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A man in his 40s with a known history of alcohol dependence syndrome was admitted with presenting symptoms of alcohol withdrawal. During his admission, he developed breathlessness, cough and wheezing. Investigations revealed raised absolute eosinophil count and serum IgE levels. Chest imaging showed ill-defined opacities and fibreoptic bronchoscopy with bronchoalveolar lavage confirmed eosinophilic pneumonia. Extensive workup for the cause of eosinophilia was negative. The patient's medicines were reviewed, and it was realised that the onset of eosinophilia occurred after starting topiramate for an alcohol withdrawal seizure. The drug was stopped, leading to the complete resolution of symptoms and radiological abnormalities. This case highlights the importance of considering drug-induced causes of eosinophilic pneumonia., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Retraction Notice: Retracted for use of material or data without authorization from third party. Reference: Asna Mohammed, Bo Tang, Sean Sadikot, Guido Barmaimon: Acute Eosinophilic Pneumonia Induced by Immune Checkpoint Inhibitor and Anti-TIGIT Therapy. Am J Case Rep 2024; 25: e943740; DOI: 10.12659/AJCR.943740.

BACKGROUND Immune checkpoint inhibitors (ICIs) have been linked to various immune-related adverse events, including pneumonitis, necessitating early recognition and potential treatment discontinuation. Acute eosinophilic pneumonia (AEP) induced by ICIs, particularly with no reported cases involving anti-TIGIT therapy, is rare. This report describes a case of AEP following treatment with pembrolizumab and anti-TIGIT therapy. CASE REPORT A 46-year-old woman with lung adenoid cystic carcinoma and chronic hypoxemic respiratory failure on long-term oxygen therapy presented with fever, cough, and shortness of breath. She underwent left pneumonectomy and radiation therapy at diagnosis 9 years earlier. She was participating in a clinical trial using pembrolizumab and anti-TIGIT EOS-448, due to cancer progression. After starting therapy, she developed stable peripheral eosinophilia and a skin rash, suggestive of a drug reaction. On admission, she was in acute-on-chronic hypoxemic respiratory failure, febrile, with an elevated eosinophil count and new multifocal infiltrates in the right lung. Despite broad antibiotics coverage for pneumonia, she developed worsening respiratory symptoms and eosinophilia. She was then empirically started on intravenous methylprednisolone for acute eosinophilic pneumonia without confirmatory bronchoscopy as she was at high risk with her previous pneumonectomy. She subsequently had rapid improvement in her symptoms. CONCLUSIONS AEP should be considered in patients treated with ICIs who develop immune-related adverse effects. Although bronchoscopy findings are part of AEP's diagnostic criteria, this case underscores the importance of clinical judgment in the prompt initiation of steroids, even without confirmatory bronchoscopy, in rapidly progressing cases. The role of anti-TIGIT therapy in this context remains uncertain.

Acute eosinophilic pneumonia (AEP) is a rare cause of acute respiratory failure. Clinical presentations can range from dyspnoea, fever and cough, to rapidly progressive and potentially fulminant respiratory failure. While its exact cause is often unknown, associations with inhalational injuries and exposures to new medications have been described.We report a case of a middle-aged, non-smoking man with a history of alcohol use disorder. He presented with 4 days of shortness of breath that started hours after taking injectable naltrexone (Vivitrol). The patient had rapidly worsening hypoxaemia, necessitating emergent bronchoscopy with transbronchial biopsies and bronchoalveolar lavage which showed 66% eosinophils. The patient was intubated for the procedure and unable to get extubated due to worsening hypoxaemic respiratory failure with high fractional inspired oxygen requirements. Chest radiograph showed worsening lung infiltrates and with a high index of suspicion for AEP, he was started empirically on methylprednisolone. He had rapid improvement in his respiratory status and was extubated on day 5 of admission then discharged on day 8. Histopathological examination confirmed acute/subacute eosinophilic pneumonia. A 3-week post-discharge follow-up chest radiograph confirmed the full resolution of pulmonary infiltrates.Naltrexone-induced AEP is rare, with only six other cases reported in the literature. Careful history taking and prompt evaluation for AEP are important given the potential for rapid progression to acute hypoxic respiratory failure and the excellent response to steroid treatment., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Abstract: Daptomycin-induced eosinophilic pneumonia (DIEP) is a rare complication of daptomycin use. Manifestations most commonly include fever, hypoxia, dyspnea, cough, eosinophilia, and lung changes on radiographs and CT. Patients typically have had recent daptomycin exposure and develop fever, dyspnea, infiltrates on chest radiograph, more than 25% eosinophils on bronchoalveolar lavage, and improvement of symptoms after withdrawal of daptomycin. Treatment includes discontinuation of daptomycin, corticosteroids, and supportive measures such as supplemental oxygen. Clinicians should have a high index of suspicion for DIEP in patients who develop new onset of pulmonary and systemic signs and symptoms after initiation of daptomycin., (Copyright © 2024 American Academy of Physician Associates.)

