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Risk factors for allergic bronchopulmonary aspergillosis and sensitisation to Aspergillus fumigatus in patients with cystic fibrosis

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Abstract

An increasing incidence of allergic bronchopulmonary aspergillosis (ABPA) as a complication in patients with cystic fibrosis (CF) is reported. The objective of this retrospective case-control study was to assess potential risk factors for ABPA and for Aspergillus fumigatus sensitisation (AFS). In a group of 160 CF patients, 11 (7%) fulfilled the diagnostic criteria for ABPA and 20 (13%) had evidence of AFS. They were compared to 62 control CF patients (25 for ABPA and 37 for AFS group) without evidence of ABPA or AFS using extended matching for sex, age and weight. AFS patients had received significantly higher cumulative doses of inhaled corticosteroids than their respective controls (OR 8.0; 95% CI 1.74–63). Bronchial colonisation with Stenotrophomonas maltophilia was strongly and independently associated with ABPA (OR 20; 95% CI 2.8– infinity). A longer duration of Pseudomonas aeruginosa colonisation was independently associated with AFS (OR per year 1.50; 95% CI 1.12– infinity). Conclusion: Cystic fibrosis patients with allergic bronchopulmonary aspergillosis have a more frequent isolation of S. maltophilia in their sputum than their controls. Longer duration of colonisation with P. aeruginosa is a risk factor for Aspergillus fumigatus sensitisation. Higher cumulative doses of inhaled corticosteroids are associated with Aspergillus fumigatus sensitisation and their role as a risk factor needs to be clarified.

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Abbreviations

ABPA :

allergic bronchopulmonary aspergillosis

AFS :

Aspergillus fumigatus sensitisation

BMI :

body mass index

CF :

cystic fibrosis

CFTR :

cystic fibrosis transmembrane regulator

IQR :

interquartile range

rAsp f :

recombinant Aspergillus fumigatus antigen

References

  1. Becker JW, Burke W, McDonald G, Greenberger PA, Henderson WR, Aitken ML (1996) Prevalence of allergic bronchopulmonary aspergillosis and atopy in adult patients with cystic fibrosis. Chest 109: 1536–1540

    CAS  PubMed  Google Scholar 

  2. Breslow NE and Day NE (1980) The analysis of case-control studies. In: Statistical methods in cancer research, vol. 1. IARC, Lyon

  3. Burns JL, Van Dalfsen JM, Shawar RM, Otto KL, Garber RL, Quan JM, Montgomery AB, Albers GM, Ramsey BW, Smith AL (1999) Effect of chronic intermittent administration of inhaled tobramycin on respiratory microbial flora in patients with cystic fibrosis. J Infect Dis 179: 1190–1196

    Article  CAS  PubMed  Google Scholar 

  4. Casella G (1986) Refining binomial confidence intervals. Can J Stat 14: 113–129

    Google Scholar 

  5. Crameri R (1998) Recombinant Aspergillus fumigatus allergens: from the nucleotide sequences to clinical applications. Int Arch Allergy Immunol 115: 99–114

    Article  CAS  PubMed  Google Scholar 

  6. Dezateux C, Walters S, Balfour-Lynn I (2000) Inhaled corticosteroids for cystic fibrosis. Cochrane Database Syst Rev 2000, CD001915

  7. Eaton TE, Miller PW, Garret E (2002) Cystic fibrosis transmembrane conductance regulator gene mutations: do they play a role in the aetiology of allergic bronchopulmonary aspergillosis? Clin Exp Allergy 32: 756–761

    Article  CAS  PubMed  Google Scholar 

  8. El-Dahr JM, Fink R, Selden R, Arruda LK, Platts-Mills TA, Hyemann PW (1994) Development of immune responses to Aspergillus at an early age in children with cystic fibrosis. Am J Respir Crit Care Med 150: 1513–1518

    CAS  PubMed  Google Scholar 

  9. Feanny S, Forsyth S, Correy M, Levison H, Zimmerman B (1988) Allergic bronchopulmonary aspergillosis in cystic fibrosis: a secretory immune response to a colonizing organism. Ann Allergy 60: 64–68

