Airway inflammation in asthma and perennial allergic rhinitis. Relationship with nonspecific bronchial responsiveness and maximal airway narrowing (original) (raw)
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Journal of Allergy and Clinical Immunology, 1997
Airway eosinophilic inflammation is a characteristic feature of asthma. This can be assessed directly by measurement of eosinophils and eosinophilic cationic protein (ECP) in sputum or indirectly by measurement of the same markers in blood. We investigated the performance of these markers of airway eosinophilic inflammation in a population of patients with asthma compared with control subjects and the extent to which the markers differed. In a cross-sectional study, subject characteristics were documented on day 1 and induced sputum and blood samples were obtained on day 2. Nineteen patients with asthma and 20 control subjects (10 healthy subjects and 10 smokers with nonobstructive bronchitis) were consecutively enrolled in the study. Sputum (selected from saliva) and blood samples were processed by persons blind to the clinical details. Results are presented as median values (minimum-maximum); differences were measured by Mann-Whitney U test. The accuracy of the tests (sensitivity and specificity) was measured by plotting the data in receiver-operating characteristic (ROC) curves and comparing the areas under the curve for each marker. Patients with asthma in comparison with control subjects had a higher proportion of sputum eosinophils (5.2% [0.2% to 93%] vs 0.3% [0% to 1.7%], p < 0.001), higher numbers of blood eosinophils (350.0 x 10(6)/L [144.0 to 1520.0 x 10(6)/L] vs 155.0 x 10(6)/L [34.0 to 426.0 x 10(6)/L], p = 0.003), and higher levels of ECP in sputum (1040.0 micrograms/L [76.8 to 32,000.0 micrograms/L] vs 455.3 micrograms/L [54.4 to 1280.0 micrograms/L], p = 0.001) but not in serum (25.0 micrograms/L [5.6 to 52.4 micrograms/L] vs 16.5 micrograms/L [3.3 to 36.0 micrograms/L], p = 0.08). Markers of airway inflammation in induced sputum and blood samples were correlated with clinical and physiologic variables. The area under the ROC curve showed that eosinophils in sputum (0.90) are significantly more accurate markers than blood eosinophils (0.72) and serum ECP (0.67) (p = 0.02). Although the area under the ROC curve for sputum ECP was greater than those for blood eosinophils and serum ECP, the differences could have occurred by chance (p > or = 0.1). We conclude that the proportion of eosinophils in sputum is a more accurate marker of asthmatic airway inflammation than the proportions of blood eosinophils or serum ECP.
Clinical & Experimental Allergy, 2014
Background Sputum eosinophil counts and eosinophil cationic protein (ECP) levels are usually increased in asthmatic patients. The correlation between sputum eosinophils or ECP and clinical findings of asthma has been previously investigated but many of these studies have been performed on small samples of asthmatic patients, considering only few clinical indices and often including patients on oral or inhaled corticosteroids, which might be confounding when interpreting the relationship between disease activity and airway inflammation. Objective To assess whether sputum eosinophils and ECP were differently related to functional and clinical parameters of asthma in a large number of steroid-na€ ıve asthmatic patients, taking into account several potential determinants of activity and chronicity of asthma. Methods One hundred and twenty-nine patients with mild-moderate asthma were studied. Sputum was induced by hypertonic saline inhalation and processed using the whole sample method. Results Sputum eosinophils and ECP significantly correlated with each other (r = 0.41, P < 0.001). When patients were grouped on the basis of high/low sputum eosinophils and high/low sputum ECP levels, significant differences were observed among groups, with patients with high sputum eosinophils and ECP showing the greatest asthma severity. In the overall sample, disease duration inversely correlated with sputum eosinophils, whereas FEV 1 and peak expiratory flow (PEF) inversely correlated with sputum ECP. Rescue b 2-agonist use and total symptom score positively correlated with both eosinophil counts and sputum ECP. Stepwise regression analysis showed that symptom score and disease duration accounted for 17.6% of sputum eosinophil variance, whereas symptom score and FEV 1 accounted for 14.7% of sputum ECP variance. Conclusions and Clinical Relevance Both sputum eosinophils and ECP are weakly related to clinical markers of asthma severity. However, ECP was more closely related to lung function parameters than eosinophil counts.
