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过敏性支气管肺曲霉病

Authors
Praveen Akuthota, MD
Peter F Weller, MD, MACP
Section Editors
Carol A Kauffman, MD
Peter J Barnes, DM, DSc, FRCP, FRS
Deputy Editor
Anna R Thorner, MD

引言

过敏性支气管肺曲霉病(allergic bronchopulmonary aspergillosis, ABPA)是曲霉菌种定植于支气管后发生的一种复杂的超敏反应，常继发于哮喘或囊性纤维化(cystic fibrosis, CF)[1-4]。支气管梗阻、炎症和黏液嵌塞的反复发作可导致支气管扩张、纤维化和呼吸功能损害[5]。

ABPA的病理生理学、诊断和治疗将总结在此。与支气管扩张相关的一般问题将单独讨论。 (参见“成人支气管扩张症的临床表现和诊断”和“成人支气管扩张的治疗”)

病理生理学

目前，ABPA的发病机制尚不完全清楚[5,6]。空气传播的曲霉菌孢子暴露强度与该真菌致敏率(通过皮肤试验获得)没有相关性[7]。虽然所有孢子足量吸入时都可成为变应原，但循环中抗真菌抗原的IgG水平和支气管肺泡灌洗液中抗真菌分泌型IgA通常较低均提示健康个体可有效清除真菌孢子[8,9]。与此相反，特应性个体暴露于真菌孢子或菌丝片段后，体内将产生IgE和IgG抗体。

T细胞在ABPA中也发挥重要作用。在支气管肺泡淋巴组织和全身，Th2 CD4+细胞对曲霉菌抗原应答均增加[5]。曲霉菌应答的T细胞产生细胞因子白细胞介素(interleukin, IL)-4、IL-5和IL-13，这些细胞因子进而导致ABPA患者的嗜酸性粒细胞增多和IgE升高。在一项研究中，研究者从3例ABPA患者外周血中检测到针对烟曲霉Asp f 1抗原的特异性T细胞克隆[10]。这些克隆大多数为产生IL-4和IL-5的Th2表型CD4+细胞[10]。对Asp f 1抗原的应答是受人类白细胞抗原(human leukocyte antigen, HLA)限制的，仅由HLA-DR2或HLA-DR5介导，且仅限于特异性T细胞受体V-β链中[10]。另外，在ABPA患者中，B细胞、T细胞、NK细胞和嗜酸性粒细胞对IL-4的敏感性增加[5]。

在另一项研究中，研究者发现：共刺激分子OX40配体对于驱动CF和ABPA患者中Th2 CD4+细胞对烟曲霉菌的应答是至关重要的[11]。这些患者Th2细胞反应性升高与较低的平均血清维生素D水平相关。

                        

