Long-term use of mepolizumab in a case of chronic eosinophilic pneumonia: extending interval dosing.

INTRODUCTION: Mepolizumab, a humanized anti IL-5 monoclonal antibody, has been used off-label for chronic eosinophilic pneumonia (CEP), inducing disease remission and saving systemic corticosteroids. CASE STUDY: We present a case of CEP, requiring long-term corticosteroids therapy due to relapse upon withdrawal. Mepolizumab was started and maintained for 2 years and 6 months. RESULTS: Corticosteroids could be withdrawn and mepolizumab dose interval was spared up to 10 wk with no disease relapse. CONCLUSION: Mepolizumab is shown to be useful for chronic eosinophilic pneumonia, allowing corticosteroid withdrawal. Dose interval may be individualized under close monitoring, for a more efficient treatment, reducing medical costs while improving patients' quality of life.

Monoclonal antibodies in idiopathic chronic eosinophilic pneumonia: a scoping review.

BACKGROUND: Idiopathic chronic eosinophilic pneumonia (ICEP) is a rare disease characterized by pulmonary radiological alterations, peripheral eosinophilia, and demonstrated pulmonary eosinophilia. Oral steroids (OSs) are the standard management, but relapses occur in up to 50% of patients during the decrease or suspension of steroids, usually requiring reinitiation of treatment, exposing patients to secondary events derived from the management. Management with monoclonal antibodies has been proposed in these cases to control the disease and limit the secondary effects. The objective is to describe the extent and type of evidence regarding the use of monoclonal antibodies for ICEP. METHODS: A panoramic review of the literature was performed. Observational and experimental studies of pediatric and adult populations that managed recurrent ICEP with monoclonal antibodies were included. Data search, selection, and extraction were performed by two independent reviewers. RESULTS: 937 studies were found. After applying the inclusion and exclusion criteria, 37 titles remained for the final analysis: a retrospective, observational, real-life study, two case series publications, and 34 case reports published in academic poster sessions and letters to the editor. In general, the use of monoclonal antibodies approved for severe asthma could be useful for the control of ICEP, since most of the results show a good response for clinical and radiological outcomes. Biological drugs seem to be a safer option for controlling relapses in ICEP, allowing lowering/suspension of OSs, and sometimes replacing them in patients intolerant to them, patients with significant comorbidities, and patients who have already developed adverse events. CONCLUSION: The extent of the evidence supporting management of ICEP with monoclonal antibodies against IL-5 and IgE (omalizumab) is limited, but it could be promising in patients who present frequent relapses, in cortico-dependent individuals, or in patients in whom the use of steroids is contraindicated. The extent of the evidence for management with dupilumab is more limited. Studies with better design and structure are needed to evaluate quality of life and outcomes during a clear follow-up period. To our knowledge, this is the first scoping review of the literature showing the extent of the evidence for the management of ICEP with monoclonal antibodies.

Real-Life Study of Mepolizumab in Idiopathic Chronic Eosinophilic Pneumonia.

INTRODUCTION: Idiopathic chronic eosinophilic pneumonia (ICEP) is an orphan lung disease characterized by concomitant systemic and local eosinophilia, along with bilateral lung infiltrates. Symptoms include dyspnea of subacute/chronic onset, cough, and general systemic signs. Although all patients do respond to oral corticosteroids, relapse rate is very high, which highlights the need for alternative therapies in case of relapsing ICEP. Mepolizumab is a fully humanized antibody directed against interleukin 5, a key growth factor of eosinophils. In the present study, we retrospectively studied the effect of off-label use of mepolizumab for relapsing ICEP. MATERIALS AND METHODS: All data from patients treated with mepolizumab for relapsing ICEP were included in our database and diagnoses were reviewed. We analyzed the effect of treatment on relapse rate, oral corticosteroids (OCS) use, and lung lesions on high-resolution computed tomography (HRCT). RESULTS: We included ten patients in the final analysis, with a median follow-up of 9 months after initiation of mepolizumab. Beside its expected effect on circulating eosinophils, treatment with mepolizumab was associated with a significant reduction of annual rate of exacerbations and a reduced consumption of corticosteroids. We also observed a remission of lung lesions on follow-up HRCT. CONCLUSIONS: In this open-label retrospective study, treatment of ICEP with mepolizumab was associated with a reduction of relapses, OCS use, and the disappearance of lung infiltrates.

