Invasive Pulmonary Aspergillosis

Aimee K. Zaas; Barbara D. Alexander

doi:10.1128/9781555815523.ch23

Chapter 23 : Invasive Pulmonary Aspergillosis

Authors: Aimee K. Zaas¹, Barbara D. Alexander²

VIEW AFFILIATIONS HIDE AFFILIATIONS

Affiliations: 1: Dept. of Medicine/Infectious Diseases, Duke University Medical Center, DUMC Box 3355, Durham, NC 27710; 2: Dept. of Medicine/Infectious Diseases and Dept. of Pathology, Duke University Medical Center, DUMC Box 3035, Durham, NC 27710

Content Type: Monograph

Publication Year: 2009

Category: Clinical Microbiology; Fungi and Fungal Pathogenesis

Book DOI: 10.1128/9781555815523

Chapter DOI: 10.1128/9781555815523.ch23

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:

Invasive Pulmonary Aspergillosis, Page 1 of 2

< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555815523/9781555814380_Chap23-1.gif /docserver/preview/fulltext/10.1128/9781555815523/9781555814380_Chap23-2.gif

Abstract:

This chapter provides a review of the spectrum of invasive pulmonary aspergillosis (IPA), including its epidemiology, clinical and radiographic presentation, outcomes, and unique situations related to IPA. Over 200 species of Aspergillus are known, although only a few have been reported as pathogenic to humans. The more commonly reported human pathogens include A. fumigatus, A. flavus, A. niger, and A. terreus. Of these, A. fumigatus is the most common species to cause invasive disease. Persons at highest risk of development of disease include those with hematologic malignancies, recipients of hematopoietic stem cell transplantation (HSCT; more so with allogeneic than autologous), and recipients of solid organ transplants (SOT). Pleuritic chest pain and hemoptysis may be present, as can altered mental status and respiratory failure. The availability of molecular markers of aspergillosis (galactomannan) allowed investigators to follow a group of 19 patients with IA during the time of neutrophil recovery. The majority of patients survived without any changes in antifungal therapy, and in the three deaths, autopsy revealed no evidence of IPA. Important issues that remain to be addressed include elucidation of the optimal monitoring strategy (diagnostic test of choice, frequency, specimen tested), the role of combination antifungal therapy in the treatment of the disease, and the role of novel adjunctive therapies in disease management. Risk groups are expanding beyond the traditional groups of hematologic malignancy patients and HSCT recipients to include rheumatologic patients on chronic corticosteroid therapy and patients with a prolonged intensive care unit admission.

Citation: Zaas A, Alexander B. 2009. Invasive Pulmonary Aspergillosis, p 293-299. In Latgé J, Steinbach W (ed), Aspergillus fumigatus and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch23

Key Concept Ranking

Central Nervous System Diseases: 0.47666976
Hematopoietic Stem Cell Transplantation: 0.4055946

0.47666976

Highlighted Text: Show | Hide

Full text loading...

References

/content/book/10.1128/9781555815523.ch23

1. Almyroudis, N. G.,, S. M. Holland, and, B. H. Segal. 2005. Invasive aspergillosis in primary immunodeficiencies. Med. Mycol. 43 (Suppl. 1): S247– 59.

2. Ascioglu, S.,, J. H. Rex,, B. de Pauw,, J. E. Bennett,, J. Bille,, F. Crokaert,, D. W. Denning,, J. P. Donnelly,, J. E. Edwards,, Z. Erjavec,, D. Fiere,, O. Lortholary,, J. Maertens,, J. F. Meis,, T. F. Patterson,, J. Ritter,, D. Selleslag,, P. M. Shah,, D. A. Stevens, and, T. J. Walsh. 2002. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin. Infect. Dis. 34: 7– 14.

3. Austin, J. H.,, N. L. Muller,, P. J. Friedman,, D. M. Hansell,, D. P. Naidich,, M. Remy-Jardin,, W. R. Webb, and, E. A. Zerhouni. 1996. Glossary of terms for CT of the lungs: recommendations of the Nomenclature Committee of the Fleischner Society. Radiology 200: 327– 331.

4. Berenguer, J.,, M. C. Allende,, J. W. Lee,, K. Garrett,, C. Lyman,, N. M. Ali,, J. Bacher,, P. A. Pizzo, and, T. J. Walsh. 1995. Pathogenesis of pulmonary aspergillosis. Granulocytopenia versus cyclosporine and methylprednisolone-induced immunosuppression. Am. J. Respir. Crit. Care Med. 152: 1079– 1086.

5. Bulpa, P.,, A. Dive, and, Y. Sibille. 2007. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. Eur. Respir. J. 30: 782– 800.

