High eosinophil blood counts are associated with a shorter length of hospital stay in exacerbated COPD patients - a retrospective analysis.

BACKGROUND: In COPD, the course of the disease including morbidity and mortality is strongly associated with severe exacerbations. The current GOLD recommendations emphasize blood eosinophil counts as a marker for responsiveness to inhaled corticosteroids (ICS). Retrospective analyses from randomized clinical trials indicate a favorable response to systemic corticosteroids in exacerbated COPD patients with blood eosinophils > 2%, however data outside clinical trials are scarce. PATIENTS AND METHODS: We retrospectively evaluated data from 1007 cases of patients who were admitted to the University Medical Center Marburg between 01/2013 and 12/2018. All patients had been diagnosed with an acute exacerbation of COPD (ICD-10 J44.0/J44.1). Our analysis was based on a subgroup of 417 patients in whom a full blood cell count was obtained at the day of admission. Patients were predominantly male (63.3%), had a median age of 74 years (IQR 65 years - 83 years) and a median FEV1 of 1.03 l (42.6% predicted). We compared the hospital length of stay and other outcome parameters using established thresholds for the eosinophil blood cell count (100 and 300 eosinophils/µl and 2%). RESULTS: Patients with low eosinophils (< 2%, <100 cells/µl) had a longer median time in hospital (length of hospital stay - LOS) as compared to patients with high eosinophils (< 2%: 9.31 vs. ≥2%:7 days, and < 100/µl: 10 vs. 100-300/µl: 8 vs. > 300/µl: 7 days). The median CRP was higher in patients with low eosinophils as compared to the other groups (< 2%: 22.7 vs. ≥2%: 9 mg/dl and < 100: 25 vs. 100-300: 13.5 vs. > 300: 7.1 mg/dl). Time to re-hospitalization or time to death did not differ between strata of eosinophils. Sensitivity analysis in a subgroup of patients in which pneumonia was excluded by chest x-ray did not significantly alter the results. CONCLUSION: The results support the hypothesis that patients with severe COPD exacerbations and elevated blood eosinophil counts respond better to systemic corticosteroid treatment than patients with a non-eosinophilic exacerbation.

Impact of genetic polymorphisms determining leukocyte/neutrophil count on chemotherapy toxicity.

Neutropenia and infection are major dose-limiting side effects of chemotherapy. The risk of initial infection and subsequent complications are directly related to the depth and duration of neutropenia. Recent genome-wide association studies identified variants in DARC and CXCL2 genes, and in ORMDL3-GSDMA-CSF3 locus on chromosome 17q21 that influence white blood cell and neutrophil counts in healthy individuals. To investigate whether polymorphisms in these loci in conjunction with chemotherapy may modulate risk of treatment complications, we analyzed 21 SNPs across these genes for an association with chemotherapy-related neutropenia and infection in 286 Caucasian children with acute lymphoblastic leukemia. After correction for multiple testing, DARC polymorphism rs3027012 in 5'-UTR was associated with higher risk of low absolute phagocyte count (APC<500 and <1000 cells per microliter, P=0.001 and P<0.0005, respectively) and hospitalization due to febrile neutropenia (P=0.002). Protective effect was instead seen for DARC rs12075 A to G substitution (P=0.004). The SNP rs3859192 in the GSDMA were associated with hospitalization due to infection (P=0.004); infection was also modulated in the additive manner by the CXCL2 rs16850408 (P=0.002). This study shows for the first time that the variations in DARC, GSDMA and CXCL2 genes may play a role in the onset of chemotherapy complications.

Short-Term Hyperprolactinemia Reduces the Expression of Purinergic P2X7 Receptors during Allergic Inflammatory Response of the Lungs.