Background: Stepwise intensification of inhaled corticosteroids (ICS) is routine for severe eosinophilic asthma, despite some poor responses to high-dose ICS. Dose reductions are recommended in patients responding to biologics, but little supporting safety evidence exists., Methods: SHAMAL was a phase 4, randomised, open-label, active-controlled study done at 22 study sites in four countries. Eligible participants were adults (aged ≥18 years) with severe eosinophilic asthma and a five-item Asthma Control Questionnaire score below 1·5 and who received at least three consecutive doses of benralizumab before screening. We randomly assigned patients (3:1) to taper their high-dose ICS to a medium-dose, low-dose, and as-needed dose (reduction group) or continue (reference group) their ICS-formoterol therapy for 32 weeks, followed by a 16-week maintenance period. The primary endpoint was the proportion of patients reducing their ICS-formoterol dose by week 32. The primary outcome was assessed in the reduction group, and safety analyses included all randomly assigned patients receiving study treatment. This study is registered at ClinicalTrials.gov, NCT04159519., Findings: Between Nov 12, 2019, and Feb 16, 2023, we screened and enrolled in the run-in period 208 patients. We randomly assigned 168 (81%) to the reduction (n=125 [74%]) and reference arms (n=43 [26%]). Overall, 110 (92%) patients reduced their ICS-formoterol dose: 18 (15%) to medium-dose, 20 (17%) to low-dose, and 72 (61%) to as-needed only. In 113 (96%) patients, reductions were maintained to week 48; 114 (91%) of patients in the reduction group had zero exacerbations during tapering. Rates of adverse events were similar between groups. 91 (73%) patients had adverse events in the reduction group and 35 (83%) in the reference group. 17 patients had serious adverse events in the study: 12 (10%) in the reduction group and five (12%) in the reference group. No deaths occurred during the study., Interpretation: These findings show that patients controlled on benralizumab can have meaningful reductions in ICS therapy while maintaining asthma control., Funding: AstraZeneca., Competing Interests: Declaration of interests DJJ has received advisory board and speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, and Sanofi. LGH has received grant funding, participated in advisory boards, and given lectures at meetings supported by Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Evelo Biosciences, GSK, Hoffmann-La Roche, Novartis, Sanofi, Teva, and Theravance; he has received grants from Aerocrine, Amgen, AstraZeneca, Genentech/Hoffman-La Roche, GSK, MedImmune, Novartis UK, Roche/Genentech, and Vitalograph; he has received sponsorship for attending international scientific meetings from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, and Napp Pharmaceuticals; he has also taken part in asthma clinical trials sponsored by AstraZeneca, Boehringer Ingelheim, GSK, and Hoffmann-La Roche, for which his institution received remuneration; he is the academic lead for the Medical Research Council Stratified Medicine UK Consortium in Severe Asthma, which involves industrial partnerships with a number of pharmaceutical companies, including Amgen, AstraZeneca, Boehringer Ingelheim, GSK, Hoffmann-La Roche, and Janssen. MH has received consulting fees from AstraZeneca, Chiesi, GSK, Novartis, and Sanofi. BDK has participated in advisory boards or received speaker fees from AstraZeneca, Chiesi, GSK, Novartis, and Teva; has received educational travel bursaries from Boehringer Ingelheim, Chiesi, and Napp Pharmaceuticals; and has received research funding from Itamar Medical. AS was an employee of AstraZeneca at the time of this study and may own stock. LH was an employee of AstraZeneca at the time of this study and may own stock. LO is an employee of Cytel and was on contract to AstraZeneca at the time of this study. DC was an employee of AstraZeneca at the time of this study and may own stock. AM-G was an employee of AstraZeneca at the time of this study and may own stock; has attended advisory boards for AstraZeneca, GSK, Novartis, Regeneron, Sanofi, and Teva; has received speaker fees from AstraZeneca, Novartis, Sanofi, and Teva; has participated in research with AstraZeneca, for which his institution was remunerated; and has had consultancy agreements with AstraZeneca and Sanofi. SK has received grants and personal fees for lectures and advisory boards from AstraZeneca, GSK, Novartis, Sanofi-Genzyme, and Teva., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Eosinophilic pneumonia (EP) is a rare but noteworthy adverse effect linked to dupilumab, an interleukin-4 (IL-4) and IL-13 inhibitor used in the managing atopic diseases. The underlying mechanisms, potential predisposing factors, clinical characteristics, and optimal management strategies for dupilumab-induced EP remain unclear. We report a 71-year-old patient who developed acute EP after the first 600-mg dose of dupilumab. Eosinophils (EOSs) were also transiently increased (up to 1,600 cells/μl). After the acute EP was effectively treated with glucocorticoids, dupilumab treatment was continued. Rash, itching, and immunoglobulin E levels continued to decrease in the patient, and no further pulmonary adverse events occurred. We combined this case with a literature review of nine articles and analyzed data from 93 cases reported in the FDA Adverse Event Reporting System (FAERS) database of patients developing EP after dupilumab use. Our findings imply that dupilumab may induce EP, particularly in individuals over 45 years old, those with a history of respiratory diseases, and those who have previously used inhaled or systemic steroids. Vigilance is required, especially when there is a persistent elevation in peripheral blood EOSs during treatment. Although steroid treatment can effectively manage EP, more data are needed to determine the safety of resuming dupilumab treatment after controlling pneumonia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhou, Yang, Zeng, Wang, Xiang, Zhao, Chen and Zhang.)

