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Pulmonary Eosinophilia

  • Author: Jussi J Saukkonen, MD; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
 
Updated: Dec 31, 2015
 

Background

Pulmonary diseases associated with tissue and/or blood eosinophilia are a heterogeneous group of disorders. Various nosologies have been offered, but this article classifies these syndromes as extrinsic or intrinsic in origin. Some syndromes overlap, but this approach is convenient from the diagnostic standpoint.[1]

Inhaled or ingested extrinsic factors, including medications and infectious agents (eg, parasites, fungi, mycobacteria), may trigger an eosinophilic immune response. This may be mild and self-limited, as in Loeffler syndrome.

Intrinsic pulmonary eosinophilic syndromes are generally idiopathic in nature. They include a diverse group of autoimmune and idiopathic syndromes ranging from blood dyscrasias to vasculitis. This group includes chronic eosinophilic pneumonia (CEP), idiopathic hypereosinophilic syndrome (IHES), Churg-Strauss syndrome (CSS), and eosinophilic granuloma (EG; pulmonary histiocytosis X or Langerhans cell granulomatosis).

Eosinophilia and pulmonary infiltrates have been reported in patients with AIDS, lymphoma, a variety of inflammatory lung diseases, and collagen vascular diseases (see Causes).

Asthma may manifest with marked eosinophilia, with or without infiltrates.

The airway inflammation of chronic obstructive pulmonary disease (COPD) is largely neutrophilic, but 20-40% of induced sputum samples from individuals with stable COPD have eosinophilic airway inflammation, associated with elevated levels of sputum interleukin (IL)–5.[2]

Eosinophilic bronchitis without asthma (EBWA) is characterized by cough for at least 2 months, a sputum eosinophil count greater than 3%, and no evidence of airway obstruction. Affected patients are usually middle-aged, are nonatopic, and have no history of smoking. Activation and eosinophilic infiltration of the superficial airway occurs, rather than of airway smooth muscle.[3]

Eosinophilia may often be seen in the bronchoalveolar lavage fluid in patients with desquamative interstitial pneumonitis.[4]

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Pathophysiology

Tissue pathology is largely related to the release of toxic eosinophil products. These products include major basic protein, eosinophil cationic protein, and eosinophil-derived neurotoxin, which damage the respiratory epithelium, induce ciliastasis, and influence mucus production. Tissue injury may also be caused by the release of reactive oxygen species. The release of platelet-activating factor and leukotrienes contributes to bronchospasm. In some syndromes, such as tropical pulmonary eosinophilia (TPE) and CEP, interstitial fibrosis may result from chronic inflammation.[1] Commonly, lung parenchyma is affected, but in certain extrinsic and intrinsic syndromes, other organs may be affected.

Extrinsic eosinophilic syndromes

See the list below:

