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1.
Respir Res ; 24(1): 235, 2023 Sep 28.
Article in English | MEDLINE | ID: mdl-37770889

ABSTRACT

BACKGROUND: The ORBE II study aimed to describe the characteristics and clinical outcomes of adult patients with severe eosinophilic asthma (SEA) treated with benralizumab in a real-world setting in Spain. METHODS: ORBE II (NCT04648839) was an observational, retrospective cohort study in adult SEA patients who had been prescribed benralizumab. Demographic and clinical data of 204 SEA patients were collected 12 months prior to benralizumab initiation (baseline) and at follow-up. Exacerbation rate, asthma symptoms, maintenance oral corticosteroid (OCS) use and lung function were evaluated, among other variables. RESULTS: A total of 204 SEA patients were evaluated. Mean (standard deviation, SD) age of the study population was 56.4 (12.4) years, 62.3% were women and mean (SD) duration of asthma was 15.1 (12.7) years. Median (Q1-Q3) follow-up duration was 19.5 (14.2-24.2) months. At baseline, 72.6% of the overall population (OP) presented blood eosinophil counts ≥ 300 cells/µL; 36.8% had comorbid chronic rhinosinusitis with nasal polyps (CRSwNP); 84.8% reported at least one severe exacerbation, and 29.1% were OCS-dependent. At 1 year of follow-up, patients receiving benralizumab treatment had a 85.6% mean reduction in exacerbations from baseline, and 81.4% of patients achieved zero exacerbations. We also found a clinically relevant mean (SD) increase in pre-bronchodilator (BD) FEV1 of 331 (413) mL, with 66.7% of patients achieving a pre-BD FEV1 increase ≥ 100 mL, and 46.3% of patients achieving a pre-BD FEV1 ≥ 80% of predicted. Regarding symptom control, 73.8% of the OP obtained an ACT score ≥ 20 points. After 1 year of follow-up, mean reduction in the daily OCS dose was 70.5%, and complete OCS withdrawal was achieved by 52.8% of the OCS-dependent patients. Almost half (43.7%) of the OP on benralizumab met all four criteria for clinical remission. Patients with concomitant CRSwNP obtained similar or enhanced outcomes. CONCLUSIONS: These data support the real-world benefits of benralizumab in SEA patients, and particularly in those with concomitant CRSwNP. TRIAL REGISTRATION: NCT04648839.


Subject(s)
Anti-Asthmatic Agents , Asthma , Pulmonary Eosinophilia , Sinusitis , Adult , Humans , Female , Middle Aged , Male , Anti-Asthmatic Agents/adverse effects , Retrospective Studies , Disease Progression , Asthma/diagnosis , Asthma/drug therapy , Asthma/epidemiology , Pulmonary Eosinophilia/diagnosis , Pulmonary Eosinophilia/drug therapy , Pulmonary Eosinophilia/epidemiology , Chronic Disease , Adrenal Cortex Hormones/therapeutic use , Sinusitis/complications
2.
J Allergy Clin Immunol Pract ; 11(9): 2724-2731.e2, 2023 09.
Article in English | MEDLINE | ID: mdl-37295671

ABSTRACT

BACKGROUND: Bronchiectasis is a common comorbidity in patients with asthma and is associated with increased disease severity. In patients with severe eosinophilic asthma, biologics targeting IL-5/5Ra have beneficial effects on oral corticosteroid (OCS) use and exacerbation frequency. However, how coexisting bronchiectasis affects the response to such treatments is unknown. OBJECTIVE: To evaluate the real-world effectiveness of anti-IL-5/5Ra therapy in patients with severe eosinophilic asthma and comorbid bronchiectasis on exacerbation frequency and daily maintenance and cumulative OCS dose. METHODS: This real-world study evaluated data from 97 adults with severe eosinophilic asthma and computed tomography-confirmed bronchiectasis from the Dutch Severe Asthma Registry, who initiated anti-IL5/5Ra biologics (mepolizumab, reslizumab, and benralizumab) and had follow-up data for 12 months or greater. The analysis was performed for the total population and subgroups with or without maintenance OCS use. RESULTS: Anti-IL-5/5Ra therapy significantly reduced exacerbation frequency in patients with maintenance OCS use as well as in those without it. In the year before biologic initiation, 74.5% of all patients had two or more exacerbations, which decreased to 22.1% in the follow-up year (P < .001). The proportion of patients on maintenance OCS decreased from 47% to 30% (P < .001), and in the OCS-dependent patients (n = 45) maintenance OCS dose decreased from median (interquartile range) of 10.0 mg/d (5-15 mg/d) to 2.5 mg/d (0-5 mg/d) after 1 year (P < .001). CONCLUSIONS: This real-world study shows that anti-IL-5/5Ra therapy reduces exacerbation frequency and daily maintenance as well as the cumulative OCS dose in patients with severe eosinophilic asthma and comorbid bronchiectasis. Although it is an exclusion criterion in phase 3 trials, comorbid bronchiectasis should not preclude anti-IL-5/5Ra therapy in patients with severe eosinophilic asthma.