6. Caillot, D.,, J. F. Couaillier,, A. Bernard,, O. Casasnovas,, D. W. Denning,, L. Mannone,, J. Lopez,, G. Couillault,, F. Piard,, O. Vagner, and, H. Guy. 2001. Increasing volume and changing characteristics of invasive pulmonary aspergillosis on sequential thoracic computed tomography scans in patients with neutropenia. J. Clin. Oncol. 19: 253– 259.

7. Chandrasekar, P. H., and, J. I. Ito. 2005. Amphotericin B lipid complex in the management of invasive aspergillosis in immunocompromised patients. Clin. Infect. Dis. 40 (Suppl. 6): S392– S400.

8. Cordonnier, C.,, P. Ribaud,, R. Herbrecht,, N. Milpied,, D. Valteau-Couanet,, C. Morgan, and, A. Wade. 2006. Prognostic factors for death due to invasive aspergillosis after hematopoietic stem cell transplantation: a 1-year retrospective study of consecutive patients at French transplantation centers. Clin. Infect. Dis. 42: 955– 963.

9. Cornillet, A.,, C. Camus,, S. Nimubona,, V. Gandemer,, P. Tattevin,, C. Belleguic,, S. Chevrier,, C. Meunier,, C. Lebert,, M. Aupee,, S. Caulet-Maugendre,, M. Faucheux,, B. Lelong,, E. Leray,, C. Guiguen, and, J. P. Gangneux. 2006. Comparison of epidemiological, clinical, and biological features of invasive aspergillosis in neutropenic and nonneutropenic patients: a 6-year survey. Clin. Infect. Dis. 43: 577– 584.

10. Denning, D. W.,, P. Ribaud,, N. Milpied,, D. Caillot,, R. Herbrecht,, E. Thiel,, A. Haas,, M. Ruhnke, and, H. Lode. 2002. Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis. Clin. Infect. Dis. 34: 563– 571.

11. Gavalda, J., and, A. Roman. 2007. Infection in lung transplantation. Enferm. Infecc. Microbiol. Clin. 25: 639– 650. (In French.)

12. Greene, R. E.,, H. T. Schlamm,, J. W. Oestmann,, P. Stark,, C. Durand,, O. Lortholary,, J. R. Wingard,, R. Herbrecht,, P. Ribaud,, T. F. Patterson,, P. F. Troke,, D. W. Denning,, J. E. Bennett,, B. E. de Pauw, and, R. H. Rubin. 2007. Imaging findings in acute invasive pulmonary aspergillosis: clinical significance of the halo sign. Clin. Infect. Dis. 44: 373– 379.

13. Groll, A. H.,, P. M. Shah,, C. Mentzel,, M. Schneider,, G. Just-Nuebling, and, K. Huebner. 1996. Trends in the postmortem epidemiology of invasive fungal infections at a university hospital. J. Infect. 33: 23– 32.

14. Hachem, R. Y.,, D. P. Kontoyiannis,, M. R. Boktour,, C. Afif,, C. Cook-sley,, G. P. Bodey,, I. Chatzinikolaou,, C. Perego,, H. M. Kantarjian, and, I. I. Raad. 2004. Aspergillus terreus: an emerging amphotericin B-resistant opportunistic mold in patients with hematologic malignancies. Cancer 101: 1594– 1600.

15. Herbrecht, R.,, D. W. Denning,, T. F. Patterson,, J. E. Bennett,, R. E. Greene,, J. W. Oestmann,, W. V. Kern,, K. A. Marr,, P. Ribaud,, O. Lortholary,, R. Sylvester,, R. H. Rubin,, J. R. Wingard,, P. Stark,, C. Durand,, D. Caillot,, E. Thiel,, P. H. Chandrasekar,, M. R. Hodges,, H. T. Schlamm,, P. F. Troke, and, B. de Pauw. 2002. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N. Engl. J. Med. 347: 408– 415.

16. Horger, M.,, H. Einsele,, U. Schumacher,, M. Wehrmann,, H. Hebart,, C. Lengerke,, R. Vonthein,, C. D. Claussen, and, C. Pfannenberg. 2005a. Invasive pulmonary aspergillosis: frequency and meaning of the “hypodense sign” on unenhanced CT. Br. J. Radiol. 78: 697– 703.

17. Horger, M.,, H. Hebart,, H. Einsele,, C. Lengerke,, C. D. Claussen,, R. Vonthein, and, C. Pfannenberg. 2005b. Initial CT manifestations of invasive pulmonary aspergillosis in 45 non-HIV immunocompro-mised patients: association with patient outcome? Eur. J. Radiol. 55: 437– 444.