    CAS  PubMed  Google Scholar 

  10. Geller DE, Kaplowitz H, Light MJ, Colin AA (1999) Allergic bronchopulmonary aspergillosis in cystic fibrosis. Chest 116: 639–646

    Article  CAS  PubMed  Google Scholar 

  11. Graff GR, Burns JL (2002) Factors affecting the incidence of Stenotrophomonas maltophilia isolation in cystic fibrosis. Chest 121: 1754–1760

    Article  PubMed  Google Scholar 

  12. Hemmann S, Nikolaizik WH, Schöni MH, Blaser K, Crameri R (1998) Differential IgE recognition of recombinant Aspergillus fumigatus allergens by cystic fibrosis patients with allergic bronchopulmonary aspergillosis or Aspergillus allergy. Eur J Immunol 10: 1155–1160

    Article  Google Scholar 

  13. Hutcheson PS, Knutsen AP, Rejent AJ, Salvin RG (1996) A 12-year longitudinal study of Aspergillus sensitivity in patients with cystic fibrosis. Chest 110: 363–366

    CAS  PubMed  Google Scholar 

  14. Knutsen AP, Hutcheson PS, Mueller KR, Slavin RG (1990) Serum immunglobulins E and G anti-aspergillus fumigatus antibody in patients with cystic fibrosis who have allergic bronchopulmonary aspergillosis. J Lab Clin Med 116: 724–727

    CAS  PubMed  Google Scholar 

  15. Knutsen AP, Hutcheson PS, Slavin RG, Kurup VP (2004) IgE antibodies to Aspergillus fumigatus recombinant allergens in cystic fibrosis patients with allergic bronchopulmonary aspergillosis. Allergy 59: 198–203

    Article  CAS  PubMed  Google Scholar 

  16. Laufer P, Fink JN, Burns WT, Unger GF, Kalbfleisch JH, Greenberger PA, Patterson R (1984) Allergic bronchopulmonary aspergillosis in cystic fibrosis. J Allergy Clin Immunol 73: 44–48

    CAS  PubMed  Google Scholar 

  17. Marchac V, Equi A, Le Bihan-Benjamin C, Hodson M, Bush A (2004) Case-control study of Stenotrophomonas maltophilia acquisition in cystic fibrosis patients. Eur Respir J 23: 98–102

    Article  CAS  PubMed  Google Scholar 

  18. Marchant JL, Warner JO, Bush A (1994) Rise in total IgE as an indicator of allergic bronchpulmonary aspergillosis in cystic fibrosis. Thorax 49: 1002–1005

    CAS  PubMed  Google Scholar 

  19. Mastella G, Rainisio M, Harms HK, Hodson ME, Koch C, Navarro J, Strandvik B, McKenzie SG (2001) Allergic bronchopulmonary aspergillosis in cystic fibrosis. A European epidemiological study. Epidemiologic Registry of Cystic Fibrosis. Eur Respir J 17: 1052–1053

    Article  CAS  PubMed  Google Scholar 

  20. Mehta C, Patel N (2002) LogXact 5 user manual. Cytel Software Corp., Cambridge MA, pp 222–226

  21. Mroueh S, Spock A (1994) Allergic bronchopulmonary aspergillosis in patients with cystic fibrosis. Chest 105: 32–36

    CAS  PubMed  Google Scholar 

  22. Nepomuceno IB, Esrig S, Moss RB (1999) Allergic bronchopulmonary aspergillosis in cystic fibrosis. Chest 115: 364–370

    Article  CAS  PubMed  Google Scholar 

  23. Ng TT, Robson GD, Denning DW (1994) Hydrocortisone-enhanced growth of Aspergillus spp.: implications for pathogenesis. Microbiology 140: 2475–2479

    Google Scholar 

  24. Nikolaizik WH, Schöni MH (1996) Pilot study to assess the effect of inhaled corticosteroids on lung function in patients with cystic fibrosis. J Pediatr 128: 271–274

    CAS  PubMed  Google Scholar 

  25. Nikolaizik WH, Brueton MJ, Warner JO (1991) Aspergillus allergy and allergic bronchopulmonary aspergillosis in cystic fibrosis. Pediatr Allergy Immunol 2: 83–86

