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.

Traction bronchiectasis on high-resolution computed tomography may predict fatal acute eosinophilic pneumonia.

BACKGROUND: Most patients with acute eosinophilic pneumonia (AEP) show rapid improvement. However, some cases of AEP prove fatal. The aims of this study were to determine the clinical, radiographic, and pathologic characteristics of patients in whom AEP has a fatal outcome and to identify predictors of a poor prognosis. METHODS: We retrospectively identified the medical records of all patients diagnosed with AEP at our institution in Japan from July 2005 to July 2013. RESULTS: There were four deaths among 41 patients diagnosed to have AEP during the study period. All the patients who died were male; three cases were idiopathic and one was medication-related. The median bronchoalveolar lavage eosinophil differential count was 59%. An autopsy was performed on the patient with medication-related AEP who died and the pathologic finding was diffuse alveolar damage with eosinophilic infiltration. Diffuse ground-glass attenuation and traction bronchiectasis (TBE) were identified on high-resolution computed tomography in the four patients with fatal AEP. TBE was observed in six patients (five with idiopathic AEP, one with medication-related AEP), and 67% of these patients died. None of the patients with smoking-related AEP had TBE; all these patients had better responses to treatment and survived. CONCLUSIONS: We observed the characteristics of patients with fatal AEP who did not respond to treatment. TBE was observed in all fatal cases and may be associated with a poor prognosis.

The utility of inflammatory markers to predict readmissions and mortality in COPD cases with or without eosinophilia.

BACKGROUND: COPD exacerbations requiring hospitalization increase morbidity and mortality. Although most COPD exacerbations are neutrophilic, approximately 10%-25% of exacerbations are eosinophilic. AIM: We aimed to evaluate mortality and outcomes of eosinophilic and non-eosinophilic COPD exacerbations and identify new biomarkers that predict survival. METHODS: A retrospective observational cohort study was carried out in a tertiary teaching hospital from January 1, 2014 to November 1, 2014. All COPD patients hospitalized with exacerbations were enrolled in the study at their initial hospitalization and followed-up for 6 months after discharge. Electronic data were collected from the hospital database. Subjects' characteristics, hemogram parameters, CRP levels, neutrophil-to-lymphocyte ratio (NLR), platelet-to-mean platelet volume ratio on admission and discharge, length of hospital stay (days), readmissions, and mortality were recorded. Patients were grouped according to peripheral blood eosinophil (PBE) levels: Group 1, >2% PBE, eosinophilic; Group 2, non-eosinophilic ≤2%. Patient survival after hospital discharge was evaluated by Kaplan-Meier survival analysis. RESULTS: A total of 1,704 patients hospitalized with COPD exacerbation were included. Approximately 20% were classified as eosinophilic. Six-month mortality was similar in eosinophilic and non-eosinophilic groups (14.2% and 15.2%, respectively); however, the hospital stay length and readmission rate were longer and higher in the non-eosinophilic group (P<0.001 and P<0.01, respectively). CRP and NLR were significantly higher in the non-eosinophilic group (both P<0.01). The platelet-to-mean platelet volume ratio was not different between the two groups. Cox regression analysis showed that survival was negatively influenced by elevated CRP (P<0.035) and NLR (P<0.001) in the non-eosinophilic group. CONCLUSION: Non-eosinophilic patients with COPD exacerbations with high CRP and NLR values had worse outcomes than eosinophilic patients. PBE and NLR can be helpful markers to guide treatment decisions.

Elevated bronchoalveolar lavage eosinophilia correlates with poor outcome after lung transplantation.