  • Loeffler syndrome: The pathogenesis of Loeffler syndrome is unknown but presumably reflects a hypersensitivity response to an ingested or inhaled antigen from food, medication, or an infectious agent. Many of the original cases of Loeffler syndrome were thought to be related to Ascaris infection.
  • DRESS syndrome: The Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a severe drug hypersensitivity reaction, notable for skin rash, fever, lymphadenopathy, and involvement of various tissues, such as hepatitis, pneumonitis, or myositis. So far, numerous drugs, such as sulfonamides, phenobarbital, sulfasalazine, carbamazepine, and phenytoin, have been reported to cause the DRESS syndrome. [5]
  • Parasitic infections: Migrating parasites traversing the lungs may cause bronchospasm, dyspnea, and pulmonary infiltrates. Embolization of microfilariae or eggs, which degenerate and expose antigens to the local immune system, leads to granuloma formation. Local elaboration of chemokines and cytokines plays a role in T-cell recruitment and granuloma formation. Persistent inflammation may lead to parenchymal necrosis and fibrosis.
  • Schistosomiasis: The most common pulmonary complication is pulmonary hypertension from chronic embolization of ova.
  • TPE: These patients have marked immune responses to filariae, while other individuals infected with Wuchereria bancrofti or Brugia malayi have suppressed parasite-specific immune responses. Patients with TPE rarely have signs of lymphatic filariasis. Elevated immunoglobulin E (IgE) and immunoglobulin G (IgG) levels in patients with TPE reflect polyclonal B-cell activation. The Brugia malayi larval gamma-glutaryl transpeptidase has similarities with that found on human pulmonary epithelium, suggesting a pathogenetic role for this transpeptidase. [6]
  • Strongyloidiasis: Patients who are immunocompromised, including those recently prescribed systemic corticosteroids, may develop hyperinfection syndrome, in which large numbers of recently released larvae burrow through the intestine and migrate to the lungs. Sepsis and respiratory failure may result from accompanying enteric bacteremia.
  • Fungal causes: Allergic bronchopulmonary aspergillosis (ABPA) is an immunologic response to Aspergillus antigens in the airways of individuals with obstructive lung disease. Both IgE-mediated and immune complex–mediated hypersensitivity responses are active. Chemokines recruit CD4 + T helper 2 antigen-specific cells to the lung. The inflammatory responses lead to airway reactivity, mucus hypersecretion, epithelial damage, bronchiectasis, eosinophilic pneumonia, and parenchymal injury and fibrosis. Aspergillus proteases likely also contribute to airway damage. Other fungi have also been found to cause a similar disorder, prompting some to suggest renaming this disorder allergic bronchopulmonary mycosis.
  • Bronchocentric granulomatosis: This idiopathic condition, in which the mucosal epithelium is supplanted by epithelioid histiocytes and then by granuloma formation, is often associated with ABPA.
  • AEP: Increasing evidence suggests an association with inhaled exposures and, in some cases, infections. [7] An association between AEP and new-onset cigarette smoking has been reported. [8] Many patients have engaged in dusty outdoor activities, suggesting a hypersensitivity response to inhaled antigens. AEP has also been reported following allogeneic hematopoietic stem cell transplantation, coexisting with graft versus host disease. [9] Eosinophilic alveolitis may be extensive, and profound hypoxemia with respiratory failure may result.

Intrinsic eosinophilic syndromes

See the list below:

  • CEP: The pathogenesis is unknown. CEP may occur in isolation and/or in association with polyarteritis nodosa, rheumatoid arthritis, scleroderma, ulcerative colitis, breast carcinoma, [10] and histiocytic lymphoma. Most patients have evidence of asthma and atopy. Although not a prominent feature, microgranulomata are occasionally seen on biopsy specimens, suggesting that an antigen-driven, T-cell–mediated process is active.
  • IHES: Some patients display overproduction of chemokines, [11] proeosinophilic factors, including interleukin (IL)–4 and IL-5 by clonally expanded differentiation clusters 3 and 4 (CD3 + and CD4 +) and Th2-like lymphocytes. These patients also have evidence of polyclonal hypergammaglobulinemia. Other patients have increased numbers of stem cells committed to the eosinophil lineage. Pulmonary involvement is manifested as wheezing, coughing, pulmonary edema, and pleural effusions. Pulmonary emboli result from a hypercoagulable state. Multiple organ systems may be affected, resulting in gastrointestinal tract dysfunction, skeletal muscle weakness (which may lead to respiratory failure), endomyocardial fibrosis, myocarditis, congestive heart failure, and/or valvular disease.
  • CSS: The pathogenesis is unknown. Inhaled or ingested antigens have been proposed as causative agents in susceptible individuals. The frequency of T regulatory cells that produce IL-10 and transforming growth factor (TGF)–beta (Treg1) has been reported to be decreased in active CSS, in comparison with asthma, EP, and inactive CSS. [12] Reports linking the syndrome with the leukotriene inhibitors zafirlukast and montelukast in the setting of steroid withdrawal suggest these agents unmask preexisting CSS rather than suggesting that CSS is a direct causal effect of these agents. Similarly, omalizumab treatment allowing weaning of corticosteroids or their initiation has been reported to unmask CSS. [13] Vasculitis may affect the sinuses, central and peripheral nervous systems, gastrointestinal tract, kidneys, and heart.
  • EG: The cause is unknown, but the reactive histiocytic proliferation suggests a reactive process, perhaps to an unknown antigen. Patients develop reticulonodular interstitial and cystic disease. EG is strongly associated with cigarette smoking. This may affect the lungs, bones (including the skull, resulting in diabetes insipidus), and other organs. Tissue and peripheral eosinophilia are generally not prominent features of this condition.
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Epidemiology