18. Ibrahim-Granet, O.,, B. Philippe,, H. Boleti,, E. Boisvieux-Ulrich,, D. Grenet,, M. Stern, and, J. P. Latgé. 2003. Phagocytosis and intracel-lular fate of Aspergillus fumigatus conidia in alveolar macrophages. Infect. Immun. 71: 891– 903.

19. Iversen, M.,, C. M. Burton,, S. Vand,, L. Skovfoged,, J. Carlsen,, N. Milman,, C. B. Andersen,, M. Rasmussen, and, M. Tvede. 2007. As-pergillus infection in lung transplant patients: incidence and prognosis. Eur. J. Clin. Microbiol. Infect. Dis. 26: 879– 886.

20. Iwen, P. C.,, M. E. Rupp,, A. N. Langnas,, E. C. Reed, and, S. H. Hin-richs. 1998. Invasive pulmonary aspergillosis due to Aspergillus ter-reus: 12-year experience and review of the literature. Clin. Infect. Dis. 26: 1092– 1097.

21. Kartsonis, N. A.,, A. J. Saah,, C. Joy Lipka,, A. F. Taylor, and, C. A. Sable. 2005. Salvage therapy with caspofungin for invasive aspergillosis: results from the caspofungin compassionate use study. J. Infect. 50: 196– 205.

22. Kaur, S.,, V. K. Gupta,, S. Thiel,, P. U. Sarma, and, T. Madan. 2007. Protective role of mannan-binding lectin in a murine model of invasive pulmonary aspergillosis. Clin. Exp. Immunol. 148: 382– 389.

23. Maertens, J.,, A. Glasmacher,, R. Herbrecht,, A. Thiebaut,, C. Cordon-nier,, B. H. Segal,, J. Killar,, A. Taylor,, N. Kartsonis,, T. F. Patterson,, M. Aoun,, D. Caillot, and, C. Sable. 2006. Multicenter, noncompar-ative study of caspofungin in combination with other antifungals as salvage therapy in adults with invasive aspergillosis. Cancer 107: 2888– 2897.

24. Maertens, J.,, K. Theunissen,, E. Verbeken,, K. Lagrou,, J. Verhaegen,, M. Boogaerts, and, J. V. Eldere. 2004. Prospective clinical evaluation of lower cut-offs for galactomannan detection in adult neutro-penic cancer patients and haematological stem cell transplant recipients. Br. J. Haematol. 126: 852– 860.

25. Maertens, J.,, J. Van Eldere,, J. Verhaegen,, E. Verbeken,, J. Verschak-elen, and, M. Boogaerts. 2002. Use of circulating galactomannan screening for early diagnosis of invasive aspergillosis in allogeneic stem cell transplant recipients. J. Infect. Dis. 186: 1297– 1306.

26. Mahfouz, T.,, M. H. Miceli,, F. Saghafifar,, S. Stroud,, L. Jones-Jackson,, R. Walker,, M. L. Grazziutti,, G. Purnell,, A. Fassas,, G. Tricot,, B. Barlogie, and, E. Anaissie. 2005. 18F-fluorodeoxyglucose positron emission tomography contributes to the diagnosis and management of infections in patients with multiple myeloma: a study of 165 infectious episodes. J. Clin. Oncol. 23: 7857– 7863.

27. Marr, K. A.,, T. Patterson, and, D. Denning. 2002. Aspergillosis: path-ogenesis, clinical manifestations, and therapy. Infect. Dis. Clin. North Am. 16: 875– 894.

28. Mehrad, B.,, R. M. Strieter, and, T. J. Standiford. 1999. Role of TNF-alpha in pulmonary host defense in murine invasive aspergillosis. J. Immunol. 162: 1633– 1640.

29. Mehrad, B.,, M. Wiekowski,, B. E. Morrison,, S. C. Chen,, E. C. Coronel,, D. J. Manfra, and, S. A. Lira. 2002. Transient lung-specific expression of the chemokine KC improves outcome in invasive aspergillosis. Am. J. Respir. Crit. Care Med. 166: 1263– 1268.

30. Miceli, M. H.,, J. Maertens,, K. Buve,, M. Grazziutti,, G. Woods,, M. Rahman,, B. Barlogie, and, E. J. Anaissie. 2007. Immune reconsti-tution inflammatory syndrome in cancer patients with pulmonary aspergillosis recovering from neutropenia: proof of principle, description, and clinical and research implications. Cancer 110: 112– 120.