Eosinophilic pneumonia: A review of the previous literature, causes, diagnosis, and management.

Eosinophilic pneumonia (EP) is a rare disorder, comprising several heterogeneous diseases. Two major types of EP are acute eosinophilic pneumonia (AEP) and chronic eosinophilic pneumonia (CEP), both of which are characterized by marked accumulation of eosinophils in lung tissues and/or BAL fluid. AEP and CEP share some similarities in terms of pathophysiology, radiological findings, and treatment response to corticosteroids. However, they distinctly differ in etiology, clinical manifestations, and the nature of disease course. Especially, although AEP and CEP respond well to corticosteroids, relapse frequently occurs in patients with CEP, but rarely in those with AEP. Although CEP occasionally persists and becomes corticosteroid dependent, most patients with AEP completely recover. This article reviews previous studies and discusses the etiology, clinical manifestations, and treatment of AEP and CEP.

Long-term management and persistent impairment of pulmonary function in chronic eosinophilic pneumonia: A review of the previous literature.

Chronic eosinophilic pneumonia (CEP) is an inflammatory disease characterized by accumulations of eosinophils in the lung with unknown etiology. Although corticosteroid treatment dramatically resolves these inflammations, relapse is common during the course of the disease. Approximately 50% of patients with CEP experience relapse. Subsequent to persistent disease and repeated relapse, and in cases of combined severe asthma, some CEP patients are administered corticosteroids indefinitely. Similar to patients with severe asthma who are often steroid dependent, a number of CEP patients exhibit prolonged persistent impairment of pulmonary function. Thus, CEP should be considered a potentially chronic disease requiring long-term management, rather than an acute or sub-acute disease requiring short-time therapy only. This review summarizes previous CEP studies, as well as our own cohort data, and discusses the long-term management of CEP with a particular focus on relapse, the prevalence of maintenance therapy, and persistent impairment of pulmonary function.

Eosinophilic pneumonia caused by daptomycin: Six cases from two institutions and a review of the literature.

Here we report six cases of daptomycin (DAP)-induced eosinophilic pneumonia (DIEP) encountered at two medical centers and present a review of 43 DIEP patients from 26 studies to compare the clinical characteristics and radiographic findings of acute and chronic eosinophilic pneumonia (AEP; CEP). Four of the six patients did not exhibit respiratory symptoms, and one patient with only fever was misdiagnosed with DAP-induced fever. According to our literature review and the present findings, male sex and old age were dominant risk factors for DIEP. Fever and fine crackles were the most common clinical manifestations. The DAP dose and duration of administration were not significant risk factors for DIEP, and we also could not find any association between allergic predisposition and DIEP. Among the reviewed patients, 51.8% did not show more than 25% eosinophils in bronchoalveolar lavage, which is a criterion for the diagnosis of drug-induced eosinophilic pneumonia. Chest images of all patients showed CEP patterns such as multiple reticulonodular infiltrates in the subpleural region and diffuse bilateral pulmonary infiltrates with ground-glass opacities. However, 66.7% of patients also exhibited pleural effusion, a feature specific to AEP. All patients showed prompt recovery after DAP withdrawal. Our results suggest that clinicians should consider DIEP as a differential diagnosis when patients receiving DAP therapy, particularly men and elderly patients, present with fever, even in the absence of respiratory symptoms. Furthermore, they should be aware that the occurrence of DIEP is independent of the DAP dose and administration duration, and allergic reaction.

