Sputum Eosinophil Counts Research Articles

Severe adult-onset asthma: A distinct phenotype

Some patients with adult-onset asthma have severe disease, whereas others have mild transient disease. It is currently unknown whether patients with severe adult-onset asthma represent a distinct clinical phenotype. We sought to investigate whether disease severity in patients with adult-onset asthma is associated with specific phenotypic characteristics. One hundred seventy-six patients with adult-onset asthma were recruited from 1 academic and 3 nonacademic outpatient clinics. Severe refractory asthma was defined according to international Innovative Medicines Initiative criteria, and mild-to-moderate persistent asthma was defined according to Global Initiative for Asthma criteria. Patients were characterized with respect to clinical, functional, and inflammatory parameters. Unpaired t tests and χ(2) tests were used for group comparisons; both univariate and multivariate logistic regression were used to determine factors associated with disease severity. Apart from the expected high symptom scores, poor quality of life, need for high-intensity treatment, low lung function, and high exacerbation rate, patients with severe adult-onset asthma were more often nonatopic (52% vs 34%, P = .02) and had more nasal symptoms and nasal polyposis (54% vs 27%, P ≤ .001), higher exhaled nitric oxide levels (38 vs 27 ppb, P = .02) and blood neutrophil counts (5.3 vs 4.0 10(9)/L, P ≤ .001) and sputum eosinophilia (11.8% vs 0.8%, P ≤ .001). Multiple logistic regression analysis showed that increased blood neutrophil (odds ratio, 10.9; P = .002) and sputum eosinophil (odds ratio, 1.5; P = .005) counts were independently associated with severe adult-onset disease. The majority of patients with severe adult-onset asthma are nonatopic and have persistent eosinophilic airway inflammation. This suggests that severe adult-onset asthma has a distinct underlying mechanism compared with milder disease.

FRI0345 Eosinophilic granulomatosis with polyangitis (EGPA): clinical presentation and long-term outcomes of different disease subsets

ObjectivesThe purpose of this single center study was to describe the epidemiologic, serological and clinical features and long term outcomes of patients who have been diagnosed with eosinophilic granulomatosis with...

Efficacy of Anti-Interleukin-5 Therapy with Mepolizumab in Patients with Asthma: A Meta-Analysis of Randomized Placebo-Controlled Trials

BackgroundInterleukin (IL)-5 is believed to be a key cytokine in eosinophil inflammatory infiltration in asthma. Previous clinical trials have evaluated the efficacy and safety of mepolizumab, a monoclonal antibody against IL-5, in patients with asthma. However, most of these studies were small, the conclusions were inconsistent, and the precise effects are therefore debatable.MethodsA meta-analysis of randomized placebo-controlled trials was conducted to evaluate the effect of intravenous infusion of mepolizumab on clinical outcomes in patients with asthma. Trials were searched in PubMed, Embase, Web of Science, Cochrane CENTRAL, Scopus, reviews, and reference lists of relevant articles. The outcome variables analyzed included eosinophil counts in blood and sputum, airways outcome measures, exacerbations, asthma control, and quality of life scores.ResultsSeven studies met final inclusion criteria (total n = 1131). From the pooled analyses, mepolizumab significantly reduced eosinophils in blood (MD −0.29×109/L, 95% CI −0.44 to −0.14×109/L, P = 0.0001) and sputum (MD −6.05%, 95% CI −9.34 to −2.77%, P = 0.0003). Mepolizumab was also associated with significantly decreased exacerbation risk than placebo (OR 0.30, 95%CI 0.13 to 0.67, P = 0.004), and with a significant improvement in the scores on the Asthma Quality of Life Questionnaire (AQLQ) (MD 0.26, 95% CI 0.03 to 0.49, P = 0.03) in patients with eosinophilic asthma. There were no statistical differences between the groups with respect to FEV1, PEF, or histamine PC20 (all P>0.05), and a non-significant trend for improvement in scores on the Juniper Asthma Control Questionnaire (JACQ) (MD −0.21, 95% CI −0.43 to 0.01, P = 0.06) in the mepolizumab group was observed.ConclusionsMepolizumab reduces the risk of exacerbations and improves quality of life in patients with eosinophilic asthma, but no significant improvement in lung function outcomes was observed. Further research is required to establish the possible role of anti–IL-5 as a therapy for asthma.