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Literature review current through: 2017-07 . | This topic last updated: 2017-06-29.
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References
Top
  1. Greenberger PA. Allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 2002; 110:685.
  2. Zander DS. Allergic bronchopulmonary aspergillosis: an overview. Arch Pathol Lab Med 2005; 129:924.
  3. Tillie-Leblond I, Tonnel AB. Allergic bronchopulmonary aspergillosis. Allergy 2005; 60:1004.
  4. Agarwal R. Allergic bronchopulmonary aspergillosis. Chest 2009; 135:805.
  5. Stevens DA, Moss RB, Kurup VP, et al. Allergic bronchopulmonary aspergillosis in cystic fibrosis--state of the art: Cystic Fibrosis Foundation Consensus Conference. Clin Infect Dis 2003; 37 Suppl 3:S225.
  6. Riscili BP, Wood KL. Noninvasive pulmonary Aspergillus infections. Clin Chest Med 2009; 30:315.
  7. Beaumont F, Kauffman HF, de Monchy JG, et al. Volumetric aerobiological survey of conidial fungi in the North-East Netherlands. II. Comparison of aerobiological data and skin tests with mould extracts in an asthmatic population. Allergy 1985; 40:181.
  8. Greenberger PA, Smith LJ, Hsu CC, et al. Analysis of bronchoalveolar lavage in allergic bronchopulmonary aspergillosis: divergent responses of antigen-specific antibodies and total IgE. J Allergy Clin Immunol 1988; 82:164.
  9. Kauffman HF, Tomee JF, van der Werf TS, et al. Review of fungus-induced asthmatic reactions. Am J Respir Crit Care Med 1995; 151:2109.
  10. Chauhan B, Knutsen Ap, Hutcheson PS, et al. T cell subsets, epitope mapping, and HLA-restriction in patients with allergic bronchopulmonary aspergillosis. J Clin Invest 1996; 97:2324.
  11. Kreindler JL, Steele C, Nguyen N, et al. Vitamin D3 attenuates Th2 responses to Aspergillus fumigatus mounted by CD4+ T cells from cystic fibrosis patients with allergic bronchopulmonary aspergillosis. J Clin Invest 2010; 120:3242.
  12. Gibson PG, Wark PA, Simpson JL, et al. Induced sputum IL-8 gene expression, neutrophil influx and MMP-9 in allergic bronchopulmonary aspergillosis. Eur Respir J 2003; 21:582.
  13. Agarwal R, Aggarwal AN, Gupta D, Jindal SK. Aspergillus hypersensitivity and allergic bronchopulmonary aspergillosis in patients with bronchial asthma: systematic review and meta-analysis. Int J Tuberc Lung Dis 2009; 13:936.
  14. Patterson R, Greenberger PA, Radin RC, Roberts M. Allergic bronchopulmonary aspergillosis: staging as an aid to management. Ann Intern Med 1982; 96:286.
  15. Buckingham SJ, Hansell DM. Aspergillus in the lung: diverse and coincident forms. Eur Radiol 2003; 13:1786.
  16. Reiff DB, Wells AU, Carr DH, et al. CT findings in bronchiectasis: limited value in distinguishing between idiopathic and specific types. AJR Am J Roentgenol 1995; 165:261.
  17. Johkoh T, Müller NL, Akira M, et al. Eosinophilic lung diseases: diagnostic accuracy of thin-section CT in 111 patients. Radiology 2000; 216:773.
  18. Neeld DA, Goodman LR, Gurney JW, et al. Computerized tomography in the evaluation of allergic bronchopulmonary aspergillosis. Am Rev Respir Dis 1990; 142:1200.
  19. Paganin F, Trussard V, Seneterre E, et al. Chest radiography and high resolution computed tomography of the lungs in asthma. Am Rev Respir Dis 1992; 146:1084.
  20. Ward S, Heyneman L, Lee MJ, et al. Accuracy of CT in the diagnosis of allergic bronchopulmonary aspergillosis in asthmatic patients. AJR Am J Roentgenol 1999; 173:937.
  21. Agarwal R, Gupta D, Aggarwal AN, et al. Clinical significance of hyperattenuating mucoid impaction in allergic bronchopulmonary aspergillosis: an analysis of 155 patients. Chest 2007; 132:1183.
  22. Malo JL, Longbottom J, Mitchell J, et al. Studies in chronic allergic bronchopulmonary aspergillosis. 3. Immunological findings. Thorax 1977; 32:269.
  23. Greenberger PA, Patterson R. Diagnosis and management of allergic bronchopulmonary aspergillosis. Ann Allergy 1986; 56:444.
  24. Vlahakis NE, Aksamit TR. Diagnosis and treatment of allergic bronchopulmonary aspergillosis. Mayo Clin Proc 2001; 76:930.
