Blood Eosinophil Cell Count Research Articles

The Potential of Fractional Exhaled Nitric Oxide as a Biomarker in Predicting and Optimizing Use of Treatment in Asthma

Asthma affects the respiratory system and causes airway inflammation. The indication of asthma includes a triad of airway inflammation, hyperresponsiveness, and obstruction. Nitric Oxide (NO) is a gas that is exhaled and is a sign of airway inflammation. NO levels in the exhaled breath of patients with type 2 asthma are elevated, and fractional exhaled nitric oxide (FeNO) is an objective biomarker of airway inflammation. Measurements of FeNO are noninvasive, require minimal patient effort, and are easy to collect in clinical settings. The current review is a systematic review performed using PubMed, Science Direct, and Google Scholar according to The Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol (PRISMA-P) guidelines. This review discusses the entanglement of understanding FeNO measurement and supplementing existing diagnostic and assessment tools for inflammatory lung diseases. Monitoring FeNO can also help identify different asthma phenotypes within the asthma syndrome and suggest the optimal administration of inhaled corticosteroids (ICS) as elevated FeNO levels indicate ICS response. Non-adherence to ICS is a significant contributor to the failure of asthma treatment. A FeNO suppression test can be done to determine non-adherence. FeNO levels should be used with a careful history, conventional spirometric testing with bronchodilator reversibility, measures of bronchial hyperreactivity using methacholine, and other measures of eosinophilic inflammation, such as a peripheral blood eosinophil cell count. FeNO is more sensitive and specific when paired with other lung function tests.

Corticosteroid Responsiveness Following Mepolizumab in Severe Eosinophilic Asthma—A Randomized, Placebo-Controlled Crossover Trial (MAPLE)

Mepolizumab inhibits IL-5 activity and reducesexacerbation frequency and maintenance oral corticosteroid (OCS) dosage in patients with severe eosinophilic asthma(SEA). Some patients remain dependent on OCS despite anti-IL-5 treatment, suggesting residual corticosteroid-responsive mechanisms. To determine the clinical and anti-inflammatory effects of OCS in patients with SEA on mepolizumab. We conducted a randomized, triple-blind, placebo-controlled crossover trial of prednisolone (0.5 mg/kg/d, maximum 40 mg/d, for 14 ± 2 days) in adults with SEA after 12 or more weeks of mepolizumab. We compared change in asthma symptoms, quality of life, lung function measured by spirometry and airwave oscillometry, fractional exhaled nitric oxide, and blood and sputum eosinophil cell count after prednisolone and placebo treatment. A total of 27 patients completed the study. Prednisolone did not improve 5-item Asthma Control Questionnaire (mean difference in change for prednisolone vs placebo,-0.23; 95% CI,-0.58 to 0.11), mini-Asthma Quality of Life Questionnaire (0.03; 95% CI,-0.26 to 0.42), St. George's Respiratory Questionnaire (0.24; 95% CI,-3.20 to 3.69), or Visual Analogue Scale scores for overall asthma symptoms (0.11; 95% CI,-0.58 to 0.80). The mean difference for FEV1 in favor of prednisolone was 105 mL (95% CI,-4 to 213 mL); forced expiratory flow at 25% and 75% 484 mL/s (95% CI, 151 to 816 mL/s); fractional exhaled nitric oxide reduction 41% (95% CI, 25% to 54%); blood eosinophil count reduction 49% (95% CI, 31% to 62%); and percentage of sputum eosinophil reduction 71% (95% CI, 26% to 89%). OCS improved small-airway obstruction and reduced biomarkers of type 2 inflammation but had no significant effect on symptoms or quality of life in patients with SEA receiving treatment with mepolizumab.

Using Blood Eosinophil Count as a Biomarker to Guide Corticosteroid Treatment for Chronic Obstructive Pulmonary Disease.

Treating patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease (COPD) usually involves administering systemic corticosteroids. The many unwanted side effects associated with this treatment have led to increased interest in minimising the accumulated corticosteroid dose necessary to treat exacerbations. Studies have shown that short-term treatment with corticosteroids is preferred, and recent trials have shown that biomarkers can be used to further reduce exposure to corticosteroids. Interestingly, high eosinophil counts in patients with acute exacerbations of COPD are indicative of an eosinophilic phenotype with a distinct response to treatment with corticosteroids. In addition, post-hoc analysis of randomised control trials have shown that higher blood eosinophil counts at the start of the study predict a greater response to inhaled corticosteroids in stable COPD. In this review, we examine the studies on this topic, describe how blood eosinophil cell count may be used as a biomarker to guide treatment with corticosteroids, and identify some relevant challenges.

