Clinical implications of fungal isolation from sputum in adult patients with cystic fibrosis

Background/aim: Cystic fibrosis is an autosomal recessive disease with a defect in mucociliary activity that is characterized by recurrent pulmonary infections. Bacterial agents frequently implicated in airway colonization are Haemophilus influenzae, Staphylococcus spp., and Pseudomonas spp. Fungal isolation from sputum is common in adults. However, growth of fungal agent only in sputum culture in patients with cystic fibrosis is insufficient for the diagnosis of fungal diseases. There is limited data about the clinical significance of fungal isolation in sputum cultures. The aim of the study was to investigate the clinical outcomes andsignificance of fungal isolation from sputum samples in adult CF. Materials and methods: This retrospective study included patients who have been admitted between October 2017 and January 2019 in an adult cystic fibrosis unit. Patients were grouped according to fungal pathogenicity as; fungal disease group, colonization group, and nonisolated group. The data of the last one year, including demographics, clinical data, laboratory, treatment modalities, results of cultured bacteria and fungus from sputum samples, respiratory function parameters, frequency of exacerbation, and hospitalizationwere compared between groups. Results: A total of 330 sputum samples from 88 adult patients with CF were collected. Patients were divided into 3 groups, the fungal disease group (n = 10, 11.4%), colonization group (n = 49, 55.7%), and nonisolated group (n = 29, 32.9%). Presence of pulmonary exacerbation, number of admissions to emergency department, and the number of positive cultures for bacteria from sputum were higher in the fungal disease group (p = 0.03, p = 0.01 and p < 0.001). The fungal disease group had higher rate of antibiotics by parenteral routethan other groups (p = 0.001) whereas lung functions were similar. Use of nutritional supplementation and parenteral antibiotherapy were the factors associated with elevated risk of fungal isolation. Conclusion: Frequent use of parenteral antibiotics and use of nutritional supplementation were found to be independent risk factors for fungal isolation from sputum in adult CF.Key words: Adult cystic fibrosis, sputum, fungi

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Boyle MP, Bell SC, Konstan MW, McColley SA, Rowe SM et al. A CFTR corrector (lumacaftor) and a CFTR potentiator (ivacaftor) for treatment of patients with cystic fibrosis who have a phe508del CFTR mutation: a phase 2 randomised controlled trial. Lancet Respiratory Medicine 2014; 2: 527-538. doi: 10.1016/ S2213-2600(14)70132-8
2. Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell S et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. New England Journal of Medicine 2011; 365: 1663- 1672. doi: 10.1056/NEJMoa1105185
3. Middleton PG, Chen SC, Meyer W.Fungal infections and treatment in cystic fibrosis. Current Opinion in Pulmonary Medicine 2013; 19 (6): 670-675. doi: 10.1097/MCP.0b013e328365ab74
4. Muthig M, Hebestreit A, Ziegler U, Seidler M, Müller FM. Persistence of Candida species in the respiratory tract of cystic fibrosis patients. Medical Mycology 2010; 48: 56-63. doi: 10.3109/13693780802716532
5. Noni M, Katelari A, Kaditis A, Theochari I, Lympari I et al. Candida albicans chronic colonisation in cystic fibrosis may be associated with inhaled antibiotics. Mycoses 2015; 58: 416-421. doi: 10.1111/myc.12338
6. Saunders R, Modha D, Claydon A, Gaillard E. Chronic Aspergillus fumigatus colonisation of the cystic fibrosis airway is common and may be associated with a more rapid decline in lung function. Journal of Cystic Fibrosis 2011; 10 (1): S37. doi: 10.1016/S1569-1993(11)60162-8
7. Milla CE, Wielinski CL, Regelmann WE. Clinical significance of the recovery ofAspergillus species from the respiratory secretions of cystic fibrosis patients.Pediatric Pulmonology 1996; 21 (1): 6-10. doi: 10.1002/(SICI)1099-0496(199601)21:1<6:AIDPPUL1>3.0.CO;2-R
8. Bakare N, Rickerts V, Bargon J, Just-Nübling G. Prevalence of Aspergillus fumigatus and other fungal species in the sputum of adult patients with cystic fibrosis. Mycoses 2003; 46 (1-2): 19- 23. doi: 10.1046/j.1439-0507.2003.00830.x
9. Valenza G, Tappe D, Turnwald D, Frosch M, König C et al. Prevalence and antimicrobial susceptibility of microorganisms isolated from sputa of patients with cystic fibrosis. Journal of Cystic Fibrosis 2008; 7 (2): 123-127. doi: 10.1016/j. jcf.2007.06.006.
