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Real-Life Effectiveness of Mepolizumab on Forced Expiratory Flow between 25% and 75% of Forced Vital Capacity in Patients with Severe Eosinophilic Asthma.

ABSTRACT: Severe eosinophilic asthma (SEA) is associated with high peripheral blood and airway eosinophilia, recurrent disease exacerbations and severe airflow limitation. Eosinophilic inflammation is also responsible for small airway disease (SAD) development. SEA patients experience poor disease control and response to standard therapy and are prime candidates for anti-IL5 biologicals, such as mepolizumab, but the effect of treatment on SAD is unclear. We investigated the effect of mepolizumab on lung function in SEA patients, focusing on SAD parameters, and searched for an association between patients' phenotypic characteristics and changes in small airways function. In this real-life study, data from 105 patients with SEA were collected at baseline and after 6, 12 and 18 months of mepolizumab treatment. Along with expected improvements in clinical and lung function parameters brought by Mepolizumab treatment, FEF2525-75% values showed a highly significant, gradual and persistent increase (from 32.7 ± 18.2% at baseline to 48.6 ± 18.4% after 18 months) and correlated with ACT scores at 18 months (r = 0.566; p ≤ 0.0001). A patient subgroup analysis showed that changes in FEF25-75% values were higher in patients with a baseline peripheral blood eosinophil count ≥400 cells/μL and oral corticosteroid use. Mepolizumab significantly improves small airway function. This effect correlates with clinical benefits and may represent an accessible parameter through which to evaluate therapeutic response. This study provides novel insights into the phenotypic characteristics associated with the improved functional outcome provided by mepolizumab treatment.

SUBMITTER: Maglio A

PROVIDER: S-EPMC8615088 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe assumption that the assessment of forced expiratory flow between 25% and 75% of vital capacity (FEF(25-75)) does not provide additional information in asthmatic children with normal FEV(1) percent predicted has not been adequately tested.ObjectiveWe sought to determine whether the measurement of FEF(25-75) percent predicted offers advantages over FEV(1) percent predicted and FEV(1)/forced vital capacity (FVC) percent predicted for the evaluation of childhood asthma.MethodsThis is a secondary analysis of data from the Pediatric Asthma Controller Trial and the Characterizing the Response to a Leukotriene Receptor Antagonist and Inhaled Corticosteroid trials. Pearson correlation coefficients, Pearson partial correlation coefficients, canonical correlations, and receiver operating characteristic (ROC) curves were constructed.ResultsAmong 437 children with normal FEV(1) percent predicted, FEF(25-75) percent predicted, and FEV(1)/FVC percent predicted were (1) positively correlated with log(2) methacholine PC(20), (2) positively correlated with morning and evening peak expiratory flow percent predicted, and (3) negatively correlated with log(10) fraction of exhaled nitric oxide and bronchodilator responsiveness. Pearson partial correlations and canonical correlations indicated that FEF(25-75) percent predicted was better correlated with bronchodilator responsiveness and log(2) methacholine PC(20) than were FEV(1) percent predicted or FEV(1)/FVC percent predicted. In the ROC curve analysis, FEF(25-75) at 65% of predicted value had a 90% sensitivity and a 67% specificity for detecting a 20% increase in FEV(1) after albuterol inhalation.ConclusionFEF(25-75) percent predicted was well correlated with bronchodilator responsiveness in asthmatic children with normal FEV(1). FEF(25-75) percent predicted should be evaluated in clinical studies of asthma in children and might be of use in predicting the presence of clinically relevant reversible airflow obstruction.

Project description:ObjectivesThe aim of this study was to assess the prevalence and determinants of post-tuberculosis chronic respiratory signs, as well as the clinical impact of a low forced expiratory flow between 25% and 75% (FEF25-75%) in a group of individuals previously treated successfully for pulmonary tuberculosis.DesignThis was a cross-sectional study involving individuals in their post-tuberculosis treatment period. They all underwent a spirometry following the 2005 criteria of the American Thoracic Society/European Respiratory Society. Distal airflow obstruction (DAO) was defined by an FEF25-75% <65% and a ratio forced expiratory volume during the first second (FEV1)/forced vital capacity (FVC) ? 0.70. Logistic regression models were used to investigate the determinants of persisting respiratory symptoms following antituberculous treatment.SettingThis study was carried out in the tuberculosis diagnosis and treatment centre at Yaounde Jamot Hospital, which serves as a referral centre for tuberculosis and respiratory diseases for the capital city of Cameroon (Yaounde) and surrounding areas.ParticipantsAll consecutive patients in their post-tuberculosis treatment period were consecutively enrolled between November 2012 and April 2013.ResultsOf the 177 patients included, 101 (57.1%) were men, whose median age (25th-75th centiles) was 32 (24-45.5) years. At least one chronic respiratory sign was present in 110 (62.1%) participants and DAO was found in 67 (62.9%). Independent determinants of persisting respiratory signs were the duration of symptoms prior to tuberculosis diagnosis higher than 12?weeks (adjusted OR 2.91; 95% CI 1.12 to 7.60, p=0.029) and presence of DAO (2.22; 1.13 to 4.38, p=0.021).ConclusionsFEF25-75%<65% is useful for the assessment and diagnosis of post-tuberculous DAO. Mass education targeting early diagnosis of pulmonary tuberculosis can potentially reduce the prevalence of post-tuberculosis respiratory signs and distal airflow obstruction.

