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Pulmonary complications of primary immunodeficiencies

James Verbsky, MD, PhD
John M Routes, MD
Section Editor
Jordan S Orange, MD, PhD
Deputy Editors
Anna M Feldweg, MD
Helen Hollingsworth, MD


Pulmonary disease is common among patients with primary immunodeficiencies (PIDs) [1-4]. As therapy for these disorders improves and life expectancy of patients with PIDs increases, the prevalence of pulmonary complications is likely to increase in parallel. Consequently, knowledge of the detection and management of pulmonary disorders related to PIDs is critical for optimal management.

This topic will review the pulmonary findings that should raise suspicion of an underlying immune disorder, as well as the various pulmonary conditions that are seen in specific immunodeficiency disorders. Monitoring patients with PIDs for the development of pulmonary problems is also discussed. The evaluation of secondary immunodeficiency (eg, due to underlying diabetes, hemoglobinopathies, malignancy, human immunodeficiency virus [HIV] infection, drug-induced immunosuppression) and an overview of the medical management of patients with immunodeficiency are found separately. (See "Approach to the adult with recurrent infections", section on 'Respiratory tract infections' and "Secondary immunodeficiency due to underlying disease states, environmental exposures, and miscellaneous causes" and "Secondary immunodeficiency induced by biologic therapies" and "Primary immunodeficiency: Overview of management".)


The spectrum of pulmonary manifestations in PIDs is broad and includes acute and chronic infection, structural abnormalities (eg, bronchiectasis), malignancy, and dysregulated inflammation resulting in tissue damage (eg, granuloma, pulmonary fibrosis) [5-9]. Pulmonary disease may be the initial manifestation of a PID, and certain clinical and radiographic findings, such as specific types of pulmonary infections and structural lung abnormalities, should prompt an immunologic evaluation for an underlying PID, regardless of patient age. The laboratory tests used to evaluate the immune system are reviewed separately. (See "Laboratory evaluation of the immune system".)

Pulmonary infections — Infections that are recurrent, recalcitrant to usual therapy, or due to opportunistic or unusual pathogens are suggestive of a possible underlying PID.

Recurrent infections — In the general population, recurrent pneumonias (ie, >2/lifetime) are unusual. The association of pneumonia with recurrent sinus infections is also a clue that a PID may be present. Recurrent pneumonias in a specific lobe are suggestive of structural abnormalities, such as aberrant lung development, neoplasm, or the presence of a foreign body. Pneumonias confined to dependent lobes may indicate recurrent aspiration due to gastroesophageal reflux disease or swallowing abnormalities. In contrast, pneumonias in varying locations of the lung, particularly with interim clearing between episodes, are more indicative of underlying immune dysfunction [10-12]. The presence of unusual complications of pneumonia, such as pneumatoceles or cavitary lesions, is also concerning for immunodeficiency [13,14].

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Literature review current through: Dec 2017. | This topic last updated: Sep 11, 2017.
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  1. Marcy TW, Reynolds HY. Pulmonary consequences of congenital and acquired primary immunodeficiency states. Clin Chest Med 1989; 10:503.
  2. Bode FR, Paré JA, Fraser RG. Pulmonary diseases in the compromised host. A review of clinical and roentgenographic manifestations in patients with impaired host defense mechanisms. Medicine (Baltimore) 1974; 53:255.
  3. Williams DM, Krick JA, Remington JS. Pulmonary infection in the compromised host: part I. Am Rev Respir Dis 1976; 114:359.
  4. Pennington DJ, Lonergan GJ, Benya EC. Pulmonary disease in the immunocompromised child. J Thorac Imaging 1999; 14:37.
  5. Buckley RH. Pulmonary complications of primary immunodeficiencies. Paediatr Respir Rev 2004; 5 Suppl A:S225.
  6. Moskaluk CA, Pogrebniak HW, Pass HI, et al. Surgical pathology of the lung in chronic granulomatous disease. Am J Clin Pathol 1994; 102:684.