PURPOSE: We have previously shown that domperidone-induced short-term hyperprolactinemia reduces the lung's allergic inflammatory response in an ovalbumin antigenic challenge model. Since purinergic receptor P2X7R activity leads to proinflammatory cytokine release and is possibly related to the pathogenesis of allergic respiratory conditions, the present study was designed to investigate a possible involvement of purinergic and prolactin receptors in this phenomenon. METHODS: To induce hyperprolactinemia, domperidone was injected intraperitoneally in rats at a dose of 5.1 mg × kg-1 per day for 5 days. P2X7 expression was evaluated by lung immunohistochemistry while prolactin receptor expression in bronchoalveolar lavage leukocytes was analyzed through flow cytometry. RESULTS: Previous reports demonstrated that rats subjected to short-term hyperprolactinemia exhibited a decrease in leukocyte counts in bronchoalveolar lavage, especially granulocytes. Here, it is revealed that hyperprolactinemia promotes an increased expression of prolactin receptors in granulocytes. Also, increased expression of purinergic P2X7R observed in allergic animals was significantly reduced by hyperprolactinemia. CONCLUSIONS: Both purinergic and prolactin receptor expression changes occur during the anti-asthmatic effect of hyperprolactinemia.

Changes in Neutrophil Count After Antipsychotic Prescription Among a Retrospective Cohort of Patients With Benign Neutropenia.

BACKGROUND: There is a paucity of literature regarding the effect of antipsychotics on absolute neutrophil count (ANC) of patients with benign neutropenia (BN). We evaluated the change in ANC after atypical antipsychotic prescription (excluding clozapine) in a retrospective cohort of 22 patients with BN. METHODS/PROCEDURES: Records of all patients with BN who were prescribed antipsychotics and who had ANC measured before and during antipsychotic treatment were obtained from Bronx VA Medical Center between 2005 and 2015 (inclusive). Twenty-two patients met criteria for inclusion. Individual and group mean ANC were calculated before treatment and during treatment. A paired, two-tailed t test was performed on the group ANC means. RESULTS: The group mean pretreatment ANC was 1.24 ± 0.220 K/cmm, and the mean ANC during the time of antipsychotic prescription increased to 1.40 ± 0.230 K/cmm, with a P value of 0.0045, t value of 3.18, degrees of freedom equal to 21, and 95% confidence interval of 1.30 to 1.49 K/cmm. CONCLUSIONS: There was a statistically significant increase in ANC among our cohort during the time of antipsychotic prescription. All BN patients who were prescribed antipsychotics maintained a stable neutrophil count, with none of the 22 patients with BN in this study developing agranulocytosis during treatment. Although this study is limited by a low patient count as well as other demographic factors, these findings provide initial evidence regarding the safety of prescribing atypical antipsychotics to BN patients. Further studies are needed to replicate these findings and assess for effects of individual medications.

White blood cell count predicts the odds of kidney function decline in a Chinese community-based population.

BACKGROUND: Inflammatory processes are very important in the development of kidney disease. Nevertheless, the association between white blood cell (WBC) count and the risk of renal dysfunction has not been well-established, especially in subjects without chronic kidney disease (CKD). Our study investigated the association between WBC count and kidney function decline in a Chinese community-based population with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2. METHODS: A total of 3768 subjects who were enrolled in an atherosclerosis cohort in Beijing were included in this study. EGFRs were calculated at baseline and follow-up using the CKD-EPI formula. The outcomes of this study were renal function decline (RFD) (a drop in eGFR stage along with a decline in eGFR of 25% or exceeding 5 mL/min/1.73 m2/year), rapid eGFR decline (an annual decrease in eGFR exceeding 3 mL/min/1.73 m2), and incident CKD (eGFR <60 min/1.73 m2 at follow-up). Multivariate logistic regression models were used to evaluate the associations between WBC count and each outcome. RESULTS: On average, the subjects were 56.6 ± 8.5 years old, and 35.9% were male. Of the participants, 48.6% had hypertension and 17.4% had diabetes. The mean (SD) WBC count at baseline was 6.1 ± 1.5 × 109/L. The mean (SD) eGFR at baseline was 101.1 ± 10.6 mL/min/1.73 m2. After 2.3 years follow-up, the incidence rates of RFD, rapid eGFR decline and new CKD were 7.7, 20.9, and 0.8%, respectively. WBC count was significantly related to RFD, rapid eGFR decline and new CKD in the univariate analyses. Even after adjustment for demographic variables, comorbidities, medications and baseline eGFR, these associations remained. Moreover, similar trends in RFD were observed in nearly all subgroups stratified by each confounding variable. The increase in the odds of RFD associated with each 109/L increase in WBC count was significantly greater in subjects not undergoing treatment with lipid-lowering drugs than those not undergoing this treatment (P-interaction: 0.05). CONCLUSIONS: In conclusion, elevated WBC count served as a predictor of the odds of kidney function decline in this population, which supports the hypothesis that systemic inflammation may serve as a risk factor for CKD development.