10. Bargon J, Dauletbaev N, Köhler B,Wolf M, Posselt HG et al. Prophylactic antibiotic therapy is associated with an increased prevalence of Aspergillus spp. colonization in adult cystic fibrosis patients. Respiratory Medicine 1999; 93 (11):835-838.doi: 10.1016/S0954-6111(99)90270-6
11. Maturu VN, Agarwal R. Prevalence of Aspergillus sensitization and allergic bronchopulmonary aspergillosis in cystic fibrosis: systematic review and metaanalysis. Clinical & Experimental Allergy 2015; 45 (12): 1765-1778. doi: 10.1111/cea.12595
12. Nelson LA, Callerame ML, Schwartz RH. Aspergillosis and atopy in cystic fibrosis. American Review of Respiratory Disease 1979; 120 (4): 863-873. doi: 10.1203/00006450-197804001-01221
13. Amin R, Dupuis A, Aaron SD, Ratjen F. The effect of chronic infection with Aspergillus fumigatus on lung function and hospitalization in patients with cystic fibrosis. Chest 2010; 137 (1):171-176. doi: 10.1378/chest.09-1103
14. Chotirmall SH, O’Donoghue E, Bennett K, Gunaratnam C, O’Neill SJ et al. Sputum Candida albicans presages FEV decline and hospital-treated exacerbations in cystic fibrosis. Chest 2010; 138 (5): 1186-1195. doi: 10.1378/chest.09-2996
15. Gileles-Hillel A, Shoseyov D, Polacheck I, Korem M, Kerem E et al. Association of chronic Candida albicans respiratory infection with a more severe lung disease in patients with cystic fibrosis. Pediatric Pulmonology 2015; 50 (11): 1082-1089. doi: 10.1002/ppul.23302
16. Nagano Y, Millar BC, Johnson E,Goldsmith CE, Elborn JS et al. Fungal infections in patients with cystic fibrosis. Reviews in Medical Microbiology 2007; 18 (1): 11-16. doi: 10.1097/ MRM.0b013e3282e1c70a.
17. Larone DH, Larone DH. Medically Important Fungi: A Guide to Identification. 5th ed. Washington, DC, USA: ASM Press; 2011.
18. Paugam A, Baixench MT, Demazes-Dufeu N, Burgel PR, Sauter E et al. Characteristics and consequences of airway colonization by filamentous fungi in 201 adult patients with cystic fibrosis in France. Sabouraudia 2010; 48 (1): 32-36. doi: 10.3109/13693786.2010.503665
19. De Vrankrijker AMM, Van Der Ent CK, Van Berkhout FT, Stellato RK, Willems RJL et al.A. fumigatus colonisation in cystic fibrosis: implications for lung function? Clinical Microbiology and Infection 2011; 17 (9): 1381-1386. doi: 10.1111/j.1469-0691.2010.03429.x
20. Muller J, Remus N, Harms KH. Mycoserological study of the treatment of pediatric cystic fibrosis patients with Saccharomyces boulardi (Saccharomyces cerevisiae Hansen CBS 5926). Mycoses 1995; 38: 119-1923. doi: 10.1111/j.1439- 0507.1995.tb00033.x
21. Baxter CG, Moore CB, Jones AM, Webb AK, Denning DW. IgE-mediated immune responses and airway detection of Aspergillus and Candida in adult cystic fibrosis. Chest 2013;143 (5):1351-1357.doi: 10.1378/chest.12-1363
22. Hong G, Psoter KJ, Jennings MT, Merlo CA, Boyle MP et al. Risk factors for persistent Aspergillus respiratory isolation in cystic fibrosis. Journal of Cystic Fibrosis 2018; 17 (5): 624-630. doi: 10.1016/j.jcf.2018.01.008
23. Milla CE, Warwick WJ, Moran A. Trends in pulmonary function in patients with cystic fibrosis correlate with the degree of glucose intolerance at baseline. American Journal of Respiratory and Critical Care Medicine 2000; 162 (3): 891-895.doi: 10.1164/ajrccm.162.3.9904075
24. Ziegler B, Oliveira CL, Rovedder PM, Schuh SJ, Silva FAA et al. Glucose intolerance in patients with cystic fibrosis: sex-based differences in clinical score, pulmonary function, radiograph score, and 6-minute walk test. Respiratory Care 2011; 56 (3): 290-297. doi: 10.4187/respcare.00726