BACKGROUND: Eosinophils are involved in the pathophysiology of many respiratory diseases, but the exact role of eosinophilia in lung transplantation has not been thoroughly investigated. METHODS: We performed a retrospective analysis of our transplanted patients between 2001 and 2011, with a minimum follow-up of 1 year. Using a cutoff of ≥2% eosinophilia in bronchoalveolar lavage (BAL) fluid, chronic lung allograft dysfunction (CLAD)-free survival and overall survival was compared between 66 patients demonstrating at least one BAL with eosinophils ≥2% and 253 control patients (never BAL ≥2%). RESULTS: Patients with increased BAL eosinophilia demonstrated worse CLAD-free and overall survival (both P<0.0001) compared with controls. Eosinophilic BAL predisposed to development of bronchiolitis obliterans syndrome but particularly to restrictive allograft syndrome (P<0.0001). After correction for covariates, the association between eosinophilic BAL and CLAD but equally death remained significant (P=0.0047 and 0.0011). Blood eosinophil and C-reactive protein levels were also elevated at the time of eosinophilic BAL. CONCLUSION: BAL eosinophilia ≥2% is associated with poor outcome in our lung transplant patients as demonstrated by worse CLAD-free and overall survival. Interestingly, increased BAL eosinophilia may be specifically associated with the development of restrictive allograft syndrome, which needs further prospective investigation.

Immunodetection of occult eosinophils in lung tissue biopsies may help predict survival in acute lung injury.

BACKGROUND: Acute lung injury (ALI) is a serious respiratory disorder for which therapy is primarily supportive once infection is excluded. Surgical lung biopsy may rule out other diagnoses, but has not been generally useful for therapy decisions or prognosis in this setting. Importantly, tissue and peripheral blood eosinophilia, the hallmarks of steroid-responsive acute eosinophilic pneumonia, are not commonly linked with ALI. We hypothesized that occult eosinophilic pneumonia may explain better outcomes for some patients with ALI. METHODS: Immunohistochemistry using a novel monoclonal antibody recognizing eosinophil peroxidase (EPX-mAb) was used to assess intrapulmonary eosinophil accumulation/degranulation. Lung biopsies from ALI patients (n = 20) were identified following review of a pathology database; 45% of which (i.e., 9/20) displayed classical diffuse alveolar damage (ALI-DAD). Controls were obtained from uninvolved tissue in patients undergoing lobectomy for lung cancer (n = 10). Serial biopsy sections were stained with hematoxylin and eosin (H&E) and subjected to EPX-mAb immunohistochemistry. RESULTS: EPX-mAb immunohistochemistry provided a >40-fold increased sensitivity to detect eosinophils in the lung relative to H&E stained sections. This increased sensitivity led to the identification of higher numbers of eosinophils in ALI patients compared with controls; differences using H&E staining alone were not significant. Clinical assessments showed that lung infiltrating eosinophil numbers were higher in ALI patients that survived hospitalization compared with non-survivors. A similar conclusion was reached quantifying eosinophil degranulation in each biopsy. CONCLUSION: The enhanced sensitivity of EPX-mAb immunohistochemistry uniquely identified eosinophil accumulation/degranulation in patients with ALI relative to controls. More importantly, this method was a prognostic indicator of patient survival. These observations suggest that EPX-mAb immunohistochemistry may represent a diagnostic biomarker identifying a subset of ALI patients with improved clinical outcomes.

Eosinophilic crystalline pneumonia as a major cause of death in 129S4/SvJae mice.