Subject(s)
Anti-Asthmatic Agents , Asthma , Biological Products , Bronchiectasis , Pulmonary Eosinophilia , Adult , Humans , Anti-Asthmatic Agents/therapeutic use , Asthma/drug therapy , Asthma/epidemiology , Biological Products/therapeutic use , Bronchiectasis/drug therapy , Bronchiectasis/epidemiology , Comorbidity , Ethnicity , Pulmonary Eosinophilia/drug therapy , Pulmonary Eosinophilia/epidemiology
3.
Respir Investig ; 61(3): 314-320, 2023 May.
Article in English | MEDLINE | ID: mdl-36868080

ABSTRACT

BACKGROUND: Validating the information recorded in administrative databases is essential. However, no study has comprehensively validated the accuracy of Japanese Diagnosis Procedure Combination (DPC) data on various respiratory diseases. Therefore, this study aimed to evaluate the validity of diagnoses of respiratory diseases in the DPC database. METHODS: We conducted chart reviews of 400 patients hospitalized in the departments of respiratory medicine in two acute-care hospitals in Tokyo, between April 1, 2019 and March 31, 2021, and used them as reference standards. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of DPC data on 25 respiratory diseases were determined. RESULTS: Sensitivity ranged from 22.2% (aspiration pneumonia) to 100% (chronic eosinophilic pneumonia and malignant pleural mesothelioma) and was <50% for eight diseases, while specificity was >90% for all diseases. PPV ranged from 40.0% (aspiration pneumonia) to 100% (coronavirus disease 2019, bronchiectasis, chronic eosinophilic pneumonia, pulmonary hypertension, squamous cell carcinoma, small cell carcinoma, lung cancer of other histological types, and malignant pleural mesothelioma) and was >80% for 16 diseases. Except for chronic obstructive pulmonary disease (82.9%) and interstitial pneumonia (other than idiopathic pulmonary fibrosis) (85.4%), NPV was >90% for all diseases. These validity indices were similar in both hospitals. CONCLUSIONS: The validity of diagnoses of respiratory diseases in the DPC database was high in general, thereby providing an important basis for future studies.


Subject(s)
Databases, Factual , Respiratory Tract Diseases , Humans , COVID-19/diagnosis , COVID-19/epidemiology , Databases, Factual/standards , Databases, Factual/statistics & numerical data , East Asian People/statistics & numerical data , Lung Neoplasms/diagnosis , Lung Neoplasms/epidemiology , Mesothelioma, Malignant/diagnosis , Mesothelioma, Malignant/epidemiology , Pneumonia, Aspiration/diagnosis , Pneumonia, Aspiration/epidemiology , Pulmonary Eosinophilia/diagnosis , Pulmonary Eosinophilia/epidemiology , Respiration Disorders/diagnosis , Respiration Disorders/epidemiology , Japan/epidemiology , Reproducibility of Results , Sensitivity and Specificity , Respiratory Tract Diseases/diagnosis , Respiratory Tract Diseases/epidemiology
4.
J Allergy Clin Immunol Pract ; 11(3): 885-895.e13, 2023 03.
Article in English | MEDLINE | ID: mdl-36572182

ABSTRACT

BACKGROUND: Comorbidities in severe asthma are common and contribute to disease burden. The severe asthma phenotype and treatment response can be impacted by comorbid conditions. Real-world data on the use of mepolizumab in severe eosinophilic asthma (SEA) in the presence of comorbidities are needed to inform clinical practice. OBJECTIVE: To investigate the impact of comorbid conditions on baseline phenotype in patients with SEA and assess the mepolizumab treatment effect by comorbidity status in SEA. METHODS: Patients enrolled in the Australian Mepolizumab Registry (n = 309) were classified into subgroups defined by the presence or absence of comorbidities, including nasal polyps, aspirin-exacerbated airway disease, asthma-chronic obstructive pulmonary disease overlap (ACO), fungal sensitization, and obesity. Patient baseline characteristics were compared, and the impacts of comorbidity on phenotype, identified by differences in patient age and/or baseline biomarker levels and/or asthma severity, were assessed. The mepolizumab treatment effects on clinical and biological outcomes at 12 months were assessed. RESULTS: Across comorbidity subgroups, mepolizumab reduced the rate of clinically significant exacerbations (range: 47%-77%), maintenance oral corticosteroid use (dose reduction: 4.2-13.3 mg/d), and improved symptom control (Asthma Control Questionnaire-5 score: 1.9-2.4 point reduction) and lung function (mean: 3.4-9.3 post-bronchodilator percent predicted forced expiratory volume in 1 second). Peripheral blood eosinophils were reduced (mean: 480-780 cells/µL). Comorbidities (nasal polyps, obesity, ACO, and fungal sensitization) modified the baseline phenotype. CONCLUSIONS: Mepolizumab treatment is associated with comparable clinical improvements in patients with SEA and comorbidities. Mepolizumab effectively minimizes the disease impact and corticosteroid burden in patients with SEA.


