Asthma exacerbations and eosinophil counts. A randomised controlled trial

Institute for Lung Health, Department of Respiratory Medicine and Thoracic Surgery, Glenfield Hospital, LE3 9PQ, Leicester, UK.
The Lancet (Impact Factor: 45.22). 12/2002; 360(9347):1715-21. DOI: 10.1016/S0140-6736(02)11679-5
Source: PubMed


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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    • "Altogether there is a need to model the relationships of the dynamic changes in blood cell counts and the morphological changes in CXR, as clinical outcome for treatment and follow up of asthma in primary care clinic. The reasons for modeling this relationship are that many general physician offices and primary clinics may have an automated CBC system which is tremendously less expensive, easy to operate and able to generate self-explanatory comprehensive CBC report [21] [12] [11] [29] [38] [20], from which the morphological changes in CXR can be easily predicted. Shwachman–Kulczycki (S–K) rating score was first implemented as a quantitative score for the assessments of the morphological changes in CXR of cystic fibrosis [45] [5] [13]. "
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    ABSTRACT: The purpose of the present study was to rate the level of spread of asthma-induced bronchial morphological changes on chest X-ray (CXR), using the modified Shwachman–Kulczycki (S–K) rating scale as predicted by the dynamic of blood cell count (CBC). A sample of 40 asthma patients’ records was classified into 4 groups based on their clinical presentations and frequency of their visits to the hospital; Group-1 ⩽2 visits per week with reversible symptoms, Group-2 ⩾2 visits per week with irreversible symptoms, Group-3: ⩾3–4 visits per week with irreversible symptoms; Group-4: patients with severe shortness of breath in whom SaO2 was threatening, hence were admitted as inpatients. Patients’ CXR were scored based on the modified Shwachman–Kulczycki (S–K) scale rating. Blood analysis showed that RBC and their indices (HCT, HGB, MCH, RDW) were highest in group-2. White blood cells and their derivatives (NEU, EOS and LYM) were highest in group 4. CXR for group-2 showed bilateral increased bronchovascular markings but normal both lung fields and ruled out for costo-phrenic angles type of fever. Chest X-ray for group-3 showed hyperinflation, perihilar marking associated with bronchial thickening and unfolding aorta. In patients in group-4 development of broncho-pneumonic infiltration type of SOB and some evidence of bronchial edema with significant (p < 0.05) elevation in WBC were observed. The regression of S–K score on the dynamic of some CBC parameters was significant (p < 0.05). The best subsets that describe the model were:
    Full-text · Article · Feb 2015
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    • "Sputum and blood eosinophils can also be increased in patients presenting to the ED with rapid onset of asthma symptoms [10]. Treatment strategies focusing on reducing sputum eosinophils have led to a reduction in the number and severity of asthma exacerbations [6] [11] [12]. Benralizumab is an investigational humanized monoclonal antibody (mAb) that binds to the α chain of the interleukin 5 (IL-5) receptor, which is expressed on eosinophils and basophils and produces apoptosis via antibody-dependent cellular cytotoxicity. "
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    ABSTRACT: Patients with frequent asthma exacerbations resulting in emergency department (ED) visits are at increased risk for future exacerbations. We examined the ability of 1 dose of benralizumab, an investigational antiinterleukin 5 receptor α monoclonal antibody, to reduce recurrence after acute asthma exacerbations. In this randomized, double-blind, placebo-controlled study, eligible subjects presented to the ED with an asthma exacerbation, had partial response to treatment, and greater than or equal to 1 additional exacerbation within the previous year. Subjects received 1 intravenous infusion of placebo (n = 38) or benralizumab (0.3 mg/kg, n = 36 or 1.0 mg/kg, n = 36) added to outpatient management. The primary outcome was the proportion of subjects with greater than or equal to 1 exacerbation at 12 weeks in placebo vs the combined benralizumab groups. Other outcomes included the time-weighted rate of exacerbations at week 12, adverse events, blood eosinophil counts, asthma symptom changes, and health care resource utilization. The proportion of subjects with greater than or equal to 1 asthma exacerbation at 12 weeks was not different between placebo and the combined benralizumab groups (38.9% vs 33.3%; P = .67). However, compared with placebo, benralizumab reduced asthma exacerbation rates by 49% (3.59 vs 1.82; P = .01) and exacerbations resulting in hospitalization by 60% (1.62 vs 0.65; P = .02) in the combined groups. Benralizumab reduced blood eosinophil counts but did not affect other outcomes, while demonstrating an acceptable safety profile. When added to usual care, 1 dose of benralizumab reduced the rate and severity of exacerbations experienced over 12 weeks by subjects who presented to the ED with acute asthma. Copyright © 2014 Elsevier Inc. All rights reserved.
    Full-text · Article · Oct 2014 · American Journal of Emergency Medicine
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    • "Importantly, in this management approach, the presence of inflammatory cells in the airways does not diagnose asthma or COPD, but their measurement can be useful for clinical assessment in guiding treatment decisions and in long-term monitoring. High quality evidence from many well-designed clinical trials109–111 and a systematic review112 report the superior effects of targeting airway eosinophilic inflammation on exacerbation reduction in both asthma and COPD. Airway inflammation in both asthma and COPD is heterogeneous, with four different airway inflammatory phenotypes having been described (Figure 1): "
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    ABSTRACT: Adult-onset asthma and chronic obstructive pulmonary disease (COPD) are major public health burdens. This review presents a comprehensive synopsis of their epidemiology, pathophysiology, and clinical presentations; describes how they can be distinguished; and considers both established and proposed new approaches to their management. Both adult-onset asthma and COPD are complex diseases arising from gene-environment interactions. Early life exposures such as childhood infections, smoke, obesity, and allergy influence adult-onset asthma. While the established environmental risk factors for COPD are adult tobacco and biomass smoke, there is emerging evidence that some childhood exposures such as maternal smoking and infections may cause COPD. Asthma has been characterized predominantly by Type 2 helper T cell (Th2) cytokine-mediated eosinophilic airway inflammation associated with airway hyperresponsiveness. In established COPD, the inflammatory cell infiltrate in small airways comprises predominantly neutrophils and cytotoxic T cells (CD8 positive lymphocytes). Parenchymal destruction (emphysema) in COPD is associated with loss of lung tissue elasticity, and small airways collapse during exhalation. The precise definition of chronic airflow limitation is affected by age; a fixed cut-off of forced expiratory volume in 1 second/forced vital capacity leads to overdiagnosis of COPD in the elderly. Traditional approaches to distinguishing between asthma and COPD have highlighted age of onset, variability of symptoms, reversibility of airflow limitation, and atopy. Each of these is associated with error due to overlap and convergence of clinical characteristics. The management of chronic stable asthma and COPD is similarly convergent. New approaches to the management of obstructive airway diseases in adults have been proposed based on inflammometry and also multidimensional assessment, which focuses on the four domains of the airways, comorbidity, self-management, and risk factors. Short-acting beta-agonists provide effective symptom relief in airway diseases. Inhalers combining a long-acting beta-agonist and corticosteroid are now widely used for both asthma and COPD. Written action plans are a cornerstone of asthma management although evidence for self-management in COPD is less compelling. The current management of chronic asthma in adults is based on achieving and maintaining control through step-up and step-down approaches, but further trials of back-titration in COPD are required before a similar approach can be endorsed. Long-acting inhaled anticholinergic medications are particularly useful in COPD. Other distinctive features of management include pulmonary rehabilitation, home oxygen, and end of life care.
    Full-text · Article · Sep 2014 · International Journal of COPD
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