Secretory Leukocyte Protease Inhibitor Is Present in Circulating and Tissue-Recruited Human Eosinophils and Regulates Their Migratory Function

Eosinophils and secretory leukocyte protease inhibitor (SLPI) are both associated with Th2 immune responses and allergic diseases, but whether the fact that they are both implicated in these conditions is pathophysiologically related remains unknown. Here we demonstrate that human eosinophils derived from normal individuals are one of the major sources of SLPI among circulating leukocytes. SLPI was found to be stored in the crystalline core of eosinophil granules, and its dislocation/rearrangement in the crystalline core likely resulted in changes in immunostaining for SLPI in these cells. High levels of SLPI were also detected in blood eosinophils from patients with allergy-associated diseases marked by eosinophilia. These include individuals with eosinophilic granulomatosis with polyangiitis (EGPA) and atopic dermatitis (AD), who were also found to have elevated SLPI levels in their plasma. In addition to the circulating eosinophils, diseased skin of AD patients also contained SLPI-positive eosinophils. Exogenous, recombinant SLPI increased numbers of migratory eosinophils and supported their chemotactic response to CCL11, one of the key chemokines that regulate eosinophil migratory cues. Together, these findings suggest a role for SLPI in controlling Th2 pathophysiologic processes via its impact on and/or from eosinophils.

Increased Peripheral Blood Eosinophils May Indicate Acute Infection in Neonates

BackgroundEosinophils are now being recognized for more varied functions such as antiviral and bactericidal effects. This study aimed to explore the association between increased blood eosinophils and frequent pathogens due to the infections in children. Methods A total of 2353 children with acute infections admitted to Guangzhou Women and Children's Medical Center from February 1, 2019 to January 31, 2020 were enrolled in the study. 277 children without infections were comprised the control group. Children’s age, peripheral blood parameters including white blood cells, eosinophils, C-reactive protein (CRP) were recorded. In addition, infection stage and departments the patients admitted to were investigated. The study protocol was approved by the institutional ethics committee of the Guangzhou Women and Children's Medical Center (NO.2020110819342581).Results Blood eosinophil numbers negatively correlated with the age of children, whereas had no relation to disease stage. The means of eosinophil for neonates (<0.1 year)，infancy (<1year) and children >1year with acute infections were 0.67±0.40, 0.40±0.68, 0.15±0.25 *109/L compared with control group matched for age(0.44±0.20, 0.45±0.27, 0.24±0.19*109/L, P <0.001, <0.001, 0.497, respectively). Among them, the mean of eosinophil in the neonates afflicted with acute infections was significantly higher than the others compared to age-matched controls (0.63±0.60 vs 0.44±0.20, P= 0.012). Areas under the curves (AUC) were 0.81 (95% CI 0.75–0.86) for eosinophil combined with CRP and 0.68 (95% CI 0.61–0.75) for CRP alone for acute infections in neonates (P=0.02). Patients admitted in ICU had higher eosinophils than outpatients (0.46±0.60 vs 0.16±0.24, P <0.001) but had no significant difference compared with control group (0.45±0.20, P >0.99). Conclusion Increased peripheral blood eosinophils may indicate acute infections among neonates. Eosinophil combined with CRP can contribute to evaluating this population.

Blood eosinophils to guide inhaled maintenance therapy in a primary care COPD population

Blood eosinophils are a potentially useful biomarker for guiding inhaled corticosteroid (ICS) treatment decisions in COPD. We investigated whether existing blood eosinophil counts predict benefit from initiation of ICS compared to bronchodilator therapy.We used routinely collected data from UK primary care in the Clinical Practice Research Datalink. Participants were ≥40 years with COPD, ICS-naïve and starting a new inhaled maintenance medication (intervention group: ICS; comparator group: long-acting bronchodilator, non-ICS). Primary outcome was time-to-first exacerbation, compared between ICS and non-ICS groups, stratified by blood eosinophils (“high” (≥150/µL) and “low” (<150/µL) groups).Of 9475 eligible patients, 53.9% initiated ICS and 46.1% non-ICS treatment with no difference in eosinophils between treatment groups (p=0.71). Exacerbation risk was higher in patients prescribed ICS than non-ICS, but with a lower risk in those with “high” eosinophils (hazard ratio 1.04, 95% CI 0.98 to 1.10) than “low” eosinophils (1.19, 95% CI 1.09 to 1.31) (p value for interaction=0.01). Risk of pneumonia hospitalisation with ICS was greatest in those with “low” eosinophils (hazard ratio 1.26, 95% CI 1.05 to 1.50; p value for interaction=0.04). Results were similar whether the most recent blood eosinophil count or the mean of blood eosinophil counts was used.In a primary care population, the most recent blood eosinophil count could be used to guide initiation of ICS in COPD patients. We suggest that ICS should be considered in those with higher eosinophils and avoided in those with lower eosinophils (<150/µL).