Treatment with the anti-IgE monoclonal antibody omalizumab in women with asthma undergoing fertility treatment: a proof-of-concept study—The PRO-ART study protocol

IntroductionAsthma is associated with prolonged time to pregnancy and a higher need for fertility treatment. However, the mechanism underlying this association remains incompletely understood. Previous research points to asthma-driven systemic...

144 Effect of sodium butyrate (SB) on growth performance and complete blood cell count in nursery pigs: Two facility study

Abstract A total of 344 weaned pigs (21 ± 2 d of age) were used at University of Arkansas (UA, n = 2 16) and University of Illinois at Urbana-Champaign (UIUC, n = 128) to evaluate increasing level of sodium butyrate (SB) on growth performance and complete blood cell count. Pigs at each facility were blocked by initial BW and randomly allotted to 1 of 4 dietary treatments with 9 replications/diet and 6 pigs/pen at UA; and 8 replications/diet and 4 pigs/pen at UIUC. Treatments included a control corn-soybean-meal based diet and 3 diets in which 0.05, 0.10, or 0.15% SB was added to the control diet. Feed was manufactured at each facility. Pigs were fed in 3 phases: 7 d, 14 d, and 14 d at UIUC and 7 d, 14 d, and 19 d at UA for phase 1, 2, and 3, respectively. At UA, blood was collected at the beginning of the experiment and at the end of each phase to determine complete blood cell count. Data for growth performance for both facilities were pooled and analysed as a RCBD using the Mixed procedure of SAS. Treatment was the fixed effect, and facility and facility by treatment interactions were random effects. Orthogonal contrasts were used to assess linear and quadratic responses to inclusion of increasing levels of SB in diets. Increasing dietary SB increased weight gain (quadratic, P < 0.05), ADFI (quadratic, P ≤ 0.05), and final BW (quadratic, P < 0.05). Total white blood cell and eosinophil cell count tended to increase with increasing SB (quadratic, P = 0.07 and P = 0.08, respectively). The lymphocyte cell count tended to decrease (linear, P = 0.09) with increasing SB. Results indicated that feeding SB during the nursery phase tended to alter blood cell count and improve growth performance.

Investigation of the relationship between atopy and psoriasis.

IntroductionThe relationship between allergic and autoimmune diseases is an important issue, which has recently attracted the researchers’ interest.AimTo determine the relationship between atopy and psoriasis.Material and methodsThis case-control study was conducted on 102 patients referred to the Ghaem Hospital, Mashhad, Iran, in 2016. The participants were assigned into two groups: experimental and control groups, including the patients suffering from psoriasis and those with no history of cutaneous or other systemic diseases, respectively. Both groups filled in the ISAAC questionnaire and had skin prick tests. In addition, the serum levels of immunoglobulin E (IgE) and blood eosinophil cell count were measured. The data were analysed using the regression test through SPSS version 16.ResultsAccording to the results of the ISAAC questionnaire, there was a significant difference between the control and experimental groups in terms of asthma (p = 0.04). The mean serum concentrations of IgE and eosinophil cell count were not significantly different between the experimental (153.93 IU/ml and 187.77 cells/μl, respectively) and control groups (152.19 IU/ml and 187.68 cells/μl, respectively) (p = 0.057 and p = 0.886, respectively). In addition, there was an indirect correlation between the eosinophil cell count and psoriasis severity (p = 0.032, r = –0.297). Furthermore, the comparison of the skin prick test results revealed no significant difference between the two groups regarding the number of positive and negative cases (p = 0.436).ConclusionsThe findings suggested that atopy was not common in the patients with psoriasis and supported the concept that atopy protects against such autoimmune diseases such as psoriasis.

Greater eosinophil counts at first COPD hospitalization are associated with more readmissions and fewer deaths.