Introduction: Acute eosinophilic pneumonia (AEP) is a rare respiratory condition caused by eosinophil accumulation in the pulmonary tissue that can be related to drug administration. Daptomycin, an antibiotic active against gram-positive bacteria, is one of the leading causes of AEP among drugs. In order to raise awareness of this rare syndrome, in our work we have described a case of an 82-year-old male with Enterococcus faecalis endocarditis treated with daptomycin, who developed a daptomycin-induced AEP. We have performed a systematic review of the literature for all similar reported cases., Methods: The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. To conduct the analysis, the terms "daptomycin AND eosinoph* AND pneum*" were entered into the databases Medline, CINAHL, and Embase on April 13, 2023. We considered all relevant records documenting AEP after daptomycin use. No restrictions in terms of year or language were made. A formal appraisal of observational studies was performed by Newcastle-Ottawa Scale. All results and data were reported by means of tables., Results: Our search identified 93 relevant records, published between 2007 and 2023. A total of 120 patients were considered. Patients who experienced AEP were mostly males (n = 88, 73.3%) with a mean age of 68.28 years (SD 11.54). Daptomycin was most frequently prescribed for osteoarticular infections (n = 75, 62.5%) and to treat gram-positive cocci infections. The most frequently isolated pathogen was methicillin-resistant Staphylococcus aureus. Daptomycin was mostly used with off-label indications (n = 89, 74%). Symptoms of AEP were usually reported after a mean of 21.75 days of treatment (range 3-84) and typically included fever, dyspnea, dry cough, and acute respiratory failure. Reported treatment strategies invariably included daptomycin withdrawal, respiratory support, and corticosteroid treatment. One hundred and sixteen patients fully recovered. A fatal outcome was described in 4 patients. Suggestive symptoms and imaging raised suspicion for AEP, confirmed with bronchoalveolar lavage in 57.5% of the cases., Discussion and Conclusions: Daptomycin-induced AEP is a rare but potentially fatal complication, mostly reported after long treatment with daptomycin. Clinicians should be aware of this syndrome, as it could be initially misdiagnosed for an acute infectious respiratory syndrome, resulting in a delay in its diagnosis and treatment. Furthermore, since the risk of developing AEP is increased by longer drug exposure, caution should be used when discussing the use of daptomycin in longer treatment regimens., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: High-dose daptomycin is increasingly used in patients with bone and joint infection (BJI). This raises concerns about a higher risk of adverse events (AEs), including daptomycin-induced eosinophilic pneumonia (DIEP) and myotoxicity. We aimed to examine pharmacokinetic and other potential determinants of DIEP and myotoxicity in patients with BJI receiving daptomycin., Methods: All patients receiving daptomycin for BJI were identified in a prospective cohort study. Cases were matched at a 1:3 ratio, with controls randomly selected from the same cohort. Bayesian estimation of the daptomycin daily area under the concentration-time curve over 24 hours (AUC24h) was performed with the Monolix software based on therapeutic drug monitoring (TDM) data. Demographic and biological data were also collected. Risk factors of AEs were analyzed using Cox proportional hazards model., Results: From 1130 patients followed over 7 years, 9 with DIEP, 26 with myotoxicity, and 106 controls were included in the final analysis. Daptomycin AUC24h, C-reactive protein, and serum protein levels were associated with the risk of AEs. The adjusted hazard ratio of DIEP or myotoxicity was 3.1 (95% confidence interval [CI], 1.48-6.5; P < .001) for daptomycin AUC24h > 939 mg/h/L, 9.8 (95% CI, 3.94-24.5; P < .001) for C-reactive protein > 21.6 mg/L, and 2.4 (95% CI, 1.02-5.65; P = .04) for serum protein <72 g/L., Conclusions: We identified common determinants of DIEP and myotoxicity in patients with BJI. Because the risk of AEs was associated with daptomycin exposure, daptomycin TDM and model-informed precision dosing may help optimize the efficacy and safety of daptomycin treatment in this setting. A target AUC24h range of 666 to 939 mg/h/L is suggested., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: We analyzed the effects of mepolizumab treatment on symptoms, asthma attacks, pulmonary function test parameters peripheral blood eosinophil level, and percentage in patients with severe eosinophilic asthma receiving mepolizumab treatment as the baseline, sixth and twelfthmonth data., Materials and Methods: The medical records of patients diagnosed with severe eosinophilic asthma and treated with mepolizumab at our clinic were retrospectively reviewed for the period between January 2018 and December 2021. Demographic data of the patients, duration of asthma disease, comorbidities such as a nasal polyp, eosinophilic granulomatous polyangiitis, and nonsteroidal anti-inflammatory drug exacerbated respiratory disease were investigated. A comparison was made of various factors before initiating mepolizumab treatment, as well as at the sixth and twelfth month after treatment initiation. These factors include asthma control test scores, frequency of asthma attacks (including emergency admissions, hospitalizations, and intensive care admissions), peripheral blood eosinophil levels and percentages, and pulmonary function test parameters. Clinic and laboratory parameters that provide a prediction of being a responder and super responder were evaluated., Result: A total of 21 patients were included in the study. Their mean age was 50.7 ± 11.9 years, and four (19%) were males. The mean duration of asthma diagnosis was 17.5 ±13.7 years. 14 patients (66.7%) were atopic. 4 patients (19%) had nasal polyps and four patients (19%) had NERD. Before mepolizumab, 13 (61.9%) patients had received omalizumab. The duration of receiving mepolizumab treatment was 29.2 ± 9.9 months. A statistically significant decrease was observed in both the number and percentage of eosinophils at months six and 12 (p<0.01). There was a statistically significant increase in FEV1 values both as a percentage and in milliliters at month 12. There was an increase in both percentage and milliliters in FEF25-75 values, but this increase did not reach statistical significance. There was a decrease in service admissions, intensive care admissions, and emergency admissions due to asthma exacerbations. Out of 21 patients, 11 (52.4%) were classified as responders, while 10 (47.6%) were classified as super responders., Conclusions: Although the number of patients in our study was limited, mepolizumab improved symptom scores in severe eosinophilic asthma, reduced the number of attacks, and improved pulmonary function test values.