Year in review 2012: Asthma and chronic obstructive pulmonary disease

Year in review 2012: Asthma and chronic obstructive pulmonary disease

Association between Eosinophilic Airway Inflammation and Persistent Airflow Limitation

Objective. We aimed to evaluate the association between eosinophilic inflammation in induced sputum and pulmonary function and persistent airflow limitation in children. Methods. A total of 92 asthmatic children and 72 controls were enrolled in this study. Eosinophil count (%) and eosinophil cationic protein (ECP) levels were measured in induced sputum. We performed spirometry and a methacholine challenge test, and measured total eosinophil count, total serum IgE, and serum ECP in all subjects. Results. Asthmatic children had significantly higher levels of sputum eosinophils (9% vs. 0%; P < 0.001) and sputum ECP (2.3 ± 0.7 vs. 1.6 ± 0.6 log µg/L, p < .001) than controls. Sputum ECP levels showed a significant negative correlation with post-bronchodilator (post-BD) FEV1 (r = –0.307; p = .001) and post-BD FEV1/FVC (r = –0.286; p = .002), whereas sputum eosinophils showed no correlation with post-BD FEV1 and post-BD FEV1/FVC. However, no significant differences in sputum ECP and sputum eosinophil counts were observed in asthmatic children with and without persistent airflow limitation. Conclusions. Our findings suggest that sputum eosinophilic inflammation, especially ECP, is associated with pulmonary function and persistent airflow limitation, which is manifested by low post-BD FEV1/FVC.

When are biomarkers useful in the management of airway diseases?

Biomarkers are characteristics that are objectively measured and evaluated as indicators of biological or pathogenic processes, or responses to therapeutic interventions, and may provide information on the prognosis or progression of the disease and response to treatment. They are likely to be helpful in the management of airway diseases because of the heterogeneity of their pathobiology. Most biomarkers have been developed and evaluated to assess the airway inflammation (or bronchitis) associated with airway diseases. These include quantitative cell counts in sputum, fraction of nitric oxide in exhaled breath, and various metabolites in exhaled breath. This review provides a brief description of these biomarkers with a particular emphasis on how eosinophil and neutrophil counts in sputum could be used to manage airway diseases such as asthma, chronic obstructive pulmonary disease, and chronic cough.

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

BackgroundPhenotyping 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.MethodsThis 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.ResultsEosinophilic (≥3%) and neutrophilic (≥76%) airway inflammation were observed in 46% and 18% of patients respectively. Predictors of sputum eosinophilia ≥3% were high blood eosinophils, FENO and IgE level and low FEV1/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/mm3 (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.ConclusionEosinophilic 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.

Sample sizes for clinical trials using sputum eosinophils as a primary outcome

Clinical trials do not report sputum eosinophil data in a consistent method and this makes it difficult to compare across studies and to evaluate the sample sizes estimated in these studies. The objectives of the paper are: 1) to systematically review reporting of effect size and sample calculations in randomised controlled trials using sputum eosinophil count as a primary outcome and 2) to illustrate sample size estimation under different methods of data representation using data from an effective anti-eosinophil treatment strategy (mepolizumab). Randomised controlled trials in adults (excluding allergen provocation models) of treatment of asthma and chronic obstructive pulmonary disease for the past 10 years were searched in Ovid MEDLINE and 20 studies were identified that met all the inclusion criteria. Only nine studies discussed sample size calculation. Change from baseline was used as an outcome in 11 studies and was expressed as change in absolute percentage count, percentage change from baseline or as fold changes. Assuming a minimal clinically important reduction of 15% in absolute terms, 18 subjects in each arm will be required to achieve 80% power using an ANCOVA analysis, which we recommend, to detect significance with an alpha error of 0.05.