PurposeThe impacts of high blood eosinophil count (HBEC) at admission for COPD exacerbation on posthospitalization outcomes are still unclear. Previous studies have focused on its associations with first readmission rates; yet, its impacts on longitudinal outcomes such as subsequent readmissions still have to be explored. The main objective of this study is to investigate outcomes associated with HBEC following a first hospitalization for COPD exacerbation.Patients and methodsThis is an observational cohort study design. We retrospectively analyzed data of patients with a first hospitalization within 5 years for COPD exacerbation between April 2006 and March 2013. Patients were stratified into the HBEC group if the blood eosinophil count at admission was ≥200 cells/µL and/or ≥2% of the total white blood cells. With information on exact dates of subsequent hospitalizations and death, we modeled readmissions and death as states in a multi-state Markov model and estimated transition probabilities to the next states. Sensitivity analyses were performed by varying thresholds for the definition of HBEC (≥300 cells/µL and/or ≥3%).ResultsA total of 479 patients were included, of which 173 had HBEC. The transition probabilities for a first readmission was 74% (95% CI, 66%–83%) for patients with HBEC vs 70% (95% CI, 63%–77%) for patients with normal blood eosinophil count (NBEC). The transition probabilities for a second readmission were 91% (95% CI, 84%–100%) for HBEC patients in contrast with 83% (95% CI, 74%–92%) for NBEC patients. Meanwhile, transition probability for death was lower in patients with HBEC. The differences enlarged in sensitivity analyses with higher cutoff.ConclusionGreater blood eosinophil cell counts during a first hospitalization for COPD predict increased susceptibility to up to two readmissions. These patients may however have a lower risk of death.

Eosinophil counts in first COPD hospitalizations: a comparison of health service utilization.

PurposeCurrent evidence suggests that a higher blood eosinophil cell count at admission for acute exacerbation of COPD (AECOPD) is associated with a favorable response to systemic steroids. However, the impact of blood eosinophil counts at admission on post-hospitalization outcomes is still unclear. The main objective of this study is to investigate readmission outcomes associated with blood eosinophilia following severe COPD exacerbation in patients with infrequent COPD hospitalizations.Patients and methodsThis is an observational cohort study design. We retrospectively analyzed data of patients with a first hospitalization within 5 years for COPD exacerbation between April 2006 and March 2013. Patients were stratified into the eosinophilic group if the blood eosinophil count on admission was ≥200 cells/µL and/or ≥2% of the total white blood cell (WBC) count. The primary outcome was 1-year COPD-related readmission. Secondary outcomes included 1-year all-cause mortality, 1-year all-cause readmission, length of stay, time to COPD-related readmission, and number of 1-year COPD-associated emergency department (ED) and ambulatory visits.ResultsA total of 479 patients were included. Of whom, 173 were stratified into the eosinophilic group. Higher blood eosinophil cell count was associated with an increased risk of 1-year COPD-related readmission (OR, 1.83 [95% CI, 1.16–2.89]; P<0.01), a shorter time to first COPD-related readmission (HR, 1.64 [95% CI, 1.14–2.36]; P<0.01), and an increased number of 1-year COPD-related ED visits (incidence rate ratio, 1.78 [95% CI, 1.21–2.61]; P<0.01). All-cause mortality, all-cause readmission, length of stay, and number of ambulatory visits did not differ between groups.ConclusionHigher blood eosinophil cell count at admission for a COPD exacerbation is associated with increased COPD readmission rates in patients with infrequent COPD hospitalizations.

Eosinophil counts in first COPD hospitalizations: a 1-year cost analysis in Quebec, Canada.