  7. Dukes RJ, Rosenow EC 3rd, Hermans PE. Pulmonary manifestations of hypogammaglobulinaemia. Thorax 1978; 33:603.
  8. Kohler P. Pulmonary manifestations and management of antibody deficiency in adults. Chest 1984; 86:24S.
  9. Bilton D. Update on non-cystic fibrosis bronchiectasis. Curr Opin Pulm Med 2008; 14:595.
  10. Reynolds JH, McDonald G, Alton H, Gordon SB. Pneumonia in the immunocompetent patient. Br J Radiol 2010; 83:998.
  11. Sánchez I, Navarro H, Méndez M, et al. Clinical characteristics of children with tracheobronchial anomalies. Pediatr Pulmonol 2003; 35:288.
  12. Vaughan D, Katkin JP. Chronic and recurrent pneumonias in children. Semin Respir Infect 2002; 17:72.
  13. McGarry T, Giosa R, Rohman M, Huang CT. Pneumatocele formation in adult pneumonia. Chest 1987; 92:717.
  14. Antachopoulos C, Walsh TJ, Roilides E. Fungal infections in primary immunodeficiencies. Eur J Pediatr 2007; 166:1099.
  15. Mason RJ, Broaddus VC, Martin TR, et al. Murray and Nadel's textbook of respiratory medicine, 5th ed, 2010.
  16. Apisarnthanarak A, Mundy LM. Etiology of community-acquired pneumonia. Clin Chest Med 2005; 26:47.
  17. de la Hoz RE, Stephens G, Sherlock C. Diagnosis and treatment approaches of CMV infections in adult patients. J Clin Virol 2002; 25 Suppl 2:S1.
  18. Williams BJ, Dehnbostel J, Blackwell TS. Pseudomonas aeruginosa: host defence in lung diseases. Respirology 2010; 15:1037.
  19. Bodey GP, Vartivarian S. Aspergillosis. Eur J Clin Microbiol Infect Dis 1989; 8:413.
  20. Bousfiha A, Picard C, Boisson-Dupuis S, et al. Primary immunodeficiencies of protective immunity to primary infections. Clin Immunol 2010; 135:204.
  21. Courtois G, Smahi A, Reichenbach J, et al. A hypermorphic IkappaBalpha mutation is associated with autosomal dominant anhidrotic ectodermal dysplasia and T cell immunodeficiency. J Clin Invest 2003; 112:1108.
  22. McDonald DR, Mooster JL, Reddy M, et al. Heterozygous N-terminal deletion of IkappaBalpha results in functional nuclear factor kappaB haploinsufficiency, ectodermal dysplasia, and immune deficiency. J Allergy Clin Immunol 2007; 120:900.
  23. Lopez-Granados E, Keenan JE, Kinney MC, et al. A novel mutation in NFKBIA/IKBA results in a degradation-resistant N-truncated protein and is associated with ectodermal dysplasia with immunodeficiency. Hum Mutat 2008; 29:861.
  24. Longo DL. Harrison's hematology and oncology, McGraw-Hill, 2010.
  25. Salavoura K, Kolialexi A, Tsangaris G, Mavrou A. Development of cancer in patients with primary immunodeficiencies. Anticancer Res 2008; 28:1263.
  26. Shapiro RS. Malignancies in the setting of primary immunodeficiency: Implications for hematologists/oncologists. Am J Hematol 2011; 86:48.
  27. Ochs HD, Smith CIE, Puck JM. Primary immunodeficiency diseases: A molecular and cellular approach, 2nd ed, Oxford University Press, 2006.
  28. Stafler P, Carr SB. Non-cystic fibrosis bronchiectasis: its diagnosis and management. Arch Dis Child Educ Pract Ed 2010; 95:73.
  29. Li AM, Sonnappa S, Lex C, et al. Non-CF bronchiectasis: does knowing the aetiology lead to changes in management? Eur Respir J 2005; 26:8.
  30. Boren EJ, Teuber SS, Gershwin ME. A review of non-cystic fibrosis pediatric bronchiectasis. Clin Rev Allergy Immunol 2008; 34:260.
  31. Parr DG, Guest PG, Reynolds JH, et al. Prevalence and impact of bronchiectasis in alpha1-antitrypsin deficiency. Am J Respir Crit Care Med 2007; 176:1215.
  32. Obregon RG, Lynch DA, Kaske T, et al. Radiologic findings of adult primary immunodeficiency disorders. Contribution of CT. Chest 1994; 106:490.
