An overview of eosinophilic lung diseases

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Eosinophilic lung diseases describes a variety of lung diseases which can be idiopathic (simple pulmonary eosinophilia, acute eosinophilic pneumonia and chronic eosinophilic pneumonia and hypereosinophilic syndrome), secondary to various clinical entities (to drugs, parasites, fungal infections, irradiation or toxic product) or associated with diffuse lung diseases (connective tissue diseases and some neoplasms). Asthma, which is the most common cause of pulmonary eosinophilia, is frequently concomitant and can be a prerequisite, as in allergic bronchopulmonary aspergillosis (ABPA) and Churg-Strauss syndrome. Herein, we aimed to review the clinical findings and differential diagnosis of eosinophilic lung diseases.

Eosinophilic lung diseases (ELD) are a group of pulmonary disorders associated with peripheral and/or tissue eosinophilia. ELDs are characterized by the accumulation of eosinophils in alveolar spaces, the interstitium, or both. ELD was first described as ‘pulmonary infiltrates with (blood) eosinophilia syndrome’. Later, it was recognized that ELD consists of several lung diseases with eosinophil infiltration in the lungs and little or no increase in the peripheral blood eosinophil numbers [1, 2]. In these patients, tissue eosinophil levels can be high while peripheral blood eosinophil levels are normal. The eosinophil count in the peripheral blood represents the balance between bone marrow production and tissue migration of eosinophils. In a healthy adult, peripheral blood eosinophil percentage can be 3-5% of white blood cells (WBC) with a corresponding absolute eosinophil count (#eosinophil) of 350-500/μL. Eosinophil amounts higher than these levels are accepted as eosinophilia [2-4]. On the other hand, tissue eosinophil levels can be high while peripheral blood eosinophil levels are normal. This situation generally occurs as a result of accumulation of the eosinophils in tissues. Thus, in many ELDs blood eosinophil levels may not be an accurate indicator of eosinophil-related tissue injury. In such cases, eosinophilia must be shown by tests directly reflecting tissue contents [5-7]. Lung biopsy is the most direct and reliable way to verify increased lung eosinophils. Considering that lung biopsy is an invasive test, it is only occasionally necessary to diagnose the various ELD or eosinophilic pneumonia (EP) cases. Instead, bronchoalveolar lavage (BAL) is frequently used to identify ELD or EP, and an increased BAL eosinophil level usually corresponds to increased lung tissue eosinophils. Accumulated eosinophils in tissues directly damage the epithelial and endothelial cells and promote the pro-inflammatory response resulting in the development of the clinical abnormalities attendant to the ELD [5, 7, 8].

ELD can be idiopathic (simple pulmonary eosinophilia, acute eosinophilic pneumonia (AEP) and chronic eosinophilic pneumonia (CEP) and hypereosinophilic syndrome], secondary to various clinical entities (to drugs, parasites, fungal infections, irradiation or toxic products) or associated with diffuse lung diseases (connective tissue diseases and some neoplasms). Asthma, which is the most common cause of pulmonary eosinophilia, is frequently concomitant as in allergic bronchopulmonary aspergillosis (ABPA) and Churg-Strauss syndrome [9-12].

In this article, we review the clinical findings and differential diagnosis of ELDs.

Simple Pulmonary Eosinophilia (Löffler syndrome): Simple pulmonary eosinophilia is characterized by patchy and migratory pulmonary infiltrates on chest radiographs with increased eosinophil counts in peripheral blood. Patients have few or no pulmonary symptoms and are often identified by incidental findings on chest x-rays or complete blood counts. It is usually associated with parasitic infections or drug reactions but can also be idiopathic. Although corticosteroids can be used for resolution of pulmonary infiltrates and blood eosinophilia, their use is rarely necessary [9, 13-15].

