Pulmonary Eosinophilia Workup

Updated: Dec 10, 2020
  • Author: Jussi J Saukkonen, MD; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
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Approach Considerations

The workup should start with the history and physical examination. Pertinent history of travel, evidence of collagen vascular disease, status of the immune system, usage of medications, duration of symptoms, and evidence of airway obstruction are essential elements to consider. The final diagnosis always rests with the response to treatment, even with infectious syndromes. Rule out infectious etiologies based on the travel history, regardless of how remote.

Pulmonary function testing may be useful in the initial evaluation to help narrow the differential diagnosis. Note the following:

  • Pulmonary function is helpful as an initial test to distinguish between obstructive and restrictive diseases and to assess the severity of airway obstruction or parenchymal restriction.

  • An obstructive pattern may be seen in persons with asthma, allergic bronchopulmonary aspergillosis (ABPA), bronchocentric granulomatosis, eosinophilic granuloma (EG), bronchiolitis obliterans organizing pneumonia (BOOP), eosinophilic granulomatosis with polyangiitis (EGPA), and, occasionally, hypereosinophilic syndrome (HES).

  • A restrictive pattern may be seen in persons with tropical pulmonary eosinophilia (TPE), intrinsic eosinophilic syndromes, and interstitial lung diseases.

Skin prick testing and intradermal testing can be performed for an immediate hypersensitivity response to Aspergillus infection. Avoid skin testing if the patient has significant wheezing.


Laboratory Studies

Initially, examine stool for ova and parasites. Specimens may be negative if intestinal infection is not established. Multiple specimens should be sent and examined by experienced laboratory personnel. Stool or gastric aspirate examination is generally useful for detecting Strongyloides species, Schistosoma species, and C sinensis; is often less useful for detecting Paragonimus, Ancylostoma, Necator, and Ascaris infection; and is usually not helpful for detecting Toxocara, Trichinella, and Echinococcus species and tropical pulmonary eosinophilia (TPE)–associated filariae.

Blood leukocyte count with differential is necessary. Leukocytosis is common in all of these syndromes.

The upper limit of normal for the range of eosinophils in the peripheral blood is 3%-5% with a corresponding absolute eosinophil count (AEC) of 350–500/µL. The severity of eosinophilia has been arbitrarily divided into mild (AEC from the upper limit of normal to 1500/µL), moderate (AEC 1500–5000/µL) and severe (AEC >5000/µL) The eosinophil percentage is less sensitive than the absolute eosinophil count (AEC). [24] CBC count and AEC should be monitored to assess the course of illness and response to treatment when appropriate.

Blood and pulmonary eosinophilia are generally present together in persons with Loeffler syndrome, parasitic and fungal infections, CEP, allergic bronchopulmonary aspergillosis (ABPA), EGPA, and HES.

Isolated pulmonary eosinophilia may be observed in persons with AEP, medication-related syndromes, P carinii pneumonia, BOOP, tuberculosis, and eosinophilic granuloma (EG) (Langerhans cell).

Microbiologic studies, rarely, may show evidence of infection with Mycobacterium tuberculosis, P carinii, or fungi. Make additional efforts to exclude parasitic or other fungal co-infection. Parasitic infections may be detected by examining stool, urine, and sputum or BAL fluid. Urine examination may be useful in cases of schistosomiasis. Sputum or BAL fluid examination may be useful for detecting Paragonimus, Ascaris, Strongyloides, and, rarely, Schistosoma infections. Fungal infection may be detected by examining respiratory secretions. ABPA is supported by growth of Aspergillus species from respiratory secretions. Coccidioides species may be cultured from respiratory secretions.

Immunologic studies, ie, serologic testing, may be useful in persons with ABPA, parasitic infection, and EGPA. Serologic testing may obviate the need for invasive testing in the case of parasitic infections. Use a targeted approach to serologic testing, bolstered by clinical information.

Total IgE values are often elevated in persons with these syndromes, and this finding has no specific diagnostic value. The following general trends may be noted:

  • Levels of less than 1000 ng/mL are usually observed in association with asthma and low-intensity infections.

  • ABPA and parasitic infections are typically associated with high levels, often greater than 2000 ng/mL.

The diagnosis of ABPA is supported by an elevated IgE level, an elevated Aspergillus -specific IgE level, a positive result for Aspergillus precipitins, and an immediate skin hypersensitivity response to Aspergillus. Levels correlate with the activity of ABPA. If levels are within the reference range in a patient with respiratory symptoms, ABPA can usually be excluded.

