Identification of Complex Pneumonia during the Outbreak of COVID-19: Bacterial Pneumonia Combined with Acute Eosinophilic Pneumonia in Patients with Maintenance Hemodialysis.

It is of crucial importance to diagnose patients in a timely and clear manner during the outbreak of COVID-19. Different causes of pneumonia makes it difficult to differentiate COVID-19 from others. Hemodialysis patients are a special group of people in this outbreak. We present a successfully treated case of a patient with maintenance hemodialysis from acute eosinophilic pneumonia for using meropenem when treating bacterial pneumonia, avoiding possible panic and waste of quarantine materials in dialysis centers.

Association between peripheral blood/bronchoalveolar lavage eosinophilia and significant oxygen requirements in patients with acute eosinophilic pneumonia.

BACKGROUND: We investigated the association between a combination of two markers, peripheral (PEC) and bronchoalveolar lavage (BAL) eosinophil percentage (BEP), and oxygen requirements in patients with acute eosinophilic pneumonia (AEP). METHODS: We retrospectively reviewed the medical records of patients with AEP treated at the Armed Forces Capital Hospital between May 2012 and May 2017. We used correlation analyses to assess the association between PEC/BEP and clinical outcomes in AEP patients. Receiver operating characteristic (ROC) curve analyses were used to calculate the cut-off value for BEP that categorised patients requiring a significant oxygen supply. The BAL/blood eosinophil (BBE) score was introduced to stratify patients with peripheral eosinophilia and elevated BEP. Clinical characteristics and outcomes were compared between the different groups. Multiple logistic regression was performed for significant oxygen requirements using two different models using age, C-reactive protein (CRP), smoking duration, and BBE score (model 1) and age, CRP, BEP, and PEC (model 2). RESULTS: Among the 338 patients, 99.7% were male, and their mean age was 20.4 ± 1.4 years. Only 0.6% of patients were never smokers and the mean number of smoking days was 26.2 ± 25.4. Correlation analyses revealed that both the PaO2/FiO2 ratio and duration of oxygen supply were associated with BEP. ROC curve analyses indicated a cut-off level of 41.5%. Patients with a high BBE score had favourable outcomes in terms of hypoxemia, hospital days, intensive care unit admission, oxygen supply days, and steroid treatment days. Multiple logistic regression revealed that BEP and BBE score tended to be associated with significant oxygen requirements. CONCLUSIONS: In this study, we revealed that both peripheral and BAL eosinophilia is associated with favourable outcomes in AEP patients.

Treatment of severe, uncontrolled eosinophilic asthma: Where we are heading.

OBJECTIVE: We sought to highlight how our understanding of the pathophysiology of severe asthma has evolved over time and discuss the role of biomarkers in treatment advances and emerging new therapies. DATA SOURCES: Nonsystematic PubMed literature search. STUDY SELECTION: Articles were selected based on areas of relevance to the classification of asthma by endotype, with an emphasis on the evolution of current treatment guidelines for severe asthma. RESULTS: Unlike older guidelines for the treatment of severe asthma, recent updates now distinguish between asthma severity and control. Moreover, asthma classification is shifting from phenotype to endotype with the development of biomarkers used to determine the mechanism driving a patient's disease. Many cases of severe asthma are associated with type-2 inflammation with elevated eosinophil counts in the airways. In recent studies, patients with severe, uncontrolled asthma and high eosinophil counts respond to biologic therapies targeting the type-2 signaling pathway and eosinophils themselves (eg, anti-IL-5 therapy). New treatments that address the pathophysiology of asthma offer a promising alternative to control severe asthma for patients who do not respond to traditional therapies. CONCLUSION: Understanding and using new treatment guidelines that separate the concepts of asthma severity and control may help clinicians to identify patients with severe, uncontrolled asthma who may benefit from new treatment options, such as anti-IL-5 therapies.

Acute Eosinophilic Pneumonia. Causes, Diagnosis, and Management.

