Search

Abstract: Waterproofing spray-associated pneumonitis (WAP) proceeds to acute respiratory failure and is characterized by diffuse bilateral ground-glass opacities on computed tomography; however, the detailed characteristics of WAP are unknown. Therefore, this study identified the characteristics of WAP from comparisons with those of acute eosinophilic pneumonia (AEP) and hypersensitivity pneumonitis (HP), which show similar features to WAP.Adult patients with WAP, AEP, and HP treated in Fukujuji Hospital from 1990 to 2018 were retrospectively enrolled. Furthermore, data from patients with WAP were collected from publications in PubMed and the Japan Medical Abstracts Society and combined with data from our patients.Thirty-three patients with WAP, eleven patients with AEP, and thirty patients with HP were reviewed. Regarding age, sex, smoking habit, and laboratory findings (white blood cell count, C-reactive protein level, and serum Krebs von den Lungen-6 level), WAP and AEP were not significantly different, while WAP and HP were significantly different. The duration from symptom appearance to hospital visit was shorter in patients with WAP (median 1 day) than in patients with AEP (median 3 days, P = .006) or HP (median 30 days, P < .001). The dominant cells in the bronchoalveolar lavage fluid of patients with WAP, AEP, and HP were different (macrophages, eosinophils, and lymphocytes, respectively).The characteristic features of WAP were rapid disease progression and macrophage dominance in the bronchoalveolar lavage fluid, and these characteristics can be used to distinguish among WAP, AEP, and HP., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To determine the pattern of pulmonary involvement in clinically confirmed patients of tropical pulmonary eosinophilia (TPE)., Method: An observational study on 13 patients with clinically confirmed TPE was performed to determine the CT scan appearances., Results: The predominant CT scan finding is the presence widespread ill-defined bronchocentric nodules, which need to be differentiated from other conditions., Conclusion: The pattern of lung involvement on a CT scan can give a clue to the diagnosis of TPE in the correct clinical context. Radiologists in tropical countries should have a high index of suspicion for this diagnosis when reading scans showing widespread ill-defined bronchocentric nodules., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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

Patients with both serous effusion and eosinophilia are rarely reported and geographically distributed; their early diagnosis is difficult.According to the ultimate diagnosis, patients (≤14 years) in West China Second hospital with serous effusion and eosinophilia were divided into two groups including a parasitic group and a non-parasitic group. Clinical data were collected and analyzed between the two groups. Subsequently, significant measurement indicators were evaluated by receiver operating characteristic (ROC) curve to explore the optimal cut-off points for the most appropriate sensitivity and specificity.A total of 884 patients were diagnosed with serous effusion and 61 of them displayed co-morbidity with eosinophilia during enrolled time. Among 61 patients, 34 patients had parasitic infection and 27 had non-parasitic diseases. There were statistical difference in effusion position, the levels of white blood cell count (WBC), eosinophil (EOS), EOS%, C-reactive protein (CRP) between parasitic group and non-parasitic group. ROC curve demonstrated that the areas under the curve of EOS count and EOS% were >80%, and the corresponding optimal cut-off values were 1.71 × 10/L and 25.6% for distinguishing between parasitic and non-parasitic infections in our patients.This study provided a quantified index for potentially quick and convenient indicators of pediatric patients presenting with both eosinophilia and effusion. Eosinophils were helpful to improve the initial diagnosis with awareness of parasitic diseases. For the cases with EOS > 1.71 × 10/L or EOS% > 25.6%, parasitic infection should be considered and serological tests are recommended in our region.

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 PaO 2 /FiO 2 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.

Background: There are limited data on the prevalence and burden of severe eosinophilic asthma (SEA) both in Japan and globally. This study aimed to assess the prevalence and burden of SEA in Japan. Methods: This study was a retrospective, observational cohort analysis using health records or health insurance claims from patients with severe asthma treated at Kyoto University Hospital. The primary outcome was the prevalence of SEA, defined as a baseline blood eosinophil count ≥300 cells/μL. Secondary outcomes included frequency and risk factors of asthma exacerbations, and asthma-related healthcare resource utilization and costs. Results: Overall, 217 patients with severe asthma were included; 160 (74%) had eosinophil assessments. Of these, 97cases (61%), 54cases (34%), and 33cases (21%) had a blood eosinophil count ≥150, ≥300, and ≥500 cells/μL, respectively. Proportion of SEA was 34%. Blood eosinophil count was not associated with a significantly increased frequency of exacerbations. In the eosinophilic group, lower % forced expiratory volume in 1 second and higher fractional exhaled nitric oxide were predictive risk factors, while the existence of exacerbation history was a predictive risk factor for asthma exacerbations in the non-eosinophilic group. Severe asthma management cost was estimated as ¥357,958/patient-year, and asthma exacerbations as ¥26,124/patient-year. Conclusions: Approximately, one-third of patients with severe asthma in Japan have SEA. While risk factors for exacerbations differed between SEA and severe non-eosinophilic asthma, both subgroups were associated with substantial disease and economic burden. From subgroup analysis, blood eosinophil counts could be an important consideration in severe asthma management.

Objective: Eosinophilic asthma with chronic rhinosinusitis and/or nasal polyposis (EA-CRS/NP) is a subphenotype of adult-onset eosinophilic asthma. Blood eosinophil levels are shown to be highly elevated in patients with EA-CRS/NP and have potential for tissue infiltration. We aimed to demonstrate the clinical features of the patients who have a blood eosinophil level above 10% and have thorax computed tomography findings due to blood eosinophilia., Methods: Patients who were followed up in our clinic between 2012 and 2017 were retrospectively evaluated. Inclusion criteria were as follows: 1) Eosinophilic severe asthma, 2) eosinophilia >10%, 3) chronic sinusitis and/or nasal polyps, 4) patients with pathologic findings on thorax computed tomography, 5) regular follow-up for at least 1 year., Results: We identified 36 patients who met the above criteria. We defined this group as "Eosinophilic Asthma with chronic Rhinosinusitis and/or nasal polyposis with Radiological findings related to blood eosinophilia" (EARR). The mean age was 44.9 ± 11 years and 64% were females. Nasal polyps, aspirin exacerbated respiratory disease, and atopy, were present in 81%, 47%, and 25% of the patients, respectively. The mean blood eosinophil count was 1828.6 cells/mm 3 (19%). The majority of EARR patients had upper lobe dominant ground-glass opacities. The mean follow-up period was 3.2 ± 2.5 years. EARR patients did not evolve into eosinophilic granulomatous polyangiitis in the follow-up., Conclusions: This phenotype is the first eosinophilic asthma sub-phenotype reported in the literature. EARR is the final stage of the allergic march of EA-CRS/NP.