White blood cell count and incidence of hypertension in the general Japanese population: ISSA-CKD study.

OBJECTIVES: This study aimed to clarify the relationship between the white blood cell (WBC) count and hypertension in the general Japanese population. METHODS: We conducted a population-based retrospective cohort study using annual health check-up data of residents of Iki City, Nagasaki Prefecture, Japan. A total of 2935 participants without hypertension at baseline were included in the present analysis. WBC counts were classified as tertile 1 (<4700/µL), tertile 2 (4700-5999/µL), and tertile 3 (≥6000/µL). The outcome was incident hypertension (blood pressure ≥140 mmHg). Multivariable-adjusted hazard ratios and 95% confidence intervals (95% CIs) were estimated using the Cox proportional hazards model. RESULT: During an average follow-up of 4.5 years, 908 participants developed hypertension. The incidence (per 100 person-years) of hypertension increased with an elevation in the WBC count (6.3 in tertile 1, 7.0 in tertile 2, and 7.4 in tertile 3). This association was significant, even after adjustment for other risk factors, including age, sex, current smoking habits, current alcohol intake, exercise habits, obesity, elevated blood pressure, diabetes mellitus, and dyslipidemia. The hazard ratios were 1.07 for tertile 2 (95% CI 0.90-1.26) and 1.27 for tertile 3 (95% CI 1.06-1.51) compared with the reference group of tertile 1 (p = 0.009). CONCLUSION: The WBC count was associated with future development of hypertension in the general Japanese population.

Prioritising outcomes for evaluating eosinophil-guided corticosteroid therapy among patients with acute COPD exacerbations requiring hospitalisation: a Delphi consensus study.

OBJECTIVES: Presently, those outcomes that should be prioritised for chronic obstructive pulmonary disease (COPD) exacerbation studies remain unclear. In order to coordinate multicentre studies on eosinophilia-driven corticosteroid therapy for patients hospitalised for acute exacerbation of COPD (AECOPD), we aimed to find consensus among experts in the domain regarding the prioritisation of outcomes. DESIGN: A modified Delphi study was proposed to recognised COPD experts. Two brainstorming questionnaires were used to collect potential outcomes. Four subsequent rounds of questionnaires were used to rank items according to a six-point Likert scale for their importance in the protocol, as well as for being the primary outcome. Priority outcome criteria were predefined as those for which ≥70% of experts indicated that the outcome was essential for interpreting study results. SETTING: COPD exacerbation management in France. PARTICIPANTS: 34 experts recommended by the French Language Pulmonology Society were invited to participate. Of the latter, 21 experts participated in brainstorming, and 19 participated in all four ranking rounds. RESULTS: 105 outcomes were ranked. Two achieved consensus as candidate primary outcomes: (1) treatment failure defined as death from any cause or the need for intubation and mechanical ventilation, readmission because of COPD or intensification of pharmacologic therapy, and (2) the time required to meet predefined discharge criteria. The 10 secondary priority outcomes included survival, time with no sign of improvement, episodes of hospitalisation, exacerbation, pneumonia, mechanical or non-invasive ventilation and oxygen use, as well as comorbidities during the initial hospitalisation. CONCLUSIONS: This Delphi consensus project generated and prioritised a great many outcomes, documenting current expert views concerning a diversity of COPD endpoints. Among the latter, 12 reached consensus as priority outcomes for evaluating the efficacy of eosinophil-driven corticosteroid therapy in AECOPD inpatients. STUDY REGISTRATION: The eo-Delphi project/protocol was registered on 23 January 2018 at https://osf.io/4ahqw/.