  33. Zonana J, Elder ME, Schneider LC, et al. A novel X-linked disorder of immune deficiency and hypohidrotic ectodermal dysplasia is allelic to incontinentia pigmenti and due to mutations in IKK-gamma (NEMO). Am J Hum Genet 2000; 67:1555.
  34. Aghamohammadi A, Allahverdi A, Abolhassani H, et al. Comparison of pulmonary diseases in common variable immunodeficiency and X-linked agammaglobulinaemia. Respirology 2010; 15:289.
  35. Niehues T, Reichenbach J, Neubert J, et al. Nuclear factor kappaB essential modulator-deficient child with immunodeficiency yet without anhidrotic ectodermal dysplasia. J Allergy Clin Immunol 2004; 114:1456.
  36. Tarzi MD, Grigoriadou S, Carr SB, et al. Clinical immunology review series: An approach to the management of pulmonary disease in primary antibody deficiency. Clin Exp Immunol 2009; 155:147.
  37. Jeanes AC, Owens CM. Chest imaging in the immunocompromised child. Paediatr Respir Rev 2002; 3:59.
  38. Goeminne P, Dupont L. Non-cystic fibrosis bronchiectasis: diagnosis and management in 21st century. Postgrad Med J 2010; 86:493.
  39. Deerojanawong J, Chang AB, Eng PA, et al. Pulmonary diseases in children with severe combined immune deficiency and DiGeorge syndrome. Pediatr Pulmonol 1997; 24:324.
  40. Ito M, Nakagawa A, Hirabayashi N, Asai J. Bronchiolitis obliterans in ataxia-telangiectasia. Virchows Arch 1997; 430:131.
  41. Thickett KM, Kumararatne DS, Banerjee AK, et al. Common variable immune deficiency: respiratory manifestations, pulmonary function and high-resolution CT scan findings. QJM 2002; 95:655.
  42. Pipavath SJ, Lynch DA, Cool C, et al. Radiologic and pathologic features of bronchiolitis. AJR Am J Roentgenol 2005; 185:354.
  43. Ryu JH, Myers JL, Swensen SJ. Bronchiolar disorders. Am J Respir Crit Care Med 2003; 168:1277.
  44. Cha SI, Fessler MB, Cool CD, et al. Lymphoid interstitial pneumonia: clinical features, associations and prognosis. Eur Respir J 2006; 28:364.
  45. Nicholson AG. Lymphocytic interstitial pneumonia and other lymphoproliferative disorders in the lung. Semin Respir Crit Care Med 2001; 22:409.
  46. Kofoed EM, Hwa V, Little B, et al. Growth hormone insensitivity associated with a STAT5b mutation. N Engl J Med 2003; 349:1139.
  47. Kaufman J, Komorowski R. Bronchiolitis obliterans organizing pneumonia in common variable immunodeficiency syndrome. Chest 1991; 100:552.
  48. Tanaka N, Kim JS, Bates CA, et al. Lung diseases in patients with common variable immunodeficiency: chest radiographic, and computed tomographic findings. J Comput Assist Tomogr 2006; 30:828.
  49. Wislez M, Sibony M, Naccache JM, et al. Organizing pneumonia related to common variable immunodeficiency. case report and literature review. Respiration 2000; 67:467.
  50. Gamboa PM, Merino JM, Maruri N, Martín-Granizo IF. Hypogammaglobulinemia resembling BOOP. Allergy 2000; 55:580.
  51. Mukhopadhyay S. Role of histology in the diagnosis of infectious causes of granulomatous lung disease. Curr Opin Pulm Med 2011; 17:189.
  52. Mukhopadhyay S, Gal AA. Granulomatous lung disease: an approach to the differential diagnosis. Arch Pathol Lab Med 2010; 134:667.
  53. van den Berg JM, van Koppen E, Ahlin A, et al. Chronic granulomatous disease: the European experience. PLoS One 2009; 4:e5234.
  54. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44 Suppl 2:S27.
  55. Cincinnati Children’s Hospital and Medical Center. Evidence-based care guideline for community acquired pneumonia in children 60 days through 17 years of age. http://www.guidelines.gov/content.aspx?id=9690. (Accessed on February 05, 2011).
  56. Ognibene FP, Pass HI, Roth JA, et al. Role of imaging and interventional techniques in the diagnosis of respiratory disease in the immunocompromised host. J Thorac Imaging 1988; 3:1.