Background: Benralizumab, a humanized, afucosylated, monoclonal antibody that targets interleukin-5 receptor α, depletes eosinophils and basophils by enhanced antibody-dependent cell-mediated cytotoxicity. It demonstrated efficacy for patients with moderate to severe asthma and, in a Phase IIa trial, for chronic obstructive pulmonary disease (COPD) with eosinophilic inflammation. We investigated effects of benralizumab 100 mg every 8 weeks (first three doses every 4 weeks) subcutaneous on blood inflammatory markers through proteomic and gene-expression analyses collected during two Phase II studies of patients with eosinophilic asthma and eosinophilic COPD., Methods: Serum samples for proteomic analysis and whole blood for gene expression analysis were collected at baseline and 52 weeks (asthma study) or 32 weeks (COPD study) post-treatment. Proteomic analyses were conducted on a custom set of 90 and 147 Rules-Based Medicine analytes for asthma and COPD, respectively. Gene expression was profiled by Affymetrix Human Genome U133 plus 2 arrays (~ 54 K probes). Gene set variation analysis (GSVA) was used to determine transcriptomic activity of immune signatures. Treatment-related differences between analytes, genes, and gene signatures were analyzed for the overall population and for patient subgroups stratified by baseline blood eosinophil count (eosinophil-high [≥300 cells/μL] and eosinophil-low [< 300 cells/μL]) via t-test and repeated measures analysis of variance., Results: Eosinophil chemokines eotaxin-1 and eotaxin-2 were significantly upregulated (false discovery rate [FDR] < 0.05) by approximately 2.1- and 1.4-fold in the asthma study and by 2.3- and 1.7-fold in the COPD study following benralizumab treatment. Magnitude of upregulation of these two chemokines was greater for eosinophil-high patients than eosinophil-low patients in both studies. Benralizumab was associated with significant reductions (FDR < 0.05) in expression of genes associated with eosinophils and basophils, such as CLC, IL-5Rα, and PRSS33; immune-signaling complex genes (FCER1A); G-protein-coupled receptor genes (HRH4, ADORA3, P2RY14); and further immune-related genes (ALOX15 and OLIG2). The magnitude of downregulation of gene expression was greater for eosinophil-high than eosinophil-low patients. GSVA on immune signatures indicated significant treatment reductions (FDR < 0.05) in eosinophil-associated signatures., Conclusions: Benralizumab is highly selective, modulating blood proteins or genes associated with eosinophils or basophils. Modulated protein and gene expression patterns are most prominently altered in eosinophil-high vs. eosinophil-low patients., Trial Registration: NCT01227278 and NCT01238861 .

Background: Eosinophilic asthma is characterized by persistently elevated blood eosinophils, adult-onset asthma and corticosteroid resistance. For stratified medicine purposes one single measurement of blood eosinophils or exhaled nitric oxide (FeNO) is commonly used. The aim of this study was to investigate in patients with new-onset asthma whether persistent blood eosinophilia can be predicted with one single measurement of these biomarkers., Methods: Blood eosinophils and exhaled nitric oxide levels were measured at yearly intervals over 5 years in 114 adults with new-onset asthma on inhaled corticosteroid treatment. Two definitions of persistent blood eosinophilia were used (1); blood eosinophils at every visit ≥0.30 × 10 9 /L, or (2) ≥0.40 × 10 9 /L. Receiver operating characteristic analyses were performed. Diagnostic cut-off values were defined at a positive predictive value of 95% (or the highest achievable)., Results: Using definition 1 (blood eosinophils ≥0.30 × 10 9 /L) the cut-off value for a single measurement of blood eosinophils was 0.47 × 10 9 /L. For definition 2 (≥0.40 × 10 9 /L) the cut-off value was 0.49 × 10 9 /L. Cut-off values for persistently low blood eosinophils were 0.17 × 10 9 /L for definition (1) and 0.21 × 10 9 /L for definition (2), respectively. For FeNO no cut-off values with sufficient accuracy could be defined., Conclusion: We showed that by using high and low cut-off values, one single measurement of blood eosinophils, but not FeNO in the initial phase of new-onset asthma in adults can be used to predict persistence or absence of blood eosinophilia in asthma., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A middle-aged woman presented with symptoms suggestive of allergic asthma but with markedly elevated peripheral eosinophilia. She did not respond to inhaled corticosteroids, thereby prompting further investigations. Chest radiograph was normal. CT of the chest revealed bi-apical ground glass opacities. Bronchoalveolar lavage revealed predominantly eosinophilic yield. Autoimmune screen was negative. Bone marrow biopsy showed a normocellular marrow with increased eosinophils. A diagnosis of chronic eosinophilic pneumonia (CEP) was made after exclusion of other causes of eosinophilia. Treatment of her CEP with systemic corticosteroids (prednisolone 0.5 mg/kg/day) resulted in dramatic improvement in symptoms and peripheral eosinophilia., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Patients with severe asthma can have eosinophilic inflammation and/or allergen sensitization. Benralizumab is an anti-eosinophilic monoclonal antibody indicated for add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype., Objective: To investigate the efficacy of benralizumab by atopic status and serum immunoglobulin E (IgE) concentrations., Methods: We analyzed pooled results from the SIROCCO (NCT01928771) and CALIMA (NCT01914757) phase III studies. Patients 12 to 75 years old with severe, uncontrolled asthma on high-dosage inhaled corticosteroids plus long-acting β 2 -agonists received 30 mg of subcutaneous benralizumab every 4 weeks or every 8 weeks (first 3 doses every 4 weeks) or placebo every 4 weeks. The analysis stratified patients who did and did not meet similar omalizumab-qualifying criteria of atopy and serum IgE levels 30 to 700 kU/L. Patients also categorized as having high serum IgE (≥150 kU/L) or low serum IgE (<150 kU/L) and as having atopy or no atopy. Efficacy outcomes were for all patients and by blood eosinophil counts and included annual exacerbation rate ratio and pre-bronchodilator forced expiratory volume in 1 second change at treatment end vs placebo., Results: Benralizumab every 8 weeks decreased exacerbations by 46% (95% confidence interval 26-61, P = .0002) and increased forced expiratory volume in 1 second by 0.125 L (95% confidence interval 0.018-0.232, P = .0218) vs placebo for patients with at least 300 eosinophils/μL who met the atopy and IgE criteria. For patients with eosinophilia and high or low IgE, treatment with benralizumab every 8 weeks resulted in 42% and 43% decreases in exacerbation rate (P ≤ .0004) and 0.123- and 0.138-L increases in forced expiratory volume in 1 second (P ≤ .0041) vs placebo, respectively., Conclusion: Benralizumab treatment decreased exacerbations and improved lung function for patients with severe, uncontrolled eosinophilic asthma regardless of serum IgE concentrations and atopy status., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objective: Eosinophilic pneumonia (EP) is an important subset of patients who present with pulmonary infiltrates and eosinophilia (PIE). EP is classified by chronicity and etiology and drug-induced EP is the main cause of secondary EP. The primary goal of this review was to examine all the case reports published since the syndrome was defined in 1990. It remains unclear whether acute or chronic EP (AEP or CEP) represent different diseases, and the secondary goal of this review is to determine if there are factors that may help distinguish these 2 entities., Methods: PubMed (MEDLINE and Medical Subject Headings) was searched for case reports of drug-induced EP or PIE syndrome published between 1990 and 2017. Case reports were only included if the diagnostic criteria for AEP or CEP were fulfilled. For each case, data were extracted pertaining to age, sex, type of medication associated with the disease, time from the onset of symptoms to diagnosis, eosinophil counts in the blood, eosinophil fractions in bronchoalveolar lavage (BAL) fluid, initial chest radiograph and computed tomography results, use of mechanical ventilation, and use of steroid treatment and recurrence., Results: We found 196 case reports describing drug-induced EP. The leading cause was daptomycin. From our review, we found that AEP is more common in younger patients with no gender preference. Eosinophilia in the blood at the time of diagnosis characterized only the CEP patients (80% in CEP vs. 20% in AEP). Abnormal findings on radiographic imagine was similar in both syndromes. A significant portion of AEP patients (20%) presented with acute respiratory failure requiring mechanical ventilation. Most patients with EP were treated with steroids with a higher rate of relapse observed in patients with CEP., Conclusion: AEP is a much more fulminant and severe disease than the gradual onset and slowly progressive nature of CEP. The pathogenesis of AEP and CEP remains unclear. However, there is significant clinical overlap among AEP and CEP that are associated with drug toxicity, suggesting the possibility that AEP and CEP are distinct clinical presentations that share a common pathogenic pathway.