Project description:Exacerbations of asthma are associated with substantial morbidity and mortality and with considerable use of health care resources. Preventing exacerbations remains an important goal of therapy. There is evidence that eosinophilic inflammation of the airway is associated with the risk of exacerbations.We conducted a randomized, double-blind, placebo-controlled, parallel-group study of 61 subjects who had refractory eosinophilic asthma and a history of recurrent severe exacerbations. Subjects received infusions of either mepolizumab, an anti-interleukin-5 monoclonal antibody (29 subjects), or placebo (32) at monthly intervals for 1 year. The primary outcome measure was the number of severe exacerbations per subject during the 50-week treatment phase. Secondary outcomes included a change in asthma symptoms, scores on the Asthma Quality of Life Questionnaire (AQLQ, in which scores range from 1 to 7, with lower values indicating more severe impairment and a change of 0.5 unit considered to be clinically important), forced expiratory volume in 1 second (FEV(1)) after use of a bronchodilator, airway hyperresponsiveness, and eosinophil counts in the blood and sputum.Mepolizumab was associated with significantly fewer severe exacerbations than placebo over the course of 50 weeks (2.0 vs. 3.4 mean exacerbations per subject; relative risk, 0.57; 95% confidence interval [CI], 0.32 to 0.92; P=0.02) and with a significant improvement in the score on the AQLQ (mean increase from baseline, 0.55 vs. 0.19; mean difference between groups, 0.35; 95% CI, 0.08 to 0.62; P=0.02). Mepolizumab significantly lowered eosinophil counts in the blood (P<0.001) and sputum (P=0.002). There were no significant differences between the groups with respect to symptoms, FEV(1) after bronchodilator use, or airway hyperresponsiveness. The only serious adverse events reported were hospitalizations for acute severe asthma.Mepolizumab therapy reduces exacerbations and improves AQLQ scores in patients with refractory eosinophilic asthma. The results of our study suggest that eosinophils have a role as important effector cells in the pathogenesis of severe exacerbations of asthma in this patient population. (Current Controlled Trials number, ISRCTN75169762.)

Project description:Rationale: The American Thoracic Society (ATS)/European Respiratory Society defines a positive bronchodilator response (BDR) by a composite of BDR in either forced expiratory volume in 1 second (FEV1) and/or forced vital capacity (FVC) greater than or equal to 12% and 200 ml (ATS-BDR). We hypothesized that ATS-BDR components would be differentially associated with important chronic obstructive pulmonary disease (COPD) outcomes. Objectives: To examine whether ATS-BDR components are differentially associated with clinical, functional, and radiographic features in COPD. Methods: We included subjects with COPD enrolled in the COPDGene study. In the main analysis, we excluded subjects with self-reported asthma. We categorized BDR into the following: 1) No-BDR, no BDR in either FEV1 or FVC; 2) FEV1-BDR, BDR in FEV1 but no BDR in FVC; 3) FVC-BDR, BDR in FVC but no BDR in FEV1; and 4) Combined-BDR, BDR in both FEV1 and FVC. We constructed multivariable logistic, linear, zero-inflated negative binomial, and Cox hazards models to examine the association of BDR categories with symptoms, computed tomography findings, change in FEV1 over time, respiratory exacerbations, and mortality. We also created models using the ATS BDR definition (ATS-BDR) as the main independent variable. Results: Of 3,340 COPD subjects included in the analysis, 1,083 (32.43%) had ATS-BDR, 182 (5.45%) had FEV1-BDR, 522 (15.63%) had FVC-BDR, and 379 (11.34%) had Combined-BDR. All BDR categories were associated with FEV1 decline compared with No-BDR. Compared with No-BDR, both ATS-BDR and Combined-BDR were associated with higher functional residual capacity %predicted, greater internal perimeter of 10 mm, and greater 6-minute-walk distance. In contrast to ATS-BDR, Combined-BDR was independently associated with less emphysema (adjusted beta regression coefficient, -1.67; 95% confidence interval [CI], -2.68 to -0.65; P = 0.001), more frequent respiratory exacerbations (incidence rate ratio, 1.25; 95% CI, 1.03-1.50; P = 0.02) and severe exacerbations (incidence rate ratio, 1.34; 95% CI, 1.05-1.71; P = 0.02), and lower mortality (adjusted hazards ratio, 0.76; 95% CI, 0.58-0.99; P = 0.046). Sensitivity analysis that included subjects with self-reported history of asthma showed similar findings. Conclusions: BDR in both FEV1 and FVC indicates a COPD phenotype with asthma-like characteristics, and provides clinically more meaningful information than current definitions of BDR.

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Real-Life Effectiveness of Mepolizumab on Forced Expiratory Flow between 25% and 75% of Forced Vital Capacity in Patients with Severe Eosinophilic Asthma.

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