Current Infectious Disease Reports

, Volume 12, Issue 6, pp 409–416 | Cite as

Invasive Pulmonary Aspergillosis in Patients with Chronic Obstructive Pulmonary Disease: An Emerging Fungal Disease



Invasive pulmonary aspergillosis (IPA) is a necrotizing pneumonia caused by airborne opportunistic fungi of Aspergillus species. Patients with advanced-stage chronic obstructive pulmonary disease (COPD) have emerged to be at risk for IPA as a result of the overall improvement of long-term management of the disease. IPA is among the most severe infectious event that may occur during the course of COPD resulting from profound immune impairment and associated with poor outcome. Many aspects of the development of IPA in COPD patients differ from hematologic patients, explaining various patterns of IPA in an expanded population of immunocompromised patients. Therefore, it is legitimate to focus on the literature-based data available regarding the factors involved in the development of IPA in this setting as well as the use and interpretation of diagnosis criteria, and the treatment options.


Invasive pulmonary aspergillosis Aspergillus Chronic obstructive pulmonary disease Corticosteroids 



No potential conflict of interest relevant to this article was reported.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 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.CrossRefPubMedGoogle Scholar
  2. 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.CrossRefPubMedGoogle Scholar
  3. 3.
    Ader F, Bienvenu AL, Rammaert B, Nseir S: Management of invasive aspergillosis in patients with COPD: rational use of voriconazole. Int J COPD 2009, 4:279–287.Google Scholar
  4. 4.
    Meersseman W, Lagrou K, Maertens J, Van Wijngaerden E. Invasive aspergillosis in the intensive care unit. Clin Infect Dis 2007, 45:205–216.CrossRefPubMedGoogle Scholar
  5. 5.
    Rabe KF, Hurd S, Anzuet A, et al.: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease; GOLD executive summary. Am J Respir Crit Care Med 2007, 176:532–555.CrossRefPubMedGoogle Scholar
  6. 6.
    Chung KF, Adcock IM: Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction. Eur Respir J 2008, 31:1334–1356.CrossRefPubMedGoogle Scholar
  7. 7.
    Sethi S, Murphy TF: Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med 2008, 359:2355–2365.CrossRefPubMedGoogle Scholar
  8. 8.
    Patterson TF, Kirkpatrick WR, White M, et al.: Invasive aspergillosis: disease spectrum, treatment practices and outcomes. Medicine 2000, 79:250–260.CrossRefPubMedGoogle Scholar
  9. 9.
    Lin SJ, Schranz J, Teutsch SM: Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis 2001, 32:358–366.CrossRefPubMedGoogle Scholar
  10. 10.
    Thommi G, Bell G, Liu J, Nugent K: Spectrum of invasive pulmonary aspergillosis in immunocompetent patients with chronic obstructive pulmonary disease. South Med J 1991, 84:828–831.PubMedGoogle Scholar
  11. 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.CrossRefPubMedGoogle Scholar
  12. 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.CrossRefPubMedGoogle Scholar
  13. 13.
    •• Bulpa P, Dive A, and 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.CrossRefPubMedGoogle Scholar
  14. 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.CrossRefPubMedGoogle Scholar
  15. 15.
    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.CrossRefPubMedGoogle Scholar
  16. 16.
    •• 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 (Epub ahead of print). This study presents and analyzes the largest retrospective series of COPD patients with positive Aspergillus specimens in LRT at admission who subsequently develop IPA.Google Scholar
  17. 17.
    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.CrossRefPubMedGoogle Scholar
  18. 18.
    Garnacho-Monteiro J, Amaya-Villar R, Ortiz-Leyba C, et al.: Isolation of Aspergillus spp. from the respiratory tract in critically ill patients: risk factors, clinical presentation and outcome. Crit Care 2005, 9:R191–R199.CrossRefGoogle Scholar
  19. 19.
    Trof RJ, Beishuizen A, Debets-Ossenkopp YJ, et al.: Management of invasive pulmonary aspergillosis in non-neutropenic critically ill patients. Int Care Med 2007, 33:1694–1703.CrossRefGoogle Scholar
  20. 20.
    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.CrossRefPubMedGoogle Scholar
  21. 21.
    Dimopoulos G, Piagnerelli M, Berre J, et al.: Disseminated aspergillosis in intensive care unit patients: an autopsy study. J Chemother 2003, 15:71–75.PubMedGoogle Scholar
  22. 22.
    Khasawneh F, Mohamad T, Moughrabieh MK, et al.: Isolation of Aspergillus in critically ill patients: a potential marker of poor outcome. J Crit Care 2006, 21:322–327.CrossRefPubMedGoogle Scholar
  23. 23.
    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.CrossRefPubMedGoogle Scholar
  24. 24.
    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.CrossRefPubMedGoogle Scholar
  25. 25.
    Romani L: Immunity to fungal infections. Nat Immunol 2004, 4:1–13.CrossRefGoogle Scholar
  26. 26.
    Betsuyaku T, Kuroki I, 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.CrossRefPubMedGoogle Scholar