Chronic Eosinophilic Pneumonia (CEP): CEP, a chronic and ultimately life-threatening entity with severe dyspnea, high fever, night sweating and weight loss, is diagnosed with the presence of these criteria: 1. Progressive and dense pulmonary infiltrates arranged in a peculiar peripheral pattern, 2. rapid resolution with corticosteroid therapy, 3. pulmonary infiltration best described as a “photonegative” or “reversal” of the shadow seen in pulmonary edema or alveolar proteionsis and 4. recurrence of lesions in the same locations during relapse [16-18]. Peripheric eosinophilia is common in CEP with a frequency of about 90%. BAL eosinophilia is also characteristic in CEP with an average percentage of 58%. Approximately half of the patients have preexisting asthma or atopic disease history. Unlike AEP, recently prior cigarette smoking or substance use is rarer, findings follow a slower course and remission may occur after corticosteroid therapy [19, 20].

Acute Eosinophilic Pneumonia (AEP): The onset of AEP is quite rapid, usually presenting within 1 to 5 days of symptom onset (average of 2.3 days). Patients can progress from mild shortness of breath to life-threatening respiratory failure in only a few hours. AEP was first recognized as a clinical entity in 1989 [21]. Various drugs, cigarette smoke, toxic gases and narcotics have been accused in the etiology of AEP. In the previous literature, AEP also has been reported to occur in human immunodeficiency virus (HIV) infection, military personnel in Iraq and a firefighter who worked in the World Trade Center rescue [22, 23]. AEP can be observed in all age groups with an average of 29 years and in both genders equally. Given that the cases reported throughout the Europe, United States and Japan, it is difficult to claim that there is a geographical endemicity [23, 24]. Diagnostic criteria of AEP consist of fever, hypoxemia,radiological diffuse alveolar or mixed alveolar-interstitial opacities, BAL eosinophilia (eosinophil >25%), exclution of parasitic, fungal or other infections which may lead to eosinophilia, prompt and complete response to corticosteroid treatment and no relapse after discontinuation of steroid therapy [23, 25, 26]. On the other hand, in patients with AEP associated with a substance use or smoking, it is prudent to recommend future avoidance of these substances because relapses may occur if patients resume their use [26]. Lung biopsy is not necessary for the diagnosis but, eosinophilic infiltration of the pulmonary interstitium and alveolar spaces are the significant pathological findings of AEP [27, 28]. Radiological findings of AEP are not specific to AEP and vary in a range from extensive airspace opacities and ground-glass opacities to interlobular septal thickenings and/or pleural effusions; however, radiological infiltrates differ from CEP with their diffuse and not peripherally based localizations [28]. Corticosteroids are the main treatment in AEP. Most patients have significant clinical improvement within 24-48 hours with corticosteroid treatment. After the corticosteroid treatment AEP patients do not generally relapse and recurrence is exceedingly rare [29-32]. Patients with AEP have a rapid and striking response to corticosteroid therapy. Most patients will have significant clinical improvement within 24 to 48 hours, and some may improve within hours of the first dose [33-36].

Churg-Strauss Syndrome (CSS) (Allergic angiitis and granulomatosis): CSS is an antineutrophil cytoplasmic antibody (ANCA)-associated and necrotizing vasculitis affecting the small and medium-sized vessels with associated eosinophilic infiltrates and granulomas. Patients with CSS typically have an initial history of allergic diseases and/or asthma for 8-10 years. Diagnostic criteria of CSS include 1. eosinophilia of more than 10% in peripheral blood, 2. pulmonary infiltrates (may be transient and migratory), 3. asthma, 4. paranasal sinusitis, 5. histological proof of vasculitis together with extravascular eosinophils and 6. mononeuritis multiplex or polyneuropathy. For the diagnosis of CSS, presence of at least four of these criteria is required [37-40].

Idiopathic Hypereosinophilic Syndrome (HES): HES is a rare clinical entity that is characterized by blood eosinophilia of ≥ 1500/μL for more than 6 months, absence of other etiologies for the eosinophilia and presence of the signs or symptoms of end organ damage [41].