  57. Newson T, Chippindale AJ, Cant AJ. Computed tomography scan assessment of lung disease in primary immunodeficiencies. Eur J Pediatr 1999; 158:29.
  58. Rusconi F, Panisi C, Dellepiane RM, et al. Pulmonary and sinus diseases in primary humoral immunodeficiencies with chronic productive cough. Arch Dis Child 2003; 88:1101.
  59. Chase NM, Verbsky JW, Hintermeyer MK, et al. Use of combination chemotherapy for treatment of granulomatous and lymphocytic interstitial lung disease (GLILD) in patients with common variable immunodeficiency (CVID). J Clin Immunol 2013; 33:30.
  60. Pellegrino R, Viegi G, Brusasco V, et al. Interpretative strategies for lung function tests. Eur Respir J 2005; 26:948.
  61. Rasekaba T, Lee AL, Naughton MT, et al. The six-minute walk test: a useful metric for the cardiopulmonary patient. Intern Med J 2009; 39:495.
  62. Enright PL. The six-minute walk test. Respir Care 2003; 48:783.
  63. Chetta A, Aiello M, Foresi A, et al. Relationship between outcome measures of six-minute walk test and baseline lung function in patients with interstitial lung disease. Sarcoidosis Vasc Diffuse Lung Dis 2001; 18:170.
  64. Deterding RR, Wagener JS. Lung biopsy in immunocompromised children: when, how, and who? J Pediatr 2000; 137:147.
  65. Sigurdsson MI, Isaksson HJ, Gudmundsson G, Gudbjartsson T. Diagnostic surgical lung biopsies for suspected interstitial lung diseases: a retrospective study. Ann Thorac Surg 2009; 88:227.
  66. Lee YC, Wu CT, Hsu HH, et al. Surgical lung biopsy for diffuse pulmonary disease: experience of 196 patients. J Thorac Cardiovasc Surg 2005; 129:984.
  67. Riley DJ, Costanzo EJ. Surgical biopsy: its appropriateness in diagnosing interstitial lung disease. Curr Opin Pulm Med 2006; 12:331.
  68. Engum SA. Minimal access thoracic surgery in the pediatric population. Semin Pediatr Surg 2007; 16:14.
  69. Rich AL, Le Jeune IR, McDermott L, Kinnear WJ. Serial lung function tests in primary immune deficiency. Clin Exp Immunol 2008; 151:110.
  70. Cunningham-Rundles C. Lung disease, antibodies and other unresolved issues in immune globulin therapy for antibody deficiency. Clin Exp Immunol 2009; 157 Suppl 1:12.
  71. Touw CM, van de Ven AA, de Jong PA, et al. Detection of pulmonary complications in common variable immunodeficiency. Pediatr Allergy Immunol 2010; 21:793.
  72. Turner PJ, Mehr S, Kemp AS. Detection of pulmonary complications in common variable immunodeficiency. Pediatr Allergy Immunol 2011; 22:449.
  73. van de Ven, de Jong PA, Terheggen-Lagro SW, van Montfrans JM. High-resolution computed tomography in pediatric common variable immunodeficiency: risks and benefits. Reply. Pediatr Allergy Immunol 2011; 22:451.
  74. Sweinberg SK, Wodell RA, Grodofsky MP, et al. Retrospective analysis of the incidence of pulmonary disease in hypogammaglobulinemia. J Allergy Clin Immunol 1991; 88:96.
  75. Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol 1999; 92:34.
  76. Roifman CM, Rao CP, Lederman HM, et al. Increased susceptibility to Mycoplasma infection in patients with hypogammaglobulinemia. Am J Med 1986; 80:590.
  77. Gelfand EW. Unique susceptibility of patients with antibody deficiency to mycoplasma infection. Clin Infect Dis 1993; 17 Suppl 1:S250.
  78. Oksenhendler E, Gérard L, Fieschi C, et al. Infections in 252 patients with common variable immunodeficiency. Clin Infect Dis 2008; 46:1547.
  79. Busse PJ, Razvi S, Cunningham-Rundles C. Efficacy of intravenous immunoglobulin in the prevention of pneumonia in patients with common variable immunodeficiency. J Allergy Clin Immunol 2002; 109:1001.
