Waterproofing spray-associated pneumonitis review: Comparison with acute eosinophilic pneumonia and hypersensitivity pneumonitis.

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.

The role of HRCT in Tropical Pulmonary Eosinophilia.

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.

Distinguishment of parasite-infected children from pediatric inpatients with both eosinophilia and effusion.

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.

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

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

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.

The prevalence and disease burden of severe eosinophilic asthma in Japan.

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.

Modulation of blood inflammatory markers by benralizumab in patients with eosinophilic airway diseases.

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 .

Last station in the eosinophilic asthma with chronic rhinosinusitis and/or nasal polyposis march: Eosinophilic asthma with radiological findings associated with blood eosinophilia.

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/mm3 (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.

Diagnosing persistent blood eosinophilia in asthma with single blood eosinophil or exhaled nitric oxide level.

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 × 109/L, or (2) ≥0.40 × 109/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 × 109/L) the cut-off value for a single measurement of blood eosinophils was 0.47 × 109/L. For definition 2 (≥0.40 × 109/L) the cut-off value was 0.49 × 109/L. Cut-off values for persistently low blood eosinophils were 0.17 × 109/L for definition (1) and 0.21 × 109/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.

Asthmatic adult with marked blood eosinophilia: is it truly asthma?

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.

First things first: Importance of eosinophil count in diagnosing occult parasites.

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.

Benralizumab efficacy by atopy status and serum immunoglobulin E for patients with severe, uncontrolled asthma.

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 ß2-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.

Drug-induced eosinophilic pneumonia: A review of 196 case reports.

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.

Chronic cough and an atypical pattern of peripheral pulmonary opacities: A case report secondary to suspected drug onset.

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 following artenimol-piperaquine exposure.

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.