Tropical pulmonary eosinophilia (TPE) is a rare allergic manifestation to the filarial nematode. A 38-year old male and a 15-year old female presented with cough and breathlessness. Their complete blood count showed eosinophilia. This finding was overshadowed by the radiological findings suggestive of tuberculosis. The diagnosis of TPE was confirmed by filarial antigen detection test and both the patients were successfully treated with diethylcarbamazine. TPE presents with cough and breathlessness and can be often confused with tuberculosis, especially in endemic settings. An important clue in differentiating the two entities is the presence of eosinophilia in the former.

Introduction: Chronic eosinophilic pneumonia (CEP) is an idiopathic interstitial lung disease with nonspecific symptoms that involves a complex inflammatory cascade., Case Study: A 36-year-old prisoner with a history of psoriasis presented with progressive worsening dyspnea, chest pain, and cough. His symptoms started 2-months after starting adalimumab, a tumor necrosis factor (TNF)-inhibitor, for psoriasis treatment., Results: Initial workup revealed 27% eosinophils on complete blood count, elevated IgE levels on bronchoalveolar lavage, and bilateral peripheral lung opacities on imaging. The patient's symptoms and eosinophilia improved markedly after starting corticosteroids. Based on these findings, the patient was diagnosed with CEP., Conclusion: To our knowledge, this is the first case of asthma and CEP in a patient taking adalimumab. We suspect adalimumab unmasked the Th2 cell pathway response that was otherwise suppressed by psoriasis, a primarily Th1 cell pathway disease. The patient's pulmonary changes can be attributed to an eosinophilic asthma phenotype with adalimumab putatively indirectly causing CEP.

Acute eosinophilic pneumonia (AEP) has been reported following chloroquine or mefloquine exposure, both structurally related to piperaquine. We report a case of AEP with typical CT scan patterns, hypereosinophilia in blood (9.8 109/l), and bronchoalveolar lavage (78% of 600 000 cells/ml), 10 days after artenimol-piperaquine exposure in a 26-year-old man., (© International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Benralizumab is a humanised, anti-interleukin 5 receptor α monoclonal antibody that directly and rapidly depletes eosinophils, reduces asthma exacerbations, and improves lung function for patients with severe eosinophilic asthma. The objective of this trial was to assess the safety and efficacy of benralizumab for patients with mild to moderate, persistent asthma., Methods: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients aged 18-75 years, weighing at least 40 kg, and with a postbronchodilator reversibility in forced expiratory volume in 1 s (FEV 1 ) of at least 12% at screening, from 52 clinical research centres in six countries. Patients must have been receiving either low- to medium-dosage inhaled corticosteroids (ICS) or low-dosage ICS plus long-acting β 2 agonist fixed-combination therapy at screening, had a morning prebronchodilator FEV 1 of more than 50% to 90% predicted at screening, and had one or more of the following symptoms within the 7 days before randomisation: a daytime or night-time asthma symptom score of at least 1 for at least 2 days, rescue short-acting β 2 agonist use for at least 2 days, or night-time awakenings due to asthma for at least one night. We converted patients' ICS treatments to 180 μg or 200 μg budesonide dry powder inhaler twice daily for the entire duration of the study using the approved dosages in the patients' respective countries and randomly allocated them (1:1; stratified by blood eosinophil count [<300 cells per μL vs ≥300 cells per μL] and region [USA vs the rest of the world]) with an interactive web-based voice response system to receive subcutaneous placebo or benralizumab 30 mg injections every 4 weeks for 12 weeks. All patients and investigators involved in patient treatment or clinical assessment and those assessing outcomes were masked to treatment allocation. The primary endpoint was change from baseline prebronchodilator FEV 1 at week 12. Efficacy analyses used an intention to treat approach. This trial is registered with ClinicalTrials.gov, number NCT02322775., Findings: Between Feb 2, 2015, and April 24, 2015, we enrolled 351 patients, with 211 (60%) randomly assigned (105 [50%] to placebo and 106 [50%] to benralizumab). Benralizumab resulted in an 80 mL (95% CI 0-150; p=0·04) greater improvement (least-squares mean difference) in prebronchodilator FEV 1 after 12 weeks than did placebo (placebo group: 2246 mL [SD 768] at baseline vs 2261 mL [796] at week 12, change from baseline of 0 mL; benralizumab group: 2248 mL [606] vs 2310 mL [670], 70 mL). 44 (42%) patients in the benralizumab group had adverse events compared with 49 (47%) in the placebo group. The most common adverse events for both groups were nasopharyngitis (eight [8%] patients in each group) and upper respiratory tract infections (five [5%] patients in each group). Serious adverse events occurred in two (2%) patients each in the benralizumab (pancytopenia and a suicide attempt, both considered unrelated to treatment) and placebo (cervix carcinoma and colon adenoma) groups., Interpretation: This study suggests that active and modifiable disease processes might be ongoing in patients with mild to moderate, persistent asthma receiving ICS. Although the lung function improvement observed does not warrant use of benralizumab in this population because it did not reach the minimum clinically important difference of 10%, further studies to assess this finding should be considered., Funding: AstraZeneca., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction and loss of lung tissue mainly consisting of extracellular matrix (ECM). Three of the main ECM components are type I collagen, the main constituent in the interstitial matrix, type VI collagen, and elastin, the signature protein of the lungs. During pathological remodeling driven by inflammatory cells and proteases, fragments of these proteins are released into the bloodstream, where they may serve as biomarkers for disease phenotypes. The aim of this study was to investigate the lung ECM remodeling in healthy controls and COPD patients in the COPDGene study., Methods: The COPDGene study recruited 10,300 COPD patients in 21 centers. A subset of 89 patients from one site (National Jewish Health), including 52 COPD patients, 12 never-smoker controls and 25 smokers without COPD controls, were studied for serum ECM biomarkers reflecting inflammation-driven type I and VI collagen breakdown (C1M and C6M, respectively), type VI collagen formation (Pro-C6), as well as elastin breakdown mediated by neutrophil elastase (EL-NE). Correlation of biomarkers with lung function, the SF-36 quality of life questionnaire, and other clinical characteristics was also performed., Results: The circulating concentrations of biomarkers C6M, Pro-C6, and EL-NE were significantly elevated in COPD patients compared to never-smoking control patients (all p < 0.05). EL-NE was significantly elevated in emphysema patients compared to smoking controls (p < 0.05) and never-smoking controls (p < 0.005), by more than 250%. C1M was inversely associated with forced expiratory volume in 1 s (FEV 1 ) (r = -0.344, p = 0.001), as was EL-NE (r = -0.302, p = 0.004) and Pro-C6 (r = -0.259, p = 0.015). In the patients with COPD, Pro-C6 was correlated with percent predicted Forced Vital Capacity (FVC) (r = 0.281, p = 0.046) and quality of life using SF-36. C6M and Pro-C6, were positively correlated with blood eosinophil numbers in COPD patients (r = 0.382, p = 0.006 and r = 0.351, p = 0.012, respectively)., Conclusions: These data suggest that type VI collagen turnover and elastin degradation by neutrophil elastase are associated with COPD-induced inflammation (eosinophil-bronchitis) and emphysema. Serological assessment of type VI collagen and elastin turnover may assist in identification of phenotypes likely to be associated with progression and amenable to precision medicine for clinical trials.

