Introduction

Acute eosinophilic pneumonia (AEP) is an uncommon and distinctive condition characterized by a rapid accumulation of eosinophils in the lung parenchyma, sometimes leading to acute respiratory failure [1]. AEP, first described by Allen et al. [2] in 1989, presents clinically with nonspecific symptoms, including fever, dyspnea, and cough. Chest radiography reveals diffuse pulmonary infiltrates, with eosinophilia in bronchoalveolar lavage (BAL) fluid. Although the etiology of AEP remains unclear, multiple factors, including drugs, infections, and inhalation exposure, are thought to trigger the condition [3-5]. Increasing evidence also suggests that cigarette smoking can be associated with AEP development [6-15]. It has been speculated that AEP is triggered by an abnormal immune response to the toxins inhaled in cigarette smoke, leading to an infiltration of eosinophils into the lungs [16]. Furthermore, it has been reported that AEP can occur not only after the initiation of smoking, but also upon resuming smoking after a period of cessation or even after exposure to secondhand smoke [15,17-20].

Although an established relationship between cigarette smoking and AEP exists, the available literature consists primarily of individual case reports and small case series. As a result, we have a limited understanding of the condition's underlying mechanisms, optimal treatment approaches, and long-term prognosis. To address this gap, this study presents a larger case series of 17 patients who developed AEP as a result of smoking, with an aim of enhancing our knowledge of its triggers, clinical presentation, and outcomes.

Methods

Ethical statements: This study was approved by the Institutional Review Board of Gyeongsang National University Changwon Hospital (No. GNUCH-2024-03-015). The need for informed consent was waived.

1. Study design and setting

This study, conducted at a university-affiliated hospital, aimed to investigate the characteristics and outcomes of patients diagnosed with AEP between March 2016 and December 2023. This study was a retrospective case series covering an 8-year period.

2. Patient selection and diagnostic criteria

Patients were considered eligible for inclusion in this study if they had a clinical diagnosis of AEP, chest radiographic evidence of diffuse pulmonary infiltrates, hypoxemia, and a notable increase in eosinophils in the BAL fluid. Patients with evidence of parasitic, fungal, or bacterial infections were excluded. This approach followed the guidelines established by Allen et al. [1,2]. We obtained detailed smoking histories, including whether patients were actively smoking at diagnosis or had recently started or resumed smoking. Data about demographic characteristics, clinical symptoms, diagnostic results, treatment approaches, and outcomes were also collected for each patient.

3. Statistical analysis

Descriptive statistics, including means and standard deviations, were used to summarize the data.

Results

1. Clinical characteristics of enrolled patients

Our study involved 17 participants, predominantly male military personnel (94.1%), but also one female university student and one male office worker. Most patients were young, aged between 18 and 22 years (mean: 20.8 years), except for one 40-year-old patient. All patients had a history of smoking, with durations ranging from 1 week to 15 years and varying levels of smoking intensity. Notably, 12 of the 17 patients (70.6%) were diagnosed with AEP within 2 months of initiating smoking. Participants reported fevers and a variety of respiratory symptoms, including shortness of breath, cough, and, in one instance, blood-tinged sputum. These symptoms had typically begun a few days prior to hospital admission. Upon admission, the mean body temperature was 37.6±0.8 °C (Table 1).

2. Laboratory and radiologic findings

The mean initial white blood cell count was 15.3×10³/μL, with an eosinophil percentage of 5.2%±5.5%, varying from 0.2% to 8.2% initially and peaking at 16.1%, with a range of 3.1% to 32.4%. The number of eosinophils was significantly elevated in the BAL fluid, with a mean of 46.6%, and levels ranging from 17% to 67%. The mean C-reactive protein and pro-B-type natriuretic peptide levels were 99.4 mg/L and 132.3 pg/mL, respectively. Chest radiographic examinations revealed bilateral ground-glass opacities, interlobular septal thickening, varying degrees of airspace consolidation, and bilateral pleural effusions in most patients (Table 2).

3. Treatment and outcomes

Of the 17 patients in this study, 70.5% (12 patients) received steroid treatment, primarily methylprednisolone and/or prednisolone. The mean duration of steroid therapy was 8.3 days. All patients showed improvement over time, even those who did not receive steroids. The length of hospital stays ranged from 3 to 11 days, with a mean of approximately 6.12 days. All participants received antibiotics as part of the standard treatment for pneumonia (Table 3, Figs. 1-3).