  80. Rubin SA. Radiology of immunologic diseases of the lung. J Thorac Imaging 1988; 3:21.
  81. Gregersen S, Aaløkken TM, Mynarek G, et al. Development of pulmonary abnormalities in patients with common variable immunodeficiency: associations with clinical and immunologic factors. Ann Allergy Asthma Immunol 2010; 104:503.
  82. Martínez García MA, de Rojas MD, Nauffal Manzur MD, et al. Respiratory disorders in common variable immunodeficiency. Respir Med 2001; 95:191.
  83. Busse PJ, Farzan S, Cunningham-Rundles C. Pulmonary complications of common variable immunodeficiency. Ann Allergy Asthma Immunol 2007; 98:1.
  84. Wehr C, Kivioja T, Schmitt C, et al. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood 2008; 111:77.
  85. Bates CA, Ellison MC, Lynch DA, et al. Granulomatous-lymphocytic lung disease shortens survival in common variable immunodeficiency. J Allergy Clin Immunol 2004; 114:415.
  86. Bouvry D, Mouthon L, Brillet PY, et al. Granulomatosis-associated common variable immunodeficiency disorder: a case-control study versus sarcoidosis. Eur Respir J 2013; 41:115.
  87. Aghamohammadi A, Parvaneh N, Tirgari F, et al. Lymphoma of mucosa-associated lymphoid tissue in common variable immunodeficiency. Leuk Lymphoma 2006; 47:343.
  88. Reichenberger F, Wyser C, Gonon M, et al. Pulmonary mucosa-associated lymphoid tissue lymphoma in a patient with common variable immunodeficiency syndrome. Respiration 2001; 68:109.
  89. Cunningham-Rundles C, Cooper DL, Duffy TP, Strauchen J. Lymphomas of mucosal-associated lymphoid tissue in common variable immunodeficiency. Am J Hematol 2002; 69:171.
  90. Hurst JR, Verma N, Lowe D, et al. British Lung Foundation/United Kingdom Primary Immunodeficiency Network Consensus Statement on the Definition, Diagnosis, and Management of Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency Disorders. J Allergy Clin Immunol Pract 2017; 5:938.
  91. Arnold DF, Wiggins J, Cunningham-Rundles C, et al. Granulomatous disease: distinguishing primary antibody disease from sarcoidosis. Clin Immunol 2008; 128:18.
  92. Mechanic LJ, Dikman S, Cunningham-Rundles C. Granulomatous disease in common variable immunodeficiency. Ann Intern Med 1997; 127:613.
  93. Popa V. Lymphocytic interstitial pneumonia of common variable immunodeficiency. Ann Allergy 1988; 60:203.
  94. Verbsky JW, Routes JM. Sarcoidosis and common variable immunodeficiency: similarities and differences. Semin Respir Crit Care Med 2014; 35:330.
  95. Rao N, Mackinnon AC, Routes JM. Granulomatous and lymphocytic interstitial lung disease: a spectrum of pulmonary histopathologic lesions in common variable immunodeficiency--histologic and immunohistochemical analyses of 16 cases. Hum Pathol 2015; 46:1306.
  96. Morimoto Y, Routes JM. Granulomatous disease in common variable immunodeficiency. Curr Allergy Asthma Rep 2005; 5:370.
  97. Aghamohammadi A, Abolhassani H, Rezaei N, et al. Cutaneous granulomas in common variable immunodeficiency: case report and review of literature. Acta Dermatovenerol Croat 2010; 18:107.
  98. Agarwal S, Smereka P, Harpaz N, et al. Characterization of immunologic defects in patients with common variable immunodeficiency (CVID) with intestinal disease. Inflamm Bowel Dis 2011; 17:251.
  99. Wheat WH, Cool CD, Morimoto Y, et al. Possible role of human herpesvirus 8 in the lymphoproliferative disorders in common variable immunodeficiency. J Exp Med 2005; 202:479.
  100. Pandolfi F, Paganelli R, Oliva A, et al. Increased IL-6 gene expression and production in patients with common variable immunodeficiency. Clin Exp Immunol 1993; 92:239.
  101. Aukrust P, Lien E, Kristoffersen AK, et al. Persistent activation of the tumor necrosis factor system in a subgroup of patients with common variable immunodeficiency--possible immunologic and clinical consequences. Blood 1996; 87:674.