Some parasitic infections may be diagnosed based on serological results. These include TPE-associated filarial infection (eg, B malayi, W bancrofti); echinococcal infection (serology results are positive in 60-90% of cases); and toxocariasis, with best results obtained by enzyme-linked immunosorbent assay (ELISA). A variety of sensitive and specific serologic tests, including complement fixation, ELISA, and immunoblot, have been developed to detect Paragonimus infection.

Tests with limited value are available for Strongyloides and Ascaris infections. In EGPA, perinuclear antineutrophil cytoplasmic antibody results are positive in at least 60% of cases. In CEP, check antinuclear antibody or rheumatoid factor levels because CEP may be associated with connective tissue diseases.

In 2009, Velthove et al report on possible biomarkers (neutrophilia, eosinophilia) for inflammation in obstructive lung disease. Based on the results of their case-control study, they suggested both neutrophil counts and eosinophil counts may be useful biomarkers for exacerbations in obstructive lung disease. [25] Additionally, Hillas et al suggest eosinophil counts are the future direction of focus for a noninvasive method of assessing airway inflammation in clinical practice and not just research settings. [26]


Imaging Studies

Chest radiography

Extrinsic syndromes

The following findings may be noted on chest radiography studies in patients with extrinsic syndromes:

  • Loeffler syndrome: Fleeting interstitial infiltrates may be evident.

  • Acute eosinophilic pneumonia (AEP): Interstitial infiltrates progress to alveolar-filling infiltrates. Small pleural effusions and Kerley B lines may be present.

  • Parasitic infections: These typically manifest as interstitial or indistinct nodular densities, usually in the middle and/or basilar lung fields. Infiltrates may be migratory. Chest x-ray films may yield normal findings in many individuals.

  • Tropical pulmonary eosinophilia (TPE): Fibrosis may be evident in persons with chronic disease.

  • Echinococcus infection: This manifests as large, smooth-edged, masslike densities, with or without calcification.

  • Chronic schistosomiasis: Patients with chronic schistosomiasis may have hilar enlargement and right ventricular enlargement as a consequence of pulmonary hypertension.

  • Allergic bronchopulmonary aspergillosis (ABPA): Fleeting infiltrates, atelectasis, pneumonitis, and bronchiectasis may be evident.

Intrinsic syndromes

The following findings may be noted on chest radiography studies in patients with intrinsic syndromes:

  • Chronic eosinophilic pneumonia (CEP): Peripheral alveolar infiltrates may be migratory, and they have the classic appearance of the photographic negative of pulmonary edema in one fourth of cases.

  • Hypereosinophilic syndrome (HES): Interstitial infiltrates, pleural effusions, pulmonary edema, pulmonary infarct, and fibrosis may be present.

  • Eosinophilic granulomatosis with polyangiitis (EGPA): Interstitial infiltrates, alveolar infiltrates, and nodular opacities may be present. Cavitary, small, patchy irregularities are not usually present.

  • Eosinophilic granuloma (EG): Reticulonodular infiltrates, increased lung volumes, cystic changes, coalescing nodules, and pneumothorax may be seen.

Chest CT scanning

Computed tomography (CT) scanning of the chest helps define the extent and distribution of the disease; helps distinguish between predominantly interstitial or alveolar infiltrates; helps detect lymphadenopathy, fibrosis, and bronchiectasis; may be helpful in distinguishing between malignancy and other etiologies; and may be needed if biopsy is contemplated. High-resolution CT scanning is preferred to enhance the evaluation of the pulmonary parenchyma. Note the following:

  • ABPA: Fleeting infiltrates, atelectasis, pneumonitis, and bronchiectasis may be evident. High attenuation mucoid impaction is associated with higher IgE levels, eosinophilia, Aspergillus -specific titers, and a greater probability of relapse. [27]

  • Parasitic diseases: CT scanning images provide finer detail of nodules and interstitial infiltrates. In schistosomiasis and echinococcal diseases, additional cysts may be seen in the liver.

  • AEP: Ground-glass infiltrates are commonly seen, but dense consolidation, nodules, and septal thickening may also be revealed.

  • CEP: Alveolar ground-glass infiltrates in a peripheral distribution are highly characteristic of CEP.

  • HES: Nodules and effusions may be seen.

  • EGPA: In addition to abnormalities seen on plain radiographs, irregular pulmonary arteries may be seen.

  • Bronchiolitis obliterans organizing pneumonia (BOOP): Peripheral triangular-shaped infiltrates are classic, but alveolar filling may be evident.

  • EG: Cystic changes, nodules, and fibrosis are seen.

  • Idiopathic pulmonary fibrosis: Interstitial infiltrates, a ground-glass alveolar pattern, nodules, and fibrosis are seen.