Acute eosinophilic pneumonia (AEP) is an uncommon acute respiratory illness of varying severity that includes presentation as acute respiratory distress syndrome with fatal outcome. AEP may be idiopathic, but identifiable causes include smoking and other inhalational exposures, medications, and infections. The pathogenesis of AEP is poorly understood but likely varies depending on the underlying cause. Airway epithelial injury, endothelial injury, and release of IL-33 are early events that subsequently promote eosinophil recruitment to the lung; eosinophilic infiltration and degranulation appear to mediate subsequent lung inflammation and associated clinical manifestations. Crucial for the diagnosis are the demonstration of pulmonary eosinophilia in the BAL fluid and the exclusion of other disease processes that can present with acute pulmonary infiltrates. Although peripheral blood eosinophilia at initial presentation may be a clue in suggesting the diagnosis of AEP, it may be absent or delayed, especially in smoking-related AEP. Optimal management of AEP depends on the recognition and elimination of the underlying cause when identifiable. The cessation of the exposure to the inciting agent (e.g., smoking), and glucocorticoids represent the mainstay of treating AEP of noninfectious origin. If AEP is recognized and treated in a timely manner, the prognosis is generally excellent, with prompt and complete clinical recovery, even in those patients manifesting acute respiratory failure.

Idiopathic acute eosinophilic pneumonia: A rare cause of hypoxic respiratory failure.

Idiopathic Acute Eosinophilic Pneumonia (IAEP) is a life-threatening cause of hypoxic respiratory failure. IAEP is challenging to diagnose as it may mimic infectious pneumonia or acute respiratory distress syndrome. Distinguishing IAEP from these alternatives is important; the mainstay of treatment for IAEP is corticosteroids, a therapy which might not otherwise be indicated. Patients treated appropriately usually experience a full recovery. In this case report we describe the presentation, evaluation, and management of a 19-year old male who presented to the emergency department (ED) in respiratory failure from IAEP. The patient was a military trainee who recently moved to the United States from Saudi Arabia. He also recently began smoking cigarettes for the first time, a known risk factor for IAEP. Upon initial presentation, the patient was in respiratory distress and had an oxygen saturation of 82% on room air. His ED diagnostic workup included chest X-ray showing diffuse interstitial thickening and chest computed tomography that demonstrated diffuse nodular opacification of pulmonary parenchyma. The patient was admitted to the intensive care unit (ICU) where bronchoscopy yielded cytology with 30% eosinophilia. The patient ultimately required 3 days of extra corporeal membrane oxygenation (ECMO) due to worsening hypoxic respiratory failure. After both intravenous and outpatient oral steroid treatments, the patient went on to have a full recovery with no ongoing respiratory issues. To our knowledge, this is the first case of IAEP requiring ECMO reported in the emergency medicine literature.

Age distribution and seasonality in acute eosinophilic pneumonia: analysis using a national inpatient database.

BACKGROUND: Acute eosinophilic pneumonia (AEP) is a rare inflammatory lung disease. Previous studies have shown that most patients with AEP are aged 20 to 40 years, whereas several case studies have included older patients with AEP. These studies also suggested that AEP is more prevalent in summer, but they were limited due to their small sample sizes. We therefore investigated the age distribution and seasonality among patients with AEP using a national inpatient database. METHODS: Using the Japanese Diagnosis Procedure Combination database, we identified patients with a recorded diagnosis of AEP from 1 July 2010 to 31 March 2015. We examined patient characteristics and clinical practices including age, sex, seasonal variation, length of stay, use of corticosteroids, use of mechanical ventilation, and in-hospital mortality. RESULTS: During the 57-month study period, we identified 213 inpatients with AEP. The age distribution of AEP peaked twice: at 15 to 24 years and 65 to 79 years. The proportion of patients with AEP was highest in summer for those aged < 40 years, whereas it was distributed evenly throughout the year for those aged ≥ 40 years. The interval from hospital admission to corticosteroid administration and the duration of corticosteroid use were significantly longer in the older than younger age group. CONCLUSIONS: The age distribution of patients with AEP was bimodal, and seasonality was undetected in older patients. Older patients may be more likely to have delayed and prolonged treatment.

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.

Healthcare resource use and costs of severe, uncontrolled eosinophilic asthma in the UK general population.

