Flavored Cigar Smoking Induces Acute Eosinophilic Pneumonia^* FREE TO VIEW

Acute eosinophilic pneumonia (AEP) is characterized by eosinophilic infiltration in the lungs, respiratory distress, a rapid therapeutic response to corticosteroids, and the absence of relapse.¹ Cigarette smoking has been recognized to cause AEP, and a report² from Japan has demonstrated an association of cigarette smoking-induced AEP with menthol-flavored cigarettes. Based on review of two cases of AEP following flavored cigar smoking, we believe that the flavoring component may have a major rule in precipitating the illness.

A previously healthy 23-year-old man presented to the emergency department with a 5-day history of shortness of breath and exercise intolerance. The patient reported a relatively sudden onset of a productive cough of yellowish sputum accompanied by fever, chills, and dyspnea on minimal exertions. The patient also reported mild headache, loss of appetite, and generalized weakness prior to hospital admission. The patient started smoking strawberry-flavored cigars 3 weeks prior to admission, approximately four cigars weekly. There was no history of any other form of tobacco or alcohol abuse or any recreational drug use. In the emergency department, the patient had a temperature of 38.3°C, BP was 129/74 mm Hg, pulse rate was 126 beats/min, and respiration rate was 22 breaths/min. Blood oxygen saturation was 88% on room air. Physical examination showed coarse crackles posteriorly in both lungs. There was no use of accessory muscles. Laboratory findings revealed WBC count of 14,250/μL; polymorphonuclear leukocytes, 75%; lymphocytes, 10%; eosinophils, 8%; and monocytes, 3%. By hospital day 5, eosinophil fraction had increased to 26%. Chest radiography showed diffuse bilateral pulmonary infiltrates. The chest CT showed a small right-sided pleural effusion, minimal pleural reaction on the left and patchy parenchymal infiltrates in both lung fields (Fig 1 ). The patient was started on ceftriaxone and azithromycin and then was switched to moxifloxacin without any improvement. Video bronchoscopy was performed and showed diffuse inflammation with copious watery secretions. There was no evidence of endobronchial tumors. BAL showed nucleated cells at 738/μL; eosinophils, 72%; and lymphocytes, 15%. All bacterial, viral, and fungal study results were negative. The patient received IV methylprednisolone after stopping antibiotics and improved dramatically within 24 h. Chest radiography demonstrated remarkable resolution of the infiltrates after steroids. The patient was discharged on a tapering dose of oral prednisone.

The second case was a 53-year-old white man with a medical history significant for coronary artery disease, diabetes mellitus type 2, and hypercholesterolemia. A history of allergy to strawberries was reported. The patient presented to the emergency department with a 2-day history of chest tightness, dry cough, and dyspnea. He reported a new onset of night sweats, chills, and wheezing. The patient denied any sick contact, recent travel, or weight loss. The patient visited his family doctor’s office 3 days prior to hospital admission and was started on azithromycin without any improvement. He quit smoking 17 years ago, but 3 weeks prior to hospital admission he restarted smoking different types of flavored cigars. On examination, the patient was found to be febrile with a temperature of 38.1°C, a heart rate of 120 beats/min, and blood oxygen saturation of 92% on 3 L/min of oxygen; later on, the oxygen saturation went down and the patient required 100% oxygen. Lung examination revealed bilateral crackles. There was no use of accessory muscles. Laboratory findings were WBC count of 17,400/μL; polymorphonuclear leukocytes, 91%; lymphocytes, 1%; eosinophils, 4%; and monocytes, 2%. By hospital day 5, eosinophil fraction had increased to 33%. Diffuse bilateral infiltrate greater on the right side was noted on chest radiograph (Fig 2 ). CT of the chest revealed bilateral diffuse infiltrates with small bilateral pleural effusions (Fig 3 ). At that point, the patient was admitted to the hospital and treated for community-acquired pneumonia with moxifloxacin without improvement. Video bronchoscopy clearly showed an inflamed mucosa of the left bronchial tree. There was no mass or any evidence of consolidation. BAL showed nucleated cells at 31,500/μL; eosinophils, 49%; and lymphocytes, 16%. The patient was started on IV methylprednisolone and improved dramatically after introducing the steroid treatment. Chest radiography revealed remarkable resolution of the infiltrates in the next few days (Fig 4 ). The patient was discharged on a tapering dose of oral prednisone.

The cause of AEP remains unknown. Some investigators³ have suggested that AEP is an acute hypersensitivity reaction to an unidentified inhaled antigen. Patients usually present with an acute febrile illness of < 3 weeks in duration, and in most cases the duration of symptoms is < 7 days. Nonproductive cough and dyspnea are present in almost every patient. Associated symptoms and signs include malaise, myalgias, night sweats, pleuritic chest pain, and hypoxemic respiratory insufficiency. Physical examination usually shows fever and tachypnea. Bibasilar inspiratory crackles and occasionally rhonchi on forced exhalation are heard on auscultation of the chest.⁴⁵ Patients generally present with an initial neutrophilic leukocytosis.²⁶ In most cases, the eosinophil count becomes markedly elevated during the subsequent course of AEP.⁵⁶⁷ Patients with AEP are uniformly responsive to IV or oral corticosteroid therapy.⁵ The response is often dramatic, occurring within 12 to 48 h, and there is no relapse following withdrawal of the steroids. The present two cases met the criteria for a diagnosis of AEP by Allen and Davis⁸: an acute febrile illness of short duration (usually < 1 week), hypoxemic respiratory failure, diffuse pulmonary opacities on chest radiograph, BAL eosinophilia > 25%, lung biopsy evidence of eosinophilic infiltrates, and absence of known causes of eosinophilic pneumonia, including drugs, infections, or asthma. We have excluded all possible causes in the initial workup.

In reviewing the literature, one study² reported flavored cigarettes, specifically menthol flavored, as the underlying cause of cigarette smoking-associated AEP. Other reports have associated AEP with World Trade Center dust exposure,⁹ as well as military personnel having this complication in Iraq after significant exposure to fine airborne sand or dust.¹⁰

In our first case, the patient was a nonsmoker and started smoking flavored cigars for the first time 3 weeks prior to hospital admission. It is difficult in this case to make a clear assumption that AEP was most likely induced by the chemical substances used for flavoring the cigar. However, smoking itself could be the triggering factor of AEP, as it has been implicated in previous reports,^11121314 and proven by a smoking challenge test. For that test, the patient was asked to smoke 20 cigarettes a day for 13 days. The challenge test reproduced typical BAL and transbronchial lung biopsy changes of AEP, but the patient had neither radiologic changes nor symptoms after the challenge test.¹⁵ We did not perform a smoking challenge test on our patients.

The second patient was an ex-smoker and had no documented history of pneumonia. The patient stopped smoking 17 years ago and resumed smoking 3 weeks prior to hospital admission, trying different types of flavored cigars. Because of a longstanding history of smoking without any history of documented respiratory events related to smoking cigarettes, we suspected a major rule of flavoring components in inducing his AEP. These cases illustrate the increasing evidence that cigarette/cigar smoking could be indeed a major factor in inducing AEP. More importantly, it demonstrates the importance of a detailed medical and smoking history to identify flavored cigar as a probable cause of AEP. More extensive investigation and research is needed to reach a solid conclusion regarding the actual rule of flavoring cigar/cigarette in inducing AEP.