Subject(s)
Anti-Asthmatic Agents , Asthma , Nasal Polyps , Pulmonary Eosinophilia , Humans , Anti-Asthmatic Agents/therapeutic use , Nasal Polyps/drug therapy , Nasal Polyps/epidemiology , Australia/epidemiology , Asthma/drug therapy , Asthma/epidemiology , Asthma/diagnosis , Pulmonary Eosinophilia/drug therapy , Pulmonary Eosinophilia/epidemiology , Comorbidity , Phenotype , Treatment Outcome , Adrenal Cortex Hormones/therapeutic use , Obesity/drug therapy
6.
BMC Pulm Med ; 22(1): 67, 2022 Feb 17.
Article in English | MEDLINE | ID: mdl-35177038

ABSTRACT

BACKGROUND: Eosinophilia is a significant factor in asthma severity; however, the prevalence of severe eosinophilic asthma in Saudi Arabia is largely unknown. We aimed to determine the prevalence of the eosinophilic (defined in this study as ≥ 300 cells/mm3 in blood), atopic (atopic phenotype 1, defined in this study as > 100 IU/mL total serum IgE; atopic phenotype 2, defined in this study as > 150 IU/mL), and overlap phenotypes among patients with severe asthma in Saudi Arabia. METHODS: A cross-sectional study was conducted in centers specialized in severe asthma management. Patients aged ≥ 12 years with severe asthma were enrolled. Study patients responded to the Global Initiative for Asthma 2018 assessment of asthma control questionnaire and provided study investigators with current information related to the study objectives. Additional medical record data and a blood sample for total serum IgE and complete blood count were collected. RESULTS: A total of 101 patients were enrolled; 83% were female and the mean (standard deviation) age was 48.7 (13.2) years. Forty-five (45%) patients had the eosinophilic phenotype, 50 (50%) had atopic phenotype 1, and 25 (25%) had phenotypic overlap (eosinophilic and atopic 1). Forty-one (41%) patients had atopic phenotype 2 and 23 (23%) had phenotypic overlap (eosinophilic and atopic 2). Asthma control and oral corticosteroid use patterns were similar and there were no significant differences in number of asthma exacerbations across phenotypes. CONCLUSIONS: In Saudi Arabia, 45% of patients with severe asthma had the eosinophilic phenotype, which is most likely an underestimation as no clinical features of eosinophilia were taken into account in the definition of eosinophilia. Approximately half of them had phenotypic overlap with the atopic phenotype. Trial registration NCT03931954; ClinicalTrials.gov, April 30, 2019.


Subject(s)
Asthma/complications , Hypersensitivity, Immediate/complications , Phenotype , Pulmonary Eosinophilia/complications , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Asthma/drug therapy , Asthma/epidemiology , Cross-Sectional Studies , Female , Humans , Hypersensitivity, Immediate/epidemiology , Male , Middle Aged , Prevalence , Pulmonary Eosinophilia/epidemiology , Saudi Arabia/epidemiology , Severity of Illness Index
8.
Clin Respir J ; 16(1): 35-42, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34610651