Allergic Bronchopulmonary Aspergillosis (ABPA): ABPA is a clinical entity caused by local airway hypersensitivity response to Aspergillus antigens colonized in airways. ABPA occurs most commonly in patients with asthma and cystic fibrosis. Diagnostic criteria of ABPA include proximal bronchiectasis (dilated bronchi in the inner two-thirds of the chest field on CT chest), asthma, immediate cutaneous reactivity to Aspergillus species or A. fumigatus antigens, elevated total serum IgE (1000 ng/mL or>417 kU/L), elevated serum A. fumigatus spesific IgE and/or IgG [42-44].

Bronchocentric Granulomatosis: Bronchocentric granulomatosis is a clinical entity with destructive and granulomatous lesion of the airways which is generally thought to represent a nonspecific response to an airway injury [45]. Bronchocentric granulomatosis has to be taken into consideration in the differential diagnosis of pulmonary nodules and tumors. Because of the lack of a single clear clinical syndrome, the presence of this lesion should generally be considered a nonspecific manifestation of lung injury, not an etiologic diagnosis. In radiological imaging, nodular or mass lesions, usually solitary, were noted in 60% of patients while parenchymal infiltrates were noted in only 20%. CT scan findings consist of a focal mass or lobar consolidation with atelectasis [46]. Surgical biopsy is a requirement for diagnosis. Patients may present with several respiratory symptoms such as dyspnea or wheezing due to airway obstruction [47].

Parasitic and Fungal Infections: Parasitic and fungal infections are common causes of peripheral eosinophilia and ELD. In differential diagnosis, they should be carefully evaluated especially in immunosuppressive patients [5, 48]. In the United States, Strongyloides, Ascaris, Toxocara, and Ancylostoma are the most common causes of ELD. Peripheral blood eosinophilia and pulmonary eosinophilic infiltrates are noted in the majority of cases of primary coccidioidomycosis. The definitive diagnosis of these infections is based ont the demonstration of the pathogen in the tissue [49, 50]. Administration of corticosteroids to these patients at this stage can result in an acceleration of the infection with mortal results, so these infections must be certainly excluded before the decision of corticosteroid therapy for other ELDs [48].

Drug-induced ELD: Drug reaction is one of the most commonly reported etiological factors of pulmonary infiltrates with blood and/or alveolar eosinophilia in patients with no history of previous pulmonary diseases. However, most of this literature is in the form of case reports, which vary in terms of documentation [51]. Over 150 drugs or categories of drugs have been associated with pulmonary eosinophilia [52, 53]. The mechanism is not known exactly for many drugs but the majority of the drugs are believed to provoke a hypersensitivity response in lungs. Patients with drug-induced ELD can vary in presentation from simple pulmonary eosinophilia to AEP-like syndrome [53]. Diagnosis is based on the responses of the lungs to withdrawal of the drug and, if possible, reintroduction to the suspected drug. Peripheral eosinophilia can be observed. Radiological findings may include ill-defined, soft, patchy, or linear /reticular infiltrates, occasionally associated with a pleural effusion. Many patients will improve by simply withdrawing the drug [53]. Corticosteroids are rarely required in these patients. Although drug-induced ELD is considered as a separate item in eosinophilic pneumonias, basically it can present as AEP or CEP [54]. The main reasons that drug-induced ELD is defined as a separate entity, are the drug use history for a certain period and clinical improvement with the cessation of the drug usually without need of additional treatment [54, 55].

As a conclusion, ELDs are a variety of lung diseases with common and distinct clinical features. Considering that there are differences between treatments, the differential diagnosis and rapid accurate diagnosis of ELDs are very important. We hope that this compilation may provide a quick overwiev to ELDs for clinicians.

Competing interests

The authors declare that they have no competing interests.


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

2. Roufosse F, Weller PF. Practical approach to the patient with hypereosinophilia. J Allergy Clin Immunol 2010;126(1):39-44.