31. Morgan, J.,, K. A. Wannemuehler,, K. A. Marr,, S. Hadley,, D. P. Kon-toyiannis,, T. J. Walsh,, S. K. Fridkin,, P. G. Pappas, and, D. W. Warnock. 2005. Incidence of invasive aspergillosis following he-matopoietic stem cell and solid organ transplantation: interim results of a prospective multicenter surveillance program. Med. Mycol. 43 (Suppl. 1): S49– S58.

32. Morrison, B. E.,, S. J. Park,, J. M. Mooney, and, B. Mehrad. 2003. Chemokine-mediated recruitment of NK cells is a critical host defense mechanism in invasive aspergillosis. J. Clin. Investig. 112: 1862– 1870.

33. Park, S. J.,, M. T. Wiekowski,, S. A. Lira, and, B. Mehrad. 2006. Neutrophils regulate airway responses in a model of fungal allergic airways disease. J. Immunol. 176: 2538– 2545.

34. Pappas, P. G.,, D. Andes,, M. Schuster,, S. Hadley,, J. Rabkin,, R. M. Merion,, C. A. Kauffman,, C. Huckabee,, G. A. Cloud,, W. E. Dismukes, and, A. W. Karchmer. 2006. Invasive fungal infections in low-risk liver transplant recipients: a multi-center prospective observation study. Am. J. Transplant. 6: 386– 391.

35. Perfect, J. R.,, G. M. Cox,, J. Y. Lee,, C. A. Kauffman,, L. de Repentigny,, S. W. Chapman,, V. A. Morrison,, P. Pappas,, J. W. Hiemenz, and, D. A. Stevens. 2001. The impact of culture isolation of Aspergillus species: a hospital-based survey of aspergillosis. Clin. Infect. Dis. 33: 1824– 1833.

36. Phadke, A. P.,, G. Akangire,, S. J. Park,, S. A. Lira, and, B. Mehrad. 2007. The role of CC chemokine receptor 6 in host defense in a model of invasive pulmonary aspergillosis. Am. J. Respir. Crit. Care Med. 175: 1165– 1172.

37. Phadke, A. P., and, B. Mehrad. 2005. Cytokines in host defense against Aspergillus: recent advances. Med. Mycol. 43 (Suppl. 1): S173– S176.

38. Philippe, B.,, O. Ibrahim-Granet,, M. C. Prevost,, M. A. Gougerot-Pocidalo,, M. Sanchez Perez,, A. Van der Meeren, and, J. P. Latgé. 2003. Killing of Aspergillus fumigatus by alveolar macrophages is mediated by reactive oxidant intermediates. Infect. Immun. 71: 3034– 3042.

39. Sainz, J.,, L. Hassan,, E. Perez,, A. Romero,, A. Moratalla,, E. Lopez-Fernandez,, S. Oyonarte, and, M. Jurado. 2007. Interleukin-10 promoter polymorphism as risk factor to develop invasive pulmonary aspergillosis. Immunol. Lett. 109: 76– 82.

40. Segal, B. H.,, N. G. Almyroudis,, M. Battiwalla,, R. Herbrecht,, J. R. Perfect,, T. J. Walsh, and, J. R. Wingard. 2007. Prevention and early treatment of invasive fungal infection in patients with cancer and neutropenia and in stem cell transplant recipients in the era of newer broad-spectrum antifungal agents and diagnostic adjuncts. Clin. Infect. Dis. 44: 402– 409.

41. Seo, K. W.,, D. H. Kim,, S. K. Sohn,, N. Y. Lee,, H. H. Chang,, S. W. Kim,, S. B. Jeon,, J. H. Baek,, J. G. Kim,, J. S. Suh, and, K. B. Lee. 2005. Protective role of interleukin-10 promoter gene polymorphism in the pathogenesis of invasive pulmonary aspergillosis after allogeneic stem cell transplantation. Bone Marrow Transplant. 36: 1089– 1095.

42. Sole, A.,, P. Morant,, M. Salavert,, J. Peman, and, P. Morales. 2005. Aspergillus infections in lung transplant recipients: risk factors and outcome. Clin. Microbiol. Infect. 11: 359– 365.

43. Soubani, A. O., and, P. H. Chandrasekar. 2002. The clinical spectrum of pulmonary aspergillosis. Chest 121: 1988– 1999.

44. Steinbach, W. J.,, D. K. Benjamin, Jr.,, D. P. Kontoyiannis,, J. R. Perfect,, I. Lutsar,, K. A. Marr,, M. S. Lionakis,, H. A. Torres,, H. Jafri, and, T. J. Walsh. 2004. Infections due to Aspergillus terreus: a multi-center retrospective analysis of 83 cases. Clin. Infect. Dis. 39: 192– 198.