A man in his mid-30s presented to the emergency department with a 1-week history of fatigue, loss of appetite, fever and productive (yellow) cough. This progressed to requiring admission to intensive care needing a oxygen therapy via high-flow nasal cannula for acute hypoxaemic respiratory failure. He had recently started vortioxetine for major depressive disorder, and his acute symptoms correlated with an increase in the dose of vortioxetine. For more than 20 years, rare but consistent reports of serotonergic medications have been implicated in eosinophilic pulmonary conditions. During this same period, serotonergic medications have become a mainstay solution for a wide range of depressive symptoms and disorders. This is the first report of an eosinophilic pneumonia-like syndrome occurring while consuming the novel serotonergic medication vortioxetine., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Approximately 1-third of patients with severe asthma are candidates for both omalizumab and mepolizumab treatment. We aimed to compare the clinical, spirometric and inflammatory efficacy of these 2 biologics in atopic and eosinophilic "overlap" severe asthma patients. In our 3-center retrospective cross-sectional observational study, the data of patients who received omalizumab or mepolizumab for at least 16 weeks to treat severe asthma were examined. Atopic (perennial allergen sensitivity and total IgE level 30-1500 IU/mL) and eosinophilic (blood eosinophil counts ≥150 cells/µL in admission; or ≥300 cells/µL in the previous year) patients with asthma suitable for both biologics were included in the study. Post-treatment changes in the asthma control test (ACT) score, number of attacks, forced expiratory volume in 1 second (FEV1), and eosinophil count were compared. The rates of any biological responder patient were compared according to whether they had high eosinophil counts (≥500 cells/µL vs <500 cells/µL). Total of 181 patients data were evaluated, of the 74 atopic and eosinophilic overlap patients included in the study, 56 were receiving omalizumab and 18 were receiving mepolizumab. When omalizumab and mepolizumab treatment efficacies were compared, there was no difference in terms of the reduction in attacks and improvement in ACT. The decrease in eosinophil levels in patients in the mepolizumab arm was significantly higher than that in patients in the omalizumab arm (46.3% vs 87.8%; P < .001). The improvement in FEV1 was greater with mepolizumab treatment, although the difference was not significant (215 mL vs 380 mL; P = .053). It has been shown that having high eosinophil counts does not affect the clinical and spirometric responder patient rates for either biological condition. The success of omalizumab and mepolizumab treatment is similar in patients with atopic and eosinophilic overlap with severe asthma. However, because the baseline patient inclusion criteria are not compatible, head-to-head studies comparing both biological agents are required., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: The association between daptomycin exposure and eosinophilic pneumonia (EP) is mainly based on case reports. The purpose of this study was to evaluate the clinical characteristics and provide more evidence for better identify and management of daptomycin-induced eosinophilic pneumonia in clinical practice., Methods: Literature from 1991 to October 31, 2021 on EP induced by daptomycin were collected for retrospective analysis., Results: A total of 47 patients (40 male and 7 female) from 35 studies were included. The median age was 67 years (range 28-89), and 78.7% of patients were ≥60 years. Daptomycin was mainly used in patients undergoing osteoarticular infections (63.8%). Typical initial symptoms were fever (91.5%), cough (55.3%) and dyspnea (59.6%). The median onset time of symptom was 3 weeks. EP recurred in 14.9% of patients after the re-administration of daptomycin, and 57.1% of EP recurred within 24h. Most cases were accompanied by marked accumulation of eosinophils in peripheral (41 cases) and/or bronchoalveolar lavage fluid (27 cases). The main radiological features were pulmonary infiltration, ground glass opacity or consolidation in CT/CXR. All patients had symptom resolution after discontinuation of daptomycin except for one patient died due to the progression of the primary disease, the median time to symptoms relief was 3 days. Corticosteroids have been shown to help symptoms relief in some cases (59.6%)., Conclusion: Daptomycin-induced eosinophilic pneumonia is a rare and serious complication. Physicians should consider eosinophilic pneumonia as a differential diagnosis when receiving daptomycin therapy, particularly in elderly male patients., (Copyright © 2022 Elsevier España, S.L.U. All rights reserved.)

Summary: Hypersensitivity reactions has been reported with COVID-19 vaccines. Acute eosinophilic pneumonia has not been reported yet after Sinovac/CoronaVac vaccine. A 73-year-old woman presented with maculopapular rash, cough and dyspnea following Sinovac/CoronaVac injection. The complete blood count (CBC) indicated eosinophilia and further evaluation of the eosinophilia with CT and bronchoscopy confirmed a diagnosis of acute eosinophilic pneumonia. After methylprednisolone therapy, her rash resolved with marked improvement of the dyspnea. She is still on treatment and on the follow up period, we plan to continue steroid treatment at least 3 months.

Acute eosinophilic pneumonia (AEP) is a rare cause of respiratory failure. It is primarily a disease of smokers, either a new smoker or an existing one with a recent increase in cigarette consumption. Other risk factors include toxic gas exposure, inhalational illicit drugs, and smoking marijuana. AEP has also been reported in patients with e-cigarette or vaping associated lung injury (EVALI). We present the case of a 20-year-old male who presented to the hospital with acute respiratory failure. The patient has been vaping heavily for the past three months and started smoking three days before presenting to the emergency department. He was hypertensive, tachycardic, tachypneic, and required high-flow nasal cannula to maintain SpO2 &gt; 92%. His condition deteriorated in the first 24 hours following hospitalization requiring noninvasive positive pressure ventilation. Bronchoalveolar lavage revealed an eosinophil count of 36%. Bronchoalveolar lavage (BAL) cytology revealed lipid-laden macrophages. He was diagnosed with AEP due to EVALI, and the patient was treated with high dose corticosteroid with subsequent improvement. Before the bronchoscopic evaluation, the clinical and radiologic findings were consistent with COVID-19, and the patient was tested twice for SARS-CoV-2 PCR. In the appropriate clinical setting, AEP should be considered in the differential diagnoses of community-acquired pneumonia, acute respiratory distress syndrome (ARDS), and COVID-19, especially in this pandemic era.

