Higher Blood Neutrophil Counts Research Articles

Neutrophil counts and cardiovascular disease

Abstract Background and Aims Anti-inflammatory trials have shown considerable benefits for cardiovascular disease. High neutrophil counts, an easily accessible inflammation biomarker, are associated with atherosclerosis in experimental studies. This study aimed to investigate the associations between neutrophil counts and risk of nine cardiovascular endpoints using observational and genetic approaches. Methods Observational studies were conducted in the Copenhagen General Population Study (n = 101 730). Genetic studies were firstly performed using one-sample Mendelian randomization (MR) with individual-level data from the UK Biobank (n = 365 913); secondly, two-sample MR analyses were performed using summary-level data from the Blood Cell Consortium (n = 563 085). Outcomes included ischaemic heart disease, myocardial infarction, peripheral arterial disease, ischaemic cerebrovascular disease, ischaemic stroke, vascular-related dementia, vascular dementia, heart failure, and atrial fibrillation. Results Observational analyses showed associations between high neutrophil counts with high risks of all outcomes. In the UK Biobank, odds ratios (95% confidence intervals) per 1-SD higher genetically predicted neutrophil counts were 1.15 (1.08, 1.21) for ischaemic heart disease, 1.22 (1.12, 1.34) for myocardial infarction, and 1.19 (1.04, 1.36) for peripheral arterial disease; similar results were observed in men and women separately. In two-sample MR, corresponding estimates were 1.14 (1.05, 1.23) for ischaemic heart disease and 1.11 (1.02, 1.20) for myocardial infarction; multiple sensitivity analyses showed consistent results. No robust associations in two-sample MR analyses were found for other types of leucocytes. Conclusions Observational and genetically determined high neutrophil counts were associated with atherosclerotic cardiovascular disease, supporting that high blood neutrophil counts is a causal risk factor for atherosclerotic cardiovascular disease.

Investigation of Endotoxin Positivity in Ascites at the Time of Cell-free and Concentrated Ascites Re-infusion Therapy.

Objective The presence of endotoxin (ET) in ascites at the time of cell-free and concentrated ascites reinfusion therapy (CART) is generally assessed in patients with infectious disease status, but the exact rate of ET positivity in ascites for patients treated with CART is unknown. Methods We evaluated ET levels in ascites at the time of CART, regardless of the presence of infectious symptoms. The analysis was performed for 529 cases in 183 patients in whom ET levels in ascites were measured at 2 time points (pre- and post-processing). Results ET in ascites was positive in 8 of 529 cases. In the positive cases, the ET level after CART was significantly decreased. ET-positive patients had a significantly higher white blood cell count, neutrophil count, and serum CRP level before CART than ET-negative patients. Conclusion Collectively, our data suggest that ET may be present in ascites, regardless of the infectious symptoms, especially in patients with a high white blood cell count, neutrophil count, and serum CRP level. Although the ET level in the re-infusion ascites seems to be decreased by CART, the possibility of endotoxemia after CART should be considered for such patients.

Characterization of Obesity in Severe Asthma in the German Asthma Net

Asthma is increasingly recognized as heterogeneous, characterized by different endotypes, with obesity not only a distinct phenotype but a risk factor for severe asthma. We sought to understand the associations of obesity with relevant parameters of severe asthma, including asthma control, disease burden, and lung function. The German Asthma Net registry is a multicenter international real-life registry capturing long-term follow-up data. This analysis included 2213 patients (52 ± 16 years, 58% female, 29% with obesity [body mass index ≥30 kg/m2], 4.2 ± 4.3 exacerbations/year). The primary analysis assessed relationships between BMI and variables through univariate tests, followed by a multiple regression model. Secondary outcomes regarded clinically relevant variables in relation to weight groups. Patients with obesity were more frequently female, more likely to have depression and gastroesophageal reflux, and suffered from worse asthma control, lower quality of life, reduced static lung volumes, more pronounced hypoxemia, and higher blood neutrophil counts, all statistically significant. Blood eosinophils, exhaled nitric oxide, and total IgE were independent of obesity. In the multiple regression analysis, obesity was significantly associated with more frequent reflux and depression, reduced static lung function values, older age, poor asthma control, and long-acting muscarinic antagonist therapy, and inversely associated with bronchiectasis and nonsmoking status. In this large, well-characterized cohort, we identified the association of obesity with a significantly higher disease burden and a similar portfolio of inflammation type 2 markers in patients with and without obesity; therefore, patients with obesity seem similarly eligible for the treatment with biologics targeting these disease endotypes.