The 5‐lipoxygenase‐activating protein inhibitor, GSK2190915, attenuates the early and late responses to inhaled allergen in mild asthma

GSK2190915, a potent 5-lipoxygenase-activating protein inhibitor, prevents the synthesis of leukotrienes and 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE). To assess the effect of GSK2190915 on the allergen-induced asthmatic responses. Nineteen eligible male subjects with mild asthma were enrolled in and completed this four-centre, double-blind, two-way crossover study (ClinicalTrials.gov NCT00748306). Subjects took GSK2190915 100mg and placebo orally once daily for 5days in randomized order. On Day 1 and 4 they had a methacholine challenge, on Day 3 they had an inhaled allergen challenge, and on Days 4 and 6 they had sputum induction. GSK2190915 attenuated the early (0-2h) and late (4-10h) asthmatic responses to inhaled allergen compared with placebo. There was a statistically significant attenuation of the early asthmatic response (EAR) by GSK2190915; treatment difference of GSK2190915 vs. placebo for the minimum FEV(1) EAR was 0.408L (0.205, 0.611). There was a statistically significant attenuation of the late asthmatic response (LAR) by GSK2190915; the treatment difference of GSK2190915 vs. placebo for the minimum FEV(1) LAR was 0.229L (0.041, 0.417). There was a statistically significant attenuation of allergen-induced sputum eosinophil count on Day 4 following GSK2190915: mean treatment difference (95% CI) between GSK2190915 and placebo was -9.95% (-18.15%, -1.77%). Compared with placebo, GSK2190915 100mg reduced median sputum LTB(4) by >90% on Days 4 and 6. There was no effect on methacholine PC(20) post allergen. GSK2190915 was generally well tolerated. GSK2190915 shows potential as a treatment for patients with asthma.

Usefulness of induced sputum eosinophil count to assess severity and treatment outcome in asthma patients

Context:Currently treatment decisions in asthma are governed by clinical assessment and spirometry. Sputum eosinophil, being a marker of airway inflammation, can serve as a tool for assessing severity and response to treatment in asthma patients.Aims:To establish correlation between change in sputum eosinophil count and forced expiratory volume in one second (FEV1)% predicted value of asthma patients in response to treatment. In this study, we also predicted prognosis and treatment outcome of asthma patients from baseline sputum eosinophil count.Settings and Design:A longitudinal study was conducted to determine the treatment outcome among newly diagnosed asthma patients who were classified into A (n = 80) and B (n = 80) groups on the basis of initial sputum eosinophil count (A ≥ 3% and B < 3%).Materials and Methods:After starting treatment according to Global Initiative for Asthma Guideline, both A and B groups were evaluated every 15 days interval for the 1st month and monthly thereafter for a total duration of 12 months. In each follow-up visit detailed history, induced sputum eosinophil count and spirometry were done to evaluate severity and treatment outcome.Results:FEV1% predicted of group A asthma patients gradually increased and sputum eosinophil count gradually decreased on treatment. Longer time was required to achieve satisfactory improvement (FEV1% predicted) in asthma patients with sputum eosinophil count ≥3%. There was statistically significant negative correlation between FEV1% predicted and sputum eosinophil count (%) in of group A patients in each follow-up visit, with most significant negative correlation found in 8th visit (r = −0.9237 and P = < 0.001). Change in mean FEV1% (predicted) from baseline showed strong positive correlation (r = 0.976) with change in reduction of mean sputum eosinophil count at each follow-up visits in group A patients.Conclusions:Sputum eosinophil count, being an excellent biomarker of airway inflammation, can serve as a useful marker to assess disease severity, treatment outcome, and prognosis in asthma patients.

Biomarkers in Airway Diseases

The inherent limitations of spirometry and clinical history have prompted clinicians and scientists to search for surrogate markers of airway diseases. Although few biomarkers have been widely accepted into the clinical armamentarium, the authors explore three sources of biomarkers that have shown promise as indicators of disease severity and treatment response. In asthma, exhaled nitric oxide measurements can predict steroid responsiveness and sputum eosinophil counts have been used to titrate anti-inflammatory therapies. In chronic obstructive pulmonary disease, inflammatory plasma biomarkers, such as fibrinogen, club cell secretory protein-16 and surfactant protein D, can denote greater severity and predict the risk of exacerbations. While the multitude of disease phenotypes in respiratory medicine make biomarker development especially challenging, these three may soon play key roles in the diagnosis and management of airway diseases.