Reports of eosinophilic pneumonia (EP) as a side effect of dupilumab administration are limited in previous studies. Herein, we report two cases in which EP developed subsequent to the administration of dupilumab for eosinophilic chronic rhinosinusitis (ECRS). Case 1: A 55-year-old woman presented with ECRS, eosinophilic otitis media, and bronchial asthma, and was treated with dupilumab for ECRS. Five weeks later, fever and dyspnea developed, and infiltration shadows were observed in her lungs. The peripheral blood eosinophil count (PBEC) was 3848/μL (26%), bronchoalveolar lavage fluid showed eosinophilic infiltration, and EP was subsequently diagnosed. Her condition improved following prednisolone treatment. Case 2: A 59-year-old man presented with fatigue and dyspnea after receiving dupilumab for ECRS. He had infiltrative shadows throughout his left lung field, and his PBEC was 4850/μL (26.5%). Prednisolone was initiated, and his condition improved. EP developed in both patients during the period of elevated PBEC after dupilumab administration, and dupilumab was suspected to be the causative agent in their EP. Hence, EP should be considered as a differential diagnosis when fever and dyspnea appear following dupilumab administration.

Background: Prostaglandin D 2 receptor 2 (DP 2 ) antagonists inhibit prostaglandin D 2 -induced effects, including recruitment and activation of cells driving asthma pathogenesis. However, challenges identifying target population and end points persist., Research Question: What is the effect of the DP 2 antagonist GB001 on asthma worsening in patients with moderate to severe eosinophilic asthma?, Study Design and Methods: In this phase IIb, randomized, double-blind, placebo-controlled, dose-ranging, parallel-group, multicenter study, GB001 or placebo was added to standard-of-care treatment in patients with moderate to severe asthma with a blood eosinophil count ≥ 250 cells/μL. Patients aged ≥ 18 years to < 75 years received one of four once-daily treatments (GB001 20 mg, 40 mg, or 60 mg or placebo). The primary end point was the proportion of patients who experienced asthma worsening by 24 weeks. Efficacy analyses were performed for the intention-to-treat population and safety analyses for patients who received at least one dose of study treatment., Results: A total of 480 patients were treated. The ORs for asthma worsening for GB001 20 mg, 40 mg, and 60 mg vs placebo were 0.674 (95% CI, 0.398-1.142), 0.677 (95% CI, 0.399-1.149), and 0.651 (95% CI, 0.385-1.100), respectively. Analysis according to baseline blood eosinophil levels and/or fractional exhaled nitric oxide did not show greater treatment effects with higher values. Elevated liver aminotransferase levels and adverse events leading to discontinuation were more frequent for GB001 60 mg than with placebo, GB001 20 mg, and GB001 40 mg., Interpretation: Although GB001 did not significantly reduce the odds of asthma worsening, reductions favoring GB001 were observed. Treatment effects were consistent regardless of high/low type 2 phenotype. The overall safety profile was acceptable, although GB001 60 mg was associated with risk of liver injury., Clinical Trial Registration: ClinicalTrials.gov; No.: NCT03683576; URL: www., Clinicaltrials: gov., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Add-on therapy with monoclonal antibodies is the recommended therapy for severe asthmatic patients refractory to maintenance treatment. In randomized control trials, mepolizumab reduced the number of exacerbations, the need of oral corticosteroids (OCS), increased asthma control, and lung function in a population of uncontrolled severe eosinophilic asthmatic patients. In this piece of work, we aimed to assess mepolizumab efficacy and safety in a cohort of patients with severe eosinophilic asthma in real-life conditions., Methods: A retrospective study was carried out at eight hospitals from Asturias (Spain). The sample included patients treated with mepolizumab from 1 January 2016 to 31 March 2019. Demographic and clinical variables were collected, including OCS use, asthma control, lung function, and exacerbation rate., Results: Sixty-nine patients (72% women) with mean age 56 ± 13 years were included. Annual exacerbation rate decreased from 4.7 (SD 3.7) to 1.3 (SD 2.5) ( p  < 0.001). The number of patients requiring OCS treatment decreased from 25 patients (36%, mean prednisone dose = 18 mg/day) to 13 patients (19%, mean prednisone dose = 9 mg/day) ( p  < 0.001). Twelve patients (48%) stopped OCS treatment. Forced expired volume in one second (FEV1) as percentage increased from 68% (SD 20) to 76% (SD 21) ( p  < 0.001). Fifty-six patients (81%) were considered responders to mepolizumab. No serious adverse events were detected during the study period., Conclusions: Overall, this study demonstrates mepolizumab efficacy and safety in a cohort of patients with uncontrolled severe eosinophilic asthma in routine clinical practice.

Neutralising antibodies against the cytokine interleukin (IL)5 have become widely used for the control of severe eosinophilic asthma. Remarkably, patients receiving neutralising anti-IL5 biological therapies retain a very stable population of residual blood eosinophils. Whether these residual eosinophils are endowed with particular biological activity has not yet been studied, but is of importance in predicting potential long-term effects of IL5 neutralisation in patients. To tackle the effect of IL5 depletion on residual eosinophils, we used a comparative RNA-sequencing approach and compared the gene expression programme of eosinophils arising in IL5-depleted or IL5-replete human or murine hosts, at steady-state in vivo and following in vitro stimulation with the eosinophil-activating alarmin IL33. We compared blood eosinophils from patients with severe allergic eosinophilic asthma treated with anti-IL5 mepolizumab therapy to those of healthy controls and matched asthma patients receiving anti-IgE omalizumab therapy. We made similar comparisons on bone marrow eosinophils from mice genetically deficient or not for IL5. We report that restriction of IL5 availability did not elicit any detectable transcriptional response in steady-state residual eosinophils in mepolizumab-treated patients or IL5-deficient mice, and influenced only a handful of genes in their response to IL33. Together, these results support the notion that treatment with IL5 neutralising antibodies spares a pool of circulating residual eosinophils largely resembling those of healthy individuals., Competing Interests: Conflict of interest: G. Van Hulst has nothing to disclose. Conflict of interest: J. Jorssen reports PhD student scholarship from Fonds de la Recherche scientifique (FRS)-FNRS (Belgium). Conflict of interest: N. Jacobs reports consulting fees and lecture fees from GSK, outside the submitted work. Conflict of interest: M. Henket has nothing to disclose. Conflict of interest: R. Louis reports grants from GSK, AZ, Novartis, Chiesi and Teva; royalties from patent AU2016328384, CA2997506, EP 3337393, US2020345266; consulting fees and lecture payments from GSK, AZ, Novartis, Sanofi and Chiesi, outside the submitted work. Conflict of interest: F. Schleich reports grants from GSK, AstraZeneca, Teva, Chiesi and Novartis; consulting fees from GSK, AstraZeneca, Amgen, Chiesi and Novartis; lecture payments from GSK, AstraZeneca, Teva, Chiesi and Novartis, outside the submitted work. Conflict of interest: F. Bureau has nothing to disclose. Conflict of interest: C.J. Desmet reports salary from Fonds de la Reherche Scientifique – FNRS (Belgium), during the submitted work; consulting fees from AstraZeneca; lecture fees for presentation at several scientific symposia from GSK, outside the submitted work., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Competing Interests: Declaration of interests We declare no competing interests.