BackgroundExacerbations explain much of the cost of COPD. Higher blood eosinophil cell counts at admission for acute exacerbation of COPD increase the risk of subsequent exacerbations and hospitalizations. However, there is no literature on the economic burden of patients with this inflammatory profile. The objective of this study is to assess the cost of health-care service utilization according to different counts of blood eosinophils.MethodsThe observational retrospective cohort included all first hospitalizations for COPD exacerbation between April 2006 and March 2013. The eosinophilic group was defined by blood eosinophil counts on admission ≥200 cells/µL and/or ≥2% of the total white blood cell count. Study outcomes were: total costs (2016 Canadian dollars) (index hospitalization and 1-year follow-up), total index hospitalization costs, total 1-year costs (all-cause readmissions, ambulatory and emergency service use), and 1-year COPD-related costs (only cost for COPD after initial discharge). Sensitivity analyses were conducted to evaluate the impact of different eosinophil cut-offs on outcomes.ResultsIn total, 479 patients were included, 173 in the eosinophilic group (92 in the higher cut-off). The average total cost was $18,263 ($6,706 for the index hospitalization), without significant difference between groups (P=0.3). The average 1-year COPD-related cost was higher in the eosinophilic group ($3,667 vs $2,472, P=0.006), with an adjusted mean difference of $1,416. Analysis of data using the higher cut-off of ≥400 cells or ≥3% was associated with a slightly larger difference in 1-year COPD-related costs between groups ($4,060 vs $2,629, P=0.003), with an adjusted mean difference of $1,640.ConclusionA higher blood eosinophil cell count at admission for a first hospitalization is associated with an increase in total 1-year COPD-related costs.

Refractory airway type 2 inflammation in a large subgroup of asthmatic patients treated with inhaled corticosteroids

Airway type 2 inflammation is usually corticosteroid sensitive, but the role of type 2 inflammation as a mechanism of asthma in patients receiving high-dose inhaled corticosteroids (ICSs) is uncertain. We sought to determine whether airway type 2 inflammation persists in patients treated with ICSs and to evaluate the clinical features of patients with steroid-resistant airway type 2 inflammation. We used quantitative PCR to generate a composite metric of type 2 cytokine gene expression (type 2 gene mean [T2GM]) in induced sputum cells from healthy control subjects, patients with severe asthma receiving ICSs (n=174), and patients with nonsevere asthma receiving ICSs (n=85). We explored relationships between asthma outcomes and T2GM values and the utility of noninvasive biomarkers of airway T2GM. Sputum cell T2GM values in asthmatic patients were significantly increased and remained high after treatment with intramuscular triamcinolone. We used the median T2GM value as a cutoff to classify steroid-treated type 2-low and steroid-resistant type 2-high (srT2-high) subgroups. Compared with patients with steroid-treated type 2-low asthma, those with srT2-high asthma were older and had more severe asthma. Blood eosinophil cell counts predicted srT2-high asthma when body mass index was less than 40kg/m2 but not when it was 40kg/m2 or greater, whereas blood IgE levels strongly predicted srT2-high asthma when age was less than 34years but not when it was 34years or greater. Despite ICS therapy, many asthmatic patients have persistent airway type 2 inflammation (srT2-high asthma), and these patients are older and have more severe disease. Body weight and age modify the performance of blood-based biomarkers of airway type 2 inflammation.

Effect of allergic phenotype on treatment response to inhaled bronchodilators with or without inhaled corticosteroids in patients with COPD.

BackgroundChronic obstructive pulmonary disease (COPD) is a heterogeneous disorder encompassing different phenotypes with different responses to treatment. The present 1-year, two-center hospital-based study investigated whether the plasma immunoglobulin E (IgE) level and/or eosinophil cell count could be used as biomarkers to stratify patients with COPD according to predicted responses to inhaled corticosteroids (ICS)-based therapy.MethodsA hospital-data based cohort study of COPD patients treated at two territory hospital centers was conducted for 1 year. Allergic biomarkers, including blood eosinophil counts and IgE levels, were assessed at baseline. Lung function parameters, including forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and the COPD Assessment Test (CAT), were also evaluated. The frequencies of acute exacerbation (AE) and pneumonia were also measured. Eosinophilia and a high IgE level were defined as >3% and 173 IU/mL, respectively.ResultsA total of 304 patients were included. Among patients with eosinophilia and high IgE levels, ICS-based therapy was associated with significant improvements in FEV1, FVC, and CAT scores, compared with bronchodilator (BD) therapy (P≤0.042). ICS-based therapy was also associated with a significantly lower incidence of AE vs BD-based therapy (11.7% vs 24.1%; P<0.008). Among patients with only eosinophilia, ICS-based therapy yielded significantly better CAT score results vs BD-based treatment (7 vs 13; P=0.032). A receiver operating characteristic curve analysis found that the combination of a high plasma IgE level and eosinophilia most sensitively and specifically identified patients who would benefit from the addition of ICS to BD therapy.ConclusionOur findings support the use of blood eosinophil cell counts plus IgE levels as predictive biomarkers of the ICS response in certain patients with COPD. Both biomarkers could potentially be used to stratify COPD patients regarding ICS-based therapy.