25. Iwanicki C, Logomarsino JV. Impaired glucose tolerance, body mass index and respiratory function in patients with cystic fibrosis: a systematic review. Clinical Respiratory Journal 2019; 13 (6): 341-354. doi: 10.1111/crj.13019
26. Elphick HE, Southern KW.Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. Cochrane Database of Systematic Reviews 2016; 11. doi: 10.1002/14651858.CD002204.pub4
27. Noni M, Katelari A, Dimopoulos G, Spoulou V, Dimopoulos G et al. Aspergillus fumigatus chronic colonization and lung function decline in cystic fibrosis may have a two-way relationship. European Journal of Clinical Microbiology & Infectious Diseases 2015; 34 (14): 2235-2241. doi: 10.1016/ S1569-1993(15)30157-0
28. Kerr J. Inhibition of fungal growth by Pseudomonas aeruginosa and Pseudomonas cepacia isolated from patients with cystic fibrosis. Journal of Infection 1994; 28 (3): 305-310. doi: 10.1016/S0163-4453(94)91943-7
29. Mowat E, Rajendran R, Williams C, McCulloch E, Jones B et al. Pseudomonas aeruginosa and their small diffusible extracellular molecules inhibit Aspergillus fumigatus biofilm formation. FEMS Microbiology Letters 2010; 313 (2): 96-102. doi: 10.1111/j.1574-6968.2010.02130.x
30. Tunney MM, Klem ER, Fodor AA, Gilpin DF, Moriarty TF et al. Use of culture and molecular analysis to determine the effect of antibiotic treatment on microbial community diversity and abundance during exacerbation in patients with cystic fibrosis. Thorax 2011; 66 (7): 579-584. doi: 10.1136/ thx.2010.137281
31. Williams C, Ranjendran R, Ramage G. Pathogenesis of fungal infections in cystic fibrosis. Current Fungal Infection Reports 2016; 10 (4): 163-169. doi: 10.1007/s12281-016-0268-z
32. Rajan S, Saiman L. Pulmonary infections in patients with cystic fibrosis. Seminars in Respiratory Infections 2002; 17 (1): 47-56. doi: 10.1053/srin.2002.31690
33. Baxter CG, Rautemaa R, Jones AM, Webb AK, Bull M et al. Intravenous antibiotics reduce the presence of Aspergillus in adult cystic fibrosis sputum. Thorax 2013; 68 (7): 652-657. doi: 10.1136/thoraxjnl-2012-202412
34. Nasri E, Fakhim H, Vaezi A, Khalilzadeh S, Ahangarkani F et al. Airway colonisation by Candida and Aspergillus species in Iranian cystic fibrosis patients. Mycoses 2019; 62 (5): 434- 440. doi: 10.1111/myc.12898
35. Burns J, Emerson JR, Stapp DL, Yim DL, Krzewinski J et al. Microbiology of sputum from patients at cystic fibrosis centers in the United States. Clinical Infectious Diseases 1998; 27: 158- 163. doi: 10.1086/514631
36. Jubin V, Ranque S, Stremler Le Bel N, Sarles J, Dubus JC. Risk factors for Aspergillus colonization and allergic bronchopulmonary aspergillosis in children with cystic fibrosis. Pediatric Pulmonology 2010; 45 (8): 764-771. doi: 10.1002/ppul.21240
37. Pencharz PB, Durie PR. Nutritional management of cystic fibrosis. The Annual Review of Nutrition 1993; 13 (1): 111-136. doi: 10.1146/annurev.nu.13.070193.000551
38. Sinaasappel M, Stern M, Littlewood J, Wolfe S, G Steinkamp et al. Nutrition in patients with cystic fibrosis: a European consensus. Journal of Cystic Fibrosis 2001; 1(2): 51-75. doi: 10.1016/S1569-1993(02)00032-2
39. Gozdzik J, Cofta S, Piorunek T, Batura-Gabryel H, Kosicki J. Relationship between nutritional status and pulmonary function in adult cystic fibrosis patients. Journal of Physiology and Pharmacology 2008; 59 (6): 253-260.