Long-term clinical outcomes of aspirin-exacerbated respiratory disease: Real-world data from an adult asthma cohort.

Aspirin-exacerbated respiratory disease (AERD) is a phenotype of severe asthma, but its disease course has not been well documented compared with that of aspirin-tolerant asthma (ATA). This study aimed to investigate the long-term clinical outcomes between AERD and ATA. AERD patients were identified by the diagnostic code and positive bronchoprovocation test in a real-world database. Longitudinal changes in lung function, blood eosinophil/neutrophil counts, and annual numbers of severe asthma exacerbations (AEx) were compared between the AERD and the ATA groups. Within a year after baseline, two or more severe AEx events indicated severe AERD, whereas less than two AEx events indicated nonsevere AERD. Among asthmatics, 353 had AERD in which 166 and 187 patients had severe and nonsevere AERD, respectively, and 717 had ATA. AERD patients had significantly lower FEV1%, higher blood neutrophil counts, and higher sputum eosinophils (%) (all p < .05) as well as higher levels of urinary LTE4 and serum periostin, and lower levels of serum myeloperoxidase and surfactant protein D (all p < .01) than those with ATA. In a 10-year follow-up, the severe AERD group maintained lower FEV1% with more severe AEs than the nonsevere AERD group. We demonstrated that AERD patients presented poorer long-term clinical outcomes than ATA patients in real-world data analyses.

Neutrophil-to-Lymphocyte Ratio (NLR) Useful as a Cost-Effective Preliminary Prognostic Marker in ST-Elevation Myocardial Infarction (STEMI): An Observational Study From a Tertiary Care Hospital in Northeast India.

Introduction Myocardial infarction, a major consequence of coronary artery disease, is an important cause of in-hospital mortality and morbidity worldwide. Blood neutrophil-to-lymphocyte ratio (NLR) is a novel laboratory marker of systemic inflammation that can predict the severity and mortality in various non-cardiovascular illnesses, including malignancy and infective pathology. We sought to evaluate its potential in predicting the outcome in hospitalized patients with myocardial infarction. Material and methods The index study was conducted at Silchar Medical College and Hospital from June 1, 2021 to May 31, 2022, with the aim of evaluating the role of NLR in determining the outcomes of ST-elevation myocardial infarction (STEMI). A total of 110 patients fulfilling the requisite criteria and admitted to the cardiology and medicine departments of the hospital with evidence of STEMI were included in the study and evaluated for the relationship of NLR with various outcome variables in STEMI. Results Out of 110 patients, 69.1% were males. The mean age of the study population was 58.2±15.3 years. The baseline characteristics and risk factors of patients who survived the acute attack of STEMI and those who died from complications of STEMI were similar. Laboratory parameters which correlated with worse outcomes included a higher fasting triglyceride level (173.4 mg vs. 215.6 mg, p < 0.001), a higher blood neutrophil count at baseline, 24 hours and 72 hours (70.1% vs. 69.04%, 66.3% vs. 75.2%, 81.6% vs. 73.8%, p<0.05), a higher NLR value at baseline, 24 hours and 72 hours (2.91 ± 1.13 vs. 3.19 ± 2.32, 2.39 ± 0.74 vs. 5.56 ± 4.11, 5.1 ± 4.38 vs. 3.01 ± 1.02, p < 0.05). Among patients hospitalized with STEMI who had high NLR, had significantly elevated incidence of complications, including a higher acute, left ventricular failure (42.8% vs. 35.9%; p < 0.05) as well as increased risk of mortality (66.7% vs. 33.3%; p < 0.05) compared to low NLR group. Conclusion NLR can predict the outcome among STEMI patients in terms of morbidity and mortality and correlates with poor left ventricular function. NLR can serve as a potential tool for early identification and efficient triage of STEMI patients during initial presentation to the ED. Its utility is more so in resource-constrained developing countries with limited access to health care. The significant advantage of NLR is its easy accessibility, rapid turnaround time, and inexpensiveness.

Blood Neutrophil Count and Neutrophil-to-Lymphocyte Ratio for Prediction of Disease Progression and Mortality in Two Independent Systemic Sclerosis Cohorts.