The Time Course of Pulmonary Function Tests in COPD Patients with Different Levels of Blood Eosinophils.

Only very few studies have investigated the influence of eosinophils on the functional progression of COPD. We aimed at retrospectively analyzing the trend of pulmonary function tests over time in patients with COPD according to two baseline blood eosinophil cell count strata (<2% [EOS−] and ≥2% [EOS+]). We used the last 9-year data present in the database of our outpatient clinic and selected only those who had two blood counts that would guarantee the stability of the value of eosinophils and serial spirometry for 4 consecutive years. The analysis of the time course of the spirometric variables analysed showed differences in FEV1 and FVC decline between the subjects of the EOS− group and those of the EOS+ group. The integrated evaluation of our results suggests that the different level of blood eosinophils in the two groups may have influenced independently the time course of the pulmonary function tests and identify two subgroups of subjects with specific disease characteristics: the hyperinflator and the rapid decliner, respectively.

Eosinophilic bronchiolitis: is it a new syndrome?

Identification of new diseases or a cluster (syndrome) of disorders with very similar pathological, radiological and clinical aspects, even sharing common pathogenic steps, is an important fact to build up the scientific soul of the complex and intriguing art called medicine. In this issue of the European Respiratory Journal , a new distinct syndrome, hypereosinophilic obliterative bronchiolitis, is described by Cordier et al. [1]. This syndrome is defined by: 1) a blood eosinophil cell count >1 G·L−1 and/or a bronchoalveolar lavage (BAL) eosinophil differential cell count >25%; 2) persistent airflow obstruction on lung function tests not modifiable after 4–6 weeks of inhaled corticosteroid therapy (2000 μg·day−1 of beclometasone or equivalent); and 3) a lung biopsy showing inflammatory bronchiolitis with prominent bronchiolar wall infiltration by eosinophils and/or characteristic direct high-resolution computed tomography (HRCT) features of bronchiolitis (poorly defined centrilobular nodules, branching opacities and tree-in-bud pattern). The first impression that a cursory clinician and/or pathologist may have, going swiftly through this list of criteria, is that “we are dealing with a severe and persistent form of asthma”. In chronic asthma the obstructive impairment becomes fixed and not modifiable, at least not easily, with steroids or bronchodilators. In chronic asthma eosinophils in lung tissue and blood may be constantly increased and HRCT scans show abnormalities in between 68% and 90% of patients (bronchial wall thickening and narrowing …

Hypereosinophilic obliterative bronchiolitis: a distinct, unrecognised syndrome

Biopsy-proven cases of eosinophilic bronchiolitis have only been reported in isolation, and all come from Japan. We present six patients with hypereosinophilic obliterative bronchiolitis (HOB), defined by the following criteria: 1) blood eosinophil cell count >1 G·L(-1) and/or bronchoalveolar lavage eosinophil count >25%; 2) persistent airflow obstruction despite high-dose inhaled bronchodilators and corticosteroids; and 3) eosinophilic bronchiolitis at lung biopsy (n=1) and/or direct signs of bronchiolitis (centrilobular nodules and branching opacities) on computed tomography (n=6). Chronic dyspnoea and cough which was often severe, without the characteristic features of asthma, were the main clinical manifestations. Atopy and asthma were present in the history of three and two patients, respectively. One patient met biological criteria of the lymphoid variant of idiopathic hypereosinophilic syndrome. Mean blood eosinophil cell count was 2.7 G·L(-1) and mean eosinophil differential percentage at bronchoalveolar lavage was 63%. Mean initial forced expiratory volume in 1 s/forced vital capacity ratio was 50%, normalising with oral corticosteroid therapy in all patients. HOB manifestations recurred when oral prednisone was decreased to 10-20 mg·day(-1), but higher doses controlled the disease. HOB is a characteristic entity deserving to be individualised among the eosinophilic respiratory disorders. Thorough analysis is needed to determine whether unrecognised and/or smouldering HOB may further be a cause of irreversible airflow obstruction in chronic eosinophilic respiratory diseases.