40. Prodanovic H, Cracco C, Massard J, Barrault C, Thabut D et al. Invasive pulmonary aspergillosis in patients with decompensated cirrhosis: case series. BMC Gastroenterology 2007; 7(1): 2. doi: 10.1186/1471-230X-7-2
41. Cabaret O, Bonnal C, Canoui-Poitrine F, Emirian A, Bizouard G et al. Concomitant presence of Aspergillus fumigatus and Stenotrophomonas maltophilia in the respiratory tract: a new risk for patients with liver disease? Journal of Medical Microbiology 2016; 65 (5): 414-419.doi: 10.1099/jmm.0.000233

APA	Irmak I, ÇELEBİOĞLU E, Karadeniz Güven D, Huseynova K, Inkaya A, Er B, Sig A, Gülmez D, Arikan-Akdagli S, Ademhan Tural D, Dogru D, Özçelik U, Kiper N, Kalyoncu A (2021). Clinical implications of fungal isolation from sputum in adult patients with cystic fibrosis. , 1191 - 1200. 10.3906/sag-2006-94
Chicago	Irmak Ilim,ÇELEBİOĞLU EBRU,Karadeniz Güven Damla,Huseynova Khurshud,Inkaya Ahmet Cagkan,Er Berrin,Sig Ali Korhan,Gülmez Dolunay,Arikan-Akdagli Sevtap,Ademhan Tural Dilber,Dogru Deniz,Özçelik Uğur,Kiper Nural,Kalyoncu Ali Fuat Clinical implications of fungal isolation from sputum in adult patients with cystic fibrosis. (2021): 1191 - 1200. 10.3906/sag-2006-94
MLA	Irmak Ilim,ÇELEBİOĞLU EBRU,Karadeniz Güven Damla,Huseynova Khurshud,Inkaya Ahmet Cagkan,Er Berrin,Sig Ali Korhan,Gülmez Dolunay,Arikan-Akdagli Sevtap,Ademhan Tural Dilber,Dogru Deniz,Özçelik Uğur,Kiper Nural,Kalyoncu Ali Fuat Clinical implications of fungal isolation from sputum in adult patients with cystic fibrosis. , 2021, ss.1191 - 1200. 10.3906/sag-2006-94
AMA	Irmak I,ÇELEBİOĞLU E,Karadeniz Güven D,Huseynova K,Inkaya A,Er B,Sig A,Gülmez D,Arikan-Akdagli S,Ademhan Tural D,Dogru D,Özçelik U,Kiper N,Kalyoncu A Clinical implications of fungal isolation from sputum in adult patients with cystic fibrosis. . 2021; 1191 - 1200. 10.3906/sag-2006-94
Vancouver	Irmak I,ÇELEBİOĞLU E,Karadeniz Güven D,Huseynova K,Inkaya A,Er B,Sig A,Gülmez D,Arikan-Akdagli S,Ademhan Tural D,Dogru D,Özçelik U,Kiper N,Kalyoncu A Clinical implications of fungal isolation from sputum in adult patients with cystic fibrosis. . 2021; 1191 - 1200. 10.3906/sag-2006-94
IEEE	Irmak I,ÇELEBİOĞLU E,Karadeniz Güven D,Huseynova K,Inkaya A,Er B,Sig A,Gülmez D,Arikan-Akdagli S,Ademhan Tural D,Dogru D,Özçelik U,Kiper N,Kalyoncu A "Clinical implications of fungal isolation from sputum in adult patients with cystic fibrosis." , ss.1191 - 1200, 2021. 10.3906/sag-2006-94
