Another Reason Not to Smoke: Acute Eosinophilic Pneumonia

Recent initiation of smoking has been associated with AEP, as was the case with this patient. This patient had no other history of airborne exposures, including burn pits, travel to sandy environments, mold, or chemical inhalants. Of all cases of AEP described to date, more than two-thirds have been associated with smoking.^13,14 One Japanese case series further established the association through a “cigarette challenge test.”^8,15,16 Typically, the patients described were in their mid-20s and rapidly developed symptoms consistent with AEP within 1 month of initiating smoking.

A high proportion of AEP has recently been described among newly deployed military personnel in Iraq.¹⁷ Out of 180,000 personnel deployed, 18 developed AEP with 14 having initiated smoking within 1 month of deployment. The authors concluded that compared with the controls, new-onset smokers had a significantly increased risk of developing AEP. Importantly, this case series describes 2 deaths associated with this disease, suggesting that this otherwise healthy population may have other environmental exposures that put them at a higher risk than that in the general population. Another case described a U.S. soldier in Korea with recent smoking history who was diagnosed with AEP on transbronchial lung biopsy.¹⁸

Given the nonspecific symptoms of the disease, early diagnosis relies on attention to clinical history, environmental exposures, and response to initial empiric treatment. Diagnosis is made based on pulmonary eosinophilia and exclusion of chronic causes of eosinophilic pulmonary disease, such as Churg-Strauss syndrome, chronic eosinophilic pneumonia, and tropical eosinophilia.^9,19

Criteria for diagnosis has evolved since AEP was initially reported. Current criteria include acute onset febrile respiratory manifestations < 1-month duration, bilateral diffuse infiltrates on chest radiograph, arterial oxygen pressure of < 60 mm Hg or pulse oximetry < 90% on room air, and BAL > 25% eosinophils. Blood, sputum, and BAL cultures must be negative for bacteria, fungi, and parasitic causes.⁷ Exposure to toxins known to cause eosinophilia should also be ruled out. Therefore, timely BAL is of paramount importance in any suspected case of AEP. Peripheral blood count will usually show a nonspecific leukocytosis, with a normal distribution of eosinophils; however, it is not uncommon for peripheral eosinophilia to occur late in the disease.^14,20 Pulmonary eosinophilia in the absence of a peripheral eosinophilia is likely due to pulmonary eosinophil sequestration.

In one case series, the mean duration of time from symptom onset until diagnosis was 3.5 days.¹³ Diagnosis usually occurs after the patient’s clinical status worsens despite broad-spectrum antibiotic therapy. Acute eosinophilic pneumonia typically appears on a chest radiograph as bilateral reticular nodules with interstitial patterning. Variability can exist between alveolar, interstitial, and mixed infiltrate patterns.¹⁹ Pleural effusions may also be seen. These nonspecific patterns allow AEP to be easily mistaken for a variety of other pathologies, such as acute respiratory distress syndrome and community acquired pneumonia.

Corticosteroid therapy is the mainstay of treatment for AEP. Intravenous methylprednisolone is typically administered at dosages of 60 mg to 125 mg every 6 hours, followed by an oral prednisone taper.²¹ Relapses of AEP are not typical, and the prognosis is typically excellent if identified rapidly and treated appropriately. In one study of 127 individuals treated with corticosteroids, all survived, and most were transferred out of the ICU after 3 days of treatment. Dyspnea improved on treatment day 3, and all symptoms disappeared with an average of 7 days of treatment.⁷

Conclusion

Acute eosinophilic pneumonia is likely to be underreported clinically. Presently, AEP is largely a diagnosis of exclusion; the current criteria for diagnosis are fairly rigid and rely on BAL while ruling out other identifiable causes (Table). Clinical suspicion should be raised in patients with a history of new-onset smoking or other airborne toxin exposure. The broad spectrum of clinical presentations and diagnostic findings leave important questions unanswered regarding the mechanisms of the disease.

This particular case illustrates the fundamental importance of taking a thorough history in any patient with a recent airborne exposure where AEP is suspected. Acute eosinophilic pneumonia should be considered in cases of pneumonia that continue to worsen despite the treatment of IV antibiotics; a BAL should be performed when appropriate.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.