Urban particulate matter (PM) is associated with an increase in asthma. PM2.5 (

Background: Benralizumab is a humanised, afucosylated, anti-interleukin-5 receptor α monoclonal antibody that induces direct, rapid, and nearly complete depletion of eosinophils. We aimed to assess the efficacy and safety of benralizumab as add-on therapy for patients with severe, uncontrolled asthma and elevated blood eosinophil counts., Methods: In this randomised, double-blind, parallel-group, placebo-controlled, phase 3 study (CALIMA) undertaken at 303 sites in 11 countries, we enrolled patients aged 12-75 years with severe asthma uncontrolled by medium-dosage to high-dosage inhaled corticosteroids plus long-acting β₂-agonists (ICS plus LABA) and a history of two or more exacerbations in the previous year. Patients were randomly assigned (1:1:1) to receive 56 weeks of benralizumab 30 mg every 4 weeks (Q4W), benralizumab 30 mg every 8 weeks (Q8W; first three doses 4 weeks apart), or placebo (all subcutaneous injection). Patients were stratified (2:1) by baseline blood eosinophil counts 300 cells per μL or greater and less than 300 cells per μL, respectively. Patients and study centre staff were masked to treatment allocation. The primary endpoint was annual exacerbation rate ratio versus placebo for patients receiving high-dosage ICS plus LABA with baseline blood eosinophils 300 cells per μL or greater (intention-to-treat analysis). Key secondary endpoints were pre-bronchodilator forced expiratory volume in 1 s (FEV 1 ) and total asthma symptom score. This study is registered with ClinicalTrials.gov, number NCT01914757., Findings: Between Aug 21, 2013, and March 16, 2015, 2505 patients were enrolled, of whom 1306 patients were randomised; 425 patients were randomly assigned to and received benralizumab 30 mg Q4W, 441 to benralizumab 30 mg Q8W, and 440 to placebo. 728 patients were included in the primary analysis population. Benralizumab resulted in significantly lower annual exacerbation rates with the Q4W regimen (rate 0·60 [95% CI 0·48-0·74], rate ratio 0·64 [95% CI 0·49-0·85], p=0·0018, n=241) and Q8W regimen (rate 0·66 [95% CI 0·54-0·82], rate ratio 0·72 [95% CI 0·54-0·95], p=0·0188, n=239) compared with placebo (rate 0·93 [95% CI 0·77-1·12], n=248). Benralizumab also significantly improved pre-bronchodilator FEV 1 (Q4W and Q8W) and total asthma symptom score (Q8W only) in these patients. The most common adverse events were nasopharyngitis (90 [21%] in the Q4W group, 79 [18%] in the Q8W group, and 92 [21%] in the placebo group) and worsening asthma (61 [14%] in the Q4W group, 47 [11%] in the Q8W group, and 68 [15%] in the group)., Interpretation: Benralizumab significantly reduced annual exacerbation rates and was generally well tolerated for patients with severe, uncontrolled asthma with blood eosinophils 300 cells per μL or greater. Our data further refine the patient population likely to receive the greatest benefit from benralizumab treatment., Funding: AstraZeneca and Kyowa Hakko Kirin., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Diagnosing eosinophilic asthma is important, because uncontrolled eosinophilic airway inflammation is associated with reduced response to glucocorticoids and increased risk of severe exacerbations., Areas Covered: Currently, the diagnosis of eosinophilic asthma is based on measurements of sputum eosinophils, which is time consuming and requires specific technical expertise. Therefore, biomarkers such as blood eosinophils, FeNO, serum IgE and periostin are being used as surrogates. These biomarkers can be used separately or in combination, and their accuracy to detect sputum eosinophilia depends on cut-off values. The demonstration of eosinophils in sputum is no guarantee for response to treatment with current biological agents targeting Type 2 inflammation, because several molecular pathways may lead to eosinophilic inflammation. In the near future, the results of large trials using 'omics' technologies will certainly identify new, more 'upstream' biomarkers of eosinophilic inflammation, that will ultimately lead to the ideal targeted treatment for patients with eosinophilic asthma. Expert commentary: Of currently used surrogate markers to diagnose eosinophilic asthma, blood eosinophils and FeNO have the highest diagnostic accuracy, in particular if used in combination to rule in or rule out eosinophilic asthma. For patients who cannot be classified by these biomarkers alone, the clinical profile may be of help.