To assess the predictive significance of blood neutrophil count and the ratio between neutrophil and lymphocyte count (neutrophil-to-lymphocyte ratio [NLR]) for disease severity and mortality in systemic sclerosis (SSc). Neutrophil and lymphocyte counts were prospectively measured in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) and the Scleroderma Lung Study II (SLS II). Forced vital capacity percent predicted (FVC%) and modified Rodnan skin thickness score (MRSS) were used as surrogate measures for disease severity. Longitudinal analyses were performed using generalized linear mixed models. Cox proportional hazards models evaluated the predictive significance of these cell counts for mortality. Of the 447 SSc patients in the GENISOS cohort at the time of analysis, 377 (84.3%) had available baseline blood neutrophil and lymphocyte counts. Higher baseline neutrophil count and NLR predicted lower serially obtained FVC% (b= -4.74, P=0.009 and b=-2.68, P=0.028, respectively) and higher serially obtained MRSS (b=4.07, P < 0.001 and b=2.32, P < 0.001, respectively). Longitudinal neutrophil and NLR measurements also significantly correlated with lower concurrently obtained FVC% measurements and higher concurrently obtained MRSS. Baseline neutrophil count and NLR predicted increased risk of long-term mortality, even after adjustment for baseline demographic and clinical factors (hazard ratio [HR] 1.42, P=0.02 and HR 1.48, P < 0.001, respectively). The predictive significance of higher baseline neutrophil count and NLR for declining FVC% and increased long-term mortality was confirmed in the SLS II. Higher blood neutrophil count and NLR are predictive of more severe disease course and increased mortality, indicating that these easily obtainable laboratory studies might be a reflection of pathologic immune processes in SSc.

High blood neutrophil counts and ischemic vascular disease: Observational and genetic studies

Background and Aims : Background: High total leukocyte and neutrophil counts and the ratio between them have been associated with high risk of cardiovascular disease. Specific ischemic vascular endpoints have however not been investigated and the causal potential of such associations remains unexplored. Our aim was to examine the associations between blood leukocyte subpopulation counts and risk of specific ischemic vascular endpoints using observational and genetic studies.

Long-Term Use of Short-Acting β2-Agonists in Patients With Adult-Onset Asthma

Short-term studies have associated high use of short-acting β2-agonists (SABA) with increased risk of exacerbations, emergency visits, and asthma-related costs. However, no studies exist on long-term SABA use, and previous studies on the topic have not included information about adherence to inhaled corticosteroids (ICS) nor disease control, both affecting the need of SABA. To evaluate the clinical characteristics of SABA and ICS usage in newly diagnosed adult-onset asthma patients during a 12-year follow-up period. In the Seinäjoki Adult Asthma Study, 203 patients with adult-onset asthma were followed for 12 years. Information on dispensed SABA and ICS during the follow-up was obtained from the Finnish Social Insurance Institution. High SABA use was defined as ≥36 canisters in 12 years, corresponding to an average of ≥3 dispensed canisters/y. Patients were dispensed median 6 (interquartile range: 3-16) SABA canisters and 48 (18-67) ICS canisters over 12 years, corresponding to 2 (1-4) and 11 (5-16) puffs/week, respectively. Only 10% of the patients were classified as high SABA users during this period. Obesity (body mass index ≥30) and high Airways Questionnaire 20 symptom scores at baseline predicted high long-term SABA use (incidence rate ratio: 1.53 [1.01-2.30] and 1.04 [1.00-1.08], respectively). High SABA users had higher ICS adherence, higher blood neutrophil counts, more comorbidities, and used more oral corticosteroid and antibiotic courses versus low SABA users. High SABA use was infrequent in patients with confirmed adult-onset asthma. However, as high SABA use is associated with more severe asthma, these patients should be recognized in clinical practice.

Neutrophils, Cancer and Thrombosis: The New Bermuda Triangle in Cancer Research.