BACKGROUND: Little is known about the prevalence of severe, uncontrolled eosinophilic asthma (SUEA) and associated costs. AIMS: We sought to determine the prevalence of SUEA and compare asthma-related healthcare resource use (HCRU) and associated costs with overall means for a general asthma population. METHODS: This cohort study evaluated anonymised medical record data (December 1989 through June 2015) from the Clinical Practice Research Datalink and the Optimum Patient Care Research Database to study UK patients with active asthma (diagnostic code and one or more drug prescriptions in the baseline year), aged 5 years and older, without concomitant COPD, and with recorded eosinophil count. SUEA was defined as two or more asthma attacks during 1 baseline year preceding a high blood eosinophil count (≥0.3×109/L) for patients prescribed long-acting ß2-agonist (LABA) and high-dosage inhaled corticosteroids (ICS) during baseline plus 1 follow-up year. We compared asthma-related HCRU and associated direct costs (2015 pounds sterling, £) during the follow-up year for SUEA versus the general asthma population. RESULTS: Of 363 558 patients with active asthma and recorded eosinophil count, 64% were women, mean (SD) age was 49 (21) years; 43% had high eosinophil counts, 7% had two or more attacks in the baseline year and 10% were prescribed high-dosage ICS/LABA for 2 study years. Overall, 2940 (0.81%; 95% CI 0.78% to 0.84%) patients had SUEA. Total mean per-patient HCRU and associated costs were four times greater for SUEA versus all patients (HCRU and cost ratios 3.9; 95% CI 3.7 to 4.1). CONCLUSIONS: Less than 1% of patients in a general asthma population had SUEA. These patients accounted for substantially greater asthma-related HCRU and costs than average patients with asthma.

In vivo neutralization of α4 and ß7 integrins inhibits eosinophil trafficking and prevents lung injury during tropical pulmonary eosinophilia in mice.

Integrins regulate leukocyte trafficking during homeostasis and inflammatory conditions. However, the role of α4 and ß7 integrins in guiding eosinophil transmigration into the lungs during filarial manifestation of Tropical Pulmonary Eosinophilia (TPE) has not been explored. In this study, mice exhibiting TPE manifestations were administered with in vivo neutralizing antibodies against integrins α4 and ß7 or their combination and immuno-pathological parameters were evaluated. Results show an intact lung barrier, significantly lower lung inflammation and reduced eosinophil counts in the Bronchoalveolar lavage fluid and lungs of mice receiving anti-α4+ ß7 treatment. Reduced eosinophil peroxidase and ß-hexosaminidase activity, downregulation of inflammatory genes, lower production of inflammatory lipid intermediates like prostaglandins E2 and D2, leukotriene B4 and cysteinyl leukotrienes were also noted in anti-α4+ ß7 treated mice. Reduced accumulation of central memory, effector memory, regulatory T cells and lower production of IL-4, IL-5, and TGF-ß were other cardinal features of anti-α4+ ß7 treated mice lungs. Flow cytometry-sorted lung eosinophils from anti-α4+ ß7 treated mice showed higher apoptotic potential, downregulated anti-apoptotic gene Bcl-2, and exhibited reduced F-actin polymerization and calcium influx as compared to IgG controls. In summary, neutralization of α4+ ß7 integrins impairs the transmigration, activation and survival of eosinophils and reduces TPE induced pathology in mice lungs.

Current Approach to Diagnosis and Management of Pulmonary Eosinophilic Syndromes: Eosinophilic Pneumonias, Eosinophilic Granulomatosis with Polyangiitis, and Hypereosinophilic Syndrome.

Eosinophils play a key role in orchestrating the complex clinicopathological pulmonary and extrapulmonary disease features in patients with eosinophilic syndromes. Eosinophilic pulmonary syndromes consist of a heterogeneous group of disorders characterized by the presence of peripheral blood eosinophilia and/or eosinophilic-related pulmonary impairment. These disorders can present with varying degrees of organ involvement, and while their presentation may be similar, it is important to define the disease state, as management and prognosis differ. In this article, we discuss acute and chronic eosinophilic pneumonias, eosinophilic granulomatosis with polyangiitis, and the hypereosinophilic syndromes. The mainstay of therapy for these disorders has been corticosteroids; however, recent and ongoing studies have provided strong grounds for optimism for specific targeted treatment approaches.

Clinical outcomes in patients with acute eosinophilic pneumonia not treated with corticosteroids.

PURPOSE: The objective of this study was to evaluate the course of clinical stability in patients with acute eosinophilic pneumonia (AEP) who did not receive corticosteroid treatment. METHODS: Secondary analysis included 19 consecutive patients with AEP who did not receive corticosteroid treatment from a cohort of 310 patients newly diagnosed with AEP between October 2007 and December 2013. RESULTS: All patients presented with dyspnea, fever, or cough with diffuse pulmonary infiltration. All but one patient (95 %) had elevated C-reactive protein (CRP), and 11 (58 %) patients had peripheral eosinophilia at the time of diagnosis. During the follow-up period, the dyspnea improved within a median of 4 (3-6) days and defervescence occurred within a median of 5 (4-7) days. Median time to clinical stability (defined as disappearance of all initial presenting symptoms) was 9 (7-12) days. In addition, the majority of pulmonary infiltrates on chest radiographs completely disappeared within 14 days after diagnosis. However, the peripheral eosinophil count and the frequency of peripheral eosinophilia increased up to 10 days and then decreased during the follow-up period. All patients experienced peripheral eosinophilia during hospitalisation. CONCLUSION: AEP-associated symptoms and radiographic abnormalities were resolved completely within 2 weeks after diagnosis even when corticosteroid treatment was not initiated. However, these findings might be limited to relatively mild cases of AEP.