Neutrophil-to-lymphocyte ratio, blood eosinophils and COPD exacerbations: a cohort study

BackgroundBlood neutrophil-to-lymphocyte ratio (NLR) and blood eosinophils (B-Eos) are emerging biomarkers in COPD. This study examined if they can predict acute exacerbations (AECOPD), and determined their longitudinal stability.MethodsIn this closed cohort study, Swedish subjects with spirometry-verified COPD attended three yearly visits in a stable phase of the disease. Blood cell counts, spirometry and questionnaire-assessed AECOPD history (worsening of COPD leading to an unscheduled visit and/or use of antibiotics and/or oral corticosteroids) were collected at each visit.ResultsOf 466 included subjects 57% were female. Baseline mean±sd forced expiratory volume in 1 s was 58±17% predicted. High NLR (≥3.0) was more common in subjects with previous AECOPDs than in those without (33.5% versus 20.4%, p=0.002). In two-level mixed-effects logistic regression models adjusted for confounders, NLR as a continuous variable (odds ratio, OR 1.20, 95% CI 1.04–1.38) and B-Eos ≥300 cells·µL−1 (OR 1.54, 95% CI 1.06–2.24) were associated with future AECOPDs. In 386 subjects with blood cell data available at all three visits, the intra-class correlation coefficient for NLR was 0.61 (95% CI 0.56–0.66) and for B-Eos 0.69 (95% CI 0.64–0.73). NLR was persistently ≥3.0 in 15.3% and B-Eos was persistently ≥300 cells·µL−1 in 10.6%.ConclusionsStable-phase NLR and B-Eos were associated with future AECOPDs. NLR on its own is probably not useful to predict AECOPDs, but might be included in a risk-scoring index. A minority of subjects with COPD had persistently elevated stable-phase NLR or B-Eos, and the biomarkers showed fair longitudinal reliability.

Stability of blood eosinophils in acute exacerbation of chronic obstructive pulmonary disease and its relationship to clinical outcomes: a prospective cohort study

Background The clinical value of blood eosinophils and their stability in chronic obstructive pulmonary disease (COPD) remains controversial. There are limited studies on association between the stability of blood eosinophils in acute exacerbation of COPD (AECOPD) and clinical outcomes. This study aimed to evaluate the stability of blood eosinophils in hospitalized AECOPD and its relationship to clinical outcomes. Methods This prospective observational study recruited patients hospitalized with AECOPD from November 2016 to July 2020. The eligible patients were divided into four groups according to their blood eosinophil counts at admission and discharge: persistently < 300 cells/μl (LL), < 300 cells/μl at admission but ≥ 300 cells/µl at discharge (LH), ≥ 300 cells/μl at admission but < 300 cells/µl at discharge (HL), and persistently ≥ 300 cells/μl (HH). Cox hazard analyses were used to study the association between eosinophil changes and exacerbations or mortality. Results In 530 patients included, 90 (17.0%) had a high blood eosinophil count (BEC) ≥ 300 cells/µl at admission but 32 (35.6%) of them showed a decreased BEC at discharge. The proportions and distribution for group LL, LH, HL, and HH were 381 (71.9%), 59 (11.1%), 32 (6.0%), and 58 (10.9%), respectively. During hospitalization, the LH group had a higher C-reactive protein level, higher rate of intensive care unit (ICU) admission, and higher total cost. The length of hospital stay of the LH group was longer compared with group LL, HL, or HH (P = 0.002, 0.017, and 0.001, respectively). During a follow-up of 12 months, the HH group was associated with a higher risk of moderate-to-severe exacerbations compared to the LL group (hazard ratio 2.00, 95% confidence interval 1.30–3.08, P = 0.002). Eosinophil changes had no significant association with mortality at 12 months. Sensitivity analyses in patients without asthma and without use of systemic corticosteroids prior to admission did not alter the results. Conclusions More attention should be paid to the LH group when evaluating the short-term prognosis of AECOPD. A persistently high BEC was a risk factor for long-term exacerbations. Eosinophil changes during hospitalization could help to predict outcomes.