Because asthma and COPD are both inflammatory chronic obstructive airway diseases, there are several clinical expressions which can cause confusion, such as: eosinophilic asthma with fixed obstruction, which is a risk factor and might progress to COPD; eosinophilic COPD; COPD with partial reversible obstruction with no asthmatic component and also eosinophilic asthma-COPD overlap syndrome (ACOS). While at the two extremes of these disorders the pathoimmunological processes are clearly different, in some patients there is overlap and the pathophysiological border between asthma and COPD is fused (or diffuse). The current guidelines are clearly insufficient for classification of the obstructive patients and, taking into account that binary separation between the two diseases is not completely clear, we should resist the temptation to label patients as ACOS and consider new airway disease taxonomy. Regardless of the condition concerned, eosinophils should be considered in the algorithm approach to obstructive patients: in COPD, as in asthma, they are related to the underlying pathological process; they have prognostic value and are related to therapeutic response. Therefore, eosinophils should be valued as useful biomarkers and included in a multidimensional diagnostic and therapeutic approach, bearing in mind the phenotypic, immunopathological and functional complexity of chronic obstructive airway disease., (Copyright © 2016 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Findings from previous studies showed that mepolizumab significantly reduces the rate of exacerbations in patients with severe eosinophilic asthma. To assess the relationship between baseline blood eosinophil counts and efficacy of mepolizumab we did a secondary analysis of data from two studies, stratifying patients by different baseline blood eosinophil thresholds., Methods: We did a post-hoc analysis of data, which was completed on Sept 25, 2015, from two randomised, double-blind, placebo-controlled studies of at least 32 weeks duration (NCT01000506 [DREAM] and NCT01691521 [MENSA]) done between 2009 and 2014. In these studies, mepolizumab (, Dream: 75 mg, 250 mg, or 750 mg intravenously; MENSA: 75 mg intravenously or 100 mg subcutaneously) versus placebo was given at 4-week intervals in addition to standard care (high-dose inhaled corticosteroids plus ≥1 additional controller with or without daily oral corticosteroids) to patients aged 12 years or older with a clinical diagnosis of asthma, a history of at least two exacerbations in the previous year that required systemic corticosteroid treatment, and evidence of eosinophilic airway inflammation. The primary endpoint in both studies was the annual rate of clinically significant exacerbations (defined as worsening of asthma that required the use of systemic corticosteroids, or admission to hospital, or an emergency-room visit, or a combination of these occurrences). In our analysis, the primary outcome was the annualised rate of exacerbations in patients stratified by baseline eosinophil counts (≥150 cells per μL, ≥300 cells per μL, ≥400 cells per μL, and ≥500 cells per μL) and baseline blood eosinophil ranges (<150 cells per μL, ≥150 cells per μL to <300 cells per μL, ≥300 cells per μL to <500 cells per μL, and ≥500 cells per μL). We based our analysis on the intention-to-treat populations of the two original studies, and all mepolizumab doses were combined for analysis., Findings: Of 1192 patients, 846 received mepolizumab and 346 received placebo. The overall rate of mean exacerbations per person per year was reduced from 1·91 with placebo to 1·01 with mepolizumab (47% reduction; rate ratio [RR] 0·53, 95% CI 0·44-0·62; p<0·0001). The exacerbation rate reduction with mepolizumab versus placebo increased progressively from 52%; 0·48, 0·39-0·58) in patients with a baseline blood eosinophil count of at least 150 cells per μL to 70%; 0·30, 0·23-0·40]) in patients with a baseline count of at least 500 cells per μL. At a baseline count less than 150 cells per μL, predicted efficacy of mepolizumab was reduced., Interpretation: Our analysis has shown a close relationship between baseline blood eosinophil count and clinical efficacy of mepolizumab in patients with severe eosinophilic asthma and a history of exacerbations. We noted clinically relevant reductions in exacerbation frequency in patients with a count of 150 cells per μL or more at baseline. The use of this baseline biomarker will help to select patients who are likely to achieve important asthma outcomes with mepolizumab., Funding: GlaxoSmithKline., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Sputum eosinophilia occurs in approximately one-third of stable chronic obstructive pulmonary disease (COPD) patients and can predict exacerbation risk and response to corticosteroid treatments. Sputum induction, however, requires expertise, may not always be successful, and does not provide point-of-care results. Easily applicable diagnostic markers that can predict sputum eosinophilia in stable COPD patients have the potential to progress COPD management. This study investigated the correlation and predictive relationship between peripheral blood and sputum eosinophils. It also examined the repeatability of blood eosinophil counts., Methods: Stable COPD patients (n=141) were classified as eosinophilic or noneosinophilic based on their sputum cell counts (≥3%), and a cross-sectional analysis was conducted comparing their demographics, clinical characteristics, and blood cell counts. Receiver operating characteristic curve analysis was used to assess the predictive ability of blood eosinophils for sputum eosinophilia. Intraclass correlation coefficient was used to examine the repeatability of blood eosinophil counts., Results: Blood eosinophil counts were significantly higher in patients with sputum eosinophilia (n=45) compared to those without (0.3×10(9)/L vs 0.15×10(9)/L; P<0.0001). Blood eosinophils correlated with both the percentage (ρ=0.535; P<0.0001) and number of sputum eosinophils (ρ=0.473; P<0.0001). Absolute blood eosinophil count was predictive of sputum eosinophilia (area under the curve =0.76, 95% confidence interval [CI] =0.67-0.84; P<0.0001). At a threshold of ≥0.3×10(9)/L (specificity =76%, sensitivity =60%, and positive likelihood ratio =2.5), peripheral blood eosinophil counts enabled identification of the presence or absence of sputum eosinophilia in 71% of the cases. A threshold of ≥0.4×10(9)/L had similar classifying ability but better specificity (91.7%) and higher positive likelihood ratio (3.7). In contrast, ≥0.2×10(9)/L offered a better sensitivity (91.1%) for ruling out sputum eosinophilia. There was a good agreement between two measurements of blood eosinophil count over a median of 28 days (intraclass correlation coefficient =0.8; 95% CI =0.66-0.88; P<0.0001)., Conclusion: Peripheral blood eosinophil counts can help identify the presence or absence of sputum eosinophilia in stable COPD patients with a reasonable degree of accuracy.

A 7-year-old female spayed Labrador Retriever was admitted to our hospital, because of cough with sputum. She was diagnosed as having canine eosinophilic pneumonia (CEP) based on blood eosinophilia, bronchial pattern and infiltrative shadow observed on thoracic radiography, bronchiolar obstruction and air-space consolidation predominantly affecting the right caudal lung lobe, as revealed by computed tomography (CT), predominant eosinophils in CT-guided fine needle aspiration and the clinical course. She exhibited a good response to steroid therapy, and the cough disappeared. The serum surfactant protein (SP)-A level increased with the aggravated symptom and decreased markedly with improvement compared with the C-reactive protein level and the number of eosinophils. We propose that serum SP-A level is a good biomarker in CEP.

