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Challenges in Diagnosing Invasive Pulmonary Aspergillosis in Patients With COPD and Other Chronic Lung Disorders

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Abstract

Invasive pulmonary aspergillosis (IPA) is a necrotizing pneumonia caused by airborne opportunistic fungi of Aspergillus species. Patients with chronic obstructive pulmonary disease (COPD) or other chronic lung disorders (CLD) have emerged to be at risk for IPA, with a related mortality rate greater than 70%. Host factors playing a role in the occurrence of IPA in CLD patients differ from those in patients with hematologic disorders and may be largely responsible for a distinct pattern of the disease. Furthermore, these host factors affect the results of standard diagnostic procedures recommended for IPA. Therefore, the diagnosis of IPA in patients with COPD and other CLD remains challenging for physicians. This review puts into perspective the host factors contributing to the pathogenesis of IPA in CLD patients and discusses the use and interpretation of the main diagnostic tools currently available.

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References

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  1. Perfect JR, Cox GM, Lee JY, et al.: The impact of culture isolation of Aspergillus species: A hospital-based survey of aspergillosis. Clin Infect Dis 2001, 33:1824–1833.

    Article  CAS  PubMed  Google Scholar 

  2. Walsh TJ, Anaissie EJ, Denning DW, et al.: Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2008, 46:327–360.

    Article  CAS  PubMed  Google Scholar 

  3. Ader F, Bienvenu AL, Rammaert B, Nseir S: Management of invasive aspergillosis in patients with COPD: rational use of voriconazole. Int J Chron Obstruct Pulmon Dis 2009, 279–287.

  4. • Meersseman W, Lagrou K, Maertens J, Van Wijngaerden E: Invasive aspergillosis in the intensive care unit. Clin Infect Dis 2007, 45:205–216. This review highlights the literature-based data available on ICU patients presenting IPA.

    Article  PubMed  Google Scholar 

  5. Roosen J, Frans E, Wilmer A, et al.: Comparison of premortem clinical diagnoses in critically ill patients and subsequent autopsy findings. Mayo Clin Proc 2000, 75:562–567.

    Article  CAS  PubMed  Google Scholar 

  6. Dimopoulos G, Piagnerelli M, Berre J, et al.: Disseminated aspergillosis in intensive care unit patients: an autopsy study. J Chemother 2003, 15:71–75.

    CAS  PubMed  Google Scholar 

  7. Patterson TF, Kirkpatrick WR, White M, et al.: Invasive aspergillosis: disease spectrum, treatment practices and outcomes. Medicine 2000, 79:250–260.

    Article  CAS  PubMed  Google Scholar 

  8. Lin SJ, Schranz J, Teutsch SM: Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis 2001, 32:358–366.

    Article  CAS  PubMed  Google Scholar 

  9. Gao X, Chen L, Hu G, Mei H: Invasive pulmonary aspergillosis in acute exacerbation of chronic obstructive pulmonary disease and the diagnostic value of combined serological tests. Ann Saudi Med 2010, 30:193–197.

    Article  PubMed  Google Scholar 

  10. •• 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 2009 Nov 10 (Epub ahead of print). This study presents and analyzes the largest retrospective series of COPD patients with positive Aspergillus specimens in the lower respiratory tract at admission who subsequently develop IPA.

  11. Rello J, Esandi ME, Mariscal D, et al.: Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: report of eight cases and review. Clin Infect Dis 1998, 26:1473–1475.

    Article  CAS  PubMed  Google Scholar 

  12. Ader F, Nseir S, Le Berre R, et al.: Invasive pulmonary aspergillosis in chronic obstructive pulmonary disease: an emerging fungal pathogen. Clin Microbiol Infect 2005, 11:427–429.

    Article  CAS  PubMed  Google Scholar 

  13. •• Bulpa P, Dive A, Sibille Y: Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. Eur Respir J 2007, 30:782–800. This study was the first to propose specific definitions of IPA in COPD patients. The “Bulpa criteria” are currently used to estimate the probability of IPA in COPD patients.

    Article  CAS  PubMed  Google Scholar 

  14. Samarakoon P, Soubani AO: Invasive pulmonary aspergillosis in patients with COPD: a report of five cases and systematic review of the literature. Chron Respir Dis 2008, 5:19–27.