ABSTRACT

INTRODUCTION: Chronic eosinophilic pneumonia (CEP) is a rare disease with unknown etiology. Due to lack of specificity of CEP symptoms, clinicians are not experienced in establishing its diagnosis. OBJECTIVES: To summarize the clinical data of CEP patients to improve the understanding of CEP and reduce misdiagnosis. METHODS: Data of patients pathologically diagnosed with CEP in the PLA General Hospital between May 2013 and May 2019 were collected, and clinical manifestations, imaging characteristics, pathological features, and treatment were retrospectively analyzed. RESULTS: Twenty patients, including 6 males and 14 females, were diagnosed with CEP. The average age was 47.0 ± 10.2 years. The main clinical manifestations were cough and dyspnea. The average duration of CEP was 15.5 ± 11.5 months. The average proportion of eosinophils in the peripheral blood was 18.9 ± 17.8%, and the average proportion of eosinophils in the bronchoalveolar lavage fluid was 41.5 ± 19.4%. The main imaging features were patchy shadows and consolidation shadows. The most common manifestations on bronchoscopic examination were congestion and edema of the bronchial mucosa. Two patients had granular protrusions of the endotracheal membrane. Histological examination indicated infiltration of numerous eosinophils. All patients improved after prednisone therapy. CONCLUSION: CEP onset is insidious, and clinical manifestations lack specificity. Typical imaging features are peripheral and subpleural distribution of lung infiltrates. Some patients have a normal proportion of eosinophils in the peripheral blood, but most have an increased number of eosinophils in the BALF, which contributes to CEP diagnosis. A biopsy is necessary when differential diagnosis is difficult. A systemic glucocorticoid is effective.


Subject(s)
Pulmonary Eosinophilia , Adult , Bronchoalveolar Lavage Fluid , China/epidemiology , Chronic Disease , Eosinophils , Female , Humans , Male , Middle Aged , Pulmonary Eosinophilia/diagnosis , Pulmonary Eosinophilia/drug therapy , Pulmonary Eosinophilia/epidemiology , Retrospective Studies , Tertiary Care Centers
9.
Int Arch Allergy Immunol ; 181(8): 613-617, 2020.
Article in English | MEDLINE | ID: mdl-32570256

ABSTRACT

INTRODUCTION: Mepolizumab is a monoclonal antibody against IL-5 for the treatment of severe eosinophilic asthma. The aim of the current study was to present a predesigned interim analysis of the data of patients who have completed 1 year of therapy with mepolizumab. METHODS: This study is a prospective multicenter, noninterventional 2-year observational study and aims to describe the clinical benefit and safety profile of mepolizumab in patients with severe eosinophilic asthma. RESULTS: Compared to the year preceding the initiation of treatment, the annual rate of exacerbations decreased significantly, from 4.3 ± 2.3 to 1.3 ± 1.8; p < 0.0001. Forty-two patients received maintenance dose of oral corticosteroids (OCS) at baseline. From these patients at the end of 1 year of therapy with mepolizumab, 17 patients (40%) had achieved OCS discontinuation. A reduction in the median dose of OCS was also achieved. After 1 year of treatment with mepolizumab, the asthma control test score significantly increased from 16.3 ± 3.7 to 21.2 ± 3.8 (p < 0.0001). This marked clinical improvement was paralleled by a significant reduction of blood eosinophil count. All patients showed a considerable improvement of airflow limitation. In respect to adverse events of treatment with mepolizumab, 19 patients (27%) were recorded to have at least one such occurrence during their 1-year treatment. CONCLUSIONS: We have shown that in patients with severe eosinophilic asthma, 1 year of treatment with mepolizumab was safe, resulted in significant reduction of the annual exacerbation rate, reduction (or even discontinuation) of the needed dose of OCS, and improvements of asthma control and lung function.


Subject(s)
Allergy and Immunology , Anti-Asthmatic Agents/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Asthma/drug therapy , Hospitals, Special , Pulmonary Eosinophilia/drug therapy , Adrenal Cortex Hormones/therapeutic use , Aged , Asthma/epidemiology , Disease Progression , Female , Follow-Up Studies , Greece/epidemiology , Humans , Male , Middle Aged , Prospective Studies , Pulmonary Eosinophilia/epidemiology , Respiratory Function Tests , Treatment Outcome
10.
Lung ; 198(2): 355-360, 2020 04.
Article in English | MEDLINE | ID: mdl-32052155

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal, Humanized , Eosinophils , Interleukin-5/antagonists & inhibitors , Pulmonary Eosinophilia , Adrenal Cortex Hormones/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Belgium/epidemiology , Female , Humans , Immunologic Factors/administration & dosage , Immunologic Factors/adverse effects , Leukocyte Count , Male , Middle Aged , Pulmonary Eosinophilia/blood , Pulmonary Eosinophilia/diagnosis , Pulmonary Eosinophilia/diagnostic imaging , Pulmonary Eosinophilia/drug therapy , Pulmonary Eosinophilia/epidemiology , Pulmonary Eosinophilia/pathology , Retrospective Studies , Secondary Prevention/methods , Tomography, X-Ray Computed/methods , Treatment Outcome
11.
Rev Mal Respir ; 37(1): 34-44, 2020 Jan.
Article in French | MEDLINE | ID: mdl-31862136