Background: In patients with severe eosinophilic asthma, local maturation rather than systemic recruitment of mature cells might contribute to persistent airway eosinophilia. Group 2 innate lymphoid cells (ILC2s) are a major source of type 2 cytokines (IL-5 and IL-13) and can facilitate eosinophilic inflammatory responses in mouse models of asthma in the absence of CD4+ lymphocytes. This study investigated the potential role of ILC2s in driving chronic airway eosinophilia in patients with severe asthma, despite regular high-dose oral corticosteroid therapy., Methods: In a cross-sectional study we enumerated blood and sputum ILC2s (lin(-)CD45(+)127(+)ST2(+)) and levels of intracellular IL-5 and IL-13 in patients with severe asthma (n = 25), patients with steroid-naive mild atopic asthma (n = 19), and nonatopic control subjects (n = 5). Results were compared with numbers of CD4+ lymphocytes, eosinophil lineage-committed progenitors (eosinophilopoietic progenitor cells [EoPs]), and mature eosinophils., Results: Significantly greater numbers of total and type 2 cytokine-producing ILC2s were detected in blood and sputum of patients with severe asthma compared to mild asthmatics. In contrast, intracellular cytokine expression by CD4 cells and EoPs within the airways did not differ between the asthmatic groups. In patients with severe asthma, although sputum CD4+ cells were more abundant than ILC2s and EoPs, proportionally, ILC2s were the predominant source of type 2 cytokines. In addition, there were significantly greater numbers of sputum IL-5(+)IL-13(+) ILC2s in patients with severe asthma whose airway eosinophilia was greater than 3%, despite normal blood eosinophil numbers (<300/μL)., Conclusions: Our findings suggest that ILC2s can promote the persistence of airway eosinophilia in patients with severe asthma through uncontrolled localized production of the type 2 cytokines IL-5 and IL-13, despite high-dose oral corticosteroid therapy., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Group 2 innate lymphoid cells (ILC2) have been implicated in the pathogenesis of allergic lung diseases. However, the upstream signals that regulate ILC2 function during pulmonary inflammation remain poorly understood. ILC2s have been shown to respond to exogenous IL-2, but the importance of endogenous IL-2 in ILC2 function in vivo remains unclear., Objective: We sought to understand the role of IL-2 in the regulation of ILC2 function in the lung., Methods: We used histology, flow cytometry, immunohistochemistry, ELISA, and quantitative PCR with knockout and reporter mice to dissect pulmonary ILC2 function in vivo. We examined the role of ILC2s in eosinophilic crystalline pneumonia, an idiopathic type 2 inflammatory lung condition of mice, and the effect of IL-2 deficiency on this disease. We determined the effect of IL-2 administration on pulmonary ILC2 numbers and function in mice in the steady state and after challenge with IL-33., Results: We discovered an unexpected role for innate cell-derived IL-2 as a major cofactor of ILC2 function during pulmonary inflammation. Specifically, we found that IL-2 was essential for the development of eosinophilic crystalline pneumonia, a type 2 disease characterized by increased numbers of activated ILC2s. We show that IL-2 signaling serves 2 distinct functions in lung ILC2s, namely promoting cell survival/proliferation and serving as a cofactor for the production of type 2 cytokines. We further demonstrate that group 3 innate lymphoid cells are an innate immune source of IL-2 in the lung., Conclusion: Innate cell-derived IL-2 is a critical cofactor in regulating ILC2 function in pulmonary type 2 pathology., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

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.

Background and Objective: Studies have shown that patients with acute eosinophilic pneumonia (AEP) and with initial eosinophilia have a milder disease than those with an initial normal peripheral eosinophil count (PEC). We investigated the effect of a rapid corticosteroid tapering strategy in AEP patients with initial eosinophilia., Methods: We performed a prospective cohort study in patients with AEP with initial eosinophilia (n = 14) who stopped corticosteroid treatment after achieving clinical stabilization compared with AEP patients with an initial normal PEC (n = 45) who received 2-week treatment with corticosteroid., Results: In total, 59 AEP patients were identified. The median duration of corticosteroid treatment was 4 days (interquartile ranges (IQR), 3-4) in patients with initial eosinophilia and 14 (IQR, 14-14) days in patients with initial normal PEC. No treatment failure occurred in the group with initial eosinophilia; one treatment failure case occurred in the group with an initially normal PEC. The median time to overall clinical stabilization was 3 days, and time to complete resolution of all symptoms and clinical instabilities from diagnosis was 4 days in AEP patients with initial eosinophilia. Both were significantly shorter than those) in the initially normal PEC group, which were 5 and 7 days respectively (both P < 0.001). Adverse effects were lower in AEP patients with initial eosinophilia, and additional medications to relieve adverse effects were only needed in AEP patients with initially normal PEC., Conclusions: Rapid corticosteroid tapering may be an acceptable treatment strategy for managing AEP patients with initial eosinophilia., (© 2015 Asian Pacific Society of Respirology.)

Background: Eosinophilic airway inflammation is associated with increased corticosteroid responsiveness in asthma, but direct airway sampling methods are invasive or laborious. Minimally invasive markers for airway eosinophilia could present an alternative method, but estimates of their accuracy vary., Methods: We did a systematic review and searched Medline, Embase, and PubMed for studies assessing the diagnostic accuracy of markers against a reference standard of induced sputum, bronchoalveolar lavage, or endobronchial biopsy in patients with asthma or suspected asthma (for inception to Aug 1, 2014). Unpublished results were obtained by contacting authors of studies that did not report on diagnostic accuracy, but had data from which estimates could be calculated. We assessed risk of bias with QUADAS-2. We used meta-analysis to produce summary estimates of accuracy., Findings: We included 32 studies: 24 in adults and eight in children. Of these, 26 (81%) showed risk of bias in at least one domain. In adults, three markers had extensively been investigated: fraction of exhaled nitric oxide (FeNO) (17 studies; 3216 patients; summary area under the receiver operator curve [AUC] 0·75 [95% CI 0·72-0·78]); blood eosinophils (14 studies; 2405 patients; 0·78 [0·74-0·82]); total IgE (seven studies; 942 patients; 0·65 [0·61-0·69]). In children, only FeNO (six studies; 349 patients; summary AUC 0·81 [0·72-0·89]) and blood eosinophils (three studies; 192 patients; 0·78 [0·71-0·85]) had been investigated in more than one study. Induced sputum was most frequently used as the reference standard. Summary estimates of sensitivity and specificity in detecting sputum eosinophils of 3% or more in adults were: 0·66 (0·57-0·75) and 0·76 (0·65-0·85) for FeNO; 0·71 (0·65-0·76) and 0·77 (0·70-0·83) for blood eosinophils; and 0·64 (0·42-0·81) and 0·71 (0·42-0·89) for IgE., Interpretation: FeNO, blood eosinophils, and IgE have moderate diagnostic accuracy. Their use as a single surrogate marker for airway eosinophilia in patients with asthma will lead to a substantial number of false positives or false negatives., Funding: None., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Hypereosinophilic asthma (HEA) is considered as a specific severe asthma phenotype. Whether eosinophils have a link with airway remodeling characterized by pathological (thickening of the basement membrane), functional (persistent airflow impairment and decline in lung function) and imaging features (increase airway wall thickness at CT scan) is still debated. In a one year prospective cohort of 142 severe asthma patients (according to IMI), 14 persistent HEA patients (defined by a persistent blood eosinophilia >500/mm(3) at two consecutive visits) were identified and compared with ten patients without any blood eosinophilia during the follow-up period (NEA, blood eosinophilia always <500/mm(3)). Airflow and lung volumes were recorded. Bronchial biopsies obtained at enrollment were stained for eosinophils (EG2) and basement membrane thickness (BM) was quantified. Imaging by CT scan acquisition was standardized and bronchial abnormalities quantified. ACQ score and exacerbations were prospectively recorded. HEA was not associated with preeminent features of airway remodeling assessed by airflow impairment (Best ever FEV1 values 97% ± 20 in HEA vs. 80 ± 24% in NEA, p = 0.020), decline of FEV1 (FEV1 Decline 40 ± 235 ml/y in HEA vs. 19 ± 40 ml/y in NEA, P = 0.319), submucosal abnormalities (BM thickness 7.80 ± 2.66 μm in HEA vs. 6.84 ± 2.59 in NEA, p = 0.37) and airway wall thickening at CT-scan (0.250 ± 0.036 mm vs. 0.261 ± 0.043, p = 0.92). Eosinophils blood count was inversely correlated with semiquantitative imaging score (rho -0.373, p = 0.039). Smoking history and positive skin prick tests were independent risk factors for increased BM thickening. Outcomes were similar in both populations (Control and exacerbations). Persistent HEA is not associated with evidences of airway remodeling., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A 47-year-old woman with marked thrombocytosis of 1,650 × 10(9)/L was diagnosed with chronic eosinophilic pneumonia (CEP) based on imaging of the lung and abundant eosinophils in bronchoalveolar lavage fluid. Known gene abnormalities that cause eosinophilia were not detected in bone marrow cells. Treatment with oral prednisolone at 20 mg/day relieved the CEP and resolved the laboratory abnormalities, including eosinophilia and thrombocytosis. Serum concentrations of interleukin (IL)-5 and IL-6 were elevated to 9.6 and 14.0 pg/mL, respectively. The megakaryocyte-potentiating activity of IL-6 and possibly, that of IL-1β, which is known to be secreted by activated eosinophils, may have caused the marked thrombocytosis in this patient.