45. Stephens-Romero, S. D.,, A. J. Mednick, and, M. Feldmesser. 2005. The pathogenesis of fatal outcome in murine pulmonary aspergillosis depends on the neutrophil depletion strategy. Infect. Immun. 73: 114– 125.

46. Stergiopoulou, T.,, J. Meletiadis,, E. Roilides,, D. E. Kleiner,, R. Schau-fele,, M. Roden,, S. Harrington,, L. Dad,, B. Segal, and, T. J. Walsh. 2007. Host-dependent patterns of tissue injury in invasive pulmonary aspergillosis. Am. J. Clin. Pathol. 127: 349– 355.

47. Takuma, T.,, K. Okada,, Y. Uchida,, A. Yamagata, and, Y. Sawae. 2002. Invasive pulmonary aspergillosis resulting in respiratory failure during neutrophil recovery from postchemotherapy neutropenia in three patients with acute leukaemia. J. Intern. Med. 252: 173– 177.

48. Todeschini, G.,, C. Murari,, R. Bonesi,, G. Pizzolo,, G. Verlato,, C. Tec-chio,, V. Meneghini,, M. Franchini,, C. Giuffrida,, G. Perona, and, P. Bellavite. 1999. Invasive aspergillosis in neutropenic patients: rapid neutrophil recovery is a risk factor for severe pulmonary complications. Eur. J. Clin. Investig. 29: 453– 457.

49. Tritz, D. M., and, G. L. Woods. 1993. Fatal disseminated infection with Aspergillus terreus in immunocompromised hosts. Clin. Infect. Dis. 16: 118– 122.

50. Trof, R. J.,, A. Beishuizen,, Y. J. Debets-Ossenkopp,, A. R. Girbes, and, A. B. Groeneveld. 2007. Management of invasive pulmonary aspergillosis in nonneutropenic critically ill patients. Intensive Care Med. 33: 1694– 1703.

51. Trullas, J. C.,, C. Cervera,, N. Benito,, J. P. de la Bellacasa,, C. Agusti,, M. Rovira,, A. Mas,, M. Navasa,, F. Cofan,, M. J. Ricart,, F. Perez-Villa, and, A. Moreno. 2005. Invasive pulmonary aspergillosis in solid organ and bone marrow transplant recipients. Transplant. Proc. 37: 4091– 4093.

52. Upton, A.,, K. A. Kirby,, P. Carpenter,, M. Boeckh, and, K. A. Marr. 2007. Invasive aspergillosis following hematopoietic cell transplantation: outcomes and prognostic factors associated with mortality. Clin. Infect. Dis. 44: 531– 540.

53. Vandewoude, K. H.,, S. I. Blot,, P. Depuydt,, D. Benoit,, W. Temmer-man,, F. Colardyn, and, D. Vogelaers. 2006. Clinical relevance of Aspergillus isolation from respiratory tract samples in critically ill patients. Crit. Care 10: R31.

54. Walsh, T. J.,, I. Raad,, T. F. Patterson,, P. Chandrasekar,, G. R. Don-owitz,, R. Graybill,, R. E. Greene,, R. Hachem,, S. Hadley,, R. Her-brecht,, A. Langston,, A. Louie,, P. Ribaud,, B. H. Segal,, D. A. Stevens,, J. A. van Burik,, C. S. White,, G. Corcoran,, J. Gogate,, G. Krishna,, L. Pedicone,, C. Hardalo, and, J. R. Perfect. 2007. Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial. Clin. Infect. Dis. 44: 2– 12.

55. Warnock, D. W. 2007. Trends in the epidemiology of invasive fungal infections. Nippon Ishinkin Gakkai Zasshi 48: 1– 12.

Tables

Invasive Pulmonary Aspergillosis

[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555815523.ch23-1,webId=/content/author/10.1128/9781555815523.ch23-1,properties={foaf_givenname=Aimee K., foaf_name=Aimee K. Zaas, foaf_surname=Zaas, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555815523.ch23-aff1]]}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555815523.ch23-2,webId=/content/author/10.1128/9781555815523.ch23-2,properties={foaf_givenname=Barbara D., foaf_name=Barbara D. Alexander, foaf_surname=Alexander, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555815523.ch23-aff2]]}]]

/content/10.1128/9781555815523.ch23.ch23tab01

Table 1.

Risk factors for IPA a

Table 1.

Risk factors for IPA a

/content/10.1128/9781555815523.ch23.ch23tab02

Table 2.

Major antifungal trials for treatment of IA (includes disseminated disease) a

Table 2.

Major antifungal trials for treatment of IA (includes disseminated disease) a