Successful discontinuation of corticosteroids through remission induction therapy with benralizumab for chronic eosinophilic pneumonia.

Chronic eosinophilic pneumonia (CEP) is an eosinophilic lung disease. Treatment for CEP includes corticosteroids; however, CEP often recurs. A 53-year-old woman was referred to our hospital because of poorly controlled asthma. She was treated with combination of moderate-dose inhaled corticosteroid (ICS), a long-acting ß2-agonist (LABA), and betamethasone/dexchlorpheniramine. She was switched to single-inhaler triple therapy, after which her asthma control improved; thus, betamethasone/dexchlorpheniramine was discontinued. Ten weeks later, she was diagnosed with CEP due to marked eosinophilia and pulmonary eosinophilic infiltrates. Oral corticosteroid treatment was initiated, symptoms improved, and peripheral blood eosinophilia decreased with improved infiltrative shadows. Remission induction therapy was initiated with benralizumab combined with corticosteroid therapy. Eosinophilia and inflammatory responses decreased. After 7 months, corticosteroid was discontinued, and she was treated with benralizumab alone. She remained in remission for 4 months. This case suggests that benralizumab may be useful as a remission induction therapy in patients with CEP.

A case of recurrent chronic eosinophilic pneumonia after switching from benralizumab to dupilumab.

Dupilumab inhibits interleukin-4Rα and suppresses type 2 inflammation. Careful administration of dupilumab is required because it increases the blood eosinophil count secondary to a decrease in local eosinophil counts, sometimes resulting in eosinophilic complications. We herein report a case of recurrent chronic eosinophilic pneumonia after switching from benralizumab to dupilumab. A 54-year-old man with a history of eosinophilic pneumonia presented to our hospital with symptoms of cough, fever, and phlegm production six months after beginning dupilumab administration for recurrent chronic rhinosinusitis. When using dupilumab, it is essential to carefully monitor patients' eosinophil trends and pulmonary symptoms.

Methylphenidate causes chronic eosinophilic pneumonia.

A man who is 38 years old and diagnosed with attention-deficit hyperactivity disorder was prescribed methylphenidate. Three weeks later, he began experiencing progressive shortness of breath and coughing. Imaging of his chest showed patchy bilateral ground-glass opacities, and bronchoscopy revealed a 15% eosinophil count in his bronchoalveolar lavage. A transbronchial biopsy confirmed a diagnosis of eosinophilic pneumonia. The patient's condition improved when he was given steroids and stopped taking methylphenidate. However, he developed the same symptoms again a few days after restarting the medication, along with a skin rash. This strongly suggests that methylphenidate was the cause of his eosinophilic pneumonia.

Successful Treatment of Relapsing Chronic Eosinophilic Pneumonia With Mepolizumab: A Case Report.

We present a case of a 73-year-old male with a five-month history of progressive dyspnea on exertion, cough, and worsening hypoxemia. Initial lab work did not identify peripheral eosinophilia. Chest computed tomography identified extensive ground-glass opacities in the mid-basilar. Diagnostic bronchoscopy showed an eosinophilic-rich bronchoalveolar lavage representing 63% of the total white blood cell count, confirming the diagnosis of chronic eosinophilic pneumonia. No etiology was identified despite extensive diagnostic workup. Our patient had a prolonged course of prednisone taper treatment complicated by frequent hospitalizations, osteopenia, and insomnia. Additionally, his chronic eosinophilic pneumonia relapsed shortly after stopping steroids. In our patient, off-label treatment with mepolizumab, an interleukin-5-inhibiting monoclonal antibody, was associated with symptomatic relief, imaging findings resolution, and remission maintenance without systemic steroids.

Cryptogenic organizing pneumonia after withdrawal of systemic corticosteroids for chronic eosinophilic pneumonia and severe asthma under benralizumab treatment.