    Article  CAS  PubMed  Google Scholar 

  15. Pihet M, Carrère J, Cimon B, et al.: Occurrence and relevance of filamentous fungi in respiratory secretions of patients with cystic fibrosis, a review. J Med Mycol 2009, 47:387–397.

    Article  Google Scholar 

  16. 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.

    Article  PubMed  Google Scholar 

  17. Chow L, Brown NE, Kunimoto D: An unusual case of pulmonary invasive aspergillosis and aspergilloma cured with voriconazole in a patient with cystic fibrosis. Clin Infect Dis 2002, 35e:106–110.

    Article  Google Scholar 

  18. Iversen M, Burton CM, Vand S, et al.: Aspergillus infection in lung transplant patients: incidence and prognosis. Eur J Clin Microbiol Infect Dis 2007, 26:879–886.

    Article  CAS  PubMed  Google Scholar 

  19. De Pauw B, Walsh TJ, Donnelly JP, et al.: Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008, 46:1813–1821.

    Article  PubMed  Google Scholar 

  20. Upton A, Kirby KA, Carpenter P, et al.: Invasive aspergillosis following hematopoietic cell transplantation: outcomes and prognostic factors associated with mortality. Clin Infect Dis 2007, 44:531–540.

    Article  PubMed  Google Scholar 

  21. Chung KF, Adcock IM: Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction. Eur Respir J 2008, 31:1334–1356.

    Article  CAS  PubMed  Google Scholar 

  22. Romani L: Immunity to fungal infections. Nat Immunol 2004, 4:1–13.

    Article  Google Scholar 

  23. • Sethi S, Murphy TF: Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med 2008, 359:2355–2365. This is an excellent overview of the role of infections in the pathogenesis and course of COPD.

    Article  CAS  PubMed  Google Scholar 

  24. Betsuyaku T, Kuroki Y, Nagai K, et al.: Effects of ageing and smoking on SP-A and SP-D levels in bronchoalveolar lavage fluid. Eur Respir J 2004, 24:964–970.

    Article  CAS  PubMed  Google Scholar 

  25. Berenson CS, Wrona CT, Grove LJ: Impaired alveolar macrophage response to Haemophilus antigens in chronic obstructive lung disease. Am J Respir Crit Care Med 2006, 174:31–40.

    Article  CAS  PubMed  Google Scholar 

  26. Cowburn AS, Condliffe AM, Farahi N, et al.: Advances in neutrophil biology: clinical implications. Chest 2008, 134:606–612.

    Article  CAS  PubMed  Google Scholar 

  27. Droemann D, Goldmann T, Tiedje T, et al.: Toll-like receptor 2 expression is decreased on alveolar macrophages in cigarette smokers and COPD patients. Respir Res 2005, 6:68.

    Article  PubMed  Google Scholar 

  28. MacRedmond RE, Greene CM, Dorscheid DR, et al.: Epithelial expression of TLR4 is modulated in COPD and by steroids, salmeterol and cigarette smoke. Respir Res 2007, 8:84.

    Article  PubMed  Google Scholar 

  29. Chignard M, Balloy V, Sallenave JM, Si-Tahar M: Role of Toll-like receptors in lung innate defense against invasive aspergillosis. Distinct impact in immunocompetent and immunocompromized hosts. Clin Immunol 2007, 124:238–243.

    Article  CAS  PubMed  Google Scholar 

  30. Hartemink KJ, Paul MA, Spijkstra JJ, et al.: Immunoparalysis as a cause of invasive aspergillosis? Int Care Med 2003, 29:2068–2071.

    Article  Google Scholar 

  31. Schaffner A: Therapeutic concentrations of glucocorticoids suppress the antimicrobial activity of human macrophages without impairing their responsiveness to gamma interferon. J Clin Invest 1985, 76:1755–1764.

    Article  CAS  PubMed  Google Scholar 

  32. Diamond RD: Inhibition of monocyte-mediated damage to fungal hyphae by steroid hormones. J Infect Dis 1983, 147:160.

    CAS  PubMed  Google Scholar 

  33. Ng TTC, Robson GD, Denning DW: Hydrocortisone enhanced growth of Aspergillus spp.: implications for pathogenesis. Microbiology 1994, 140:2475–2479.

    Article  CAS  PubMed  Google Scholar 

  34. Peter E, Bakri F, Ball DM, et al.: Invasive pulmonary filamentous fungal infection in a patient receiving inhaled corticosteroid therapy. Clin Infect Dis 2002, 36:54–56.