Discussion

This case series strongly supports the link between cigarette smoking and the development of AEP. Our findings are also consistent with previous studies showing a significant connection between a change in smoking habits, including starting, resuming, or increasing smoking, and the onset of AEP. In Korea, young adults who begin or escalate smoking during military service appear to be at particular risk. Many patients in our study likely started or intensified their smoking after enlistment, which underscores the relationship between modified smoking behaviors during military service and AEP. The hospital involved in this study was located in the southern region of Korea near the Republic of Korea Naval Training Center and Academy, which could explain the prevalence of smoking-related AEP cases in this area.

Several studies have documented the occurrence of AEP among military personnel. Yoon et al. [21] analyzed 333 AEP cases from 2007 to 2013 at Korean military hospitals and found that most patients were 22-year-old male smokers, with 87% of them having recently changed their smoking habits. Similarly, a study of US military personnel deployed near Iraq from March 2003 to March 2004 identified 18 AEP cases among 183,000 soldiers, primarily affecting young male smokers, many of whom had recently started smoking [19]. The majority of patients (70.6%) developed AEP within 2 months of starting smoking. Unlike these studies, which diagnosed AEP based on clinical features, our study used BAL fluid analysis to confirm an increase in eosinophils, providing a more precise diagnosis. While a BAL fluid eosinophil count >25% is frequently used as a diagnostic criterion for AEP, clinical presentation, radiological findings, and response to corticosteroid therapy should also be considered. In cases 1 and 14, despite lower eosinophil counts, their clinical symptoms and radiological evidence were consistent with AEP, justifying their inclusion in the study. In this study, two non-military person cases provided additional insights. One involved a young university student who developed AEP after her first exposure to cigarette smoke, while the other was a middle-aged man whose condition was triggered by a significant increase in smoking quantity. However, this rapid onset suggests a potential acute triggering effect of smoking on eosinophilic inflammation, consistent with findings from previous case series reporting similar temporal associations.

Patients with AEP often present with fever and an elevated peripheral white blood cell count but with normal blood eosinophil levels. This pattern can make it challenging to distinguish AEP from bacterial pneumonia, and a normal eosinophil count can delay the suspicion for AEP. Therefore, clinical suspicion and comprehensive diagnostic assessments, such as BAL, can be used for a more accurate diagnosis and effective treatment [2,3,5].

Chest computed tomography findings in AEP typically include bilateral ground-glass attenuation, interlobular septal thickening, bronchovascular bundle thickening, pleural effusions, airspace consolidation in areas, and poorly defined centrilobular nodules [22,23]. Interlobular septal thickening is particularly notable in most patients, indicating inflammation and edema in the interstitial spaces of the lungs [23]. This feature may distinguish AEP from bacterial pneumonia, which is usually characterized by airspace consolidation and a ground-glass appearance. Thus, the presence of interlobular septal thickening combined with diffuse ground-glass opacities and an appropriate clinical background may be crucial for differentiating AEP from bacterial pneumonia.

AEP caused by cigarette smoke involves immune responses characterized by chemokine and cytokine activity. Cigarette smoke stimulates alveolar macrophages and dendritic cells to produce chemokines such as macrophage-derived chemokine and thymus- and activation-regulated chemokine, which recruit eosinophils into the lungs [24]. This process is enhanced by interleukin (IL)-4. Additionally, increased levels of IL-5 and IL-1 receptor antagonist promote eosinophil activation and survival, driving inflammation [20]. These responses are dose-dependent, correlating with smoking intensity and changes in smoking habits, highlighting the significant role of cigarette smoke in AEP pathogenesis and the importance of smoking cessation for prevention.

The use of steroids is crucial and often leads to a rapid improvement in AEP. However, determining the appropriate dosage and duration of steroid treatment remains challenging. A study conducted at the Armed Forces Capital Hospital in Korea established a standardized treatment protocol. In patients with respiratory failure, this protocol starts with the aggressive administration of methylprednisolone at a recommended dosage of 60 mg intravenously every 6 hours for 3 days, followed by a switch to 30 mg of oral prednisolone administered twice daily. For patients without respiratory failure, treatment with 30 mg oral prednisolone is initiated twice daily. The duration of corticosteroid therapy is typically adjusted to between 2 to 4 weeks in order to balance the efficacy of this treatment with the risk of potential side effects [25]. In this study, five out of 17 patients experienced spontaneous recovery without the use of corticosteroids. Most of these patients had relatively mild symptoms and less severe findings on chest radiographs, suggesting that the absence of severe clinical manifestations may have allowed for natural resolution of the disease. These findings align with previous reports that some AEP cases follow a self-limiting course [26]. While corticosteroids remain the primary treatment for AEP, this highlights the importance of considering the clinical severity and radiological findings when deciding on the necessity of steroid therapy.