Introduction: Ustekinumab-induced eosinophilic pneumonia is rare and to our knowledge, this is the fifth reported case of such an entity., Case Study: A 60-year-old female was admitted with worsening shortness of breath and a nonproductive cough for 4 months. Her past medical history was significant for Crohn's disease and psoriatic arthritis that was previously managed with adalimumab and switched to ustekinumab 2 months before symptoms. Initial diagnostic workup showed 10% peripheral eosinophilia and a CT chest showed numerous 5 mm nodules scattered throughout the lungs along with some peripheral reticulations. Her BAL fluid analysis showed abnormally high eosinophil count (67%), greatly limiting her potential diagnoses to eosinophilic pneumonia, EGPA, and tropical pulmonary eosinophilia (TPE). AEP typically causes more severe disease with a rapid onset, and there was low suspicion for TPE based on history, leaving EGPA and CEP. Based on her negative autoimmune serology, a negative biopsy of the nasal mucosa (no vasculitis/granulomata or eosinophils), and negative infectious workup, the patient was diagnosed with CEP secondary to ustekinumab and the drug was stopped. She was started on high dose prednisone and after a prolonged taper over 5 months, her symptoms and nodules and reticulations on her CT scan resolved., Discussion: This case exemplifies the importance of identifying drug-induced lung diseases which in many cases might not have a strong temporal association with the symptom onset. It also highlights that some drugs owing to their long elimination half-time can remain in the system for a prolonged period and continues to cause symptoms despite their cessation and require prolonged treatment and reassurance., Conclusion: The association of eosinophilic pneumonia with ustekinumab, a drug used in the treatment of psoriasis and other autoimmune diseases, is rare and there is a paucity of literature regarding this association.