Neutrophil-lymphocyte ratio is increased in elderly patients with first episode depression, but not in recurrent depression.

Association between inflammation and depression, especially in elderly patients, leads to conclusions about their shared influence on risk of cardiovascular disease and death. It might be found useful to predict those issues by monitoring inflammatory parameters, such as neutrophil/lymphocyte ratio (NLR). The aim of this study was to determine the NLR in elderly patients with unipolar depression compared with non-depressed elderly patients. NLR was measured in 684 Caucasian subjects (depressed: n = 465, non-depressed: n = 219), aged ≥ 60 (depressed: mean age 74.8 ±â€¯7.8 years, non-depressed: mean age: 71.1 ±â€¯5.7 years). There were two subgroups within depressed patients: first episode depression (n = 138, 29.6%) and recurrent depression (n = 328, 70.3%). NLR was calculated as ratio between absolute neutrophil count to absolute lymphocyte count. NLR was significantly higher in unmedicated patients with depression compared with healthy control (2.10 ±â€¯2.13 vs. 2.01 ±â€¯0.75, p = 0.004). It was higher in first episode depression compared with recurrent depression (2.11 ±â€¯1.76 vs 1.64 ±â€¯1.04, p < 0.05). There was a positive correlation with severity of symptoms. We found non-specific effect of treatment with antidepressants or antipsychotics on lower NLR. Increased NLR in patients with first episode of depression compared to recurrent depression and healthy control may have important clinical consequences. Severity of symptoms are positively correlated with NLR, which may indicate that with increasing severity of depression, the risk of cardiovascular events is also rising, which leads to higher mortality. In elderly patients with depression even a small reduction of such risk may translate into better prognosis and improve quality of live. The difference between first episode and recurrent depression in terms of inflammatory biomarkers requires further studies.

Prognostic Value of White Blood Cell Counts and C-reactive Protein in Acute Ischemic Stroke Patients After Intravenous Thrombolysis.

BACKGROUND: The prognostic value of White Blood Cell (WBC) counts and C-reactive Protein (CRP) in clinical outcomes of Acute Ischemic Stroke (AIS) patients after Intravenous Thrombolysis (IVT) remains unknown. We investigated the association of WBC counts and CRP with 3-month functional outcomes and all-cause mortality in AIS patients. METHODS: 447 AIS patients treated with IVT between May 2010 and May 2017 were enrolled. WBC counts and CRP were measured within 24 hours after IVT. The main outcomes included poor functional outcomes (modified Rankin score ≥3) at 3 months and 3-month all-cause mortality. RESULTS: High WBC counts were associated with poor functional outcomes (adjusted OR (odds ratio) 4.48; 95% CI (confidence interval) 2.00-10.03; P-trend<0.001) and with all-cause mortality (adjusted HR (hazard ratio) 2.19; 95% CI 1.07-4.49; P-trend=0.018). In addition, high CRP levels were associated with poor functional outcomes (adjusted OR 4.95; 95% CI 1.39-17.65; Ptrend= 0.002). However, no significant association between high CRP levels and all-cause mortality was observed (adjusted HR 2.61; 95% CI 0.80-8.47; P-trend=0.138). CONCLUSION: Our analysis indicated that elevated WBC counts and CRP levels after IVT can independently predict poor outcome among AIS patients.

White blood cell counts: reference methodology.