Clinical implications of initial peripheral eosinophilia in acute eosinophilic pneumonia.

BACKGROUND AND OBJECTIVE: The initial peripheral eosinophil count (PEC) is rarely elevated but tends to increase during the clinical course of acute eosinophilic pneumonia (AEP). We evaluated whether initial peripheral eosinophilia is an indicator of mild disease in patients with AEP. METHODS: We retrospectively examined associations between initial peripheral absolute eosinophil count, inflammatory markers and clinical characteristics in 85 patients with AEP. RESULTS: Of 85 patients, 24 (28%) had initial peripheral eosinophilia (>500/µL). Initial peripheral absolute eosinophil count was inversely correlated to white blood cell (WBC) count (ρ = -0.386, P < 0.001), neutrophil percentage (ρ = -0.645, P < 0.001) and C-reactive protein (CRP; ρ = -0.495, P < 0.001). During treatment, peripheral absolute eosinophil counts increased, while inflammatory markers (WBC, neutrophil percentage, and CRP) decreased. Patients with initial peripheral eosinophilia had a longer duration from onset of symptoms to admission (P = 0.006), had lower WBC counts, neutrophil percentages and CRP values (all P < 0.001), and higher oxygen saturation (P = 0.004) than patients with normal peripheral eosinophil counts. Oxygen requirements (P = 0.013), duration of oxygen administration (P = 0.028) and intensive care unit admission rates (P = 0.003) were lower in patients with initial peripheral eosinophilia. All patients survived and recovered fully after corticosteroid or conservative treatment. CONCLUSIONS: Initial PEC may be related to a milder disease status on admission, compared with normal PEC in patients with AEP. This may help to stratify disease severity in AEP.

A chronic eosinophilic pneumonia case with long exposure to isocyanates.

Chronic eosinophilic pneumonia (CEP) is a disease with unknown etiology, characterized by peripheral blood eosinophilia and abnormal eosinophil accumulation in the lungs. A 43-year-old male with 30 years history of exposure to isocyanates was admitted with the complaint of sputum, cough, progressive dyspnoea, and weight loss. Physical examination revealed bilaterally decreased breath sounds and extensive rales. On laboratory analysis; leukocytosis (12.3 10(3)/proportional variant L), hypereosinophilia (30%), elevated CRP and RF (1000 IU/ml), and IgE levels (1160 IU/ml) in the serum were observed. Chest radiograph and computed tomography on admission showed reticulonodular pattern at both lung fields. Pulmonary function tests assumed a restrictive pattern and a low diffusing capacity. Bronchoalveolar lavage revealed a marked eosinophilia (50%). Transbronchial lung biopsy indicated eosinophilic pneumonia. In this case we aimed to describe a rare case of CEP probably caused by exposure to isocyanate.

Primary eosinophilic lung diseases.

Eosinophilic lung diseases typically present as a triad of pulmonary symptoms, an abnormal chest radiograph, and elevated levels of eosinophils in the sputum and lung tissue. This article focuses on primary causes of eosinophilic lung disease including acute eosinophilic pneumonia, chronic eosinophilic pneumonia, Churg-Strauss syndrome, and hypereosinophilic syndromes. In these disorders elevated eosinophil levels in the tissue lead to inflammation and tissue damage. Peripheral eosinophilia can often be measured when tissue levels are elevated but this is not as reliable a marker as tissue biopsy. Because corticosteroids act through a variety of mechanisms to inhibit eosinophil function and induce apoptosis, they are first-line therapy for eosinophilic lung diseases. Targeted immunosuppressive therapies, such as monoclonal antibodies against key regulatory cytokines for eosinophil production and survival, are not formally approved for eosinophilic lung disease but have shown promising results in published research studies.

[Symptomatic diseases in pneumology]. / Krankheitsbilder in der Pneumologie.