Although our study offers detailed insights into the relationship between AEP and cigarette smoking, it had some limitations. First, its retrospective design limited our ability to establish definitive causality. Furthermore, the exact mechanism by which cigarette smoke triggers an abnormal immune response leading to eosinophilic infiltration remains unclear. This limitation underscores the need for further studies to elucidate these underlying mechanisms.

In conclusion, our case series reinforces the link between cigarette smoking and AEP, underscoring the need for targeted prevention strategies, such as smoking cessation programs, especially for high-risk groups like military personnel. Furthermore, the substantial improvement seen in our patient population following corticosteroid treatment highlights the importance of early detection and intervention.

Article information

Conflicts of interest

No potential conflict of interest relevant to this article was reported.

Funding

None.

Author contributions

Conceptualization: HCK. Data curation: IRH, HCK. Formal analysis; Investigation: HCK. Methodology: IRH, HCK. Project administration: HCK. Resources: IRH, THK, KNJ, HCK. Software: HCK. Supervision: THK, HCK. Validation: THK, HCK. Visualization: KNJ, HCK. Writing - original draft: IRH, HCK. Writing - review & editing: all authors. All authors read and approved the final manuscript.

Fig. 1.

A 19-year-old male military soldier experienced shortness of breath and coughing for the past day. The patient, a smoker of a half-pack of cigarettes daily for 1 year, initially had a blood eosinophil count of 0.6%, which later increased to 11.4%. Bronchoalveolar lavage fluid analysis revealed 17% eosinophils. (A) The initial chest X-ray showed bilateral and diffuse consolidation with pleural effusions, and (B) a chest computed tomography scan indicated interlobular septal thickening, airspace consolidation with ground-glass opacities, and bilateral pleural effusions. (C) Treatment with 40 mg/day of methylprednisolone resulted in significant clinical improvement, as demonstrated in the follow-up chest X-ray.

Fig. 2.

An 18-year-old female university student developed dyspnea 2 days prior to presentation. Despite previously being a nonsmoker, she reported smoking a half-pack of cigarettes daily for 1 week. Initially, the white blood cell count showed 3% eosinophils, which increased to 15.2%. Bronchoalveolar lavage fluid analysis revealed the presence of 26% eosinophils. (A) Chest radiography revealed bilateral airspace consolidation, and (B) a computed tomography scan showed bilateral consolidation with ground-glass opacities and septal thickening in both lower lobes. (C) Treatment involved administration of 30 mg/day of methylprednisolone followed by prednisolone over a 10-day period, leading to improvements that were visible on the follow-up chest radiograph.

Fig. 3.

A 20-year-old male military soldier had been smoking 0.7 packs of cigarettes per day for 6 months. He started experiencing shortness of breath 1 day prior to presentation, and his body temperature at presentation was 37.7 °C. Initially, his eosinophil count in the peripheral blood was 0.2%, but it increased to 14.4% 3 days later. Bronchoalveolar lavage fluid analysis revealed eosinophils comprising 45% of white blood cells. (A) The initial chest X-ray showed bilateral airspace consolidation, (B) while a computed tomography scan demonstrated bilateral consolidation with ground-glass opacities, interlobular septal thickening, and bilateral pleural effusions. (C) Treatment began with methylprednisolone and was later switched to prednisolone for a period of 28 days, resulting in the clinical improvements seen in a follow-up chest X-ray.