  102. Mullighan CG, Fanning GC, Chapel HM, Welsh KI. TNF and lymphotoxin-alpha polymorphisms associated with common variable immunodeficiency: role in the pathogenesis of granulomatous disease. J Immunol 1997; 159:6236.
  103. Mullighan CG, Marshall SE, Bunce M, Welsh KI. Variation in immunoregulatory genes determines the clinical phenotype of common variable immunodeficiency. Genes Immun 1999; 1:137.
  104. Bondioni MP, Soresina A, Lougaris V, et al. Common variable immunodeficiency: computed tomography evaluation of bronchopulmonary changes including nodular lesions in 40 patients. Correlation with clinical and immunological data. J Comput Assist Tomogr 2010; 34:395.
  105. Mellemkjaer L, Hammarstrom L, Andersen V, et al. Cancer risk among patients with IgA deficiency or common variable immunodeficiency and their relatives: a combined Danish and Swedish study. Clin Exp Immunol 2002; 130:495.
  106. Cunningham-Rundles C, Lieberman P, Hellman G, Chaganti RS. Non-Hodgkin lymphoma in common variable immunodeficiency. Am J Hematol 1991; 37:69.
  107. Park JH, Levinson AI. Granulomatous-lymphocytic interstitial lung disease (GLILD) in common variable immunodeficiency (CVID). Clin Immunol 2010; 134:97.
  108. Maglione PJ, Overbey JR, Cunningham-Rundles C. Progression of Common Variable Immunodeficiency Interstitial Lung Disease Accompanies Distinct Pulmonary and Laboratory Findings. J Allergy Clin Immunol Pract 2015; 3:941.
  109. Mannina A, Chung JH, Swigris JJ, et al. Clinical Predictors of a Diagnosis of Common Variable Immunodeficiency-related Granulomatous-Lymphocytic Interstitial Lung Disease. Ann Am Thorac Soc 2016; 13:1042.
  110. Fasano MB, Sullivan KE, Sarpong SB, et al. Sarcoidosis and common variable immunodeficiency. Report of 8 cases and review of the literature. Medicine (Baltimore) 1996; 75:251.
  111. Pathria M, Urbine D, Zumberg MS, Guarderas J. Management of granulomatous lymphocytic interstitial lung disease in a patient with common variable immune deficiency. BMJ Case Rep 2016; 2016.
  112. Jolles S, Carne E, Brouns M, et al. FDG PET-CT imaging of therapeutic response in granulomatous lymphocytic interstitial lung disease (GLILD) in common variable immunodeficiency (CVID). Clin Exp Immunol 2017; 187:138.
  113. Lopez-Herrera G, Tampella G, Pan-Hammarström Q, et al. Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity. Am J Hum Genet 2012; 90:986.
  114. Schubert D, Bode C, Kenefeck R, et al. Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations. Nat Med 2014; 20:1410.
  115. Kuehn HS, Ouyang W, Lo B, et al. Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4. Science 2014; 345:1623.
  116. Buchbinder D, Baker R, Lee YN, et al. Identification of patients with RAG mutations previously diagnosed with common variable immunodeficiency disorders. J Clin Immunol 2015; 35:119.
  117. Winkelstein JA, Marino MC, Lederman HM, et al. X-linked agammaglobulinemia: report on a United States registry of 201 patients. Medicine (Baltimore) 2006; 85:193.
  118. Conley ME, Rohrer J, Minegishi Y. X-linked agammaglobulinemia. Clin Rev Allergy Immunol 2000; 19:183.
  119. Bondioni MP, Duse M, Plebani A, et al. Pulmonary and sinusal changes in 45 patients with primary immunodeficiencies: computed tomography evaluation. J Comput Assist Tomogr 2007; 31:620.
  120. Plebani A, Soresina A, Rondelli R, et al. Clinical, immunological, and molecular analysis in a large cohort of patients with X-linked agammaglobulinemia: an Italian multicenter study. Clin Immunol 2002; 104:221.
  121. Kainulainen L, Varpula M, Liippo K, et al. Pulmonary abnormalities in patients with primary hypogammaglobulinemia. J Allergy Clin Immunol 1999; 104:1031.
  122. Curtin JJ, Webster AD, Farrant J, Katz D. Bronchiectasis in hypogammaglobulinaemia--a computed tomography assessment. Clin Radiol 1991; 44:82.