    Article  Google Scholar 

  35. Barouky R, Badet M, Saint Denis M, et al.: Inhaled corticosteroids in chronic obstructive pulmonary disease and disseminated aspergillosis. Eur J Intern Med 2003, 14:380–382.

    Article  CAS  PubMed  Google Scholar 

  36. Cornet M, Mallat H, Somme D, et al.: Fulminant invasive pulmonary aspergillosis in immunocompetent patients—a two-case report. Clin Microbiol Infect 2003, 9:1224–1227.

    Article  CAS  PubMed  Google Scholar 

  37. Martinez-Solano L, Macia MD, Fajardo A, et al.: Chronic Pseudomonas aeruginosa infection in chronic obstructive pulmonary disease. Clin Infect Dis 2008, 47:1526–1533.

    Article  CAS  PubMed  Google Scholar 

  38. • Seidler MJ, Salvenmoser S, Müller FMC: Aspergillus fumigatus forms biofilms with reduced antifungal drug susceptibility on bronchial epithelial cells. Antimicrob Agents Chemother 2008, 52:4130–4136. This is the first report of biofilm production by A. fumigatus on bronchial epithelial cells.

    Article  CAS  PubMed  Google Scholar 

  39. 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.

    Article  PubMed  Google Scholar 

  40. Patel IS, Vlahos I, Wilkinson TM, et al.: Bronchiectasis, exacerbation indices, and inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004, 170:400–407.

    Article  PubMed  Google Scholar 

  41. Landbo C, Prescott E, Lange P, et al.: Prognostic value of nutritional status in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999, 160:1856–1861.

    CAS  PubMed  Google Scholar 

  42. Hallin R, Koivisto-Hursti UK, Lindberg E, Janson C: Nutritional status, dietary energy intake and the risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). Respir Med 2006, 100:561–567.

    Article  PubMed  Google Scholar 

  43. Jantunen E, Piilonen A, Volin L, et al.: Diagnostic aspects of invasive Aspergillus infections in allogeneic BMT recipients. Bone Marrow Transplant 2000, 25:867–871.

    Article  CAS  PubMed  Google Scholar 

  44. Kahn FW, Jones JM, England DM: The role of bronchoalveolar lavage in the diagnosis of invasive pulmonary aspergillosis. Am J Clin Pathol 1986, 86:518–523.

    CAS  PubMed  Google Scholar 

  45. Andreas S, Heindl S, Wattky C, et al.: Diagnosis of pulmonary aspergillosis using optical brighteners. Eur Respir J 2000, 15:407–411.

    Article  CAS  PubMed  Google Scholar 

  46. Maertens J, Verhaegen J, Lagrou K, et al.: Screening for circulating galactomannan as a noninvasive diagnostic tool for invasive aspergillosis in prolonged neutropenic patients and stem cell transplantation recipients: a prospective validation. Blood 2001, 97:1604–1610.

    Article  CAS  PubMed  Google Scholar 

  47. Pfeiffer CD, Fine JP, Safdar N: Diagnosis of invasive aspergillosis using a galactomannan assay: a meta–analysis. Clin Infect Dis 2006, 42:1417–1427.

    Article  CAS  PubMed  Google Scholar 

  48. Meersseman W, Vandecasteele SJ, Wilmer A, et al.: Invasive aspergillosis in critically ill patients without malignancy. Am J Respir Crit Care Med 2004, 170:621–625.

    Article  PubMed  Google Scholar 

  49. Sulahian A, Touratier S, Ribaud P: False positive test for Aspergillus antigenemia related to concomitant administration of piperacillin and tazobactam. N Engl J Med 2003, 349:2366–2367.

    Article  CAS  PubMed  Google Scholar 

  50. Viscoli C, Machetti M, Cappellano P, et al.: False-positive galactomannan platelia Aspergillus test results for patients receiving piperacillin–tazobactam. Clin Infect Dis 2004, 38:913–916.

    Article  PubMed  Google Scholar 

  51. Sanguinetti M, Posteraro B, Pagano L, et al.: Comparison of real-time PCR, conventional PCR, and galactomannan antigen detection by enzyme-linked immunosorbent assay using bronchoalveolar lavage fluid samples from hematology patients for diagnosis of invasive pulmonary aspergillosis. J Clin Microbiol 2003, 41:3922–3925.