Modern hematology laboratories use automated hematology analyzers to perform cell counts. These instruments provide accurate, precise, low-cost differential counts with fast turnaround times. Technologies commonly used include electrical impedance, radiofrequency conductivity, laser light scattering, and cytochemistry. This article reviews the principles of these methodologies and possible sources of error, provides guidance for selecting flagging criteria, and discusses novel, clinically relevant white blood cell parameters provided by new instruments, including immature granulocyte count and granularity index.

Automated image processing. Past, present, and future of blood cell morphology identification.

Automated image processing analysis for leukocyte differential counting started 30 years ago principally as a mimic of the traditional microscopic method. Several types of systems were used in the 1970s and 1980s. In the late 1990s, two new image processing systems were developed with new technology for cell image analysis. They possess an intelligent neural network software and can be connected to an Ethernet for telehematologic diagnosis and consultation.

Higher leukocyte count is associated with higher risk of 3-year mortality in non-diabetic patients with first-ever ischemic stroke.

Leukocyte count predicted the risk of first-time myocardial infarction and ischemic stroke. The aim of this study was to determine the role of elevated leukocyte count in non-diabetic patients admitted for acute first-ever ischemic stroke on clinical presentation and 3-year mortality. We studied 462 patients with acute first-ever ischemic stroke without diabetes mellitus or active infection at admission. Patients were classified into 2 groups according to their leukocyte count. A white blood cell (WBC) count ≥ 10,000/µL was defined as an elevated leukocyte count, otherwise as normal. Clinical presentation, risk factors for stroke, laboratory data, co-morbidities, and outcomes were recorded. 64 patients (13.9%) had elevated leukocytes. Multivariate logistic regression showed that an elevated platelet count was positively associated with the elevated leukocyte count, while a low serum sodium level was negatively associated with an elevated leukocyte count (P=0.008, P=0.003, respectively). An elevated leukocyte count was associated with a higher risk of a stroke in evolution (P=0.021). Multivariate Cox regression analysis revealed that an elevated leukocyte count is a significant predictor of 3-year mortality [P=0.010, HR=3.26 (1.33-7.98)]. In conclusion, higher leukocyte counts during the acute stroke stage are associated with increased risk of 3-year mortality in patients with acute, first-ever ischemic stroke.

Longitudinal study on white blood cell count and the incidence of metabolic syndrome.

OBJECTIVE: Many studies have revealed that white blood cell count (WBC) is related to insulin resistance which is a central mechanism of metabolic syndrome (MetS). However, few cohort studies have examined the role of WBC in the development of MetS. We hypothesized that WBC is associated with the future development of MetS, and investigated the longitudinal incidence of MetS in healthy workers. METHODS: WBC was measured in 5,073 workers (mean age 42.5 years) without MetS at baseline. The incidence of MetS was monitored over 7 years of follow-up, in relation to quartiles of WBC. During the follow-up, 925 participants were diagnosed as MetS. RESULTS: Incidence of MetS was increased in participants with higher WBC: the rates of incidence of MetS were 22.6, 32.9, 42.9, and 57.5 per 1,000 person-years of follow-up in the 1st, 2nd, 3rd, and 4th quartiles of WBC, respectively. After adjustments for confounding factors, the adjusted hazards ratio (95% confidence interval) for MetS was 1.00 (reference), 1.22 (0.98 to 1.51), 1.52 (1.24 to 1.87), and 1.66 (1.35 to 2.04) through the quartiles of WBC, respectively, (p <0.001). This relationship was consistent among current smokers and never smokers, and among male and female genders, respectively. CONCLUSION: WBC is useful in predicting the future development of MetS which leads to atherosclerotic diseases.

Low birth weight and markers of inflammation and endothelial activation in adulthood: the ARIC study.