Update on Clinical Inflammometry for the Management of Airway Diseases

Airway inflammation is a central feature of many airway diseases such as asthma, chronic bronchitis, bronchiectasis and chronic cough; therefore, it is only logical that it is measured to optimize its treatment. However, most treatment recommendations, including the use of anti-inflammatory therapies such as corticosteroids, are based on assessments of only airflow and symptoms. Over the past 10 years, methods have been developed to assess airway inflammation relatively noninvasively. Quantitative cell counts in sputum and the fraction of exhaled nitric oxide are the most validated tests. Judicious use of currently available drugs, such as corticosteroids, bronchodilators and antibiotics, and other anti-inflammatory therapies guided by sputum eosinophil and neutrophil counts, have been demonstrated to decrease exacerbations of asthma and chronic obstructive pulmonary disease, ameliorate cough, improve quality of life in patients with these diseases and is cost effective compared with treatment strategies based on guidelines that do not incorporate these measurements. Thus, it is unfortunate that this is not used more widely in the management of airway diseases, particularly in patients with severe asthma and chronic obstructive pulmonary disease who experience frequent exacerbations.

La prise en charge de la crise d’asthme au service de pneumologie

Both smokers and patients with asthma can experience fixed airflow obstruction, which is associated with distinctive patterns of airway pathology. The influence of fixed airflow obstruction on the prognosis of these patients is unknown.We sought to investigate lung function decline and exacerbations in a 5-year prospective study of subjects with fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease (COPD). We also sought to explore correlations between functional, pathological, and clinical features.Patients with fixed airflow obstruction due to asthma (n = 16) or COPD (n = 21) and a control group of asthmatic patients with fully reversible airflow obstruction (n = 15) were followed for 5 years.The rates of decline in FEV1 were similar in patients with fixed airflow obstruction caused by asthma (−49.7 ± 10.6 mL/y) or COPD (−51.4 ± 9.8 mL/y) and were higher than in asthmatic patients with reversible airflow obstruction (−18.1 ± 10.1 mL/y, P < .01). Exacerbation rates were also higher in patients with fixed airflow obstruction caused by asthma (1.41 ± 0.26 per patient-year) or COPD (1.98 ± 0.3 per patient-year) compared with those seen in asthmatic patients with reversible airflow obstruction (0.53 ± 0.11 per patient-year, P < .01). Baseline exhaled nitric oxide levels and sputum eosinophil counts correlated with the FEV1 decline in asthmatic patients with fixed airflow obstruction. By contrast, baseline sputum neutrophil counts, emphysema scores, comorbidities, and exacerbation frequency correlated directly and pulmonary diffusion capacity correlated inversely with the FEV1 decline in patients with COPD.In both patients with asthma and those with COPD, fixed airflow obstruction is associated with increased lung function decline and frequency of exacerbations. Nevertheless, the decline in lung function entails the specific pathological and clinical features of the underlying diseases.

S78 Phenotypes of Induced Sputum in Difficult to Treat Asthma

Introduction and ObjectivesThe clinical value of repeated induced sputum tests to monitor airway inflammation in children with severe asthma is contentious. In adult patients with severe asthma a management based...