    Article  CAS  PubMed  Google Scholar 

  52. Musher B, Fredricks D, Leisenring W, et al.: Aspergillus galactomannan enzyme immunoassay and quantitative PCR for diagnosis of invasive aspergillosis with bronchoalveolar lavage fluid. J Clin Microbiol 2004, 42:5517–5522.

    Article  CAS  PubMed  Google Scholar 

  53. Seyfarth HJ, Nenoff P, Winkler J, et al.: Aspergillus detection in bronchoscopically acquired material. Significance and interpretation. Mycoses 2001, 44:356–360.

    Article  CAS  PubMed  Google Scholar 

  54. Clancy CJ, Jaber RA, Leather HL, et al.: Bronchoalveolar lavage galactomannan in diagnosis of invasive pulmonary aspergillosis among solid-organ transplant recipients. J Clin Microbiol 2007, 45:1759–1765.

    Article  CAS  PubMed  Google Scholar 

  55. • Meersseman W, Lagrou K, Maertens J, et al.: Galactomannan in bronchoalveolar lavage fluid: a tool for diagnosing aspergillosis in intensive care unit patients. Am J Respir Crit Care Med 2008, 177:27–34. This clinical study investigated GM detection in BAL fluid of ICU patients and underscored the usefulness of GM detection in establishing or excluding the diagnosis of IPA in the ICU.

    Article  PubMed  Google Scholar 

  56. Ansorg R, Van den Boom R, Rath PM: Detection of Aspergillus galactomannan antigen in foods and antibiotics. Mycoses 1997, 40:353–357.

    Article  CAS  PubMed  Google Scholar 

  57. Becker MJ, De Marie S, Fens MH, et al.: Effect of amphotericin B treatment on kinetics of cytokines and parameters of fungal load in neutropenic rats with invasive pulmonary aspergillosis. J Antimicrob Chemother 2003, 52:428–434.

    Article  CAS  PubMed  Google Scholar 

  58. Marr KA, Laverdiere M, Gugel A, Leisenring W: Antifungal therapy decreases sensitivity of the Aspergillus galactomannan enzyme immunoassay. Clin Infect Dis 2005, 40:1762–1769.

    Article  CAS  PubMed  Google Scholar 

  59. Ostrosky-Zeichner L, Alexander BD, Kett DH, et al.: Multicenter clinical evaluation of the (1-- > 3) beta-D-glucan assay as an aid to diagnosis of fungal infections in humans. Clin Infect Dis 2005, 41:654–659.

    Article  CAS  PubMed  Google Scholar 

  60. Okada S, Teramoto S, Takizawa H, et al.: Clinical insignificance of (1-- > 3)-β-D-glucan in early diagnosis of invasive pulmonary aspergillosis in a patient with chronic obstructive pulmonary disease. J Med Microbiol 2003, 52(Pt 11):1031–1032.

    Article  PubMed  Google Scholar 

  61. 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(Suppl 3):S265–S280.

    Article  PubMed  Google Scholar 

  62. Vandewoude KH, Blot SI, Benoit D, et al.: Invasive aspergillosis in critically ill patients: attributable mortality and excesses in length of ICU stay and ventilator dependence. J Hosp Infect 2004, 56:269–276.

    Article  CAS  PubMed  Google Scholar 

  63. Greene RE, Schlamm HT, Oestmann JW, et al.: Imaging findings in acute invasive pulmonary aspergillosis: clinical significance of the halo sign. Clin Infect Dis 2007, 44:373–379.

    Article  PubMed  Google Scholar 

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Acknowledgment

The author gratefully acknowledges Dr. Ana-Maria Dragoi for providing useful comments.

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No potential conflicts of interest relevant to this article were reported.

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  1. Infectious Diseases Department, Croix-Rousse Hospital Inserm U851 Innate Immunity and Bacterial Pathogenesis Claude Bernard Lyon 1 University Lyon, Lyon, France

    Florence Ader

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Correspondence to Florence Ader.

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Ader, F. Challenges in Diagnosing Invasive Pulmonary Aspergillosis in Patients With COPD and Other Chronic Lung Disorders. Curr Fungal Infect Rep 4, 179–185 (2010). https://doi.org/10.1007/s12281-010-0025-7

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