  123. Notarangelo LD. Primary immunodeficiencies. J Allergy Clin Immunol 2010; 125:S182.
  124. Myers LA, Patel DD, Puck JM, Buckley RH. Hematopoietic stem cell transplantation for severe combined immunodeficiency in the neonatal period leads to superior thymic output and improved survival. Blood 2002; 99:872.
  125. Blackburn MR, Kellems RE. Adenosine deaminase deficiency: metabolic basis of immune deficiency and pulmonary inflammation. Adv Immunol 2005; 86:1.
  126. Sauer AV, Aiuti A. New insights into the pathogenesis of adenosine deaminase-severe combined immunodeficiency and progress in gene therapy. Curr Opin Allergy Clin Immunol 2009; 9:496.
  127. Somech R, Lai YH, Grunebaum E, et al. Polyethylene glycol-modified adenosine deaminase improved lung disease but not liver disease in partial adenosine deaminase deficiency. J Allergy Clin Immunol 2009; 124:848.
  128. Nowak-Wegrzyn A, Crawford TO, Winkelstein JA, et al. Immunodeficiency and infections in ataxia-telangiectasia. J Pediatr 2004; 144:505.
  129. Bott L, Lebreton J, Thumerelle C, et al. Lung disease in ataxia-telangiectasia. Acta Paediatr 2007; 96:1021.
  130. Schroeder SA, Swift M, Sandoval C, Langston C. Interstitial lung disease in patients with ataxia-telangiectasia. Pediatr Pulmonol 2005; 39:537.
  131. McGrath-Morrow SA, Gower WA, Rothblum-Oviatt C, et al. Evaluation and management of pulmonary disease in ataxia-telangiectasia. Pediatr Pulmonol 2010; 45:847.
  132. Morrell D, Cromartie E, Swift M. Mortality and cancer incidence in 263 patients with ataxia-telangiectasia. J Natl Cancer Inst 1986; 77:89.
  133. Sandoval C, Swift M. Hodgkin disease in ataxia-telangiectasia patients with poor outcomes. Med Pediatr Oncol 2003; 40:162.
  134. Winkelstein JA, Marino MC, Ochs H, et al. The X-linked hyper-IgM syndrome: clinical and immunologic features of 79 patients. Medicine (Baltimore) 2003; 82:373.
  135. Lougaris V, Badolato R, Ferrari S, Plebani A. Hyper immunoglobulin M syndrome due to CD40 deficiency: clinical, molecular, and immunological features. Immunol Rev 2005; 203:48.
  136. Hostoffer RW, Berger M, Clark HT, Schreiber JR. Disseminated Histoplasma capsulatum in a patient with hyper IgM immunodeficiency. Pediatrics 1994; 94:234.
  137. Lee MY, Chung JH, Shin JH, et al. Lymphonodular cryptococcosis diagnosed by fine needle aspiration cytology in hyper-IgM syndrome. A case report. Acta Cytol 2001; 45:241.
  138. Antachopoulos C. Invasive fungal infections in congenital immunodeficiencies. Clin Microbiol Infect 2010; 16:1335.
  139. Jesus AA, Duarte AJ, Oliveira JB. Autoimmunity in hyper-IgM syndrome. J Clin Immunol 2008; 28 Suppl 1:S62.
  140. Salvator H, Mahlaoui N, Catherinot E, et al. Pulmonary manifestations in adult patients with chronic granulomatous disease. Eur Respir J 2015; 45:1613.
  141. Winkelstein JA, Marino MC, Johnston RB Jr, et al. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore) 2000; 79:155.
  142. Lee PP, Chan KW, Jiang L, et al. Susceptibility to mycobacterial infections in children with X-linked chronic granulomatous disease: a review of 17 patients living in a region endemic for tuberculosis. Pediatr Infect Dis J 2008; 27:224.
  143. Khanna G, Kao SC, Kirby P, Sato Y. Imaging of chronic granulomatous disease in children. Radiographics 2005; 25:1183.
  144. Morgenstern DE, Gifford MA, Li LL, et al. Absence of respiratory burst in X-linked chronic granulomatous disease mice leads to abnormalities in both host defense and inflammatory response to Aspergillus fumigatus. J Exp Med 1997; 185:207.