The clinical observation for the pruritus of hemodialysis patients with different menstruum recycling

Objective To observe the effect on pruritus with two different menstruum for hemodialyrsis recycling.Methods 22 patients of HD were randomly divided into two groups,treatment group of 11 casesandcontrol group of 11 cases.The treatment group used with model of 5% glucose rinsing.The control group used with model of sodium chloride injection.The hemodialysis patients were observed for 15 times continuously.The dialysis parameters were consistent,including the EPO using,blood flowing volume,the model of dialysis machine and dialyze.Itches degree、glycated hemoglobin、total cholesterol,fasting blood glucose,Complement C3 and Eosinophil Cell Count were also measured.Results Compared with the control group,the treatment group used with model of5%slucosecould alleviate the pruritus occurrence(P 0.05).Conclusion The dialysis model used with5% glucoserecycling could alleviate the pruritus occurrence,and it was no manifest effect on the patients's blood glucose and total cholesterol.It is a relatively safe and effective fashion for dialysis in some aspect. Key words: Hemodlalysis; Disposable dialyzer; Pruritus; Menstruum

Peripheral blood eosinophilia in association with generalized pustular and erythrodermic psoriasis

In recent studies, it has been documented that the eosinophil cells play active role in many kinds of inflammatory disorders. Measurements of the mediators released by eosinophils and cell counts in serum and skin have provided some evidence indicating the role of eosinophils in psoriasis. To evaluate the blood eosinophil cell count in patients with erythrodermic psoriasis and generalized pustular psoriasis. In this study, 48 patients with histopathologically proven psoriasis (33 with erythrodermic, 15 with generalized pustular); 43 patients with maculopapular, erythematous, or bullous drug eruption with widespread involvement; and 51 patients with basal cell carcinoma were included. These three groups were compared with each other in terms of their absolute eosinophil cell counts and percentage of eosinophils. Forty-one point seven per cent of patients with psoriasis had peripheral blood eosinophilia compared with 58.1% of the patients with drug eruption and 11.8% of patients with basal cell carcinoma. The percentage of patients with eosinophilia both in patients suffering from psoriasis and drug eruption were significantly increased compared with the patients with basal cell carcinoma (P < 0.001). The absolute median eosinophil cell counts both in patients with psoriasis and drug eruption were also significantly differed from patients with basal cell carcinoma (259.2, 439.1 and 183.1, respectively; P < 0.001) Peripheral blood eosinophilia seems to be associated with severe forms of psoriasis. This finding may suggest that the eosinophils have significant roles in the pathogenesis of these types of psoriasis.

Peripheral blood eosinophilia and eosinophil accumulation in coronary microvessels in acute Kawasaki disease.

Early stage Kawasaki disease (KD) histopathology includes perivasculitis and vasculitis of the microvessels. The lesions then extend to larger vessels. Therefore the analysis of microvessel lesions is important to better understand the initial pathogenesis of KD vasculitis. We studied epicardial microvessel lesions (<50 microm) and aneurysm lesions of paraffin-embedded cardiac tissues from 4 Japanese patients who died 7 to 22 days after KD onset. The cellular composition in the microvessel lesions was different from that in coronary aneurysm lesions; eosinophils were preferentially accumulated in the microvessel lesions. The average population of eosinophils was 16% of total infiltrated cells in the microvessel lesions, whereas it was 3% in the intima of aneurysm walls. We examined peripheral blood eosinophil cell counts in 95 KD patients and 95 febrile age-matched controls. Baseline eosinophil cell counts in KD patients were higher than those in febrile control patients (361 +/- 441 65 +/- 133; < 0.0001). Eosinophilia (>350 cells/microl) before therapy was documented in 36% of KD patients, but in only 4% of febrile controls ( < 0.0001). Sixty-six KD patients (69%) developed eosinophilia within 2 weeks of illness. Because the numbers of circulating eosinophils in the body are tightly regulated, eosinophil accumulation in blood or tissues may reflect the host's immune response against KD related antigen(s).