A 79-year-old woman with severe asthma developed chronic eosinophilic pneumonia (CEP). After CEP resolved with oral prednisolone at 30 mg/day, prednisolone was tapered and discontinued under introduction of benralizumab for her severe asthma. However, 8 weeks later, symptoms and bilateral patchy infiltrates on chest radiography appeared. Lymphocytosis without eosinophilia was seen in bronchoalveolar lavage fluids, and transbronchial biopsy indicated organizing pneumonia. Cryptogenic organizing pneumonia (COP) was diagnosed and resolved with prednisolone at 30 mg/day. Prednisolone was tapered to 3 mg/day without relapse of CEP or COP. This case suggests the overlap and similar pathogenesis of CEP and COP.

Acute and chronic eosinophilic pneumonia: an overview.

Acute and chronic eosinophilic pneumonia (AEP and CEP) include a group of rare interstitial lung diseases characterized by peripheral blood eosinophilia, increased eosinophils in bronchoalveolar lavage fluid, or eosinophilic infiltration of lung parenchyma. AEP is characterized by rapid onset, fast response to steroid treatment, and no relapse. CEP is characterized by marked tissue and peripheral blood eosinophilia, rapid response to steroid therapy, and tendency to disease recurrence. In addition, we briefly describe other eosinophilic lung diseases that must be considered in differential diagnosis of AEP and CEP. Eosinophilic pneumonias may be idiopathic or due to known causes such as medications or environmental exposure. At variance with previous reviews on this topic, a particular look in this overview was directed at pathological findings and radiological patterns.

E-cigarette-/Vape-Associated Lung Injury as a Cause of Interstitial Lung Disease.

E-cigarette-/vape-associated lung injury (EVALI) refers to damage to lung tissue occurring as a result of e-cigarette utilization or via vaping of inhaled nicotine products. Vaping refers to the practice of inhaling an aerosol derived from heating a liquid or gas containing substances such as nicotine, cannabinoids, flavoring, or additives. Battery-operated e-cigarettes or vape pens are the vessels commonly used in this practice. EVALI, first described in the literature in 2019, has a non-specific course, presenting initially with cough and dyspnea. It can progress, however, to interstitial lung disease or result in damage to the lung parenchyma with concomitant inflammation and fibrosis. Imaging findings reflect the development of this inflammation and fibrosis, often visualized as ground-glass opacities on computed tomography (CT) scans. Formal biopsies are not required to make the diagnosis of EVALI, and thus, a gap exists in the scientific literature with regard to the pathology of lungs exposed to non-tetrahydrocannabinol (THC) e-cigarettes. The following case details the clinical course of a 62-year-old male who presented to the outpatient pulmonology office with symptomology and exposure history consistent with EVALI, unique in presentation due to the timeline of his disease development. The patient initially presented to the clinic for the evaluation of a non-productive cough and exertional dyspnea beginning one year ago, with an associated new home oxygen requirement of 2 liters via nasal cannula. The patient's past medical history was relevant for diffuse large B-cell lymphoma treated with the chemotherapeutic regimen that consists of etoposide phosphate, prednisone, vincristine sulfate (Oncovin), cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), and rituximab, commonly known as EPOCH-R, as well as a social history relevant for a 35-pack-year smoking history. On further questioning, the patient revealed that following cessation of cigarette smoking, he began using non-THC e-cigarettes daily and had been doing so for 10 years prior to symptom onset. Imaging and biopsy findings consisted of a CT of the chest demonstrating concern for interstitial lung disease and an open lung biopsy demonstrating diffuse alveolar damage with eosinophilia. Given the patient's history, clinical symptoms, and imaging findings, a diagnosis of EVALI was established. This case was documented not only to increase awareness of the rising incidence of EVALI as the use of e-cigarettes and vapes becomes increasingly popular but also to further understand the inhalational injury sustained from non-THC e-cigarettes and other inhalational practices.

Case Report: Mepolizumab in the treatment of idiopathic chronic eosinophilic pneumonia.