ISNAD	Irmak, Ilim vd. "Clinical implications of fungal isolation from sputum in adult patients with cystic fibrosis". (2021), 1191-1200. https://doi.org/10.3906/sag-2006-94

APA	Irmak I, ÇELEBİOĞLU E, Karadeniz Güven D, Huseynova K, Inkaya A, Er B, Sig A, Gülmez D, Arikan-Akdagli S, Ademhan Tural D, Dogru D, Özçelik U, Kiper N, Kalyoncu A (2021). Clinical implications of fungal isolation from sputum in adult patients with cystic fibrosis. Turkish Journal of Medical Sciences, 51(3), 1191 - 1200. 10.3906/sag-2006-94
Chicago	Irmak Ilim,ÇELEBİOĞLU EBRU,Karadeniz Güven Damla,Huseynova Khurshud,Inkaya Ahmet Cagkan,Er Berrin,Sig Ali Korhan,Gülmez Dolunay,Arikan-Akdagli Sevtap,Ademhan Tural Dilber,Dogru Deniz,Özçelik Uğur,Kiper Nural,Kalyoncu Ali Fuat Clinical implications of fungal isolation from sputum in adult patients with cystic fibrosis. Turkish Journal of Medical Sciences 51, no.3 (2021): 1191 - 1200. 10.3906/sag-2006-94
MLA	Irmak Ilim,ÇELEBİOĞLU EBRU,Karadeniz Güven Damla,Huseynova Khurshud,Inkaya Ahmet Cagkan,Er Berrin,Sig Ali Korhan,Gülmez Dolunay,Arikan-Akdagli Sevtap,Ademhan Tural Dilber,Dogru Deniz,Özçelik Uğur,Kiper Nural,Kalyoncu Ali Fuat Clinical implications of fungal isolation from sputum in adult patients with cystic fibrosis. Turkish Journal of Medical Sciences, vol.51, no.3, 2021, ss.1191 - 1200. 10.3906/sag-2006-94
AMA	Irmak I,ÇELEBİOĞLU E,Karadeniz Güven D,Huseynova K,Inkaya A,Er B,Sig A,Gülmez D,Arikan-Akdagli S,Ademhan Tural D,Dogru D,Özçelik U,Kiper N,Kalyoncu A Clinical implications of fungal isolation from sputum in adult patients with cystic fibrosis. Turkish Journal of Medical Sciences. 2021; 51(3): 1191 - 1200. 10.3906/sag-2006-94
Vancouver	Irmak I,ÇELEBİOĞLU E,Karadeniz Güven D,Huseynova K,Inkaya A,Er B,Sig A,Gülmez D,Arikan-Akdagli S,Ademhan Tural D,Dogru D,Özçelik U,Kiper N,Kalyoncu A Clinical implications of fungal isolation from sputum in adult patients with cystic fibrosis. Turkish Journal of Medical Sciences. 2021; 51(3): 1191 - 1200. 10.3906/sag-2006-94
IEEE	Irmak I,ÇELEBİOĞLU E,Karadeniz Güven D,Huseynova K,Inkaya A,Er B,Sig A,Gülmez D,Arikan-Akdagli S,Ademhan Tural D,Dogru D,Özçelik U,Kiper N,Kalyoncu A "Clinical implications of fungal isolation from sputum in adult patients with cystic fibrosis." Turkish Journal of Medical Sciences, 51, ss.1191 - 1200, 2021. 10.3906/sag-2006-94
ISNAD	Irmak, Ilim vd. "Clinical implications of fungal isolation from sputum in adult patients with cystic fibrosis". Turkish Journal of Medical Sciences 51/3 (2021), 1191-1200. https://doi.org/10.3906/sag-2006-94