ABSTRACT

Illicit psychoactive substance (IPAS) use can lead to a number of respiratory complications, including acute eosinophilic pneumonia (AEP). Systematic literature review of data on AEP in IPAS users (cannabis, cocaine, heroin and amphetamine). Of two cases of cannabis and tobacco users reported to have developed AEP, one, a teenage15 year old boy presented with acute respiratory distress syndrome (ARSD) which necessitated extracorporeal membrane oxygenation (ECMO). Five cases of AEP in cocaine smokers (crack) are reported, one of which was fatal. The patient presented with acute pulmonary edema and ARDS which progressed to ventricular fibrillation and asystole. A 24-year-old woman presented with AEP after repeated inhalation of heroin. Finally, a case of an amphetamine abuser who developed AEP and ARDS after amphetamine inhalation is reported. The time between the first IPAS use and admission in cases reported ranged from 7 days to 4 years, while time between the last IPAS use and admission was short (less than 15 days). IPAS use must be sought in case of AEP, especially in young adults, and practitioners must advise and help users to stop their consumption.


Subject(s)
Illicit Drugs/toxicity , Psychotropic Drugs/toxicity , Pulmonary Eosinophilia/chemically induced , Acute Disease , Adolescent , Adult , Female , Humans , Male , Pulmonary Eosinophilia/diagnosis , Pulmonary Eosinophilia/epidemiology , Substance-Related Disorders/complications , Substance-Related Disorders/diagnosis , Substance-Related Disorders/epidemiology , Young Adult
12.
Respir Res ; 20(1): 169, 2019 Jul 30.
Article in English | MEDLINE | ID: mdl-31362741

ABSTRACT

BACKGROUND: We assessed the efficacy of the licensed mepolizumab dose (100 mg subcutaneously [SC]) in patients with severe eosinophilic asthma according to body weight/body mass index (BMI). METHODS: This was a post hoc individual patient-level meta-analysis of data from the Phase 3 studies MENSA (MEA115588/NCT01691521) and MUSCA (200862/NCT02281318). Patients aged ≥12 years with severe eosinophilic asthma and a history of exacerbations were randomised to 4-weekly placebo, mepolizumab 75 mg intravenously (IV) or 100 mg SC (MENSA) or placebo or mepolizumab 100 mg SC (MUSCA) for 32 (MENSA) or 24 (MUSCA) weeks. The primary endpoint was the annual rate of clinically significant exacerbations; other outcomes included the proportion of patients with no exacerbations, lung function, St George's Respiratory Questionnaire (SGRQ) and Asthma Control Questionnaire-5 (ACQ-5) scores and blood eosinophil counts. Analyses were performed by baseline body weight and BMI (≤60, > 60-75, > 75-90, > 90, < 100, ≥100 kg; ≤25, > 25-30, > 30, < 36, ≥36 kg/m2). RESULTS: Overall, 936 patients received placebo or mepolizumab 100 mg SC. Across all body weight/BMI categories, mepolizumab reduced the rate of clinically significant exacerbations by 49-70% versus placebo. Improvements with mepolizumab versus placebo were also seen in lung function in all body weight/BMI categories except > 90 kg; improvements in SGRQ and ACQ-5 scores were seen across all categories. CONCLUSIONS: Mepolizumab 100 mg SC has consistent clinical benefits in patients with severe eosinophilic asthma across a range of body weights and BMIs. Data show that the fixed-dose regimen of mepolizumab is suitable, without the need for weight-based dosing. TRIAL REGISTRATION: This manuscript is a post hoc meta-analysis of data from the Phase 3 studies MENSA and MUSCA. ClinicalTrials.gov, NCT01691521 (MEA115588; MENSA). Registered September 24, 2012. ClinicalTrials.gov, NCT02281318 (200862; MUSCA). Registered November 3, 2014.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Asthma/drug therapy , Body Mass Index , Body Weight/drug effects , Pulmonary Eosinophilia/drug therapy , Severity of Illness Index , Adult , Aged , Antibodies, Monoclonal, Humanized/pharmacology , Asthma/diagnosis , Asthma/epidemiology , Body Weight/physiology , Female , Humans , Male , Middle Aged , Pulmonary Eosinophilia/diagnosis , Pulmonary Eosinophilia/epidemiology
13.
Allergol Int ; 68(4): 413-419, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31253537

ABSTRACT

Eosinophilic pneumonia (EP) is a rare disorder, comprising several heterogeneous diseases. Two major types of EP are acute eosinophilic pneumonia (AEP) and chronic eosinophilic pneumonia (CEP), both of which are characterized by marked accumulation of eosinophils in lung tissues and/or BAL fluid. AEP and CEP share some similarities in terms of pathophysiology, radiological findings, and treatment response to corticosteroids. However, they distinctly differ in etiology, clinical manifestations, and the nature of disease course. Especially, although AEP and CEP respond well to corticosteroids, relapse frequently occurs in patients with CEP, but rarely in those with AEP. Although CEP occasionally persists and becomes corticosteroid dependent, most patients with AEP completely recover. This article reviews previous studies and discusses the etiology, clinical manifestations, and treatment of AEP and CEP.