Frequency

United States

Intrinsic syndromes are uncommon. Regarding extrinsic syndromes, medication- or food-related syndromes are sporadic. Occasionally, outbreaks are related to contaminated food or medication, eg, L-tryptophan and toxic oil syndrome.

  • Strongyloidiasis is the most common infection in the United States and is usually observed in individuals from the south, southeast, and Caribbean areas.
  • Schistosoma mansoni infection is observed in the Caribbean.
  • Toxocariasis (visceral larva migrans) is usually found in the southeast region of the country, but it can be found worldwide.
  • Ascariasis, because it is prevalent worldwide, is likely to be observed in the United States.
  • Among the hookworms, Necator americanus is endemic to the southeastern United States.
  • Occasionally, international visitors or recent immigrants may present with other parasitic infections such as TPE and paragonimiasis.
  • For fungal causes, ABPA is relatively common, with some estimates indicating that 5-10% of people who are steroid-dependent and have asthma meet the criteria. Of persons with cystic fibrosis, 10% have ABPA. Coccidioidomycosis is found predominantly in the southwestern part of the United States or among individuals with a relevant travel history.

International

Intrinsic syndromes are uncommon. Regarding extrinsic syndromes, in much of the world, parasitic infections are endemic.

  • Ascaris is likely the most prevalent nematode infecting humans worldwide but tends to occur in tropical or subtropical areas.
  • Ancylostoma duodenale is commonly found in the Eastern Hemisphere.
  • Visceral larva migrans is found throughout the world.
  • Strongyloidiasis, which usually occurs in warmer climates, has a worldwide prevalence of approximately 50-100 million individuals.
  • Schistosomiasis is common in Africa, Asia, Latin America, and South America. Paragonimiasis and clonorchiasis are common in Asia.
  • TPE is often observed in southern Asia, Southeast Asia, and South America. Most reported cases have occurred in ethnic Indians, while it is uncommon in Chinese persons. TPE is actually observed in a minority of patients infected with the causative filariae.

Mortality/Morbidity

See the list below:

  • With the exception of Loeffler syndrome and drug-induced disease, these syndromes may be associated with significant morbidity. While most are responsive to corticosteroids, recognition of infection and institution of an appropriate therapy are important in preventing chronicity of symptoms and, in some cases, respiratory failure.
  • Patients with IHES may develop congestive heart failure, pulmonary emboli, and multiorgan-system dysfunction. Mortality in cases of IHES has been improving with increasing therapeutic options; now, 80% of patients are surviving at 5 years and 40% are surviving at 10-15 years.
  • The mortality rate in cases of CSS has been decreasing, with approximately 75% of patients surviving 5 years.

Race

See the list below:

  • No clearly defined racial predispositions have been identified in these syndromes.
  • Parasitic infections are endemic in many geographic areas, but they reflect public health conditions rather than racial predispositions.

Sex

See the list below:

  • TPE has been reported to have a male predominance, at a male-to-female ratio of 4:1. AEP is more common in men than in women, unlike CEP.
  • Among the intrinsic syndromes, CEP is twice as common in women as in men, but this sexual disparity declines with increasing age. For IHES, approximately 90% of cases are found in men and 10% are found in women. For CSS, no sexual predisposition has been reported. For EG, no sexual predominance is described. The older literature suggests a male predominance, but more recent data suggest equal distribution between sexes, possibly reflecting the changing demographics of cigarette smoking, which is thought to be etiologic.