Objectives: Daptomycin is a widely used antibiotic. Rhabdomyolysis related to daptomycin is one of the adverse effects of treatment, justifying the need for regular monitoring of muscle enzymes throughout treatment. Daptomycin may also lead to eosinophilic pneumonia. However, risk factors for this adverse reaction have not been identified and do not permit targeting of at-risk populations who could benefit from appropriate monitoring., Patients and Methods: Literature was reviewed for cases of daptomycin-induced eosinophilic pneumonia (DIEP), which that were compared to cases of patients without this adverse effect., Results: Fifty patients with DIEP and 54 controls were identified. Age, sex, and treatment dose are not associated with the occurrence of DIEP. A high dose of daptomycin is not associated with an early onset of DIEP. About one third of patients with eosinophilic lung disease have diabetes or renal impairment., Conclusions: Further studies may help to identify additional factors., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Ado-trastuzumab emtansine (T-DM1) is a monoclonal antibody drug conjugate approved for the treatment of HER2-positive breast cancers. Presented here is a case report of a patient who developed fatal pulmonary toxicity in the form of acute eosinophilic pneumonia while undergoing treatment with T-DM1. Prior to beginning T-DM1 therapy, this patient had been treated with two HER2-targeted agents (trastuzumab, pertuzumab) per National Comprehensive Cancer Network (NCCN) guidelines. This case represents a novel presentation of toxicity associated with T-DM1 while perhaps demonstrating additive toxicity associated with multiple lines of HER2 targeted therapies., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Inhalation of toxic agents can induce eosinophilic pneumonia. However, only a few case reports demonstrate that exposure to materials can induce chronic eosinophilic pneumonia (CEP). Here, we describe a rare case of CEP with mild alveolar hemorrhage due to the inhalation of aerosols from face lotion. This is the first report of eosinophilic pneumonia caused by face lotion exposure., Patient Concerns: A 39-year-old woman was admitted to our hospital with cough and dyspnea for 2 months, which coincided when she started to use a new aerosolized face lotion. Laboratory findings showed high blood eosinophil levels, and chest computed tomography (CT) scans revealed bilateral peripheral consolidation and ground-glass opacity mainly in the left upper lobe. She underwent flexible bronchoscopy. Eosinophils in bronchoalveolar lavage fluid (BALF) were slightly elevated, and the gross appearance of BALF was bloody. The histological examination of the transbronchial lung biopsy showed infiltration of eosinophils and macrophages in alveolar septa with edema and without vasculitis and granuloma formation; a small number of hemosiderin-laden macrophages were also observed. An inhalation challenge test involving the face lotion was performed. Six hours after the test, the blood test showed an increased white blood cell (WBC) count, and chest radiography showed slight exacerbation. Forced vital capacity decreased the following day., Diagnosis: According to histological analysis and positive result of an inhalation challenge test, she was diagnosed with CEP with mild alveolar hemorrhage due to inhalation of aerosols from the face lotion., Interventions and Outcomes: She gradually improved without medication after stopping the use of face lotion., Lessons: To the best of our knowledge, this is the first report of CEP with mild alveolar hemorrhage due to the inhalation of face lotion. Various inhaled agents, such as face lotion, can induce CEP in rare cases., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Case Presentation: An 84-year-old physician was seen in the pulmonary clinic with 10 days of progressive exertional dyspnea, night sweats, and dry cough. For the past 5 months, he had been taking ibuprofen for lumbar radiculopathy from spinal stenosis. Ten days earlier, ibuprofen was switched to naproxen 250 mg twice daily because of its longer half-life. He denied fever, weight loss, rash, dysphagia, proximal muscle weakness, wheeze, sinus congestion, and peripheral numbness/tingling. Medical history included paroxysmal atrial fibrillation, hypertension, Hashimoto's thyroiditis, and OSA. Long-term medications included aspirin, flecainide, atorvastatin, amlodipine, levothyroxine, and candesartan. He was a lifelong nonsmoker. There was no history of recent travel., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Introduction: Acute eosinophilic pneumonia (AEP) is a rare and potentially severe disorder, characterized by an acute febrile respiratory illness with diffuse pulmonary infiltrates, pleural effusions and an eosinophilic alveolitis identified on broncho-alveolar lavage or lung biopsy. The condition can be idiopathic, or induced by the inhalation of toxic substances, by infections or by medications. The condition tends to respond rapidly to treatment with systemic steroids., Case Report: We report the case of a 16-year old patient who presented severe acute interstitial pneumonia with eosinophilia (1.17g/L). They had taken a seven-day course of amoxicillin treatment two weeks previously for a dental abscess. The patient initially required respiratory support by mechanical ventilation followed by extracorporeal membrane oxygenation due to severe refractory hypoxemia. After exhaustive investigation a diagnosis of amoxicillin-induced acute eosinophilic pneumonia was made. After steroid treatment was initiated the clinical response was rapidly favorable and remission was achieved. The patient has been advised to avoid beta lactam antibiotics for life., Conclusion: This case illustrates a rare case of severe acute eosinophilic pneumonia induced by amoxicillin., (Copyright © 2021 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Ethnopharmacological Relevance: Traditionally, the roots of Angelica reflexa B.Y.Lee (AR) have been used to treat cough, phlegm, neuralgia, and arthralgia in Northeast Asia., Aim of the Study: The anti-asthmatic effect of AR root extract (ARE) was determined using a murine airway allergic inflammation model and the primary T cell polarization assay., Materials and Methods: To evaluate the anti-asthmatic effect of ARE, inflammatory cell infiltration was determined histologically and inflammatory mediators were measured in bronchoalveolar lavage fluid (BALF). Furthermore, the effects of AREs on Th2 cell differentiation and activation were determined by western blotting and flow cytometry., Results: Asthmatic phenotypes were alleviated by ARE treatment, which reduced mucus production, inflammatory cell infiltration (especially eosinophilia), and type 2 cytokine levels in BALF. ARE administration to mice reduced the number of activated Th2 (CD4 + CD25 + ) cells and level of GATA3 in the lungs. Furthermore, ARE treatment inhibited the differentiation of Th2 cells in primary cell culture systems via interferon regulatory factor 4 (IRF4) signaling., Conclusions: Our findings indicate that the anti-asthmatic effect of AREs is mediated by the reduction in Th2 cell activation by regulating IRF4., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A 78-year-old male with renal cell carcinoma was treated with combined immunotherapy of nivolumab and ipilimumab. After four courses of the treatment, a chest computed tomography (CT) revealed newly formed ground-glass opacities (GGOs) in both the lower lung lobes; drug-induced pneumonia was speculated. Eosinophil counts were elevated in both peripheral blood and bronchoalveolar lavage fluid. Both the immune checkpoint inhibitors (ICIs) were discontinued, following which the chest CT findings improved. Based on these findings, a diagnosis of ICI-induced eosinophilic pneumonia was made. Hence, clinicians should be wary of the risk of eosinophilic pneumonia during ICI-anticancer therapy., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Whether eosinophilic pneumonitis represents a true manifestation of e-cigarette, or vaping, product use-associated lung injury remains uncertain, and this ambiguity stems from a lack of histopathological data. We present a previously healthy young woman whose asthma-like symptoms and histopathologic finding of eosinophilic pneumonitis were caused by inhalation of vaporized cannabis hash oil concentrates. This report provides compelling evidence that eosinophilic pneumonitis can result from cannabis hash oil inhalation., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Introduction: Sertraline is a selective serotonin reuptake inhibitor which is often used as first-line treatment for depression. Several patterns of interstitial lung disease attributable to sertraline have been reported in the literature., Case Report: A 69-year-old patient, who had been taking sertraline to treat severe depression for 10 months, presented with a deterioration in his general condition and respiratory symptoms found to be associated with bilateral pneumonitis. An exhaustive assessment did not reveal any infectious or autoimmune aetiology. Transthoracic lung biopsy revealed a pattern of eosinophilic lung disease. Sertraline-induced lung toxicity was then suspected and this treatment was therefore stopped. The patient's symptoms resolved and the chest imaging normalized., Conclusions: Our observation suggests that sertraline was the cause of chronic eosinophilic pneumonia characterized by an insidious clinical presentation several months after starting the medication. Given its widespread prescription, we encourage any clinician facing this disease to pay attention to possible drug-induced origins of lung disease., (Copyright © 2020 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Silica crystals (silica), which are a major mineral component of volcanic ash and desert dust, contribute to the pathogenesis of pulmonary disorders such as asthma and fibrosis. Although administration of silica or sand dust to rodents exacerbates development of ovalbumin-induced or house dust mite-induced asthma-like airway inflammation, the detailed mechanisms remain unclear. Here, using murine models, we found that silica can induce IL-33 expression in pulmonary epithelial cells. IL-33, but not IL-25 or TSLP, and type 2 cytokines such as IL-5 and IL-13 were critically involved in silica's exacerbation of OVA-induced airway eosinophilia in mice. Innate lymphoid cells (ILCs), but not T, B or NKT cells, were also involved in the setting. Moreover, a scavenger receptor that recognized silica was important for silica's exacerbating effect. These observations suggest that IL-33 induced in epithelial cells by silica activates ILCs to produce IL-5 and/or IL-13, contributing to silica's exacerbation of OVA-induced airway eosinophilia in mice. Our findings provide new insight into the underlying mechanisms of exacerbation of pulmonary disorders such as asthma following inhalation of silica-containing materials such as volcanic ash and desert dust., Competing Interests: Declaration of competing interest The authors declare that they have no known competing interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Acute eosinophilic pneumonia (AEP) is an acute respiratory illness with diffuse pulmonary infiltrates and pulmonary eosinophilia. While the etiology of AEP remains unclear, a relationship between cigarette smoking and AEP onset has been suggested. The use of heated tobacco products (HTPs) has been growing, but the impact of these products on our health is not fully understood. We herein report a case of AEP that developed after switching from conventional cigarette to HTP smoking. The patient's condition improved after the cessation of HTP smoking and corticosteroid treatment initiation. In cases of AEP, physicians should consider HTPs use as a possible cause.