Subject(s)
Pulmonary Eosinophilia/diagnosis , Pulmonary Eosinophilia/etiology , Pulmonary Eosinophilia/therapy , Acute Disease , Adolescent , Adult , Chronic Disease , Diagnostic Imaging/methods , Disease Management , Disease Susceptibility , Humans , Phenotype , Pulmonary Eosinophilia/epidemiology , Young Adult
14.
J Asthma ; 56(11): 1147-1158, 2019 11.
Article in English | MEDLINE | ID: mdl-30822174

ABSTRACT

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.


Subject(s)
Anti-Asthmatic Agents/therapeutic use , Asthma/economics , Asthma/epidemiology , Cost of Illness , Pulmonary Eosinophilia/epidemiology , Adolescent , Adult , Age Distribution , Analysis of Variance , Asthma/blood , Asthma/drug therapy , Cohort Studies , Databases, Factual , Disease Management , Disease Progression , Eosinophils/immunology , Female , Health Care Costs , Hospitals, University , Humans , Japan/epidemiology , Leukocyte Count , Male , Middle Aged , Multivariate Analysis , Prevalence , Pulmonary Eosinophilia/blood , Pulmonary Eosinophilia/drug therapy , Respiratory Function Tests , Retrospective Studies , Risk Assessment , Severity of Illness Index , Sex Distribution , Young Adult
15.
J Allergy Clin Immunol Pract ; 7(2): 589-596.e3, 2019 02.
Article in English | MEDLINE | ID: mdl-30193936

ABSTRACT

BACKGROUND: An estimated 7% of patients with asthma have chronic rhinosinusitis with nasal polyps (CRSwNP), and more than 80% have at least some radiographic evidence of sinonasal inflammation. Aspirin sensitivity is strongly associated with elevated blood eosinophil levels and increased asthma severity. Intravenous (IV) reslizumab has been shown to improve asthma control in patients with nasal polyps. OBJECTIVE: These post hoc analyses of pooled data from 2 BREATH phase 3 clinical trials, studies 1 and 2 (NCT01287039 and NCT01285323), examined asthma-related outcomes in patients with comorbid, self-reported CRSwNP with and without aspirin sensitivity. METHODS: Patients aged 12-75 years with elevated blood eosinophils (≥400 cells/µL) and inadequately controlled asthma were randomized to receive placebo or reslizumab (3 mg/kg IV) every 4 weeks for 52 weeks. Patients continued their background asthma maintenance therapy during the study. Information regarding the presence of CRSwNP was obtained through patient-reported medical history. RESULTS: Add-on reslizumab treatment reduced the frequency of clinical asthma exacerbations by 83% versus placebo among patients with CRSwNP. Among patients with and without aspirin sensitivity, reductions of 79% and 84%, respectively, were observed. Patients with CRSwNP (with and without aspirin sensitivity) treated with reslizumab add-on therapy also had significant improvements in lung function, as measured by forced expiratory volume in 1 second, compared with placebo. Among patients with CRSwNP, reslizumab was also associated with improvements in patient-reported asthma control and asthma quality of life. CONCLUSIONS: Patients with eosinophilic asthma and self-reported CRSwNP, with and without aspirin sensitivity, are highly responsive to treatment with reslizumab for asthma-related outcomes. These findings suggest that prospective investigation of reslizumab in this patient population is warranted.