Age

See the list below:

  • Extrinsic syndromes tend to affect adults, but exceptions exist. Toxocariasis tends to occur in children and is often associated with geophagia. Ascariasis tends to occur in children. ABPA usually occurs in adults but may occur in children, including some patients with cystic fibrosis. AEP usually occurs in persons in their third decade of life.
  • Intrinsic syndromes generally affect adults. CEP peak incidence is in the fourth decade of life. IHES usually occurs in people aged 20-50 years; however, it has also been infrequently reported in children. Most cases of CSS have been reported in adults. EG may affect individuals ranging in age from infancy to old age, but it most frequently affects patients in their second to third decade of life.
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Contributor Information and Disclosures
Author

Jussi J Saukkonen, MD Associate Professor, Department of Internal Medicine, Division of Pulmonary/Critical Care Medicine, Boston University School of Medicine, Boston Medical Center

Jussi J Saukkonen, MD is a member of the following medical societies: American Thoracic Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD, FACP, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society

Disclosure: Nothing to disclose.

Additional Contributors

Gregory Tino, MD Director of Pulmonary Outpatient Practices, Associate Professor, Department of Medicine, Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania Medical Center and Hospital

Gregory Tino, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

References
  1. Sharma P, Sharma A, Vishwakarma AL, Agnihotri PK, Sharma S, Srivastava M. Host lung immunity is severely compromised during tropical pulmonary eosinophilia: role of lung eosinophils and macrophages. J Leukoc Biol. 2015 Oct 21. [Medline].

  2. Bafadhel M, Saha S, Siva R, et al. Sputum IL-5 concentration is associated with a sputum eosinophilia and attenuated by corticosteroid therapy in COPD. Respiration. 2009. 78(3):256-62. [Medline]. [Full Text].

  3. Gonlugur U, Gonlugur TE. Eosinophilic bronchitis without asthma. Int Arch Allergy Immunol. 2008. 147(1):1-5. [Medline].

  4. Kawabata Y, Takemura T, Hebisawa A, et al. Eosinophilia in bronchoalveolar lavage fluid and architectural destruction are features of desquamative interstitial pneumonia. Histopathology. 2008 Jan. 52(2):194-202. [Medline].

  5. Lee JH, Park HK, Heo J, et al. Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome induced by celecoxib and anti-tuberculosis drugs. J Korean Med Sci. 2008 Jun. 23(3):521-5. [Medline]. [Full Text].

  6. Vijayan VK. Tropical pulmonary eosinophilia: pathogenesis, diagnosis and management. Curr Opin Pulm Med. 2007 Sep. 13(5):428-33. [Medline].

  7. Swartz J, Stoller JK. Acute eosinophilic pneumonia complicating Coccidioides immitis pneumonia: a case report and literature review. Respiration. 2009. 77(1):102-6. [Medline].

  8. Uchiyama H, Suda T, Nakamura Y, et al. Alterations in smoking habits are associated with acute eosinophilic pneumonia. Chest. 2008 May. 133(5):1174-80. [Medline].

  9. Yoshimi M, Nannya Y, Watanabe T, et al. Acute eosinophilic pneumonia is a non-infectious lung complication after allogeneic hematopoietic stem cell transplantation. Int J Hematol. 2009 Mar. 89(2):244-8. [Medline].

  10. Cottin V, Frognier R, Monnot H, Levy A, DeVuyst P, Cordier JF. Chronic eosinophilic pneumonia after radiation therapy for breast cancer. Eur Respir J. 2004 Jan. 23(1):9-13. [Medline].