  25. Angus RM, Davies ML, Cowan MD, et al. Computed tomographic scanning of the lung in patients with allergic bronchopulmonary aspergillosis and in asthmatic patients with a positive skin test to Aspergillus fumigatus. Thorax 1994; 49:586.
  26. Glancy JJ, Elder JL, McAleer R. Allergic bronchopulmonary fungal disease without clinical asthma. Thorax 1981; 36:345.
  27. Berkin KE, Vernon DR, Kerr JW. Lung collapse caused by allergic bronchopulmonary aspergillosis in non-asthmatic patients. Br Med J (Clin Res Ed) 1982; 285:552.
  28. Greenberger PA, Patterson R. Allergic bronchopulmonary aspergillosis and the evaluation of the patient with asthma. J Allergy Clin Immunol 1988; 81:646.
  29. Schwartz HJ, Citron KM, Chester EH, et al. A comparison of the prevalence of sensitization to Aspergillus antigens among asthmatics in Cleveland and London. J Allergy Clin Immunol 1978; 62:9.
  30. Schwartz HJ, Greenberger PA. The prevalence of allergic bronchopulmonary aspergillosis in patients with asthma, determined by serologic and radiologic criteria in patients at risk. J Lab Clin Med 1991; 117:138.
  31. Basich JE, Graves TS, Baz MN, et al. Allergic bronchopulmonary aspergillosis in corticosteroid-dependent asthmatics. J Allergy Clin Immunol 1981; 68:98.
  32. Eaton T, Garrett J, Milne D, et al. Allergic bronchopulmonary aspergillosis in the asthma clinic. A prospective evaluation of CT in the diagnostic algorithm. Chest 2000; 118:66.
  33. Denning DW, O'Driscoll BR, Powell G, et al. Randomized controlled trial of oral antifungal treatment for severe asthma with fungal sensitization: The Fungal Asthma Sensitization Trial (FAST) study. Am J Respir Crit Care Med 2009; 179:11.
  34. Bahous J, Malo JL, Paquin R, et al. Allergic bronchopulmonary aspergillosis and sensitization to Aspergillus fumigatus in chronic bronchiectasis in adults. Clin Allergy 1985; 15:571.
  35. Faux JA, Shale DJ, Lane DJ. Precipitins and specific IgG antibody to Aspergillus fumigatus in a chest unit population. Thorax 1992; 47:48.
  36. Simmonds EJ, Littlewood JM, Evans EG. Cystic fibrosis and allergic bronchopulmonary aspergillosis. Arch Dis Child 1990; 65:507.
  37. Hiller EJ. Aspergillosis. J R Soc Med 1992; 85 Suppl 19:33.
  38. Laufer P, Fink JN, Bruns WT, et al. Allergic bronchopulmonary aspergillosis in cystic fibrosis. J Allergy Clin Immunol 1984; 73:44.
  39. Knutsen AP, Hutcheson PS, Mueller KR, Slavin RG. Serum immunoglobulins E and G anti-Aspergillus fumigatus antibody in patients with cystic fibrosis who have allergic bronchopulmonary aspergillosis. J Lab Clin Med 1990; 116:724.
  40. Becker JW, Burke W, McDonald G, et al. Prevalence of allergic bronchopulmonary aspergillosis and atopy in adult patients with cystic fibrosis. Chest 1996; 109:1536.
  41. Nepomuceno IB, Esrig S, Moss RB. Allergic bronchopulmonary aspergillosis in cystic fibrosis: role of atopy and response to itraconazole. Chest 1999; 115:364.
  42. Geller DE, Kaplowitz H, Light MJ, Colin AA. Allergic bronchopulmonary aspergillosis in cystic fibrosis: reported prevalence, regional distribution, and patient characteristics. Scientific Advisory Group, Investigators, and Coordinators of the Epidemiologic Study of Cystic Fibrosis. Chest 1999; 116:639.
  43. Fitzsimons EJ, Aris R, Patterson R. Recurrence of allergic bronchopulmonary aspergillosis in the posttransplant lungs of a cystic fibrosis patient. Chest 1997; 112:281.
  44. CAMPBELL MJ, CLAYTON YM. BRONCHOPULMONARY ASPERGILLOSIS. A CORRELATION OF THE CLINICAL AND LABORATORY FINDINGS IN 272 PATIENTS INVESTIGATED FOR BRONCHOPULMONARY ASPERGILLOSIS. Am Rev Respir Dis 1964; 89:186.
  45. McCarthy DS, Pepys J. Allergic broncho-pulmonary aspergillosis. Clinical immunology. 2. Skin, nasal and bronchial tests. Clin Allergy 1971; 1:415.
  46. Rosenberg M, Patterson R, Mintzer R, et al. Clinical and immunologic criteria for the diagnosis of allergic bronchopulmonary aspergillosis. Ann Intern Med 1977; 86:405.
  47. Chapman BJ, Capewell S, Gibson R, et al. Pulmonary eosinophilia with and without allergic bronchopulmonary aspergillosis. Thorax 1989; 44:919.
  48. 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.
  49. Breslin AB, Jenkins CR. Experience with allergic bronchopulmonary aspergillosis: some unusual features. Clin Allergy 1984; 14:21.