Spontaneous venous thrombosis is often the first clinical sign of cancer, and it is linked to a worsened survival rate. Traditionally, tumor-cell induced platelet activation has been the main actor studied in cancer-associated-thrombosis. However, platelet involvement alone does not seem to be sufficient to explain this heightened pro-thrombotic state. Neutrophils are emerging as key players in both thrombus generation and cancer progression. Neutrophils can impact thrombosis through the release of pro-inflammatory cytokines and expression of molecules like P-selectin and Tissue Factor (TF) on their membrane and on neutrophil-derived microvesicles. Their role in cancer progression is evidenced by the fact that patients with high blood-neutrophil counts have a worsened prognosis. Tumors can attract neutrophils to the cancer site via pro-inflammatory cytokine secretions and induce a switch to pro-tumoral (or N2) neutrophils, which support metastatic spread and have an immunosuppressive role. They can also expel their nuclear contents to entrap pathogens forming Neutrophil Extracellular Traps (NETs) and can also capture coagulation factors, enhancing the thrombus formation. These NETs are also known to have pro-tumoral effects by supporting the metastatic process. Here, we strived to do a comprehensive literature review of the role of neutrophils as drivers of both cancer-associated thrombosis (CAT) and cancer progression.

Association between occupational exposure to irritant agents and a distinct asthma endotype in adults

AimThe biological mechanisms of work-related asthma induced by irritants remain unclear. We investigated the associations between occupational exposure to irritants and respiratory endotypes previously identified among never asthmatics (NA) and...

Comparison of exacerbation phenotypes among patients with severe asthma.

Background: Exacerbation phenotypes among patients with severe asthma have been largely characterized during stable periods. Little is known about severe asthma patients during exacerbation periods. Objective: To compare persistently frequent exacerbators (PFE), non-persistently frequent exacerbators (NPFE), and infrequent exacerbators (IFE) among patients with severe asthma during stable and exacerbation periods. Methods: Patients with severe asthma who were admitted for asthma exacerbations from 2011 to 2017 and on follow up at Singapore General Hospital were recruited and categorized as PFEs (two or more exacerbations per year over 2 consecutive years), NPFEs (two or more exacerbations in 1 year only), or IFEs (fewer than two exacerbations per year over 2 consecutive years). Demographic, clinical, and laboratory data were collected at baseline and during exacerbation periods. Results: The participants were categorized as the following: 20 PFEs, 36 NPFEs, and 57 IFEs, with no significant demographic differences. The participants as PFEs (versus NPFEs and IFEs) were characterized by having a higher prevalence of psychiatric disorders (25% versus 8% versus 5%; p = 0.046), more comorbidities (7 versus 4 versus 2; p < 0.001), and a higher steroid burden per year (1150 versus 456 versus 350 mg; p < 0.001). The participants who were PFEs (versus IFEs) had a higher total immunoglobulin E (IgE) level (625 versus 232 IU/mL; p = 0.046) and longer duration of admission stay (3 versus 2 days; p = 0.009). All three groups had higher blood neutrophil counts during exacerbation periods than during stable periods (p = 0.008 versus p < 0.001 versus p = 0.004). Conclusion: The participants categorized as PFEs were characterized by comorbidities, higher steroid burden, IgE levels, and longer hospital stays. Exacerbations in the participants with severe asthma, regardless of exacerbation phenotype, were characterized by neutrophilia. These findings provided insights into potential therapeutic strategies to reduce exacerbations in patients with severe asthma.

Risks for cold frequency vary by sex: role of asthma, age, TLR7 and leukocyte subsets.

Viral respiratory infections are usually benign but can trigger asthma exacerbations. The factors associated with upper respiratory tract infection (cold) frequency are not fully understood, nor is it clear whether such factors differ between women and men.To determine which immunological and clinical variables associate with the frequency of self-reported respiratory infections (colds), 150 asthma cases and 151 controls were recruited. Associations between antiviral immune response variables: toll-like receptor (TLR)7/8 gene expression, plasmacytoid dendritic cell (pDC) numbers and interferon-α, tumour necrosis factor and interleukin-12 production, and asthma were then examined that might explain cold frequency.People with asthma cases reported more colds per year (median 3 versus 2; p<0.001) and had lower baseline TLR7 gene expression (odds ratio 0.12; p=0.02) than controls. Associations between many variables and cold frequency differed between women and men. In women, high blood neutrophil counts (β=0.096, p=0.002), and younger age (β=-0.017, p<0.001), but not exposure to children, were independently associated with more frequent colds. In men, low TLR7 expression (β=-0.96, p=0.041) and high CLEC4C gene expression (a marker of pDC; β=0.88, p=0.008) were independently associated with more frequent colds. Poor asthma symptom control was independently associated with reduced TLR8 gene expression (β=-1.4, p=0.036) and high body mass index (β=0.041, p=0.004).Asthma, age and markers of inflammation and antiviral immunity in peripheral blood are associated with frequent colds. Interestingly, the variables associated with cold frequency differed between women and men.