Positron-emission tomography (PET) scanning

Patients with pulmonary eosinophilia have been reported to have F-18 fluorodeoxyglucose (FDG)–avid uptake on positron emission scans. [28]


Establishing an estimation of right ventricular, left ventricular, and valvular function is indicated in individuals with certain intrinsic syndromes (eg, EGPA, HES) or in individuals with sustained high-level eosinophilia in which cardiac complications are relatively common.

Establishing an estimation of pulmonary systolic pressure and right ventricle function is indicated in persons with chronic schistosomiasis because pulmonary hypertension is common.

Ventilation/perfusion scanning

This scan may be useful in some patients with HES in the appropriate clinical setting who have a propensity to develop pulmonary emboli. Schistosomiasis and other parasitic diseases may result in matched and unmatched defects.



Fiberoptic bronchoscopy with bronchoalveolar lavage

Bronchoalveolar lavage (BAL) is often necessary to obtain adequate specimens to help rule out infection, particularly in the instance of CEP and other intrinsic syndromes. Note the following:

  • BAL fluid leukocyte and differential cell counts may provide the presenting or only sign of eosinophilic pulmonary syndrome. Normally, few eosinophils are obtained from BAL fluid. The presence of more than 20% suggests Loeffler syndrome, AEP, CEP, or HES.

  • Pulmonary eosinophilia alone may be present in persons with AEP, medication-related syndromes, P carinii pneumonia, BOOP, tuberculosis, and EG (Langerhans cell).

  • BAL examination may be useful for detecting Paragonimus, Ascaris, Strongyloides, and, rarely, Schistosoma infections.

  • BAL fluid cytology findings may be useful for excluding malignancy.

  • BAL cytology findings may also be useful for detecting EG, for which immunohistochemical staining for the S-100 antigen or electron microscopy (demonstrating the pentilaminar Birbeck granule) can be diagnostic.

Transbronchial biopsy

Transbronchial biopsy may be performed to help determine if an invasive fungal infection is present. The size of the tissue specimens obtained is generally insufficient to reliably provide the histopathologic information for the syndromes discussed.

Transthoracic needle aspiration/biopsy

Transthoracic needle aspiration/biopsy occasionally may be used to help distinguish infection from malignancy when the results of other, less-invasive studies have been unrevealing. Dirofilariasis, which is difficult to diagnose with noninvasive methods, has been diagnosed based on findings from this method. Avoid aspiration of echinococcal cysts because of the risk posed by dissemination, resulting in a massive hypersensitivity reaction.

Open lung biopsy

Open lung biopsy is rarely necessary, but it is usually performed if EGPA, interstitial lung disease, or malignancy is suggested. For AEP and CEP, BAL is usually performed. Once infection is excluded, the rapid response to therapy contributes to a clinical diagnosis.

Other biopsies

Other biopsies are indicated based on clinical presentation as follows:

  • Liver biopsy is performed for chronic schistosomiasis with cor pulmonale. It rarely is performed for TPE (which is usually confirmed based on serology findings) and toxocariasis. 

  • Lymph node biopsy is occasionally used in cases of TPE.

  • Skin biopsy is performed for trichinosis, and it is occasionally performed for toxocariasis or when skin manifestations of other diseases are prominent.

  • Rectal biopsy is occasionally pursued in persons with schistosomiasis.

  • Muscle biopsy findings may indicate trichinosis.


Histologic Findings

Histologic findings may include the following:

  • Parasitic diseases: Findings include increased histiocytes, eosinophilic and lymphocytic infiltration of airspaces, eosinophilic abscesses, granulomas, and areas of fibrosis.

  • Allergic bronchopulmonary aspergillosis (ABPA): Findings include eosinophilic, lymphocytic, plasmacytic, and monocytic infiltration around bronchi; granulomas; fibrosis; microabscesses; and bronchiectasis.

  • Acute eosinophilic pneumonia (AEP): Findings include eosinophilic infiltration of airspaces and airway walls and edema, but not vasculitis.

  • Chronic eosinophilic pneumonia (CEP): Findings include eosinophilic and lymphocytic accumulation in alveoli, eosinophilic abscess formation, bronchiolitis, and fibrosis. Granulomas are not seen. Occasionally, mild vasculitis is seen.

  • Eosinophilic granulomatosis with polyangiitis (EGPA): Eosinophilic necrotizing vasculitis of small vessels and granulomas are common.

  • Hypereosinophilic syndrome (HES): Findings include eosinophilic infiltration of interstitium and airways and intravascular thrombi.

  • Eosinophilic granuloma (EG): Findings include Langerhans cell proliferation and granulomas, lymphocytic and monocytic infiltration, desquamative interstitial pneumonitis, granulomatous vasculitis, lymphoid follicles, S-100 antigen staining of Langerhans cells, and, with electron microscopy, the Birbeck (X-body) within cytoplasm of Langerhans cells.