BACKGROUND: To investigate the hypothesis that intrauterine growth restriction might produce a longstanding pro-inflammatory tendency, we investigated the association of low birth weight with blood levels of markers of inflammation and endothelial activation in middle-aged adults. METHODS: The ARIC Study enrolled subjects aged 45-64 years sampled from four U.S. communities. An inflammation/endothelial activation score from 0 to 6 was created, one point being given for each above-median value of white blood cell count, fibrinogen, von Willebrand factor and Factor VIII, and for each below-median value of albumin and activated partial thromboplastin time. RESULTS: Of the 9809 individuals reporting birth weight and having all inflammation/endothelial markers and covariates, 349 (3.6%) reported low birth weight (LBW). The mean (standard deviation) score was 3.5 (1.5) for those with and 3.1 (1.6) for those without LBW (p<0.001). In robust poisson regression models adjusting for gender, ethnicity, age, study center, educational level, and current drinking and smoking status and amount, those with LBW were more likely to have a high score (> or =4 points) (RR=1.16, 95% CI: 1.05-1.29). CONCLUSION: In the ARIC Study, LBW predicted greater inflammation and endothelial activation, as indicated by the higher score of blood markers, consistent with the hypothesis that early life events may result in a hyper-responsive innate immune system. Such a pro-inflammatory tendency could help explain the association of low birth weight with elements of the metabolic syndrome and ischemic heart disease.

In critically ill patients, B-type natriuretic peptide (BNP) and N-terminal pro-BNP levels correlate with C-reactive protein values and leukocyte counts.

BACKGROUND: B-type natriuretic peptide (BNP) and its N-terminal portion (NT-pro-BNP) are used for the assessment of cardiac dysfunction in patients with heart failure. However, it remains controversial whether or not this option is still valid in critically ill patients because of a possible interaction between the systemic inflammatory response and the natriuretic peptide levels. The aim of this study was to assess the relationship between natriuretic peptic levels, laboratory parameters of systemic inflammation, and pulmonary artery occlusion pressure (PAOP) in critically patients. METHODS: Twelve haemodyamic unstable patients, all monitored with a pulmonary artery catheter, were included in this study. Subgroups were compared using measurement values on ICU admission. Within patient associations between different variables were evaluated by a repeated measurement ancova. RESULTS: Acute heart failure and septic shock were diagnosed in 6 patients each. Despite significant differences in cardiac index and troponin T plasma level, BNP and NT-pro-BNP levels did not differ significantly between the two groups. Within patient, changes in BNP and NT-pro-BNP levels correlated significantly (p<0.01) with those in C-reactive protein values and those in leukocyte counts, but did not follow changes in PAOP. CONCLUSION: Our results add further evidence to the hypothesis that there is an interaction between the systemic inflammatory response and the natriuretic peptides. Thus, BNP and NT-pro-BNP levels should only be used cautiously as surrogates of cardiac filling and function in haemodynamic unstable critically ill patients.

Does the band cell survive the 21st century?

OBJECTIVES: The differentiation of white blood cells is a worldwide-accepted method to obtain medical information. The conventional microscopic differential, however, is a laborious and expensive test with a low statistical value. Especially for band cell identification there is a wide range of variance. In this report we describe the intervariability of band cell enumeration. METHODS: From a septic patient, an EDTA anti-coagulated blood sample was obtained and a smear was made and stained (May-Grünwald Giemsa). A PowerPoint presentation was made twice of 100 random cells and sent to 157 different hospital laboratories in the Netherlands for a leukocyte differential. In the first survey neutrophils were differentiated in segmented and band neutrophils whereas in the second survey no discrimination was made between segmented and band neutrophils. RESULTS: The first survey was responded by 68% of the laboratories (756 individuals) and the second survey by 73% of the laboratories (637 individuals). The laboratory mean values of the segmented neutrophils were 42.9% (SD: 7.8, range 22-64%) and 69.9% (SD: 1.4, range 62-72%) for the first and second survey respectively. For the individual technicians the values of the segmented neutrophils were 43.9% (SD: 11.2, range 15-72%) and 70.0% (SD: 2.0, range 59-77%) for the first and second survey respectively. CONCLUSIONS: Because of the enormous variation of band cell counting we recommend to cease quantitative reporting of band cells, especially since the results only have a clinical relevance in a limited number of pathological circumstances.