  11. Hartl D, Latzin P, Zissel G, Krane M, Krauss-Etschmann S, Griese M. Chemokines indicate allergic bronchopulmonary aspergillosis in patients with cystic fibrosis. Am J Respir Crit Care Med. 2006 Jun 15. 173(12):1370-6. [Medline].

  12. Saito H, Tsurikisawa N, Tsuburai T, Akiyama K. Involvement of regulatory T cells in the pathogenesis of Churg-Strauss syndrome. Int Arch Allergy Immunol. 2008. 146 Suppl 1:73-6. [Medline].

  13. Wechsler ME, Wong DA, Miller MK, Lawrence-Miyasaki L. Churg-strauss syndrome in patients treated with omalizumab. Chest. 2009 Aug. 136(2):507-18. [Medline].

  14. Kumar R. Mild, moderate, and severe forms of allergic bronchopulmonary aspergillosis: a clinical and serologic evaluation. Chest. 2003 Sep. 124(3):890-2. [Medline].

  15. Kaliterna DM, Perkovic D, Radic M. Churg-Strauss syndrome associated with montelukast therapy. J Asthma. 2009 Aug. 46(6):604-5. [Medline].

  16. de Gorgolas M, Casado V, Renedo G, Alen JF, Fernandez Guerrero ML. Nodular lung schistosomiais lesions after chemotherapy for dysgerminoma. Am J Trop Med Hyg. 2009 Sep. 81(3):424-7. [Medline].

  17. Velthove KJ, Bracke M, Souverein PC, et al. Identification of exacerbations in obstructive lung disease through biomarkers. Biomarkers. 2009 Sep 7. [Medline].

  18. Hillas G, Loukides S, Kostikas K, Bakakos P. Biomarkers Obtained by Non-Invasive Methods in Patients with COPD: Where do we Stand, what do we Expect?. Curr Med Chem. 2009. 16(22):2824-38. [Medline].

  19. Agarwal R, Gupta D, Aggarwal AN, Saxena AK, Chakrabarti A, Jindal SK. Clinical significance of hyperattenuating mucoid impaction in allergic bronchopulmonary aspergillosis: an analysis of 155 patients. Chest. 2007 Oct. 132(4):1183-90. [Medline].

  20. Chung SY, Lee JH, Kim TH, et al. F-18 FDG PET scan findings in patients with Loeffler's syndrome. Clin Nucl Med. 2009 Sep. 34(9):570-5. [Medline].

  21. Chu E, Whitlock WL, Dietrich RA. Pulmonary hyperinfection syndrome with Strongyloides stercoralis. Chest. 1990 Jun. 97(6):1475-7. [Medline].

  22. Tsurikisawa N, Taniguchi M, Saito H, et al. Treatment of Churg-Strauss syndrome with high-dose intravenous immunoglobulin. Ann Allergy Asthma Immunol. 2004 Jan. 92(1):80-7. [Medline].

  23. Hellmich B, Gross WL. Recent progress in the pharmacotherapy of Churg-Strauss syndrome. Expert Opin Pharmacother. 2004 Jan. 5(1):25-35. [Medline].

  24. [Guideline] Dicpinigaitis PV. Chronic cough due to asthma: ACCP evidence-based clinical practice guidelines. Chest. 2006 Jan. 129(1 Suppl):75S-79S. [Medline].

  25. [Guideline] Tarlo SM. Cough: occupational and environmental considerations: ACCP evidence-based clinical practice guidelines. Chest. 2006 Jan. 129(1 Suppl):186S-196S. [Medline].

  26. Wark P. Pathogenesis of allergic bronchopulmonary aspergillosis and an evidence-based review of azoles in treatment. Respir Med. 2004 Oct. 98(10):915-23. [Medline].

  27. Allen JN, Davis WB. Eosinophilic lung diseases. Am J Respir Crit Care Med. 1994 Nov. 150(5 Pt 1):1423-38. [Medline].

  28. Allen JN, Pacht ER, Gadek JE, Davis WB. Acute eosinophilic pneumonia as a reversible cause of noninfectious respiratory failure. N Engl J Med. 1989 Aug 31. 321(9):569-74. [Medline].