3. Sheikh J, Weller PF. Advances in diagnosis and treatment of eosinophilia. Curr Opin Hematol 2009;16(1):3-8.

4. Gotlib J. World Health Organization-defined eosinophilic disorders: 2014 update on diagnosis, risk stratification, and management. Am J Hematol 2014;89(3):325-37.

5. Tefferi A, Patnaik MM, Pardanani A. Eosinophilia: secondary, clonal and idiopathic. Br J Haematol 2006;133(5):468-92.

6. Lee W, Chung WS, Hong KS, Huh J. Clinical usefulness of bronchoalveolar lavage cellular analysis and lymphocyte subsets in diffuse interstitial lung diseases. Ann Lab Med 2015;35(2):220-5.

7. Shiota Y, Kawai T, Matsumoto H, Hiyama J, Tokuda Y, Marukawa M, et al. Acute eosinophilic pneumonia following cigarette smoking. Intern Med 2000;39(10):830-3.

8. Lee W, Chung WS, Hong KS, Huh J. Eosinophilia in bronchoalveolar lavage fluid and architectural destruction are features of desquamative interstitial pneumonia. Histopathology 2008;52(2):194-202.

9. Mann B. Eosinophilic Lung Disease. Clinical Medicine: Circulatory, Respiratory and Pulmonary Medicine 2008;2:99-108.

10. Wechsler ME. Pulmonary eosinophilic syndromes. Immunol Allergy Clin North Am 2007;27(3):477-92.

11. Song JI, Kim YK, Hwang JH, Yang HJ. Early diagnosis based on clinical history and BALF for successful management of smoking-induced acute eosinophilic pneumonia without unnecessary antibiotic usage: a case report. J Asthma 2015;5:1-14.

12. Allen J. Acute eosinophilic pneumonia. Semin Respir Crit Care Med 2006;27(2):142-7.

13. Cottin V, Cordier JF. Eosinophilic lung diseases. In: Mason RJ, Broaddus VC, Martin TR, King TE, Schraufnagel DE, Murray JF, Nadel JA editors. Murray and Nadel’s Textbook of Respiratory Medicine. 5th ed. Philadelphia: PA: Saunders Elsevier; 2010. p.1221-42.

14. Del Giudice P, Desalvador F, Bernard E, Caumes E, Vandenbos F, Marty P, et al. Loeffler’s syndrome and cutaneous larva migrans: a rare association. Br J Dermatol 2002;147(2):386-8.

15. Ford RM. Transient pulmonary eosinophilia and asthma. A review of 20 cases occurring in 5,702 asthma sufferers. Am Rev Respir Dis 1966;93(5):797-803.

16. Carrington CB, Addington WW, Goff AM, Madoff IM, Marks A, Schwaber JR, et al. Chronic eosinophilic pneumonia. N Engl J Med 1969;280(15):787-98.

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

18. Johkoh T, Müller NL, Akira M, Ichikado K, Suga M, Ando M, et al. Eosinophilic lung diseases: diagnostic accuracy of thin-section CT in 111 patients. Radiology 2000;216(3):773-80.

19. Marchand E, Reynaud-Gaubert M, Lauque D, Durieu J, Tonnel AB, Cordier JF. Idiopathic chronic eosinophilic pneumonia. A clinical and follow-up study of 62 cases. The Groupe d’Etudes et de Recherche sur les Maladies “Orphelines” Pulmonaires (GERM”O”P). Medicine (Baltimore) 1998;77(5):299-312.

20. Gaensler EA, Carrington CB. Peripheral opacities in chronic eosinophilic pneumonia: the photographic negative of pulmonary edema. AJR Am J Roentgenol 1977;128(1):1-13.

21. Rom WN, Weiden M, Garcia R, Yie TA, Vathesatogkit P, Tse DB, et al. Acute eosinophilic pneumonia in a New York City firefighter exposed to World Trade Center dust. Am J Respir Crit Care Med 2002;166(6):797-800.

