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      Distribution of sputum cellular phenotype in a large asthma cohort: predicting factors for eosinophilic vs neutrophilic inflammation

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          Abstract

          Background

          Phenotyping asthma according to airway inflammation allows identification of responders to targeted therapy. Induced sputum is technically demanding. We aimed to identify predictors of sputum inflammatory phenotypes according to easily available clinical characteristics.

          Methods

          This retrospective study was conducted in 508 asthmatics with successful sputum induction recruited from the University Asthma Clinic of Liege. Receiver-operating characteristic (ROC) curve and multiple logistic regression analysis were used to assess the relationship between sputum eosinophil or neutrophil count and a set of covariates. Equations predicting sputum eosinophils and neutrophils were then validated in an independent group of asthmatics.

          Results

          Eosinophilic (≥3%) and neutrophilic (≥76%) airway inflammation were observed in 46% and 18% of patients respectively. Predictors of sputum eosinophilia ≥3% were high blood eosinophils, FE NO and IgE level and low FEV 1/FVC. The derived equation was validated with a Cohen’s kappa coefficient of 0.59 (p < 0.0001). ROC curves showed a cut-off value of 220/mm 3 (AUC = 0.79, p < 0.0001) or 3% (AUC = 0.81, p < 0.0001) for blood eosinophils to identify sputum eosinophilia ≥3%. Independent predictors of sputum neutrophilia were advanced age and high FRC but not blood neutrophil count.

          Conclusion

          Eosinophilic and paucigranulocytic asthma are the dominant inflammatory phenotypes. Blood eosinophils provide a practical alternative to predict sputum eosinophilia but sputum neutrophil count is poorly related to blood neutrophils.

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          Most cited references35

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          Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial.

          Treatment decisions in asthma are based on assessments of symptoms and simple measures of lung function, which do not relate closely to underlying eosinophilic airway inflammation. We aimed to assess whether a management strategy that minimises eosinophilic inflammation reduces asthma exacerbations compared with a standard management strategy. We recruited 74 patients with moderate to severe asthma from hospital clinics and randomly allocated them to management either by standard British Thoracic Society asthma guidelines (BTS management group) or by normalisation of the induced sputum eosinophil count and reduction of symptoms (sputum management group). We assessed patients nine times over 12 months. The results were used to manage those in the sputum management group, but were not disclosed in the BTS group. The primary outcomes were the number of severe exacerbations and control of eosinophilic inflammation, measured by induced sputum eosinophil count. Analyses were by intention to treat. The sputum eosinophil count was 63% (95% CI 24-100) lower over 12 months in the sputum management group than in the BTS management group (p=0.002). Patients in the sputum management group had significantly fewer severe asthma exacerbations than did patients in the BTS management group (35 vs 109; p=0.01) and significantly fewer patients were admitted to hospital with asthma (one vs six, p=0.047). The average daily dose of inhaled or oral corticosteroids did not differ between the two groups. A treatment strategy directed at normalisation of the induced sputum eosinophil count reduces asthma exacerbations and admissions without the need for additional anti-inflammatory treatment.
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            Mepolizumab for prednisone-dependent asthma with sputum eosinophilia.

            Eosinophilic inflammation, which may be a consequence of interleukin-5 action, is a characteristic feature of some forms of asthma. However, in three previous clinical trials involving patients with asthma, blockade of this cytokine did not result in a significant improvement in outcomes. We studied the prednisone-sparing effect of mepolizumab, a monoclonal antibody against interleukin-5, in a rare subgroup of patients who have sputum eosinophilia and airway symptoms despite continued treatment with prednisone. Secondary objectives were to examine its effect on the number of eosinophils in sputum and blood, symptoms, and airflow limitation. In this randomized, double-blind, parallel-group trial involving patients with persistent sputum eosinophilia and symptoms despite prednisone treatment, we assigned 9 patients to receive mepolizumab (administered in five monthly infusions of 750 mg each) and 11 patients to receive placebo. There were 12 asthma exacerbations in 10 patients who received placebo, 9 of whom had sputum eosinophilia at the time of exacerbation. In comparison, only one patient who received mepolizumab had an asthma exacerbation, and this episode was not associated with sputum eosinophilia (P=0.002). Patients who received mepolizumab were able to reduce their prednisone dose by a mean (+/-SD) of 83.8+/-33.4% of their maximum possible dose, as compared with 47.7+/-40.5% in the placebo group (P=0.04). The use of mepolizumab was associated with a significant decrease in the number of sputum and blood eosinophils. Improvements in eosinophil numbers, asthma control, and forced expiratory volume in 1 second were maintained for 8 weeks after the last infusion. There were no serious adverse events. Mepolizumab reduced the number of blood and sputum eosinophils and allowed prednisone sparing in patients who had asthma with sputum eosinophilia despite prednisone treatment. (ClinicalTrials.gov number, NCT00292877.) 2009 Massachusetts Medical Society
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              Development and validation of a questionnaire to measure asthma control.

              International guidelines on asthma management indicate that the primary goal of treatment should be optimum asthma control. The aim of this study was to develop and validate the Asthma Control Questionnaire (ACQ). The authors generated a list of all symptoms used to assess control and sent it to 100 asthma clinicians who were members of guidelines committees (18 countries). They scored each symptom for its importance in evaluating asthma control. From the 91 responses, the five highest scoring symptoms were selected for the ACQ. In addition, there is one question on beta2-agonist use and another on airway calibre (total questions=7). The ACQ was tested in a 9-week observational study of 50 adults with symptomatic asthma. The ACQ and other measures of asthma health status were assessed at baseline, 1, 5 and 9 weeks. In patients whose asthma was stable between clinic visits, reliability of the ACQ was high (intraclass correlation coefficient (ICC)=0.90). The questionnaire was very responsive to change in asthma control (p<0.0001). Cross-sectional and longitudinal validity were supported by correlations between the ACQ and other measures of asthma health status being close to a priori predictions. In conclusion, the Asthma Control Questionnaire has strong evaluative and discriminative properties and can be used with confidence to measure asthma control.
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                Author and article information

                Journal
                BMC Pulm Med
                BMC Pulm Med
                BMC Pulmonary Medicine
                BioMed Central
                1471-2466
                2013
                26 February 2013
                : 13
                : 11
                Affiliations
                [1 ]Department of Respiratory Medicine, CHU Sart-Tilman B35, Liege 4000, Belgium
                [2 ]Medical Informatics and Biostatistics, University of Liege, Liege, Belgium
                Article
                1471-2466-13-11
                10.1186/1471-2466-13-11
                3657295
                23442497
                66a7cb58-2677-4a1d-8a79-b994867e9636
                Copyright ©2013 Schleich et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 September 2012
                : 22 February 2013
                Categories
                Research Article

                Respiratory medicine
                asthma,induced sputum,eosinophil,neutrophil
                Respiratory medicine
                asthma, induced sputum, eosinophil, neutrophil

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