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., (© 2014 Asian Pacific Society of Respirology.)

Particulate matter can exacerbate respiratory diseases such as asthma. Diesel exhaust particles are the substantial portion of ambient particulate matter with a <2.5 µm diameter in urban areas. Epidemiological data indicate increased respiratory health effects of particulate matter in obese individuals; however, the association between obesity and diesel exhaust particle-induced airway inflammation remains unclear. We aimed to investigate the differences in susceptibility to airway inflammation induced by exposure to diesel exhaust particles between obese mice (db/db) and lean mice (db/+m). Female db/db and db/+m mice were intratracheally administered diesel exhaust particles or vehicle every 2 weeks for a total of seven times. The cellular profile of bronchoalveolar lavage fluid and histological changes in the lungs were assessed and the lungs and serum were analyzed for the generation of cytokines, chemokines and soluble intercellular adhesion molecule 1. Diesel exhaust particle exposure-induced eosinophilic infiltration in db/+m mice accompanied by T-helper 2 cytokine, chemokine and soluble intercellular adhesion molecule 1 expression in the lungs. In contrast, it induced mild neutrophilic airway inflammation accompanied by elevated cytokines and chemokines in db/db mice. The lungs of db/db mice exhibited decreased expression of eosinophil activators/chemoattractants such as interleukin-5, interleukin-13 and eotaxin compared with those of db/+m mice. In addition, serum eotaxin and monocyte chemotactic protein-1 levels were significantly higher in db/db mice than in db/+m mice. In conclusion, obesity can affect susceptibility to diesel exhaust particle-induced airway inflammation, which is possibly due to differences in local and systemic inflammatory responses between lean and obese individuals., (Copyright © 2013 John Wiley & Sons, Ltd.)

Eosinophils are mediators of allergic inflammation and are implicated in the pathogenesis of numerous conditions including asthma, parasitic infections, neoplasms, hyper-eosinophilic syndromes, vasculitic disorders, and organ-specific conditions. Assessing eosinophilic inflammation is therefore important in establishing a diagnosis, in monitoring and assessing response to treatment, and in testing novel therapeutics. Clinical markers of atopy and eosinophilic inflammation include indirect tests such as lung function, exhaled breath condensate analysis, fractional exhaled nitric oxide, serum immunoglobulin E levels and serum periostin. Direct measures, which quantify but do not anatomically localise inflammation include blood eosinophil counts, serum or plasma eosinophil cationic protein and sputum eosinophil levels. Cytology from bronchoalveolar lavage and histology from endobronchial and transbronchial biopsies are better at localising inflammation but are more invasive. Novel approaches using radiolabelled eosinophils with single-photon emission computed tomography, offer the prospect of non-invasive methods to localise eosinophilic inflammation.

Although the effects of fish oil supplements on airway inflammation in asthma have been studied with varying results, the independent effects of the fish oil components, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), administered separately, are untested. Here, we investigated airway inflammation and hyperresponsiveness using a mouse ovalbumin exposure model of asthma assessing the effects of consuming EPA (1.5% wt/wt), DHA (1.5% wt/wt), EPA plus DHA (0.75% each), or a control diet with no added omega-3 polyunsaturated fatty acids. Consuming these diets for 6 weeks resulted in erythrocyte membrane EPA contents (molar %) of 9.0 (± 0.6), 3.2 (± 0.2), 6.8 (± 0.5), and 0.01 (± 0.0)%; DHA contents were 6.8 (± 0.1), 15.6 (± 0.5), 12.3 (± 0.3), and 3.8 (± 0.2)%, respectively. The DHA group had the highest bronchoalveolar lavage (BAL) fluid eosinophil and IL-6 levels (P < 0.05). Similar trends were seen for macrophages, IL-4, and IL-13, whereas TNF-α was lower in omega-3 polyunsaturated fatty acid groups than the control (P < 0.05). The DHA group also had the highest airway resistance, which differed significantly from the EPA plus DHA group (P < 0.05), which had the lowest. Oxylipins were measured in plasma and BAL fluid, with DHA and EPA suppressing arachidonic acid-derived oxylipin production. DHA-derived oxylipins from the cytochrome P450 and 15-lipoxygenase pathways correlated significantly with BAL eosinophil levels. The proinflammatory effects of DHA suggest that the adverse effects of individual fatty acid formulations should be thoroughly considered before any use as therapeutic agents in asthma.

Pneumonia is a common diagnosis with significant morbidity and mortality. However, pneumonia is a commonly overdiagnosed entity, with many similar-appearing conditions. A young, previously healthy woman was misdiagnosed with a variety of respiratory tract infections over the course of five months before establishing the correct diagnosis - chronic eosinophilic pneumonia.

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.