Comparison between eosinophilic markers in induced sputum and blood in asthmatic patients
Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy, 1998
Background The usefulness and safety of the analysis of blood inflammatory markers in asthma are widely recognized. Recently, the analysis of induced sputum has been proposed as a safe, non-invasive tool in the study of airway inflammation in asthma. Objective Our aim was to test whether sputum analysis is more useful than blood analysis in the evaluation of airway inflammation in untreated and treated asthmatic patients. Methods Twelve untreated patients with mild to moderate asthma underwent a methacholine challenge test, sputum induction and blood sampling. A group of 14 normal subjects was also evaluated for baseline comparison. The same evaluation was repeated after 3 months of budesonide treatment. Before and after treatment, we tested the relationship of eosinophilic markers in induced sputum and blood with clinical and functional data. We also compared eosinophilic markers in induced sputum with the same markers in blood. Results Untreated patients showed a significant relationship between sputum eosinophils and symptom score, and between sputum eosinophilic cationic protein and symptom score, FEV 1 and PD 20 FEV 1. No relationship between blood eosinophilic markers and clinical or functional data was observed. In budesonide-treated patients, both sputum and blood eosinophils were significantly lower than in untreated patients, but eosinophil decrease was greater in sputum than in blood. Sputum eosinophilic proteins were also significantly lower in treated patients, whereas serum eosinophilic proteins were low at baseline and remained unchanged after treatment. Sputum eosinophilic markers were lower in normal subjects than in both untreated and treated patients, while blood eosinophils, but not serum eosinophilic cationic protein, were lower in normals than in untreated patients. Conclusions The analysis of induced sputum is more useful than the analysis of blood in the evaluation of asthma severity and of the effect of glucocorticoid treatment in patients with mild to moderate asthma.
Induced sputum is a reproducible method to assess airway inflammation in asthma
Mediators of Inflammation, 2002
To evaluate the reproducibility of induced sputum analysis, and to estimate the sample size required to obtained reliable results, sputum was induced by hypertonic saline inhalation in 29 asthmatic subjects on two different days. The whole sample method was used for analysis, and inflammatory cells were counted on cytospin slides. Reproducibility, expressed by intra-class correlation coefficients, was good for macrophages (+0.80), neutrophils (+0.85), and eosinophils (+0.87), but not for lymphocytes (+0.15). Detectable differences were 5.5% for macrophages, 0.6% for lymphocytes, 5.2% for neutrophils, and 3.0% for eosinophils. We conclude that analysis of induced sputum is a reproducible method to study airway inflammation in asthma. Sample sizes greater than ours give little improvement in the detectable difference of eosinophil percentages.
Induced sputum to assess airway inflammation: a study of reproducibility
Clinical & Experimental Allergy, 1997
Background Infiltration of the airways mucosa with activated inflammatory cells appears to be a major factor in the pathogenesis of asthma and other airway diseases. Examination of sputum provides a direct method to investigate airway inflammation non-invasively. Objectives The aim of the present study was to evaluate the reproducibility of cell counts on cytospins and fluid phase (eosinophil cationic protein, ECP) measurements in a selected portion of induced sputum. We aimed to confirm the validity of the tecnique by comparing measurements between stable asthmatics, allergic rhinithis and healthy subjects. Methods Sputum was induced with hypertonic saline (4.5%) twice within one week in 53 stable asthmatics, 16 subjects with seasonal rhinitis {out of the pollen season), and 19 healthy subjects. Reproducibility was examined within sample (two different plugs of the same sample) between sample (two specimens of induced sputum obtained within one week) and between examiners on stable subjects taking into account sample size, number of examinations per patients and Confidence Interval (CI) of the estimates. Results We have found that the method is highly reproducible within sample and between examiners for all types of cells and fluid phase measurements of ECP. It is reproducible between sample for eosinophils, macrophages, neutrophils and ECP, but not for lymphocytes and weakly for epithelial cells. Sputum from asthmatics, in comparison with the sputum of healthy subjects and subjects with rhinitis had higher eosinophils (asthmatics: 12.2% ±12.9, rhinitis: 0.4 ± 0.8, normals: 0.4±0.7(%) and ECP (asthmatics: 827 ± 491 figfL, rhinitis: 127 ± 82 normals: 157 ± 203). No significant differences were found between healthy subjects and subjects with rhinitis. Eosinophil counts were inversely correlated with F^V, {r=-0.37) expressed as percentage of predicted, but not significantly correlated with PC20 methacholine {r=-0.28) or blood eosinophils (r-0.26). Conclusions The importance of this study is the confirmation, within important statistical guidelines for a study of reproducibility, that the methods examined are reproducible and valid.