Clinical characteristics of eosinophilic and noneosinophilic asthma in children

Asthma is a heterogeneous and complex chronic inflammatory disease of the airways. Asthma can be classified as eosinophilic asthma (EA) or noneosinophilic asthma (NEA). We investigated whether children with EA manifest different clinical characteristics than those with NEA. We enrolled 288 steroid-naive asthmatic children and classified them, based on the cell counts in induced sputum, into EA (158 children) and NEA (89 children) groups. No significant differences were observed between the groups with regard to age, sex, family history of atopy, secondary smoking or asthma exacerbations. Moderate-to-severe asthma was more frequent in the EA group than in the NEA group. Blood eosinophil counts and serum eosinophil cationic protein were higher in EA patients than in NEA patients. The forced expiratory volume in 1 sec was lower in children with EA than in those with NEA (% of predicted value, 88.6 ± 18.5 vs. 93.6 ± 15.6, p < 0.05). The sputum eosinophil (in EA) and neutrophil (in NEA) counts increased with increasing asthma severity. Airway inflammation, especially eosinophilic inflammation, was associated with asthma severity and reduced pulmonary function in children.

Smoking influences response to inhaled corticosteroids in patients with asthma: a meta-analysis

Objective:To determine the effects of smoking on efficacy of inhaled corticosteroids in asthmatics.Research design and methods:Prospective/retrospective, controlled studies published up to May 2012 in smokers versus non-smokers with asthma using inhaled corticosteroids (ICSs) were retrieved from PubMed, Highwire and Embase databases.Main outcome measures:The primary outcomes were pulmonary function parameters [FEV1 (forced expiratory volume in 1 second), a.m. PEF (a.m. peak expiratory flow) and p.m. PEF (p.m. peak expiratory flow)]. Secondary outcomes included differential eosinophil counts in sputum and peripheral blood, asthma control questionnaire-5 (ACQ-5) and concomitant use of medication. Pooled SMDs (standardized mean differences) were estimated by using a random-effect model and a fixed-effect model based on between-study heterogeneity.Results:Of 242 studies identified, ten (N = 4070) met the inclusion criteria (seven of budesonide-based interventions, two of fluticasone and one unknown ICS trial). Both smokers and non-smokers were similar in age and baseline FEV1. Smoking yielded considerably reduced mean change in FEV1 [SMD = −0.197, 95% CI: (−0.327, −0.066), p = 0.003], morning PEF [SMD = −0.796, 95% CI: (−1.047, −0.545), p < 0.001], night-time PEF [SMD = −0.501, 95% CI: (−0.797, −0.204), p = 0.001] and post-treatment FEV1 [SMD = −0.178, 95% CI: (−0.309, −0.046), p = 0.008] and increased use of concomitant medications [SMD = 0.537, 95% CI: (0.166, 0.908), p = 0.005] in smokers, but not non-smokers with asthma, although there was no statistical difference in allergy-related endpoints and asthma score (ACQ-5).Conclusion:Smoking is associated with attenuated response to inhaled corticosteroids in asthmatics. This offers a rationale for persuasion of smoking cessation. Treatment outcomes might be improved by smoking cessation leading to improved lung function and ameliorated symptoms.

Drug Treatment of Eosinophilic Oesophagitis

Eosinophilic oesophagitis is a clinicopathological disease characterized by oesophageal eosinophilia and gastrointestinal symptoms. Currently, the optimal treatment regimens remain unclear. The pathogenesis of eosinophilic oesophagitis appears to involve immune dysregulation, while acid reflux may have a secondary role; the mainstays in treatment are aimed principally at these dual processes. While a trial of a PPI is worthwhile it is likely that PPI therapy is treating concurrent acid reflux rather than true eosinophilic oesophagitis. Dietary elimination with elemental feed is safe but poorly tolerated. Swallowed topical steroids are the mainstay of commercially available therapies. Both fluticasone and budesonide have been proven to be beneficial both symptomatically and in reducing oesophageal eosinophil counts in the short and medium term. Basic studies have determined a role for IL-5 in oesophageal remodelling in eosinophilic esophagitis. Initial clinical studies have shown single or multiple infusions of monoclonal antibody to IL-5 to be well tolerated and to cause a long-term decrease in both peripheral and sputum eosinophil count in these eosinophil driven conditions. At present, swallowed corticosteroids are the mainstay of treatment for patients with eosinophilic oesophagitis in patients failing PPI therapy. Studies have been heterogenous in their diagnostic criteria for eosinophilic oesophagitis and in the definition of response to therapy, making comparison of results difficult.