Background: There is a strong association between tobacco smoking and acute eosinophilic pneumonia (AEP) and tobacco smoking has been related to onset of AEP, but the mechanisms for causing AEP are largely unknown. AEP is characterized by locally high levels of interleukin-5 (IL-5) and interleukin-1 receptor antagonist (IL-1RA). Thus, tobacco smoking may relate to the high levels of IL-5 and IL-1RA in AEP., Aim: We aimed to determine whether the rate of tobacco smoking positively related to the high levels of IL-5 and IL-1RA., Patients and Methods: In the study, 155 AEP patients and 135 control healthy subjects were recruited by the Clinical Research Center at General Hospital of Shenyang Military Area Command (Shenyang, China). All the subjects were interviewed regarding for the tobacco smoking rate. The number of eosinophils was counted in all subjects. The relative expressive levels of IL-5 and IL-1RA were measured with ELISA in Bronchoalveolar lavage (BAL) and serum., Results: The BAL levels of IL-5, IL-1ra, eosinophils and lymphocytes positively correlates with the rate of tobacco smoking in AEP patients (p < 0.005) comparing with those in healthy control groups. No significant association was observed between the serum levels IL-5 and IL-1ra and the rate of tobacco smoking in AEP patients (p > 0.05) comparing with those in healthy control groups., Conclusions: Smoking increases the BAL levels of IL-5 and IL-1RA, which is associated with the onset of AEP.

Background: With the increase in production and use of engineered nanoparticles (NP; ≤ 100 nm), safety concerns have risen about the potential health effects of occupational or environmental NP exposure. Results of animal toxicology studies suggest that inhalation of NP may cause pulmonary injury with subsequent acute or chronic inflammation. People with chronic respiratory diseases like asthma or allergic rhinitis may be even more susceptible to toxic effects of inhaled NP. Few studies, however, have investigated adverse effects of inhaled NP that may enhance the development of allergic airway disease., Methods: We investigated the potential of polyethylene glycol coated amorphous silica NP (SNP; 90 nm diameter) to promote allergic airway disease when co-exposed during sensitization with an allergen. BALB/c mice were sensitized by intranasal instillation with 0.02% ovalbumin (OVA; allergen) or saline (control), and co-exposed to 0, 10, 100, or 400 μg of SNP. OVA-sensitized mice were then challenged intranasally with 0.5% OVA 14 and 15 days after sensitization, and all animals were sacrificed a day after the last OVA challenge. Blood and bronchoalveolar lavage fluid (BALF) were collected, and pulmonary tissue was processed for histopathology and biochemical and molecular analyses., Results: Co-exposure to SNP during OVA sensitization caused a dose-dependent enhancement of allergic airway disease upon challenge with OVA alone. This adjuvant-like effect was manifested by significantly greater OVA-specific serum IgE, airway eosinophil infiltration, mucous cell metaplasia, and Th2 and Th17 cytokine gene and protein expression, as compared to mice that were sensitized to OVA without SNP. In saline controls, SNP exposure did cause a moderate increase in airway neutrophils at the highest doses., Conclusions: These results suggest that airway exposure to engineered SNP could enhance allergen sensitization and foster greater manifestation of allergic airway disease upon secondary allergen exposures. Whereas SNP caused innate immune responses at high doses in non-allergic mice, the adjuvant effects of SNP were found at lower doses in allergic mice and were Th2/Th17 related. In conclusion, these findings in mice suggest that individuals exposed to SNP might be more prone to manifest allergic airway disease, due to adjuvant-like properties of SNP.

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., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Some patients with severe asthma have recurrent asthma exacerbations associated with eosinophilic airway inflammation. Early studies suggest that inhibition of eosinophilic airway inflammation with mepolizumab-a monoclonal antibody against interleukin 5-is associated with a reduced risk of exacerbations. We aimed to establish efficacy, safety, and patient characteristics associated with the response to mepolizumab., Methods: We undertook a multicentre, double-blind, placebo-controlled trial at 81 centres in 13 countries between Nov 9, 2009, and Dec 5, 2011. Eligible patients were aged 12-74 years, had a history of recurrent severe asthma exacerbations, and had signs of eosinophilic inflammation. They were randomly assigned (in a 1:1:1:1 ratio) to receive one of three doses of intravenous mepolizumab (75 mg, 250 mg, or 750 mg) or matched placebo (100 mL 0·9% NaCl) with a central telephone-based system and computer-generated randomly permuted block schedule stratified by whether treatment with oral corticosteroids was required. Patients received 13 infusions at 4-week intervals. The primary outcome was the rate of clinically significant asthma exacerbations, which were defined as validated episodes of acute asthma requiring treatment with oral corticosteroids, admission, or a visit to an emergency department. Patients, clinicians, and data analysts were masked to treatment assignment. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01000506., Findings: 621 patients were randomised: 159 were assigned to placebo, 154 to 75 mg mepolizumab, 152 to 250 mg mepolizumab, and 156 to 750 mg mepolizumab. 776 exacerbations were deemed to be clinically significant. The rate of clinically significant exacerbations was 2·40 per patient per year in the placebo group, 1·24 in the 75 mg mepolizumab group (48% reduction, 95% CI 31-61%; p<0·0001), 1·46 in the 250 mg mepolizumab group (39% reduction, 19-54%; p=0·0005), and 1·15 in the 750 mg mepolizumab group (52% reduction, 36-64%; p<0·0001). Three patients died during the study, but the deaths were not deemed to be related to treatment., Interpretation: Mepolizumab is an effective and well tolerated treatment that reduces the risk of asthma exacerbations in patients with severe eosinophilic asthma., Funding: GlaxoSmithKline., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background and Objectives: Eosinophilic lung diseases are a diverse group of disorders characterized by pulmonary opacities associated with tissue or peripheral eosinophilia., Design and Setting: A retrospective study conducted at two tertiary care hospitals from January 1999 to December 2009., Methods: All cases with the diagnosis of pulmonary eosinophilia were reviewed over a period of 10 years. Data on demographic, clinical, and radiologic characteristics were collected., Results: Thirty-five patients with a mean age of 33.9 (16.2) years, of which 20 (57.1%) were male and meeting the criteria of eosinophilic lung disease were identified. Cough and dyspnea were the most frequent symptoms at presentation in 29 (82.9%) and 27 (77.1%) patients, respectively. Reticulonodular and airspace patterns were the most common radiographic findings in 17 (48.6%) and 15 (42.9%) patients, respectively. Peripheral eosinophilia was present in 33 (94.3%) patients. Twenty-four patients (68.6%) were labeled as having idiopathic pulmonary infiltrate with eosinophilia. Complete remission was achieved in 13 (54.2%) of 24 patients, while 10 (41.7%) patients relapsed within a few months of discontinuation of therapy. Specific therapy for a specific disease was administered in 8 patients: 2 patients for pulmonary tuberculosis, 2 for Churg-Strauss syndrome, 1 for lymphoma, 1 for schistosomiasis, 1 for acute eosinophilic pneumonia, and 1 for Wegener granuloma; 3 patients were treated as allergic bronchopulmonary aspergillosis., Conclusions: Pulmonary eosinophilia remains rare but challenging, and it can have the same diverse clinical and radiographic presentations seen with other common pulmonary conditions. Clinicians should be alert to these syndromes and must think of them in any lung disease differential diagnoses.