Subject(s)
Anti-Asthmatic Agents/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Asthma/drug therapy , Nasal Polyps/drug therapy , Pulmonary Eosinophilia/drug therapy , Rhinitis/drug therapy , Sinusitis/drug therapy , Adolescent , Adult , Aged , Anti-Inflammatory Agents, Non-Steroidal , Aspirin , Asthma/epidemiology , Asthma/immunology , Child , Chronic Disease , Comorbidity , Eosinophils/immunology , Female , Humans , Male , Middle Aged , Nasal Polyps/epidemiology , Nasal Polyps/immunology , Pulmonary Eosinophilia/epidemiology , Pulmonary Eosinophilia/immunology , Rhinitis/epidemiology , Rhinitis/immunology , Self Report , Sinusitis/epidemiology , Sinusitis/immunology , Treatment Outcome , Young Adult
16.
Tuberk Toraks ; 67(4): 292-299, 2019 Dec.
Article in English | MEDLINE | ID: mdl-32050871

ABSTRACT

The current understanding in severe asthma management is the targeted therapy approach with the evaluation of phenotypes and biomarkers. Therefore, personalized treatments are recently more prominent. Eosinophilic asthma with chronic rhinosinusitis/nasal polyps (CRSwNP) is one of the severe asthma phenotypes which needs a personalized treatment approach. Biological agents which specifically target type 2 (T2) high inflammation have been used in this severe asthma phenotype with a preferable safety profile. In the present review, biological agents in eosinophilic asthma with CRSwNP will be discussed.


Subject(s)
Asthma/epidemiology , Nasal Polyps/epidemiology , Pulmonary Eosinophilia/epidemiology , Rhinitis/epidemiology , Sinusitis/epidemiology , Biological Factors , Biomarkers , Chronic Disease , Humans , Inflammation/epidemiology , Male
17.
Therapie ; 73(6): 473-482, 2018 Dec.
Article in English | MEDLINE | ID: mdl-29789133

ABSTRACT

INTRODUCTION: Eosinophilic pneumonia (EP) is a rare but serious adverse drug reaction (ADR) induced by non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: We describe the second published case of EP induced by oral diclofenac. We also reviewed the literature as well as French pharmacovigilance database. Case presentation A 63 year-old woman with polyarthralgia had taken diclofenac for three days for analgesic purposes. Progressively, the patient presented weakness, dyspnea and fever. Computed tomography (CT) scan revealed bilateral interstitial infiltration. Broncho-alveolar lavage (BAL) showed an elevated level of eosinophils. After ruling out all other possible etiologies, drug-induced EP was diagnosed and treatment by corticosteroid was initiated. The patient recovered in three months. RESULTS: In the French pharmacovigilance database, six cases of EP were recorded (3 with naproxen, 2 with ibuprofen, 1 with piroxicam). In the literature, twenty-six cases of EP with NSAIDs were published. The most commonly involved drug was naproxen (n=8), followed by fenbufen (n=4), ibuprofen (n=3) and diclofenac (n=2). A high level of eosinophils was systematically observed in the blood cell count or BAL. Corticosteroid therapy was started in eleven cases. All patients recovered. CONCLUSION: Complete history taking and examination should be done to rule out other etiological diagnoses. BAL is sufficient to diagnose EP. Corticosteroid therapy should be indicated for more severe or refractory cases. This adverse drug reaction is underestimated, healthcare professionals should be informed.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Arthralgia/drug therapy , Diclofenac/adverse effects , Pulmonary Eosinophilia/chemically induced , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Diclofenac/therapeutic use , Female , Humans , Middle Aged , Pharmacovigilance , Prevalence , Pulmonary Eosinophilia/diagnosis , Pulmonary Eosinophilia/epidemiology , Risk Factors
18.
Respir Med ; 137: 123-128, 2018 04.
Article in English | MEDLINE | ID: mdl-29605194

ABSTRACT

RATIONALE: Acute eosinophilic pneumonia (AEP) is a rare but important cause of severe respiratory failure most typically caused by cigarette smoking, but can also be caused by medications, illicit drugs, infections and environmental exposures. There is growing evidence that disease severity varies and not all patients require mechanical ventilation or even supplemental oxygen. OBJECTIVES: To compare patients with AEP treated at Landstuhl Regional Medical Center (LRMC) to those in other published series, and to provide recommendations regarding diagnosis and treatment of AEP. METHODS: A retrospective chart review was completed on forty-three cases of AEP which were identified from March 2003 through March 2010 at LRMC, Germany. RESULTS: Tobacco smoking was reported by 91% of our patients. Only 33% of patients in our series had a fever (temperature > 100.4 °F) at presentation. Peripheral eosinophilia (>5%) was present in 35% on initial CBC, but was seen in 72% of patients during their hospital course. Hypoxemia, as measured by PaO2/FiO2 ratio, seemed to be less severe in patients with higher levels of bronchoalveolar (BAL) eosinophilia percentage. CONCLUSIONS: Based on our experience and literature review, we recommend adjustments to the diagnostic criteria which may increase consideration of this etiology for acute respiratory illnesses as well as provide clinical clues we have found particularly helpful. Similar to recent reports of initial peripheral eosinophilia correlating with less severe presentation we found that higher BAL eosinophilia correlated with less severe hypoxemia.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Military Personnel/statistics & numerical data , Pulmonary Eosinophilia/epidemiology , Respiration, Artificial/methods , Acute Disease , Adrenal Cortex Hormones/administration & dosage , Adult , Bronchoalveolar Lavage Fluid/immunology , Bronchoscopy/instrumentation , Eosinophilia/diagnosis , Eosinophilia/metabolism , Female , Germany , Humans , Hypoxia/physiopathology , Male , Middle Aged , Pulmonary Eosinophilia/diagnostic imaging , Pulmonary Eosinophilia/therapy , Respiration, Artificial/statistics & numerical data , Respiratory Insufficiency/etiology , Retrospective Studies , Severity of Illness Index , Tobacco Smoking/epidemiology , United States/epidemiology
19.
Clin Toxicol (Phila) ; 56(6): 442-445, 2018 06.
Article in English | MEDLINE | ID: mdl-29129117

