Acute eosinophilic pneumonia (AEP) is an uncommon, acute-onset form of eosinophilic lung disease which varies in severity. Eosinophilic lung diseases are a group of diseases caused by damage to the alveolar sacs and surrounding tissues of the inner lung.[1] Though poorly understood, the pathogenesis of AEP likely varies depending on the underlying cause which may include smoking, inhalation exposure, medication, and infection.[2] In most patients, AEP is idiopathic, or has no known cause.[3] Eosinophilic pneumonia can be acute or chronic.[4]
AEP is characterized by airway injury, vascular injury, and the release of IL-33, a pro-inflammatory cytokine. This results in the recruitment of eosinophils, a type of white blood cell, to the lungs with subsequent inflammation and symptoms. Symptoms are nonspecific and include cough, shortness of breath, malaise, myalgia, night sweats, and pleuritic chest pain.[2]
Signs and Symptoms
Classic signs and symptoms of AEP include:
shortness of breath,
moderate fever,
cough,
chest pain worse with breathing,
muscle aches,
night sweats,
and abdominal pain
These signs and symptoms could progress to acute respiratory distress syndrome (ARDS) and severe hypoxemic respiratory failure requiring mechanical ventilation. Patients are often hospitalized within 7 days to a month after symptom onset. Clinicians caring for patients with ARDS without a clear cause should consider AEP on their differential diagnosis.[1]
Pathogenesis
The causes and pathogenesis of AEP are still poorly understood, but it has been hypothesized that inhaled antigens from various environmental triggers are considered risk factors for AEP.[4]
Risk factors of AEP include recent initiation of tobacco smoking, reintroduction of tobacco smoking after a break, changes in smoking patterns, vaping with e-sigs, adding flavors to the smoking, large-scale smoking, second-hand smoke exposure, and inhalation of oils. Other environmental risk factors include inhaling parasites, fungi, viruses, spiders, and exposure to certain drugs like heroin and over-the-counter medications.[1][5]
A proposed model of AEP pathogenesis suggests that these antigens cause airway damage, leading to the release of IL-33 and the recruitment of eosinophils. This leads to a hypersensitivity reaction, a type of inflammatory process, causing clinical symptoms.[4] IL-5 from this process is also responsible for eosinophil differentiation, allowing for the development of drugs that target these specific receptors to reduce AEP symptoms.[1]
Diagnosis
The diagnosis of AEP requires taking a comprehensive medical history with specific attention to the smoking history, environmental exposures, use of drugs associated with eosinophils in the blood, and no history of asthma.[1][2]
Although AEP is often a diagnosis of exclusion, there are several criteria that needs to be met to make a diagnosis of AEP:[1]
Fever that occurred ≤1 month and especially ≤7 days before medical examination.
Bilateral diffuse opacities on chest imaging.
PaO2 ≤ 60 mmHg, PaO2/FiO2 ≤300 mm Hg, or oxygen saturation < 90% on room air.
Presence of eosinophils in the lungs with ≥25% eosinophils at bronchoalveolar lavage (BAL) differential cell count (or eosinophilic pneumonia at lung biopsy when done).
Absence of other known causes of lung eosinophilia such as infection or exposure to drugs. Recent onset of tobacco smoking or exposure to inhaled dusts may be present.
Imaging: High resolution computed tomography (HRCT) is the gold standard chest imaging for eosinophilic pneumonias. AEP will show patchy ground glass consolidation or areas of increased grainy density with pleural effusions on both sides. Instead, chronic eosinophilic pneumonia will show a more fibrous plug or pattern.[4]
Laboratory testing may show leukocytosis (increased white blood cell count), delayed increase in blood eosinophil count up to 7 days after presentation, BAL that contained at least 25% eosinophils or higher (but may not reach those levels in patients who received corticosteroids prior to bronchoscopy), and increased IL-5 levels. Thoracentesis may show a nonspecific increase in pleural eosinophils. Pulmonary function tests may show a restrictive pattern, reduced DLCO, and increased A-a O2 gradient.[1][4]
Pathology: While not necessary for diagnosis, a lung biopsy often shows swelling and eosinophils in the bronchial walls, interstitium, and alveolar spaces. The presence of damage to the alveolar spaces, hyaline membranes, and/or fibroblasts are suggestive of AEP.[1][4]
Differential diagnoses when considering Acute Eosinophilic Pneumonia (AEP):[4]
Chronic eosinophilic pneumonia (CEP)
Eosinophilic lung diseases of known causes
Löffler syndrome (Simple pulmonary eosinophilia)
Allergic Broncho-Pulmonary Aspergillosis (ABPA)
Drug induced Eosinophilic Pneumonia
Parasitic Infection
Fungal Infection
Eosinophilic lung diseases with extrapulmonary involvement
Hypereosinophilic syndrome
Eosinophilic Granulomatosis with Polyangiitis (EGPA)—Churg Strauss Syndrome
Interstitial lung diseases that may show lung eosinophilia
Acute respiratory distress syndrome (ARDS)
Cryptogenic Organizing Pneumonia (COP)
Pulmonary Langerhans Cell Histiocytosis (PLCH)
Idiopathic Pulmonary Fibrosis
Sarcoidosis
Desquamative interstitial pneumonia (DIP)
Treatment
Corticosteroids are the first line of treatment for patients with AEP. They typically improve within 48 hours of treatment, and their chest imaging shows dramatic improvement within 1 month. Dosage depends on the severity of the disease progression. Patients with respiratory failure require high dose IV methylprednisolone and are switched to oral prednisone upon clinical improvement to be continued for 2-4 weeks and tapered over several weeks.[4] Most patients with mild symptoms are started on oral prednisone for 2 weeks and tapered off.[1] Patients should be counseled to quit smoking and avoid exposure to the offending agent, when applicable, to reduce recurrence of AEP.[2] Relapse of disease is rare.[6]
History
AEP was first described in 1989 by Allen, Pacht, Gadek, and Davis, with eight proposed diagnostic criteria.[2] These criteria included: acute febrile illness, hypoxemia, pulmonary infiltrates on imaging, alveolar eosinophils, ruled out infection, ruled out asthma, quick response to steroids, and followed by resolution of disease with no long-term effects.[2]
Epidemiology
As of 2018, approximately 400 cases of AEP have been reported with an estimated incidence of 9.1 to 11 per 100,000 person-years.[2][4] It occurs most commonly in men ages 20-40, smokers, and no history of asthma.[2][4] The number of cases peaks during the summer time with increasing disease severity.[2]
Future Research Directions
More research is required on the details of the pathogenesis of AEP, as it is still incompletely understood. Although there is a clear role of eosinophils in AEP, the mechanisms of damage to the lung tissues are yet to be discovered. Also, while there is a link between cigarette smoking and AEP, the number of cases of AEP compared to cigarette smokers is relatively low, indicating a possible genetic component of AEP, which requires further research into how genes may play a role in the development of AEP.[2]
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