. Pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: incidence, risk factors, and outcome. Clin Microbiol Infect, 2010, 16(7): 870-877.
9. Everaerts S, Lagrou K, Dubbeldam A, et al. Sensitization to Aspergillus fumigatus as a risk factor for bronchiectasis in COPD. Int J Chron Obstruct Pulmon Dis, 2017, 12: 2629-2638.
10. Jin JM, Liu XF, Sun YC. The prevalence of increased serum IgE and Aspergillus sensitization in patients with COPD and their association with symptoms and lung function. Respir Res, 2014, 15: 130.
11. Bafadhel M, Mckenna S, Agbetile J, et al. Aspergillus fumigatus during stable state and exacerbations of COPD. Eur Respir J, 2014, 43(1): 64-71.
12. American Thoracic Society. Proceedings of the ATS workshop on refractory asthma: current understanding, recommendations, and unanswered questions. Am J Respir Crit Care Med, 2000, 162(6): 2341-2351.
13. Zureik M, Neukirch C, Leynaert B, et al. Sensitisation to airborne moulds and severity of asthma: cross sectional study from European community respiratory health survey. BMJ, 2002, 325(7361): 411-414.
14. Leung JM, Tiew PY, Mac Aogain M, et al. The role of acute and chronic respiratory colonization and infections in the pathogenesis of COPD. Respirology, 2017, 22(4): 634-650.
15. Peng L, Xu ZP, Huo ZY, et al. New insights into the clinical characteristics and prognostic factors of pulmonary fungal infections from a retrospective study in Southwestern China. Infect Drug Resist, 2018, 11: 307-315.
16. Mohedano Del Pozo RB, Rubio Alonso M, Cuetara Garcia MS. Diagnosis of invasive fungal disease in hospitalized patients with chronic obstructive pulmonary disease. Rev Iberoam Micol, 2018, 35(3): 117-122.
17. Gago S, Denning DW, Bowyer P. Pathophysiological aspects of Aspergillus colonization in disease. Med Mycol, 2019, 57(Supplement_2): S219-S227.
18. Kontoyiannis DP, Marr KA, Park BJ, et al. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001-2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis, 2010, 50(8): 1091-1100.
19. Soubani AO, Chandrasekar PH. The clinical spectrum of pulmonary aspergillosis. Chest, 2002, 121(6): 1988-1999.
20. Pashley CH, Fairs A, Morley JP, et al. Routine processing procedures for isolating filamentous fungi from respiratory sputum samples may underestimate fungal prevalence. Med Mycol, 2012, 50(4): 433-438.
21. Tong X, Cheng A, Xu H, et al. Aspergillus fumigatus during COPD exacerbation: a pair-matched retrospective study. BMC Pulm Med, 2018, 18(1): 55.
22. Salzer HJF, Prattes J, Hoenigl M. Editorial: Diagnostic approaches for aspergillus infections. Front Microbiol, 2019, 10: 446.
23. Singh M, Paul N, Singh S, et al. Asthma and fungus: role in allergic bronchopulmonary aspergillosis (ABPA) and other conditions. Indian J Pediatr, 2018, 85(10): 899-904.
24. Barberan J, Garcia-Perez FJ, Villena V, et al. Development of Aspergillosis in a cohort of non-neutropenic, non-transplant patients colonised by Aspergillus spp. BMC Infect Dis, 2017, 17(1): 34.
25. Denning DW, Cadranel J, Beigelman-Aubry C, et al. Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management. Eur Respir J, 2016, 47(1): 45-68.
26. Guo Y, Bai Y, Yang C, et al. Evaluation of Aspergillus IgG, IgM antibody for diagnosing in chronic pulmonary aspergillosis: a prospective study from a single center in China. Medicine (Baltimore), 2019, 98(16): e15021.
27. 中华医学会呼吸病学分会哮喘学组. 变应性支气管肺曲霉病诊治专家共识. 中华医学杂志, 2017, 97(34): 2650-2656.
28. Pasqualotto AC, Powell G, Niven R, et al. The effects of antifungal therapy on severe asthma with fungal sensitization and allergic bronchopulmonary aspergillosis. Respirology, 2009, 14(8): 1121-1127.
29. Agarwal R, Dua D, Choudhary H, et al. Role of Aspergillus fumigatus-specific IgG in diagnosis and monitoring treatment response in allergic bronchopulmonary aspergillosis. Mycoses, 2017, 60(1): 33-39.
30. Sehgal IS, Dhooria S, Choudhary H, et al. Monitoring treatment response in chronic pulmonary aspergillosis: role of clinical, spirometric and immunological markers. Clin Microbiol Infect, 2019, 25(9): 1157 e1-1157 e7.

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