  27. 27.
    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.CrossRefPubMedGoogle Scholar
  28. 28.
    Cowburn AS, Condliffe AM, Farahi N, et al.: Advances in neutrophil biology: clinical implications. Chest 2008, 134: 606–612.CrossRefPubMedGoogle Scholar
  29. 29.
    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.CrossRefPubMedGoogle Scholar
  30. 30.
    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.CrossRefPubMedGoogle Scholar
  31. 31.
    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 immunocompromised hosts. Clin Immunol 2007, 124:238–243.CrossRefPubMedGoogle Scholar
  32. 32.
    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.CrossRefPubMedGoogle Scholar
  33. 33.
    Diamond RD: Inhibition of monocyte-mediated damage to fungal hyphae by steroid hormones. J Infect Dis 1983, 147:160–162.PubMedGoogle Scholar
  34. 34.
    Ng TTC, Robson GD, Denning DW: Hydrocortisone enhanced growth of Aspergillus spp.: implications for pathogenesis. Microbiology 1994, 140:2475–2479.CrossRefPubMedGoogle Scholar
  35. 35.
    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.CrossRefGoogle Scholar
  36. 36.
    Barouky R, Badet M, Saint Denis M, et al.: Inhaled corticosteroids in COPD and disseminated aspergillosis. Eur J Int Med 2003, 14:380–382.CrossRefGoogle Scholar
  37. 37.
    Cornet M, Hallat H, Somme D, et al.: Fulminant invasive pulmonary aspergillosis in immunocompetent patients. A two-case report. Clin Microbiol Infect 2003, 9: 1224–1227.CrossRefPubMedGoogle Scholar
  38. 38.
    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.CrossRefPubMedGoogle Scholar
  39. 39.
    • 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.CrossRefPubMedGoogle Scholar
  40. 40.
    Patel IS, Vlahos I, Wilkinson TM: Bronchiectasis, exacerbation indices, and inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004, 170:400–407.CrossRefPubMedGoogle Scholar
  41. 41.
    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.CrossRefGoogle Scholar
  42. 42.
    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.CrossRefPubMedGoogle Scholar
  43. 43.
    Andreas S, Heindl S, Wattky C, et al.: Diagnosis of pulmonary aspergillosis using optical brighteners. Eur Respir J 2000, 15:407–411.CrossRefPubMedGoogle Scholar
  44. 44.
    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.CrossRefPubMedGoogle Scholar
  45. 45.
    Pfeiffer CD, Fine JP, Safdar N: Diagnosis of invasive aspergillosis using a galactomannan assay: a meta–analysis. Clin Infect Dis 2006, 42:1417–1427.CrossRefPubMedGoogle Scholar
  46. 46.
    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.CrossRefPubMedGoogle Scholar
  47. 47.
    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.CrossRefPubMedGoogle Scholar
  48. 48.
    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.CrossRefPubMedGoogle Scholar
  49. 49.
    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.CrossRefPubMedGoogle Scholar
  50. 50.
    Seyfarth HJ, Nenoff P, Winkler J, et al.: Aspergillus detection in bronchoscopically acquired material. Significance and interpretation. Mycoses 2001, 44:356–360.CrossRefPubMedGoogle Scholar
  51. 51.
    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.CrossRefPubMedGoogle Scholar
  52. 52.
    • 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.CrossRefPubMedGoogle Scholar
  53. 53.
    Ansorg R, Van den Boom R, Rath PM: Detection of Aspergillus galactomannan antigen in foods and antibiotics. Mycoses 1997, 40:353–357.CrossRefPubMedGoogle Scholar
  54. 54.
    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.CrossRefPubMedGoogle Scholar
  55. 55.
    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.CrossRefPubMedGoogle Scholar
  56. 56.
    Ostrosky-Zeichner L, Alexander BD, Kett DH, et al.: Multicenter clinical evaluation of the [1–> 3]-β-D-glucan assay as an aid to diagnosis of fungal infections in humans. Clin Infect Dis 2005, 41:654–659.CrossRefPubMedGoogle Scholar
  57. 57.
    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 Microb 2003, 52:1031–1032.CrossRefGoogle Scholar
  58. 58.
    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.CrossRefPubMedGoogle Scholar
  59. 59.
    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.CrossRefPubMedGoogle Scholar
  60. 60.
    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.CrossRefPubMedGoogle Scholar
  61. 61.
    Hope WW, Drusano GL: Antifungal pharmacokinetics and pharmacodynamics: bridging from the bench to bedside. Clin Microbiol Infect 2009, 15:602–612.CrossRefPubMedGoogle Scholar
  62. 62.
    Herbrecht R, Denning DW, Patterson TF, et al.: Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 2002, 347:408–415.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Infectious DiseasesCroix-Rousse HospitalLyonFrance
  2. 2.Inserm U851 Finovi Centre d’Infectiologie Innate Immunity and Bacterial PathogenesisClaude Bernard Lyon 1 UniversityLyonFrance
  3. 3.Inserm U851, Finovi Centre d’Infectiologie, Bâtiment DomiLyonLyonFrance

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