Idiopathic chronic eosinophilic pneumonia (ICEP) is a rare interstitial lung disease of unknown cause. It usually responds well to systemic corticosteroid therapy, but relapses are frequent. We describe two cases of 21- and 27-year-old patients, presenting with dyspnea. The diagnosis of steroid-relapsing and steroid-dependent ICEP was made respectively. Mepolizumab was prescribed to both patients. This treatment resulted in successful long-term disease management with much fewer side effects than a traditional corticosteroid therapy.

Pneumothorax with Eosinophilia is an Important Diagnostic Clue for Distinguishing Paragonimiasis from Chronic Eosinophilic Pneumonia: A Case Report.

The Paragonimus westermani infection is a parasitic foodborne infection that induces systemic symptoms with eosinophilia in humans. Here, we described pneumothorax in addition to pulmonary opacities with eosinophilia in a man with a positive P. westermani serology. He was misdiagnosed with chronic eosinophilic pneumonia (CEP) during the initial phase. Paragonimiasis can share similar clinical findings with CEP in cases where the worm is confined to the lungs. The findings of the current study suggest that paragonimiasis and CEP can be distinguished from each other by the presence of various symptoms. Notably, eosinophilia with pneumothorax should be an important diagnostic factor for paragonimiasis.

Dupilumab suppresses relapsing chronic eosinophilic pneumonia with severe asthma.

Dupilumab-induced hypereosinophilia is mediated by blockade of the IL-4/IL-13 pathway, which reduces eosinophil migration from peripheral blood. The increase in peripheral blood eosinophils may lead to chronic eosinophilic pneumonia (CEP) and/or eosinophilic granulomatosis with polyangiitis, but a direct causal connection between dupilumab and eosinophilic lung diseases has not been established. A 33-year-old Japanese woman with bronchial asthma since age three was treated with fluticasone propionate plus salmeterol twice daily after several asthma exacerbations at age 17. Her course was complicated by CEP at age 33 which resolved without the need for systemic steroids. However, in the four months following resolution of her CEP, the patient had three asthma exacerbations, and a recurrence of CEP, with blood leukocytes of 8500/µL, of which 25.0% were eosinophils. She was treated with prednisolone 50 mg/day, but she could not continue this dose due to the onset of myalgia. Then she had relapsing CEP twice within three months. She was treated with prednisolone 15 mg/day for CEP, but she had persistent asthma for more than one month; dupilumab was added at 600 mg, followed by 300 mg every two weeks. In the first month of treatment with dupilumab, the patient's asthma symptoms resolved completely, and she had only one relapse of CEP. In 12 months of follow-up, she had neither an asthma exacerbation nor another relapse of CEP. Dupilumab may be a promising treatment for patients with refractory asthma complicated by recurring CEP and undesirable steroid side effects.

Comorbidity of eosinophilic chronic rhinosinusitis in chronic eosinophilic pneumonia.

We aimed to elucidate details of comorbid chronic rhinosinusitis (CRS) in chronic eosinophilic pneumonia (CEP) under the collaboration between otolaryngologists and pulmonologists in a prospective study. The CEP diagnosis was performed by pulmonologists based on clinical symptoms, laboratory findings, and/or eosinophilia detected in bronchoalveolar lavage. All patients were referred to otolaryngologists before undergoing oral corticosteroid treatment for CEP. Ten CEP cases visited to otolaryngologists. All cases showed bilateral sinonasal inflammation in computed tomography (CT), indicating comorbid CRS. Nasal polyps (NPs) were observed in 50% of patients on endoscopy. Eighty percent of patients were diagnosed with eosinophilic CRS. In blood eosinophil levels and the mucosal eosinophil count, there were no significant differences between CRS without and with NPs. In Lund-Mackay CT total scores, among-individual variability was observed in CRS with NPs. The collaboration revealed blood/sinonasal eosinophilia and the variability in Lund-Mackay CT total scores as remarkable findings about the comorbid CRS.