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

23. Badesch DB, King Jr TE, Schwarz MI. Acute eosinophilic pneumonia: a hypersensitivity phenomenon? Am Rev Respir Dis 1989;139(1):249-52.

24. Hayakawa H, Sato A, Toyoshima M, Imokawa S, Taniguchi M. A clinical study of idiopathic eosinophilic pneumonia. Chest 1994;105(5):1462-6.

25. Pope-Harman AL, Davis WB, Allen ED, Christoforidis AJ, Allen JN. Acute eosinophilic pneumonia. A summary of 15 cases and review of the literature. Medicine (Baltimore) 1996;75(6):334-42.

26. Shintani H, Fujimura M, Ishiura Y, Noto M. A case of cigarette smoking-induced acute eosinophilic pneumonia showing tolerance. Chest 2000;117(1):277-9.

27. King MA, Pope-Harman AL, Allen JN, Christoforidis GA, Christoforidis AJ. Acute eosinophilic pneumonia: radiologic and clinical features. Radiology 1997;203(3):715-9.

28. Uchiyama H, Suda T, Nakamura Y, Shirai M, Gemma H, Shirai T, et al. Alterations in smoking habits are associated with acute eosinophilic pneumonia. Chest 2008;133(5):1174-80.

29. Glazer CS, Cohen LB, Schwarz MI. Acute eosinophilic pneumonia in AIDS. Chest 2001;120(5):1732-5.

30. Philit F, Etienne-Mastroïanni B, Parrot A, Guérin C, Robert D, Cordier JF. Idiopathic acute eosinophilic pneumonia: a study of 22 patients. Am J Respir Crit Care Med 2002;166(9):1235-9.

31. Shorr AF, Scoville SL, Cersovsky SB, Shanks GD, Ockenhouse CF, Smoak BL, et al. Acute eosinophilic pneumonia among US Military personnel deployed in or near Iraq. JAMA 2004;292(24):2997-3005.

32. Trawick D, Kotch A, Matthay R, Homer RJ. Eosinophilic pneumonia as a presentation of occult chronic granulomatous disease. Eur Respir J 1997;10(9):2166-70.

33. Brander PE, Tukiainen P. Acute eosinophilic pneumonia in a heroin smoker. Eur Respir J 1993;6(5):750-2.

34. Ogawa H, Fujimura M, Matsuda T, Nakamura H, Kumabashiri I, Kitagawa S. Transient wheeze. Eosinophilic bronchobronchiolitis in acute eosinophilic pneumonia. Chest 1993;104(2):493-6.

35. Chung MK, Lee SJ, Kim MY, Lee JH, Chang JH, Sim SS,et al. Acute eosinophilic pneumonia following secondhand cigarette smoke exposure. Tuberc Respir Dis (Seoul) 2014;76(4):188-91.

36. Mochimaru H, Kawamoto M, Fukuda Y, Kudoh S. Clinicopathological differences between acute and chronic eosinophilic pneumonia. Respirology 2005;10(1):76-85.

37. Guillevin L, Cohen P, Gayraud M, Lhote F, Jarrousse B, Casassus P. Churg-Strauss syndrome. Clinical study and long-term follow-up of 96 patients. Medicine (Baltimore) 1999;78(1):26-37.

38. Churg A. Recent advances in the diagnosis of Churg-Strauss syndrome. Mod Pathol 2001;14(12):1284-93.

39. Keogh KA, Specks U. Churg-Strauss syndrome: clinical presentation, antineutrophil cytoplasmic antibodies, and leukotriene receptor antagonists. Am J Med 2003;115(4):284-90.

40. Mouthon L, Le Toumelin P, Andre MH, Gayraud M, Casassus P, Guillevin L. Polyarteritis nodosa and Churg-Strauss angiitis: characteristics and outcome in 38 patients over 65 years. Medicine (Baltimore) 2002;81(1):27-40.