Infection-Related Hospitalization in Heart Failure With Reduced Ejection Fraction: A Prospective Observational Cohort Study.

Hospitalization is a common adverse event in people with heart failure and reduced ejection fraction, yet is often not primarily due to decompensated heart failure (HF). We investigated the long-term prognosis following infection-related hospitalization. We conducted a prospective observational cohort study of 711 people with heart failure and reduced ejection fraction recruited from 4 specialist HF clinics in the United Kingdom. All hospitalization episodes (n=1568) were recorded and categorized as primarily due to decompensated HF, other cardiovascular disease, infection-related, or other noncardiovascular disease. Survival was determined after the first hospitalization. During 2900 patient-years of follow-up, there were a total of 14 686 hospital days. At least one hospitalization occurred in 467 people (66%); 25% of first hospitalizations were primarily due to infection and these were not associated with typical signs including tachycardia and pyrexia. Compared with other categories of hospitalization, infection-related was associated with older age, lower serum albumin, higher blood neutrophil counts, and greater prevalence of chronic obstructive pulmonary disease at recruitment. Median survival after first infection-related hospitalization was 18.6 months, comparable to that after first decompensated HF hospitalization, even after age-sex adjustment. The burden of all-cause rehospitalization was comparable irrespective of the category of first hospitalization, but infection more commonly caused re-hospitalization after index infection hospitalization. Infection is a common driver of hospitalization in heart failure and reduced ejection fraction and often presents without classical signs. It is associated with high mortality rates, comparable to decompensated HF, and a major burden of rehospitalization caused by recurrent episodes of infection.

Serum Alpha-1 Antitrypsin Levels and the Clinical Course of Chronic Obstructive Pulmonary Disease.

PurposeAlpha-1 antitrypsin deficiency is associated with the development of chronic obstructive pulmonary disease (COPD), whereas increased levels of serum alpha-1antitrypsin occur in response to inflammation. The effects of alpha-1 antitrypsin levels on the clinical course of COPD had been unclear. We investigated the association of serum alpha-1 antitrypsin levels with the clinical course of COPD patients based on data from a 10-year prospective cohort study.Patients and methodsWe analyzed 278 COPD patients who participated in the Hokkaido COPD cohort study and who did not meet the criteria for alpha-1 antitrypsin deficiency. We divided the subjects into 3 groups according to quartiles of serum alpha-1 antitrypsin levels at baseline: lower group (<116 mg/dL, n = 66); middle group (116 to ≤141 mg/dL, n = 145); and higher group (>141 mg/dL, n = 67). The annual change in forced expiratory volume in 1 s (FEV1) and events of COPD exacerbation were monitored during the first 5 years, and mortality was followed-up during the entire 10 years.ResultsAt baseline, the higher group showed lower body mass index; higher computed tomography emphysema score; lower diffusing capacity; higher levels of acute-phase proteins; and higher blood neutrophil counts. Longitudinal analyses revealed that in the higher group, the annual decline in FEV1 was rapid and the 10-year mortality was higher, but there was no association between serum alpha-1 antitrypsin levels and time to first exacerbation.ConclusionCOPD subjects with higher serum alpha-1 antitrypsin levels were associated with a worse systemic inflammation status and higher 10-year mortality.

118. Nasopharyngeal (NP) Bacterial Detection in Infants With Respiratory Syncytial Virus (RSV) Infection: Impact on Clinical Outcomes