References

• 1. Allen JN, Davis WB. Eosinophilic lung diseases. Am J Respir Crit Care Med 1994;150(5 Pt 1):1423–38.ArticlePubMed
• 2. Allen JN, Pacht ER, Gadek JE, Davis WB. Acute eosinophilic pneumonia as a reversible cause of noninfectious respiratory failure. N Engl J Med 1989;321:569–74.ArticlePubMed
• 3. Philit F, Etienne-Mastroianni B, Parrot A, Guerin C, Robert D, Cordier JF. Idiopathic acute eosinophilic pneumonia: a study of 22 patients. Am J Respir Crit Care Med 2002;166:1235–9.ArticlePubMed
• 4. Marchand E, Reynaud-Gaubert M, Lauque D, Durieu J, Tonnel AB, Cordier JF, et al. Idiopathic chronic eosinophilic pneumonia: a clinical and follow-up study of 62 cases. Medicine 1998;77:299–312.ArticlePubMed
• 5. De Giacomi F, Vassallo R, Yi ES, Ryu JH. Acute eosinophilic pneumonia: causes, diagnosis, and management. Am J Respir Crit Care Med 2018;197:728–36.ArticlePubMed
• 6. Brackel CL, Ropers FG, Vermaas-Fricot SF, Koens L, Willems LN, Rikkers-Mutsaerts ER. Acute eosinophilic pneumonia after recent start of smoking. Lancet 2015;385:1150.ArticlePubMed
• 7. Park SY, Kim JH, Chung MJ, Rhee CH, Park SJ. Acute eosinophilic pneumonia and tracheitis associated with smoking. Am J Respir Crit Care Med 2017;195:1671–2.ArticlePubMed
• 8. Nakajima M, Manabe T, Sasaki T, Niki Y, Matsushima T. Acute eosinophilic pneumonia caused by cigarette smoking. Intern Med 2000;39:1131–2.ArticlePubMed
• 9. Shintani H, Fujimura M, Yasui M, Ueda K, Kameda S, Noto M, et al. Acute eosinophilic pneumonia caused by cigarette smoking. Intern Med 2000;39:66–8.ArticlePubMed
• 10. Shiota Y, Kawai T, Matsumoto H, Hiyama J, Tokuda Y, Marukawa M, et al. Acute eosinophilic pneumonia following cigarette smoking. Intern Med 2000;39:830–3.ArticlePubMed
• 11. Thakur LK, Jha KK. Acute eosinophilic pneumonia following recent cigarette smoking. Respir Med Case Rep 2016;19:103–5.ArticlePubMedPMC
• 12. 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;133:1174–80.ArticlePubMed
• 13. Al-Saieg N, Moammar O, Kartan R. Flavored cigar smoking induces acute eosinophilic pneumonia. Chest 2007;131:1234–7.ArticlePubMed
• 14. Youn JS, Kwon JW, Kim BJ, Hong SJ. Smoking-induced acute eosinophilic pneumonia in a 15-year-old girl: a case report. Allergy Asthma Immunol Res 2010;2:144–8.ArticlePubMedPMC
• 15. Watanabe K, Fujimura M, Kasahara K, Yasui M, Myou S, Kita T, et al. Acute eosinophilic pneumonia following cigarette smoking: a case report including cigarette-smoking challenge test. Intern Med 2002;41:1016–20.ArticlePubMed
• 16. Cottin V. Eosinophilic lung diseases. Clin Chest Med 2016;37:535–56.ArticlePubMed
• 17. Bok GH, Kim YK, Lee YM, Kim KU, Uh ST, Hwang JH, et al. Cigarette smoking-induced acute eosinophilic pneumonia: a case report including a provocation test. J Korean Med Sci 2008;23:134–7.ArticlePubMedPMC
• 18. Kono Y, Tsushima K, Yamaguchi K, Soeda S, Fujiwara A, Sugiyama S, et al. The relationship between the clinical course and cytokine in a patient with cigarette smoking-induced acute eosinophilic pneumonia: a case report. Respir Med Case Rep 2012;5:16–9.ArticlePubMedPMC
• 19. 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;292:2997–3005.ArticlePubMed
• 20. Teng Y, Gao Y. Tobacco smoking associated with the increases of the bronchoalveolar levels of interleukin-5 and interleukin-1 receptor antagonist in acute eosinophilic pneumonia. Eur Rev Med Pharmacol Sci 2014;18:887–93.PubMed
• 21. Yoon CG, Kim SJ, Kim K, Lee JE, Jhun BW. Clinical characteristics and factors influencing the occurrence of acute eosinophilic pneumonia in Korean military personnel. J Korean Med Sci 2016;31:247–53.ArticlePubMedPMCPDF
• 22. Cheon JE, Lee KS, Jung GS, Chung MH, Cho YD. Acute eosinophilic pneumonia: radiographic and CT findings in six patients. AJR Am J Roentgenol 1996;167:1195–9.ArticlePubMed
• 23. Daimon T, Johkoh T, Sumikawa H, Honda O, Fujimoto K, Koga T, et al. Acute eosinophilic pneumonia: thin-section CT findings in 29 patients. Eur J Radiol 2008;65:462–7.ArticlePubMed
• 24. Nureki S, Miyazaki E, Ando M, Kumamoto T, Tsuda T. CC chemokine receptor 4 ligand production by bronchoalveolar lavage fluid cells in cigarette-smoke-associated acute eosinophilic pneumonia. Clin Immunol 2005;116:83–93.ArticlePubMed
• 25. Rhee CK, Min KH, Yim NY, Lee JE, Lee NR, Chung MP, et al. Clinical characteristics and corticosteroid treatment of acute eosinophilic pneumonia. Eur Respir J 2013;41:402–9.ArticlePubMed
• 26. Jhun BW, Kim SJ, Son RC, Yoo H, Jeong BH, Chung MP, et al. Clinical outcomes in patients with acute eosinophilic pneumonia not treated with corticosteroids. Lung 2015;193:361–7.ArticlePubMedPDF

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References

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