Airway Inflammation Is Present during Clinical Remission of Atopic Asthma

Symptoms of atopic asthma often disappear at puberty. However, asthmatic subjects in clinical remission will frequently have a relapse later in life. The aim of this study was to investigate whether subjects in clinical remission of atopic asthma have persistent airway inflammation and/or airway remodeling. Bronchial biopsies were obtained from subjects in clinical remission, asthmatic subjects, and healthy control subjects. The presence and/or activation state of eosinophils, mast cells, macrophages, T lymphocytes, interleukin (IL)-5, eotaxin, and inducible nitric oxide synthase (iNOS) were analyzed. Results were compared with less invasive indicators of airway inflammation. Also aspects of airway remodeling were determined. Eosinophils, T cells, mast cells, and IL-5 were significantly elevated in the airway mucosa of subjects in remission compared with control subjects. Also, blood eosinophil cell counts were significantly higher in subjects in clinical remission. Blood eosinophil cell counts, exhaled nitric oxide (eNO) levels, and bronchial response to adenosine-5'-monophosphate correlated significantly with the quantity of tissue eosinophils. Significant airway remodeling was found in subjects in clinical remission. Our study has shown ongoing airway inflammation and airway remodeling in adolescents in clinical remission of atopic asthma. Subclinical airway inflammation may well determine the risk of an asthma relapse later in life.

Urinary eosinophil-derived neurotoxin/protein X: A simple method for assessing eosinophil degranulation in vivo

Background: Eosinophil-derived neurotoxin/protein X (EDN/EPX), one of the cationic granule proteins released by polymorphonuclear eosinophils, can be detected in human urine. Objective: We sought to evaluate whether the urinary release of EDN/EPX was dependent on the blood eosinophil cell count, the bronchoalveolar eosinophil cell count, or both and on the clinical diagnosis. We also attempted to determine the precise kinetics of decrease of EDN excretion and eosinophil counts after the onset of corticosteroid treatment. Methods: Daily urinary release of EDN/EPX was measured by radioimmunoassay in 28 patients with high hypereosinophilia (group 1), 32 patients with moderate hypereosinophilia (group 2), 26 patients without hypereosinophilia at the time of the study but with a known pulmonary disease involving eosinophils (group 3), and 13 control patients (group 4). Results: The urinary excretion of EDN/EPX was significantly higher in patients from groups 1 or 2 than in patients from groups 3 or 4. Particularly high levels of EDN/EPX excretion were observed in patients from groups 1 or 2 with chronic eosinophilic pneumonia (chronic eosinophilic pneumonia: 4.7 ± 8.1 mg/day, control subjects: 0.39 ± 0.33 mg/day, p < 0.001). Urinary excretion of EDN/EPX was significantly correlated with blood ( r = 0.66, p < 0.001) and differential bronchoalveolar ( r = 0.62, p = 0.04) eosinophil cell counts in patients from group 1 but not from the other groups. Corticosteroid treatment was followed by a significant decrease in EDN/EPX excretion. The kinetics of decrease in EDN/EPX were delayed as compared with the dramatic drop in peripheral eosinophil counts. Distinct kinetics between urinary EDN/EPX and eosinophil counts differentiated the recurrence of chronic eosinophilic pneumonia from an asthma attack in one patient. Conclusion: Measurement of urinary EDN/EPX excretion may be a useful indicator of eosinophil degranulation in vivo. (J Allergy Clin Immunol 1998;101:116-23.)

Steroid-induced changes of eosinophils in atopic dermatitis.

We investigated whether apoptosis of eosinophils is specific to atopic dermatitis (AD), or also occurs in other diseases with eosinophilia. We examined the survival of eosinophils cultured with corticosteroids: (1) Clinically, steroid administration significantly decreased high peripheral blood eosinophil cell counts in patients with AD. (2) Treatment with recombinant human (rh) IL-5 prolonged the life span of eosinophils derived from patients with AD and of those derived from non-AD patients with eosinophilia. However, there were differences in the survival rates in the presence of rhIL-5: the eosinophils from non-AD patients showed 1.4-fold higher survival rates than those from AD patients at 24 h. In the presence of steroids, the eosinophils from non-AD patients showed a survival rate double that of those from AD patients at 24 h. (3) In eosinophils from patients with AD, the survival rate decreased significantly in a time- and steroid-concentration-dependent manner. Steroid administration significantly inhibited the survival rate of eosinophils from patients with AD compared to those of monocytes and neutrophils. These findings suggest that apoptosis induced by steroids decreases the eosinophil count in vivo in patients with AD. There may be a difference in the incidence of steroid-induced apoptosis between eosinophil cells from patients with AD and those from patients with eosinophilia due to other underlying diseases.