  29. Barrett-Connor E. Parasitic pulmonary disease. Am Rev Respir Dis. 1982 Sep. 126(3):558-63. [Medline].

  30. Cordier JF. Eosinophilic pneumonias. Schwarz MI, King TE, eds. Interstitial Lung Disease. Hamilton, Ontario: BC Decker; 1998. 559-95.

  31. Davis WB, Fells GA, Sun XH, Gadek JE, Venet A, Crystal RG. Eosinophil-mediated injury to lung parenchymal cells and interstitial matrix. A possible role for eosinophils in chronic inflammatory disorders of the lower respiratory tract. J Clin Invest. 1984 Jul. 74(1):269-78. [Medline]. [Full Text].

  32. Fauci AS, Harley JB, Roberts WC, Ferrans VJ, Gralnick HR, Bjornson BH. NIH conference. The idiopathic hypereosinophilic syndrome. Clinical, pathophysiologic, and therapeutic considerations. Ann Intern Med. 1982 Jul. 97(1):78-92. [Medline].

  33. Jederlinic PJ, Sicilian L, Gaensler EA. Chronic eosinophilic pneumonia. A report of 19 cases and a review of the literature. Medicine (Baltimore). 1988 May. 67(3):154-62. [Medline].

  34. Lanham JG, Elkon KB, Pusey CD, Hughes GR. Systemic vasculitis with asthma and eosinophilia: a clinical approach to the Churg-Strauss syndrome. Medicine (Baltimore). 1984 Mar. 63(2):65-81. [Medline].

  35. Naughton M, Fahy J, FitzGerald MX. Chronic eosinophilic pneumonia. A long-term follow-up of 12 patients. Chest. 1993 Jan. 103(1):162-5. [Medline].

  36. Ottesen EA, Nutman TB. Tropical pulmonary eosinophilia. Annu Rev Med. 1992. 43:417-24. [Medline].

  37. Peros-Golubicic T, Smojver-Jezek S. Hypereosinophilic syndrome: diagnosis and treatment. Curr Opin Pulm Med. 2007 Sep. 13(5):422-7. [Medline].

  38. Pinkston P, Vijayan VK, Nutman TB, et al. Acute tropical pulmonary eosinophilia. Characterization of the lower respiratory tract inflammation and its response to therapy. J Clin Invest. 1987 Jul. 80(1):216-25. [Medline]. [Full Text].

  39. Powers MA, Askin FB, Cresson DH. Pulmonary eosinophilic granuloma. 25-year follow-up. Am Rev Respir Dis. 1984 Mar. 129(3):503-7. [Medline].

  40. Slavin RG, Hutcheson PS, Chauhan B, Bellone CJ. An overview of allergic bronchopulmonary aspergillosis with some new insights. Allergy Asthma Proc. 2004 Nov-Dec. 25(6):395-9. [Medline].

  41. Sterk PJ, Hiemstra PS. Eosinophil progenitors in sputum: throwing out the baby with the bath water?. Am J Respir Crit Care Med. 2004 Mar 1. 169(5):549-50. [Medline].

  42. Tillie-Leblond I, Tonnel AB. Allergic bronchopulmonary aspergillosis. Allergy. 2005 Aug. 60(8):1004-13. [Medline].

  43. Wardlaw A, Geddes DM. Allergic bronchopulmonary aspergillosis: a review. J R Soc Med. 1992 Dec. 85(12):747-51. [Medline].

  44. Weller PF. The immunobiology of eosinophils. N Engl J Med. 1991 Apr 18. 324(16):1110-8. [Medline].

  45. Woolnough K, Wardlaw AJ. Eosinophilia in Pulmonary Disorders. Immunol Allergy Clin North Am. 2015 Aug. 35 (3):477-92. [Medline].

 
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