Nagehan EMİRALİOĞLU, DENİZ DOĞRU ERSÖZ, Özlem AKGÜN DOĞAN, Dolunay GÜLMEZ, SEVTAP ARIKAN AKDAĞLI, Sanem ERYILMAZ POLAT, Gökçen Dilşa TUĞCU, Mina HIZAL, Ebru YALÇIN, Uğur ÖZÇELİK, Burçin ŞENER, Nural KİPER

Diverse clinical characteristics of Aspergillus growth in patients with cystic fibrosis

Background and objectives. Patients with cystic fibrosis (CF) have a varying spectrum of clinically significant Aspergillus disease in addition to allergic bronchopulmonary aspergillosis (ABPA). Here we aimed to review the different clinical phenotypes related with Aspergillus growth on the airway culture of patients with CF, we also aimed to investigate the effect of Aspergillus growth on lung function tests. Method. The medical records of 100 patients with CF who had Aspergillus growth on airway culture within the period of April 2001 and June 2016 were retrospectively analyzed. Age, gender, symptoms, physical examination findings, pulmonary function tests, the diagnosis of ABPA, and airway culture results were recorded for every visit. Patients with Aspergillus growth on airway cultures were classified into different groups as ABPA, Aspergillus sensitization, Aspergillus colonization and Aspergillus bronchitis. Results. Medical records of 83 patients and 147 sputum cultures were attained from 100 patients. The mean age of the patients was 17.6±7.6 years and the mean age of the first Aspergillus growth in sputum culture was 12.5±6.7 years. At first isolation, Aspergillus fumigatus SC was the most common Aspergillus SC in sputum (76.3%) and 14.5% of these patients required hospitalization. Aspergillus sensitization was diagnosed in 3.6% (n= 3) of the patients. Aspergillus colonization was diagnosed in 18.1% (n= 15) of all patients and led to a decline in FEV1%, FVC% and FEF25-75% which was not statistically significant, furthermore. ABPA was detected in 9.6% (n= 8) of all patients and led to a statistically significant decline in FEV1% (p= 0.02); nonsignificant decline in FVC% and FEF25-75%. Aspergillus bronchitis was detected in 43.4% (n= 36) of all patients and led to nonsignificant decline in FEV1%, FVC% and FEF25-75%. Conclusion. ABPA is recognized as the most common Aspergillus associated disorder in CF patients and is related to deteriorated pulmonary function tests; however Aspergillus colonization and bronchitis may also be associated with worsening lung function.

PDF

___

1. Chotirmall SH, Martin-Gomez MT. Aspergillus species in bronchiectasis: challenges in the cystic fibrosis and non-cystic fibrosis airways. Mycopathologia 2018; 183(Suppl 1): 45-59.

2. Chaudhary N, Datta K, Askin FB, Staab JF, Marr KA. Cystic fibrosis transmembrane conductance regulator regulates epithelial cell response to Aspergillus and resultant pulmonary inflammation. Am J Respir Crit Care Med 2012; 185: 301-310.

3. Fillaux J, Bremont F, Murris M, et al. Assessment of Aspergillus sensitization or persistent carriage as a factor in lung function impairment in cystic fibrosis patients. Scand J Infect Dis 2012; 44: 842-847.

4. 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: 1351-1357.

5. Shoseyov D, Brownlee KG, Conway SP, Kerem E. Aspergillus bronchitis in cystic fibrosis. Chest 2006; 130: 222-226.

6. Schwarz C, Hartl D, Eickmeier O, et al. Progress in definition, prevention and treatment of fungal infections in cystic fibrosis. Mycopathologia 2018; 183: 21-32.

7. Singh A, Ralhan A, Schwarz C, Hartl D, Hector A. Fungal pathogens in CF airways: leave or treat? Mycopathologia 2018; 183: 119-137.

8. Cowley AC, Thornton DJ, Denning DW, Horsley A. Aspergillosis and the role of mucins in cystic fibrosis. Pediatr Pulmonol 2017; 52: 548-555.