  145. Meissner F, Seger RA, Moshous D, et al. Inflammasome activation in NADPH oxidase defective mononuclear phagocytes from patients with chronic granulomatous disease. Blood 2010; 116:1570.
  146. Schäppi MG, Jaquet V, Belli DC, Krause KH. Hyperinflammation in chronic granulomatous disease and anti-inflammatory role of the phagocyte NADPH oxidase. Semin Immunopathol 2008; 30:255.
  147. Rosenzweig SD. Inflammatory manifestations in chronic granulomatous disease (CGD). J Clin Immunol 2008; 28 Suppl 1:S67.
  148. De Ravin SS, Naumann N, Cowen EW, et al. Chronic granulomatous disease as a risk factor for autoimmune disease. J Allergy Clin Immunol 2008; 122:1097.
  149. Hauck F, Heine S, Beier R, et al. Chronic granulomatous disease (CGD) mimicking neoplasms: a suspected mediastinal teratoma unmasking as thymic granulomas due to X-linked CGD, and 2 related cases. J Pediatr Hematol Oncol 2008; 30:877.
  150. McLean-Tooke AP, Aldridge C, Gilmour K, et al. An unusual cause of granulomatous disease. BMC Clin Pathol 2007; 7:1.
  151. Brunner J, Dockter G, Rösen-Wolff A, Roesler J. X-linked chronic granulomatous disease (CGD) caused by an intra-exonic splice mutation (CYBB exon 3, c.262G->A) is mimicking juvenile sarcoidosis. Clin Exp Rheumatol 2007; 25:336.
  152. Godoy MC, Vos PM, Cooperberg PL, et al. Chest radiographic and CT manifestations of chronic granulomatous disease in adults. AJR Am J Roentgenol 2008; 191:1570.
  153. De Ravin SS, Naumann N, Robinson MR, et al. Sarcoidosis in chronic granulomatous disease. Pediatrics 2006; 117:e590.
  154. Towbin AJ, Chaves I. Chronic granulomatous disease. Pediatr Radiol 2010; 40:657.
  155. Tabarsi P, Mirsaeidi M, Karimi S, et al. Lymphocytic bronchiolitis as presenting disorder in an undiagnosed adult patient with chronic granulomatous disease. Iran J Allergy Asthma Immunol 2007; 6:219.
  156. Siddiqui S, Anderson VL, Hilligoss DM, et al. Fulminant mulch pneumonitis: an emergency presentation of chronic granulomatous disease. Clin Infect Dis 2007; 45:673.
  157. Ameratunga R, Woon ST, Vyas J, Roberts S. Fulminant mulch pneumonitis in undiagnosed chronic granulomatous disease: a medical emergency. Clin Pediatr (Phila) 2010; 49:1143.
  158. Freeman AF, Holland SM. Clinical manifestations of hyper IgE syndromes. Dis Markers 2010; 29:123.
  159. Grimbacher B, Holland SM, Gallin JI, et al. Hyper-IgE syndrome with recurrent infections--an autosomal dominant multisystem disorder. N Engl J Med 1999; 340:692.
  160. Holland SM, DeLeo FR, Elloumi HZ, et al. STAT3 mutations in the hyper-IgE syndrome. N Engl J Med 2007; 357:1608.
  161. Minegishi Y, Saito M, Tsuchiya S, et al. Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature 2007; 448:1058.
  162. Buckley RH, Wray BB, Belmaker EZ. Extreme hyperimmunoglobulinemia E and undue susceptibility to infection. Pediatrics 1972; 49:59.
  163. Freeman AF, Holland SM. The hyper-IgE syndromes. Immunol Allergy Clin North Am 2008; 28:277.
  164. Freeman AF, Kleiner DE, Nadiminti H, et al. Causes of death in hyper-IgE syndrome. J Allergy Clin Immunol 2007; 119:1234.
  165. Melia E, Freeman AF, Shea YR, et al. Pulmonary nontuberculous mycobacterial infections in hyper-IgE syndrome. J Allergy Clin Immunol 2009; 124:617.
  166. Leonard GD, Posadas E, Herrmann PC, et al. Non-Hodgkin's lymphoma in Job's syndrome: a case report and literature review. Leuk Lymphoma 2004; 45:2521.