Eosinophilic crystalline pneumonia is an idiopathic disease that occurs in many strains and stocks of mice, more commonly in strains on a C57BL/6 background. The disease occurs sporadically in most strains of mice and varies from mild and subclinical to severe and fulminating, sometimes resulting in respiratory distress and death. In this study, 94 aged male and female 129S4/SvJae mice were evaluated for eosinophilic crystalline pneumonia lesions. There was an 87% incidence, with females overrepresented. Histologically, there were multifocal to coalescing inflammatory infiltrates composed of numerous large eosinophilic macrophages and multinucleate cells admixed with eosinophils, neutrophils, lymphocytes, and plasma cells within alveolar and bronchiolar spaces, associated with refractile, brightly eosinophilic, angular crystals. Alveolar macrophages and multinucleate cells contained fine needlelike to rectangular intracytoplasmic crystalline material. Similar crystals were often free within alveoli and conducting airways, often associated with mucous metaplasia of bronchiolar epithelium. This disease may occur spontaneously or in concert with other pulmonary lesions, such as pulmonary adenomas, lymphoproliferative disease, allergic pulmonary disease, and parasitic or fungal infections. The characteristic crystals morphologically resemble Charcot-Leyden crystals, which represent eosinophil breakdown products in humans with eosinophil-related disease. However, crystals in eosinophilic crystalline pneumonia are composed predominantly of Ym1 protein, a chitinase-like protein associated with neutrophil granule products and secreted by activated macrophages. The function of Ym1 protein is not fully understood but is believed to be involved in host immune defense, eosinophil recruitment, and cell-cell and cell-matrix interactions consistent with tissue repair. The mechanism of induction of eosinophilic crystalline pneumonia with Ym1 crystal formation is unknown.

The chemokine macrophage-inflammatory protein-1 alpha and its receptor CCR1 control pulmonary inflammation and antiviral host defense in paramyxovirus infection.

In this work, we explore the responses of specific gene-deleted mice to infection with the paramyxovirus pneumonia virus of mice (PVM). We have shown previously that infection of wild type mice with PVM results in pulmonary neutrophilia and eosinophilia accompanied by local production of macrophage-inflammatory protein-1 alpha (MIP-1 alpha). Here we examine the role of MIP-1 alpha in the pathogenesis of this disease using mice deficient in MIP-1 alpha or its receptor, CCR1. The inflammatory response to PVM in MIP-1 alpha-deficient mice was minimal, with approximately 10-60 neutrophils/ml and no eosinophils detected in bronchoalveolar lavage fluid. Higher levels of infectious virus were recovered from lung tissue excised from MIP-1 alpha-deficient than from fully competent mice, suggesting that the inflammatory response limits the rate of virus replication in vivo. PVM infection of CCR1-deficient mice was also associated with attenuated inflammation, with enhanced recovery of infectious virus, and with accelerated mortality. These results suggest that the MIP-1 alpha/CCR1-mediated acute inflammatory response protects mice by delaying the lethal sequelae of infection.

Chronic eosinophilic pneumonia.

Chronic eosinophilic pneumonia (CEP) belongs to a group of syndromes manifested by pulmonary infiltrates with peripheral eosinophilia (PIE syndromes). The role of the eosinophil as a destructive agent in CEP is discussed. The degree of manifested eosinophilia at the time of diagnosis, the frequency of relapses of pneumonia, the response to steroid therapy, the status of current physical and x-ray findings, and especially the trend in pulmonary function data, all appear to be critical factors in determining the potential mortality risk of CEP cases.

The hypereosinophilic syndrome: dramatic response to therapeutic intervention.

The Hypereosinophilic Syndrome (HES) is a disease of unknown etiology and pathogenesis characterized by blood and bone marrow eosinophilia associated with infiltration of eosinophils into tissues and multi-system organ dysfunction. Patients with HES historically have very significant morbidity and a high mortality of 77% at 3 years. This study is a prospective (9 years) and retrospective (24 years) analysis of the therapy and prognosis of 26 patients with HES. Five patients (19%) showed no evidence of progressive organ system dysfunction and were given no therapy; all have done well. Sixteen patients with progressive organ dysfunction were treated with corticosteroids; 6 of the 16 (38%) had a good response and required no further therapy. Six of 8 patients who were corticosteroid unresponsive and had serious prognostic signs had excellent responses to hydroxyurea therapy, while 2 patients showed partial responses. Employing the above regimen, we have demonstrated that our 26 patients (including 12 with poor prognostic indicators) have a marked increase in survival (3 year mortality 4%) when compared with the historical control.