    Google Scholar 

  26. Nikolaizik WH, Crameri R, Blaser K, Schoni MH (1996) Skin test reactivity to recombinant Af-allergen I/a in patients with cystic fibrosis. Int Arch Allergy Immunol 111: 403–408

    CAS  PubMed  Google Scholar 

  27. Nir M, Lanng S, Johansen HK, Koch C (1996) Long-term survival and nutritional data in patients with cystic fibrosis treated in a Danish centre. Thorax 51: 1023–1027

    CAS  PubMed  Google Scholar 

  28. Peterson ML, Jacobs DR, Milla CE (2003) Longitudinal changes in growth parameters are correlated with changes in pulmonary function in children with cystic fibrosis. Pediatrics 112: 588–592

    Article  PubMed  Google Scholar 

  29. Prader A, Largo RH, Molinari L, Issler C (1989) Physical growth of Swiss children from birth to 20 years of age (First Zurich Longitudinal Study of Growth and Development). Helv Pediatr Acta Suppl 52: 1–125

    CAS  Google Scholar 

  30. Schonheyder H, Jensen T, Hoiby N, Koch C (1988) Clinical and serological survey of pulmonary aspergillosis in patients with cystic fibrosis. Int Arch Allergy Appl Immunol 85: 472–477

    CAS  PubMed  Google Scholar 

  31. Simmonds EJ, Littlewood JM, Evans EGV (1990) Cystic fibrosis and allergic bronchopulmonary aspergillosis. Arch Dis Child 65: 507–511

    CAS  PubMed  Google Scholar 

  32. Stanta and Walker A (1986) Radiation and lung cancer. Harvard School of Public Health Technical Report

  33. Stevens DA, Moss RB, Kurup VP, Knutsen AP, Greenberger P, Judson MA, Denning DW, Crameri R, Brody AS, Light M, Skov M, Maish W, Mastella G (2003) Allergic bronchopulmonary aspergillosis in cystic fibrosis – State of the Art: Cystic Fibrosis Foundation Consensus Conference. Clin Infect Dis 37[Suppl 3]: S225–S264

  34. Wojnarowski C, Eichler I, Gartner C, Gotz M, Renner S, Koller DY, Frischer T (1997) Sensitisation to Aspergillus fumigatus and lung function in children with cystic fibrosis. Am J Respir Crit Care Med 155: 1902–1907

    CAS  PubMed  Google Scholar 

  35. Zeaske R, Burns WT, Fink JN, Greenberger PA, Colby H, Liotta JL, Roberts M (1988) Immune responses to Aspergillus in cystic fibrosis. J Allergy Clin Immunol 82: 73–77

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Prof. Dr. Kurt Blaser and Prof. Dr. Reto Crameri from the Swiss Institute for Allergy and Asthma Research (SIAF), Davos, for determining specific IgG and IgE against rAsp f in the sera of the CF patients. Carmen Casaulta Aebischer was supported by a grant from the Silva Casa Foundation, Berne, Switzerland and Franziska Schoeni-Affolter by a grant from Roche Pharma (Schweiz), Switzerland.

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Authors and Affiliations

  1. Department of Paediatrics, University of Berne, 3010 , Berne, Switzerland

    Nicole Ritz, Roland A. Ammann, Carmen Casaulta Aebischer & Martin H. Schoeni

  2. Department of Embryology, University of Fribourg, Fribourg, Switzerland

    Franziska Schoeni-Affolter

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  1. Nicole Ritz
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  2. Roland A. Ammann
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  4. Franziska Schoeni-Affolter
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  5. Martin H. Schoeni
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Correspondence to Martin H. Schoeni.

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Ritz, N., Ammann, R.A., Casaulta Aebischer, C. et al. Risk factors for allergic bronchopulmonary aspergillosis and sensitisation to Aspergillus fumigatus in patients with cystic fibrosis. Eur J Pediatr 164, 577–582 (2005). https://doi.org/10.1007/s00431-005-1701-4

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  • DOI: https://doi.org/10.1007/s00431-005-1701-4

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