9. Larone DH. Medically Important Fungi: A Guide to Identification.(5th ed).Washington: DC. ASM Press, 2011.

10. Baxter CG, Dunn G, Jones AM, et al. Novel immunologic classification of aspergillosis in adult cystic fibrosis. J Allergy Clin Immunol 2013; 132: 560-566.e10.

11. Jones AM, Horsley A, Denning DW. What is the importance of classifying Aspergillus disease in cystic fibrosis patients? Expert Rev Respir Med 2014; 8: 389-392.

12. Brandt C, Roehmel J, Rickerts V, Melichar V, Niemann N, Schwarz C. Aspergillus bronchitis in patients with cystic fibrosis. Mycopathologia 2018; 183: 61-69.

13. Stevens DA, Moss RB, Kurup VP, et al; Participants in the Cystic Fibrosis Foundation Consensus Conference. Allergic bronchopulmonary aspergillosis in cystic fibrosis-state of the art: Cystic Fibrosis Foundation Consensus Conference. Clin Infect Dis 2003; 37(Suppl 3): S225-S264.

14. Ziesing S, Suerbaum S, Sedlacek L. Fungal epidemiology and diversity in cystic fibrosis patients over a 5-year period in a national reference center. Med Mycol 2016; 54: 781-786.

15. de Vrankrijker AM, van der Ent CK, van Berkhout FT, et al. Aspergillus fumigatus colonization in cystic fibrosis: implications for lung function? Clin Microbiol Infect 2011; 17: 1381-1386.

16. Saunders RV, Modha DE, Claydon A, Gaillard EA. Chronic Aspergillus fumigatus colonization of the pediatric cystic fibrosis airway is common and may be associated with a more rapid decline in lung function. Med Mycol 2016; 54: 537-543.

17. Maturu VN, Agarwal R. Prevalence of Aspergillus sensitization and allergic bronchopulmonary aspergillosis in cystic fibrosis: systematic review and meta-analysis. Clin Exp Allergy 2015; 45: 1765-1778.

18. Noni M, Katelari A, Dimopoulos G, Doudounakis SE, Tzoumaka-Bakoula C, Spoulou V. Aspergillus fumigatus chronic colonization and lung function decline in cystic fibrosis may have a two-way relationship. Eur J Clin Microbiol Infect Dis 2015; 34: 2235-2241.

19. Bargon J, Dauletbaev N, Kohler B, Wolf M, Posselt HG, Wagner TO. Prophylactic antibiotic therapy is associated with an increased prevalence of Aspergillus colonization in adult cystic fibrosis patients. Respir Med 1999; 93: 835-838.

20. Burns JL, Van Dalfsen JM, Shawar RM, et al. Effect of chronic intermittent administration of inhaled tobramycin on respiratory microbial flora in patients with cystic fibrosis. J Infect Dis 1999; 179: 1190-1196.

21. Speirs JJ, van der Ent CK, Beekman JM. Effects of Aspergillus fumigatus colonization on lung function in cystic fibrosis. Curr Opin Pulm Med 2012; 18: 632- 638.

22. 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: 171-176.

23. Navarro J, Rainisio M, Harms HK, et al. Factors associated with poor pulmonary function: crosssectional analysis of data from the ERCF. European Epidemiologic Registry of Cystic Fibrosis. Eur Respir J 2001; 18: 298-305.

24. Kraemer R, Delosea N, Ballinari P, Gallati S, Crameri R. Effect of allergic bronchopulmonary aspergillosis on lung function in children with cystic fibrosis. Am J Respir Crit Care Med 2006; 174: 1211-1220.

25. King J, Brunel SF, Warris A. Aspergillus infections in cystic fibrosis. J Infect 2016; 72 (Suppl): S50-S55.

26. Aaron SD, Vandemheen KL, Freitag A, et al. Treatment of Aspergillus fumigatus in patients with cystic fibrosis: a randomized, placebo-controlled pilot study. PLoS One 2012; 7: e36077.