Evaluation of correlation between airway and serum inflammatory markers in asthmatic patients
Lung India, 2012
Context: Asthma is one of the most common chronic diseases all over the world, resulting from a state of persistent sub-acute inflammation of the airways. Beside local inflammation, systemic inflammation is also present, which can be shown by increased levels of C-reactive protein (CRP). One of the most important cells in this disease is eosinophil, and sputum eosinophilia is used for its diagnosis. Aims: The purpose of the present study was to compare and evaluate the correlation between CRP level and sputum eosinophilia in asthmatic and control subjects. Materials and Methods: A total of 61 patients suffering from mild-to-moderate asthma participated in this study. They were divided into two groups based on whether they used inhaled steroid or not. Sputum was induced by ultrasonic nebulizer, and then samples of peripheral venous blood were collected to measure peripheral cell count and CRP by Enzyme-linked immunosorbent assay (ELISA). Thirty-seven healthy subjects were selected and their blood samples were taken. Thirty-seven healthy subjects were selected and their blood samples were taken. Results: Thirty asthmatic patients in user group (14 females/16 males) with the mean age of 39.4±9.37 years, 31 asthmatic patients in non-user group (13 females/18 males) with the mean age of 35.5±8.87 years, and 37 healthy controls (17 females/20 males) were included in our study. The mean serum concentration of CRP was 2.6 mg/mL, 3.32 mg/mL, and 1.16 mg/mL in user, non-user, and control groups, respectively. Compared to healthy controls, serum concentrations of high sensitivity-CRP (hs-CRP) significantly increased in the non-user group (P=0.0001), and user group as well. (P=0.016). The number of sputum eosinophils and peripheral blood eosinophils significantly increased in the non-users compared to the healthy controls (P=0.0001, P=0.003, respectively). In the non-user group, serum hs-CRP levels correlated negatively with FEV 1 and positively with numbers of sputum eosinophils, which was not statistically significant. Atopy status, age, and sex did not affect hs-CRP levels in both asthmatic groups. Conclusions: It was found that serum concentrations of hs-CRP significantly increased in asthmatic patients, and in the steroid-native group it partly correlated with FEV 1 and numbers of sputum eosinophils. It suggests that serum hs-CRP can indirectly indicate the degree of airway inflammation.
European Respiratory Journal, 1996
i in nf fl la am mm ma at ti io on n i in n i in nd du uc ce ed d s sp pu ut tu um m f fr ro om m p pa at ti ie en nt ts s w wi it th h a as st th hm ma a ABSTRACT: Sputum induced by inhalation of nebulized hypertonic saline is increasingly used to monitor airways inflammation in asthma. The aim of this study was to assess the repeatability of measuring cellular and soluble markers of inflammation in whole sputum samples as obtained by sputum induction in patients both with mild and moderate-to-severe asthma.
Disconnect between sputum neutrophils and other measures of airway inflammation in asthma
European Respiratory Journal, 2014
Asthma heterogeneity has been described by the nature and intensity of granulocytic infiltration into the airways [1, 2]. Sputum, endobronchial biopsies and bronchoalveolar lavage (BAL) sample different anatomical regions of the airways. Few studies have directly compared the inflammatory cell infiltrates in these regions within a large cohort of moderate-severe asthma patients using standard techniques.