Asthma is a common chronic inflammatory airway disease. Recent studies have reported that interleukin (IL)‑33 is a potential link between the airway epithelium and Th2‑type inflammatory responses, which are closely related to the progression of asthma. The IL‑33 receptor, ST2, is highly expressed in group 2 innate lymphoid cells (ILC2s), Th2 cells, mast cells, eosinophils and natural killer (NK) cells. Cnidii Fructus is a Chinese herb with a long history of use in the treatment of asthma in China. Osthole is one of the major components of Cnidii Fructus. The present study examined the anti‑asthmatic effects of osthole in mice and aimed to elucidate the underlying mechanisms involving the IL‑33/ST2 pathway. BALB/c mice were sensitized and challenged with ovalbumin and then treated with an intraperitoneal injection of osthole (25 and 50 mg/kg). Subsequently, the airway hyper‑responsiveness (AHR) and inflammation of the lungs were evaluated. The amounts of IL‑4, IL‑5, IL‑13, interferon (IFN)‑γ and IL‑33 in the bronchoalveolar lavage fluid (BALF) were measured by Luminex assay and their mRNA levels in the lungs were measured by reverse transcription‑quantitative PCR. The histopathology of the lungs was performed with H&E, PAS and Masson's staining. The expression of ST2 in the lungs was evaluated by immunohistochemistry. The data demonstrated that osthole markedly reduced AHR and decreased the number of eosinophils and lymphocytes in BALF. It was also observed that osthole significantly inhibited the release of Th2‑type cytokines (IL‑4, IL‑5 and IL‑13) and upregulated the IFN‑γ level in BALF. Moreover, osthole significantly attenuated the IL‑33 and ST2 expression in the lungs of asthmatic mice. On the whole, osthole attenuated ovalbumin‑induced lung inflammation through the inhibition of IL‑33/ST2 signaling in an asthmatic mouse model. These results suggest that osthole is a promising target for the development of an asthma medication.

Clozapine is an atypical antipsychotic known to cause multiple hematologic abnormalities, most seriously agranulocytosis, but also notably eosinophilia. It is considered as an allergic reaction with a spontaneous remission, however, sometimes, it may predict subsequent major inflammatory complications. The aim of this study was to investigate the relationship between clozapine usage and drug-induced pneumonia based on characteristic respiratory symptoms and radiological findings, retrospectively in 69 Japanese treatment-resistant schizophrenia patients. Comparisons of the 26 weeks consecutive levels: white blood cell count with neutrophil and eosinophil, relative to their baseline levels were performed within total subjects and two groups divided by the findings of pneumonia. The crude odds ratios with 95% confidence intervals for developing pneumonia and potential confounders were calculated. The levels of eosinophils significantly increased at 1 month in each group. The introduction season between October and January and higher eosinophil level at first month were correlated with the risk of pneumonia, which occurred independent of clozapine dosage and term and relapsed in subjects when developed within initial 1 month. Clozapine-induced eosinophilic pneumonia was considered transient and reversible, however, the risks and benefits must be considered and close monitoring should be done to avoid life-threatening conditions during clozapine treatment.

Introduction: Eosinophilic pneumonias are characterized by an increase in lung eosinophils. These disorders can be induced by drug reactions., Case Report: A 57-year-old woman suffering from bipolar disorder and treated by sodium divalproate for more than 2 years was hospitalised in the department of respiratory medicine for dyspnoea and cough. The investigations showed severe hypoxaemia, airflow limitation, multiple ground-glass opacities and crazy paving on the chest CT-scan and a blood eosinophilia. A significant alveolar eosinophilia was found in the broncho-alveolar lavage. A complete assessment of possible causes was made. Finally, we made the diagnosis of eosinophilic pneumonia secondary to sodium divalproate. The treatment was stopped and systemic corticosteroid therapy was not introduced. The patient showed an improvement of her dyspnoea in a few days. Lung function and the CT-scan were normal within a few months., Conclusions: Sodium divalproate, frequently used in the treatment of bipolar disorder, is a rare cause of eosinophilic lung disease, even years after its introduction. Rapid diagnosis and withdrawal of treatment led to complete resolution in the reported case., (Copyright © 2020. Published by Elsevier Masson SAS.)