ABSTRACT

Over the past decade, smoking behaviors have changed in the US. Hookah or waterpipe smoking is increasing, especially among youth and young adults. Social media sites describe the "hookah high" or "buzz", which may be related to nicotine, carbon monoxide, or other inhalants in hookah smoke. Most important is the risk of carbon monoxide poisoning. Case reports include a high number of victims presenting with loss of consciousness from either syncope or seizures. Anaphylaxis and a very rare respiratory hypersensitivity reaction, acute eosinophilic pneumonia, have also been reported from hookah smoking in previously healthy young adults. This article provides background information on hookah smoking, describes hookah-induced acute injuries that could precipitate poison center calls, and offers suggestions for exposure characterization.


Subject(s)
Poison Control Centers/statistics & numerical data , Water Pipe Smoking/adverse effects , Carbon Monoxide Poisoning/epidemiology , Carbon Monoxide Poisoning/etiology , Humans , Pulmonary Eosinophilia/epidemiology , Pulmonary Eosinophilia/etiology , Water Pipe Smoking/epidemiology , Young Adult
20.
Ann Allergy Asthma Immunol ; 119(5): 422-428.e2, 2017 11.
Article in English | MEDLINE | ID: mdl-28942952

ABSTRACT

BACKGROUND: Chronic eosinophilic pneumonia (CEP) is characterized by the accumulation of eosinophils in the lung with unknown etiology. Although systemic corticosteroid administration leads to dramatic improvement, nearly half the patients with CEP experience relapse and some develop persistent impairment of pulmonary function. However, predictive factors for this persistent impairment have not been determined. OBJECTIVE: To investigate the occurrence of persistent impairment of pulmonary function in CEP and determine its predictive factors. METHODS: This observational study consisted of 133 consecutive patients with CEP who were followed for longer than 1 year. Spirometry was performed at the time of diagnosis and at follow-up. RESULTS: During the observational period (6.1 ± 4.1 years), relapse occurred in 75 patients (56.4%). Remarkably, 42 patients (31.6%) had a persistent pulmonary function defect (27 obstructive, 10 restrictive, and 4 obstructive and restrictive cases) at the last evaluation. Logistic analyses showed that the relapse was associated with neither persistent obstructive nor restrictive defects. Persistent obstructive defect was significantly associated with the comorbidity of asthma and obstructive defect at the initial CEP diagnosis, whereas persistent restrictive defect was significantly related to reticulation at high-resolution computer tomography and restrictive defect at diagnosis. CONCLUSION: Persistent impairment of pulmonary function is common in CEP. Concurrent asthma and obstructive defects at diagnosis were predictors for persistent obstructive impairments, whereas reticulation at high-resolution computer tomography and restrictive defect at diagnosis predicted persistent restrictive impairment. Attention should be paid to these persistent impairments in the management of CEP. TRIAL REGISTRATION: http://www.umin.ac.jp/ctr/index-j.htm Identifier: UMIN000019092 (principal investigator, Takafumi Suda, MD, PhD).


Subject(s)
Asthma/epidemiology , Eosinophils/immunology , Lung/physiology , Pulmonary Eosinophilia/diagnosis , Adult , Aged , Aged, 80 and over , Chronic Disease , Comorbidity , Female , Glucocorticoids/therapeutic use , Humans , Japan/epidemiology , Longitudinal Studies , Male , Middle Aged , Prednisolone/therapeutic use , Prognosis , Pulmonary Eosinophilia/drug therapy , Pulmonary Eosinophilia/epidemiology , Recurrence , Spirometry , Young Adult
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