  50. Golbert TM, Patterson R. Pulmonary allergic aspergillosis. Ann Intern Med 1970; 72:395.
  51. Ricketti AJ, Greenberger PA, Patterson R. Serum IgE as an important aid in management of allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 1984; 74:68.
  52. Agarwal R, Gupta D, Aggarwal AN, et al. Clinical significance of decline in serum IgE levels in allergic bronchopulmonary aspergillosis. Respir Med 2010; 104:204.
  53. Marchant JL, Warner JO, Bush A. Rise in total IgE as an indicator of allergic bronchopulmonary aspergillosis in cystic fibrosis. Thorax 1994; 49:1002.
  54. Stevens DA, Schwartz HJ, Lee JY, et al. A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis. N Engl J Med 2000; 342:756.
  55. Wark PA, Gibson PG, Wilson AJ. Azoles for allergic bronchopulmonary aspergillosis associated with asthma. Cochrane Database Syst Rev 2004; :CD001108.
  56. Wark PA, Hensley MJ, Saltos N, et al. Anti-inflammatory effect of itraconazole in stable allergic bronchopulmonary aspergillosis: a randomized controlled trial. J Allergy Clin Immunol 2003; 111:952.
  57. Pasqualotto AC, Powell G, Niven R, Denning DW. The effects of antifungal therapy on severe asthma with fungal sensitization and allergic bronchopulmonary aspergillosis. Respirology 2009; 14:1121.
  58. Salez F, Brichet A, Desurmont S, et al. Effects of itraconazole therapy in allergic bronchopulmonary aspergillosis. Chest 1999; 116:1665.
  59. Lebrun-Vignes B, Archer VC, Diquet B, et al. Effect of itraconazole on the pharmacokinetics of prednisolone and methylprednisolone and cortisol secretion in healthy subjects. Br J Clin Pharmacol 2001; 51:443.
  60. Varis T, Kaukonen KM, Kivistö KT, Neuvonen PJ. Plasma concentrations and effects of oral methylprednisolone are considerably increased by itraconazole. Clin Pharmacol Ther 1998; 64:363.
  61. Bolland MJ, Bagg W, Thomas MG, et al. Cushing's syndrome due to interaction between inhaled corticosteroids and itraconazole. Ann Pharmacother 2004; 38:46.
  62. Woods DR, Arun CS, Corris PA, Perros P. Cushing's syndrome without excess cortisol. BMJ 2006; 332:469.
  63. Parmar JS, Howell T, Kelly J, Bilton D. Profound adrenal suppression secondary to treatment with low dose inhaled steroids and itraconazole in allergic bronchopulmonary aspergillosis in cystic fibrosis. Thorax 2002; 57:749.
  64. Skov M, Main KM, Sillesen IB, et al. Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide. Eur Respir J 2002; 20:127.
  65. Wong J, Black P. Acute adrenal insufficiency associated with high dose inhaled steroids. BMJ 1992; 304:1415.
  66. Erwin GE, Fitzgerald JE. Case report: allergic bronchopulmonary aspergillosis and allergic fungal sinusitis successfully treated with voriconazole. J Asthma 2007; 44:891.
  67. Glackin L, Leen G, Elnazir B, Greally P. Voriconazole in the treatment of allergic bronchopulmonary aspergillosis in cystic fibrosis. Ir Med J 2009; 102:29.
  68. Laoudi Y, Paolini JB, Grimfed A, Just J. Nebulised corticosteroid and amphotericin B: an alternative treatment for ABPA? Eur Respir J 2008; 31:908.
  69. Knutsen AP, Bush RK, Demain JG, et al. Fungi and allergic lower respiratory tract diseases. J Allergy Clin Immunol 2012; 129:280.
  70. Zirbes JM, Milla CE. Steroid-sparing effect of omalizumab for allergic bronchopulmonary aspergillosis and cystic fibrosis. Pediatr Pulmonol 2008; 43:607.
  71. van der Ent CK, Hoekstra H, Rijkers GT. Successful treatment of allergic bronchopulmonary aspergillosis with recombinant anti-IgE antibody. Thorax 2007; 62:276.
  72. Kanu A, Patel K. Treatment of allergic bronchopulmonary aspergillosis (ABPA) in CF with anti-IgE antibody (omalizumab). Pediatr Pulmonol 2008; 43:1249.
  73. Lebecque P, Leonard A, Pilette C. Omalizumab for treatment of ABPA exacerbations in CF patients. Pediatr Pulmonol 2009; 44:516.
  74. Brinkmann F, Schwerk N, Hansen G, Ballmann M. Steroid dependency despite omalizumab treatment of ABPA in cystic fibrosis. Allergy 2010; 65:134.
  75. Tillie-Leblond I, Germaud P, Leroyer C, et al. Allergic bronchopulmonary aspergillosis and omalizumab. Allergy 2011; 66:1254.