Tryptase and IL-33 in Bronchoalveolar Lavage Fluid May Predict the Types of Eosinophilic Pneumonia and Disease Recurrence

<b><i>Introduction:</i></b> Eosinophilic pneumonia (EP) is characterized by a marked accumulation of eosinophils in the lungs and blood. Eosinophils and mast cells play an important role in the pathogenesis of EP via release of biomarkers such as tryptase and interleukin (IL)-33. However, the potential role of these biomarkers is not fully understood. <b><i>Objectives:</i></b> We aimed to evaluate the differences among the levels of tryptase and IL-33 in bronchoalveolar lavage fluid (BALF) from several types of EP. We evaluated the differences between the levels of these biomarkers in the recurrent and nonrecurrent cases. <b><i>Method:</i></b> We prospectively collected the clinical data of patients with EP, diagnosed between 2006 and 2015 in our institution. Bronchoscopy was performed before steroid treatment; BALF was collected. The clinical characteristics of EP patients and the levels of tryptase and IL-33 in BALF were evaluated. <b><i>Results:</i></b> We enrolled 15 patients with chronic EP (CEP), 5 with acute EP (AEP), 10 with drug-induced EP, and 6 with angiitis-related EP. Tryptase levels in the CEP group were significantly higher than that in the drug-induced EP group (<i>p</i> = 0.048), while the AEP group had the highest IL-33 levels. Recurrence of EP was noted in 67% of patients with CEP. The levels of tryptase and IL-33 were notably higher in the recurrent cases than that in the nonrecurrent CEP group (<i>p</i> = 0.004, <i>p</i> = 0.04, respectively). Furthermore, there was a positive correlation between the levels of tryptase and IL-33 in the BALF of patients with CEP (ρ = 0.69, <i>p</i> = 0.004). <b><i>Conclusions:</i></b> Tryptase and IL-33 in BALF are useful biomarkers for the assessment of EP types. These biomarkers could be used to predict disease recurrence.

Blood Eosinophils and Pulmonary Rehabilitation in COPD

Background. Blood eosinophils predict the response to therapy, risk of exacerbation, and readmission in COPD. This study investigates whether blood eosinophils predict pulmonary rehabilitation (PR) outcomes in COPD. Methods. We categorized patients into eosinophilic (blood eosinophils ≥300 cells/ml) or noneosinophilic (<300 cells/ml). In a retrospective design, we compared changes within and between the two groups on BODE index, 6-minute walk test (6MWT), FEV1, and mMRC dyspnea scale. Results. Of 206 patients enrolled, 176 were included for analysis; 90 were eosinophilic. BODE index improved in both groups: (MD −1.25; 95% CI (−0.45, −4.25), P ≤ 0.001 ) in the eosinophilic and (MD −1.33; 95% CI (−1.72, −0.94), P ≤ 0.001 ) in the noneosinophilic, but a higher BODE index remained in the eosinophilic (4.98); adjusted mean change (β): 0.7 (95% CI (0.15, 1.26), P = 0.01 ). 6MWT improved by 29.3 m in the eosinophilic (95% CI (14.2, 44.4), P ≤ 0.001 ) vs. 115.1 m in the noneosinophilic (95% CI (−30.4, 260.6), P = 0.12 ). FEV1 did not change in the eosinophilic (MD −0.6; 95% CI (−2.64, 1.48), P = 0.58 ), but improved by 2.5% in the noneosinophilic (MD 2.5; 95% CI (0.77, 4.17), P = 0.005 ). There were no significant between-group differences in 6MWT and FEV1; adjusted mean changes (β) were −9.69 m (95% CI (−39.51, 20.14), P = 0.52 ) and −2.31% (95% CI (−5.69, 1.08), P = 0.18 ), respectively. There were no significant within- or between-group changes in the mMRC scale. Conclusion. Although PR improves the BODE index in both eosinophilic and noneosinophilic COPD, a higher eosinophil count (≥300 cells/ml) is associated with a higher (worse) BODE index. Blood eosinophils may predict PR outcomes.