41. Ogbogu PU, Bochner BS, Butterfield JH, Gleich GJ, Huss-Marp J, Kahn JE, et al. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. J Allergy Clin Immunol 2009;124(6):1319-25.

42. Vlahakis NE, Aksamit TR. Diagnosis and treatment of allergic bronchopulmonary aspergillosis. Mayo Clin Proc 2001;76(9):930-8.

43. Capewell S, Chapman BJ, Alexander F, Greening AP, Crompton GK. Corticosteroid treatment and prognosis in pulmonary eosinophilia. Thorax 1989;44(11):925-9.

44. Mastella G, Rainisio M, Harms HK, Hodson ME, Koch C, Navarro J, et al. Allergic bronchopulmonary aspergillosis in cystic fibrosis. Eur Respir J 2001;17(5):1052-3.

45. Wiedemann HP, Bensinger RE, Hudson LD. Bronchocentric granulomatosis with eye involvement. Am Rev Respir Dis 1982;126(2):347-50.

46. Robinson RG, Wehunt WD, Tsou E, Koss MN, Hochholzer L. Bronchocentric granulomatosis: roentgenographic manifestations. Am Rev Respir Dis 1982;125(6):751-6.

47. Katzenstein AL, Liebow AA, Friedman PJ. Bronchocentric granulomatosis, mucoid impaction, and hypersensitivity reactions to fungi. Am Rev Respir Dis. 1975;111(4):497-537.

48. Gelpi AP, Mustafa A. Ascaris pneumonia. Am J Med 1968;44(3):377-89.

49. Lombard CM, Tazelaar HD, Krasne DL. Pulmonary eosinophilia in coccidioidal infections. Chest 1987;91(5):734-6.

50. Kang YR, Kim SA, Jeon K, Koh WJ, Suh GY, Chung MP, et al. Toxocariasis as a cause of new pulmonary infiltrates. Int J Tuberc Lung Dis 2013;17(3):412-7.

51. Kaufman LD, Seidman RJ, Gruber BL. L-tryptophan-associated eosinophilic perimyositis, neuritis, and fasciitis: a clinicopathologic and laboratory study of 25 patients. Medicine (Baltimore) 1990;69(4):187-99.

52. Philen RM, Hill Jr RH, Flanders WD, Caudill SP, Needham L, Sewell L,et al. Tryptophan contaminants associated with eosinophilia-myalgia syndrome. The Eosinophilia-Myalgia Studies of Oregon, New York and New Mexico. Am J Epidemiol 1993;138(3):154-9.

53. Kamb ML, Murphy JJ, Jones JL, Caston JC, Nederlof K, Horney LF, et al. Eosinophilia-myalgia syndrome in L-tryptophan-exposed patients. JAMA 1992;267(1):77-82.

54. Kim PW, Sorbello AF, Wassel RT, Pham TM, Tonning JM, Nambiar S. Eosinophilic pneumonia in patients treated with daptomycin: review of the literature and US FDA adverse event reporting system reports. Drug Saf 2012;35(6):447-57.

55. Patel JJ, Antony A, Herrera M, Lipchik RJ. Daptomycin-induced acute eosinophilic pneumonia. WMJ 2014;113(5):199-201.

Additional Info

  • Recieved: 25.11.2015
  • Accepted: 05.12.2015
  • Published Online: 15.12.2015
  • Printed: 01.01.2016
  • DOI: 10.4328/AEMED.72
  • Author: Nesrin Ocal, Ramazan Ocal, Deniz Dogan
  • Identifier: J Ann Eu Med 2016;4(1): 12-5
  • Index Page: 12-15
  • How to Cite: Nesrin Ocal, Ramazan Ocal, Deniz Dogan . An overview of eosinophilic lung diseases. J Ann Eu Med 2016;4(1): 12-5
  • Running Title: Eosinophilic lung diseases

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