Galectin-10, a Potential Biomarker of Eosinophilic Airway Inflammation

Measurement of eosinophilic airway inflammation can assist in the diagnosis of allergic asthma and in the management of exacerbations, however its clinical implementation remains difficult. Galectin-10 has been associated with eosinophilic inflammation and has the potential to be used as a surrogate biomarker. This study aimed to assess the relationship between galectin-10 in sputum with sputum eosinophil counts, the current gold standard of eosinophil inflammation in the lung. Thirty-eight sputum samples were processed for both eosinophil counts by cytospins and semi-quantitative measurements of galectin-10 by western blots. A strong association was observed between galectin-10 levels in sputum and sputum eosinophil measurements, and they accurately determined sputum eosinophilia. The results support the potential for galectin-10 to be used as a surrogate biomarker of eosinophilic airway inflammation.

A cross-sectional study of patterns of airway dysfunction, symptoms and morbidity in primary care asthma

Most patients with asthma are managed exclusively in primary care. Little is known about the patterns of airway dysfunction in these patients and how these relate to other aspects of the disease. We set out to assess this in a cross-sectional study of 262 patients. Symptoms, spirometry, airway responsiveness, reversibility, and airway inflammation were all assessed. Exacerbations requiring oral corticosteroids in the preceding year were enumerated. Patients had heterogeneous patterns of airway dysfunction. Those with a post-bronchodilator forced expiratory volume in 1 sec/ forced vital capacity ratio of <0.7 had more exacerbations in the previous year (2.2 vs. 0.8; mean difference 1.4; 95% CI 0.4 to 2.4; p=0.007). Patients with normal results had less inflammation (proportion with a sputum eosinophil count of >1.9%, 20% vs. 48%, χ²=14.8, df=3; p<0.001) and fewer exacerbations (0.5 vs. 1.4; mean difference -0.9; 95% CI -1.4 to -0.4; p=0.001) but similar symptom scores (6.2 vs. 6.9; p=0.2) compared with patients with any abnormality. Patients with a diagnosis of asthma have mixed patterns of physiological impairment; many have no airflow obstruction or airway hyper-responsiveness. The physiological characterisation of asthma is not related to symptoms and is of little value in predicting exacerbations or eosinophilic airway inflammation.

A Mobile Phone Short Message Service Improves Perceived Control of Asthma: A Randomized Controlled Trial

Mobile phone short message service (SMS) has been suggested as a potentially powerful tool to improve asthma outcomes, and it can overcome external barriers such as time and distance to participate education programs. We wanted to know whether SMS can help to overcome intrinsic barriers such as perceived control of asthma (PCA). One hundred fifty outpatients with asthma were randomly assigned to the control, traditional, and SMS groups. Patients in all groups received verbal education based on the Global Initiative for Asthma, and patients in the traditional group received additional individualized asthma action plan for self-management with peak expiratory flow monitoring and recording asthma diary, while patients in the SMS group received additional daily SMS reminders on their mobile phone. The six-item PCA Questionnaire (PCAQ-6), Standard Asthma-Specific Quality of Life [AQLQ(S)], spirometry, blood and induced sputum cell count, follow-up compliance rate, medicine compliance rate, and emergency department (ED) visits data were collected at the initial visit and at 12 weeks. In total, 71 participants completed the trial for analysis. Patients' PCAQ-6 score was significantly increased in the SMS and traditional groups (p<0.001) after 12 weeks, and the change of patients' PCAQ-6 score in the SMS group was higher than in the traditional group (p=0.018). Patients in the SMS group had the highest AQLQ(S) score and follow-up rate after 12 weeks. The change in PCAQ-6 score was associated with change in AQLQ(S) score (r=0.442). Patients in all groups had better forced expiratory volume in 1 s (FEV1%) and fewer ED visits after 12 weeks, but no significant differences were found among the three groups in the changes of FEV1% and blood and induced sputum eosinophil counts and neutrophil counts. SMS can improve PCA, and it has a greater advantage in improving follow-up rate and asthma-specific quality of life than traditional programs.