The diagnosis and treatment of granulomatous lung diseases is challenging. This article describes two of these entities: (1) eosinophilic vasculitis with polyangiitis which is clinically characterized as a combination of bronchial asthma and eosinophilic granulomatous vasculitis. Antoneutrophil cytoplasmic antibodies are present in approximately 40 % of patients. Treatment with steroids is sufficient in patients with isolated pulmonary manifestation but extrapulmonary manifestations, e.g. heart, central nervous system (CNS), kidneys and gastrointestinal tract warrant combined immunosuppression with prednisolone and cyclophosphamide. (2) In Germany tuberculosis is an orphan disease with an incidence of 5.3/100,000 in the year 2011. Prolonged cough, night sweats and weight loss should be considered suspicious of tuberculosis. Microbiological diagnosis has been improved by gene and PCR technology. The traditional Mendel-Mantoux skin test has widely been replaced by the interferon gamma release assay (IGRA). Standard treatment of non-resistant mycobacterium tuberculosis is based on a combination of isonizide, rifampicine, pyrazinamide and ethambutol for 2 months followed by 4 months of isoniazide plus rifampicine. Therapy resistant, multiple drug resistant (MDR) and extensively drug resistant (XDR) tuberculosis bacteria should be treated by experienced specialists.

Eosinophilic Lung Diseases.

The eosinophilic lung diseases may manifest as chronic eosinophilic pneumonia, acute eosinophilic pneumonia, or as the Löffler syndrome (generally of parasitic etiology). The diagnosis of eosinophilic pneumonia is made when both characteristic clinical-imaging features and alveolar eosinophilia are present. Peripheral blood eosinophils are generally markedly elevated; however, eosinophilia may be absent at presentation. Lung biopsy is not indicated except in atypical cases after multidisciplinary discussion. The inquiry to possible causes (medications, toxic drugs, exposures, and infections especially parasitic) must be meticulous. Idiopathic acute eosinophilic pneumonia may be misdiagnosed as infectious pneumonia. Extrathoracic manifestations raise the suspicion of a systemic disease especially eosinophilic granulomatosis with polyangiitis. Airflow obstruction is frequent in allergic bronchopulmonary aspergillosis, idiopathic chronic eosinophilic pneumonia, eosinophilic granulomatosis with polyangiitis, and hypereosinophilic obliterative bronchiolitis. Corticosteroids are the cornerstone of therapy, but relapses are common. Therapies targeting interleukin 5/interleukin-5 are increasingly used in eosinophilic lung diseases.

Update on eosinophilic lung diseases.

The eosinophilic lung diseases are a group of pulmonary disorders characterized by an increase in blood and/or lung eosinophils. These disorders can be primary pulmonary disorders or the secondary manifestation of other systemic or pulmonary conditions, infection, drug reaction, or malignancy. The approach to a patient with eosinophilic lung disease involves a thorough history and physical examination, review of exposures and appropriate testing, often including bronchoscopy or lung biopsy, to establish a specific etiology and determine therapy. Eosinophilic lung disease can be suspected based on either the finding of pulmonary disease with blood eosinophilia, pulmonary disease with bronchoalveolar lavage eosinophilia, or pulmonary disease with lung tissue eosinophilia on lung biopsy.

The non-casual relation between eosinophilia and thrombotic microangiopathy.

There are only a few cases in the literature that describes the association between hypereosinophilic syndromes and thrombotic microangiopathy (TMA). Here we present the case of a man who suddenly developed a TMA in the context of eosinophilic pneumonia, who recovered successfully with six sessions of plasmapheresis and corticoids. Although the Pathophysiology is unknown, we hypothesize about the prothrombotic effects of the eosinophils. Also we describe a literature review.

Acute lymphocytic leukemia with eosinophilia: a case report and review of the literature.

We present a 61-year-old man with marked peripheral blood eosinophilia, feature of hypereosinophilic syndrome, that later evolved into acute lymphocytic leukemia (ALL-L2). Initially the patient suffered from significant complications related to eosinophilic toxicity, including large urticarial hyperpigmented plaques, myocardial infarction, and eosinophilic pneumonia. He was treated with high dose of steroids resulting in a rapid suppression of the eosinophilia. Two weeks later, the eosinophilia had relapsed, so a bone marrow aspiration was performed. Cytomorphological examination of the bone marrow showed typical ALL features, while flow cytometric analysis revealed an My+pre-B-ALL immunophenotype, and chromosome analysis of bone marrow showed a normal karyotype. He received chemotherapy according to the standard protocol for ALL and died from refractory respiratory failure and congestive heart failure immediately after antileukemic therapy. We review the literature and compare the demographics, clinical features, and outcomes of several cases and reported studies.