BackgroundPrevious studies suggest that RSV increases NP bacterial colonization and may facilitate infection. However, the role of NP colonization with potentially pathogenic bacteria (PPB) in the pathogenesis of RSV bronchiolitis is not well understood. We sought to determine the frequency, type, and density of NP PPB detection in infants with RSV infection compared with healthy controls (HC), and its association with clinical outcomes.MethodsSingle-center, prospective study of previously healthy infants with RSV infection and age-matched HC. Inpatients (IP) were enrolled within 24 hours of hospitalization, outpatients (OP) at the ED or primary clinics and HC at well-child visits. RSV infection and the following PPB: [S. pneumoniae, M. catarrhalis, H. influenzae, and S. aureus] were detected and quantified by PCR. We compared demographic, clinical characteristics, and outcomes of care according to NP PPB detection.ResultsFrom 2010 to 2018, we enrolled 815 infants: 664 with RSV infection [IP, 560; OP, 104] and 151 HC. RSV+ OP (6.1 [3.7–10.7] months) and HC (6.9 [3.8–10.8] months) were older than IP (2.5 [1.4–5.4] months; P < 0.001). Identification of ≥1 PPB was 89% in RSV+ infants [IP, 88%; OP, 90%] versus 63% of HC (P < 0.0001). While H. influenzae or >1 PPB detection was higher in RSV infection (P < 0.001), S. aureus detection predominated in HC (P < 0.05; Figure 1). Frequency of S. pneumoniae detection was comparable between groups; however, S. pneumoniae loads were one log higher in RSV+ infants versus HC (P = 0.001) adjusted for antibiotic use. Differences in colonization rates remained different in RSV+ infants versus HC across age ranges (<3, 3–6, >6–12, and >12–24 months; Figure 2). Last, RSV patients (both IP and OP) with S. pneumoniae or H. influenzae detection had fever more frequently (70%–74% vs. 25%–47%; P < 0.0001), higher clinical disease severity scores (P = 0.01), and higher blood neutrophil counts (34%–36% vs. 16%–19%; P < 0.001), versus those with M. catarrhalis, S. aureus detection or PCR negative. In addition, NP detection of H. influenzae in RSV children was associated with higher frequency of atelectasis/consolidation by chest X-ray (P < 0.005).ConclusionThese data suggest that NP colonization with PPB is high in infants with RSV infection independent of age, and that specific bacteria, namely S. pneumoniae and H. influenzae, are associated with enhanced clinical disease severity. Disclosures A. Leber, Nationwide Children’s Hospital: Research Contractor, Research support. O. Ramilo, Janssen Scientific Affairs, LLC: Consultant, Consulting fee. A. Mejias, Janssen: Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Abbvie: CME talks, Speaker honorarium.

Acute bronchiolitis: Influence of viral co-infection in infants hospitalized over 12 consecutive epidemic seasons.

Bronchiolitis is the first lower respiratory tract viral infection manifesting in infants younger than 12 months of age. Our aim was to evaluate clinical and serological differences in infants with bronchiolitis from a single or from multiple viruses. Our secondary aim was to investigate differences in recurrent wheezing episodes after 12‐24‐36 months of follow‐up. We reviewed the clinical records for 486 full‐term infants hospitalized for bronchiolitis with at least one virus detected in the nasopharyngeal aspirate. In 431 (88.7%) patients one virus was detected and in 55 (11.3%) infants more than one virus was found. No differences were observed in the length of hospitalization, clinical severity score, O2 supplementation or admission to the intensive care unit. Single virus was associated with higher serum C‐reactive protein (C‐RP) than infants with multiple viruses and higher blood neutrophil counts. Respiratory syncytial virus (RSV) was the most frequently detected virus. RSV alone was associated with higher C‐RP (P = 0.007), compared to RSV coinfection. Infants with human rhinovirus (hRV) alone had higher white blood cell counts, higher blood neutrophils, and higher serum C‐RP levels than hRV co‐infection (P = 0.029, P = 0.008, P = 0.008). RSV + hRV, the most frequent co‐infection, was associated with lower neutrophil count and lower C‐RP levels (P = 0.008, P = 0.016) and less fever (P = 0.012), when comparing RSV versus hRV versus RSV + hRV. No differences were found in the frequency of recurrent wheezing between single versus multiple viruses after bronchiolitis. Our findings suggest that in infants with bronchiolitis multiple viral co‐infections can occur, without influence in the clinical severity of the disease. Infants with co‐infection seems to mount a lower inflammatory response.

Association of Blood Eosinophil and Blood Neutrophil Counts with Asthma Exacerbations in the Copenhagen General Population Study.

Blood eosinophil count is a marker of eosinophilic airway inflammation and disease severity in asthma. However, blood neutrophil count might also be associated with disease severity. We tested the hypothesis that high blood eosinophil and neutrophil counts are both associated with the risk of asthma exacerbations among individuals with asthma from the general population. From the Copenhagen General Population Study with 81351 participants, we included 4838 with self-reported asthma. We recorded baseline blood eosinophil and neutrophil counts, and asthma exacerbations during follow-up in 2003-2011, defined as moderate (short-course treatment of prednisolone) or severe (hospitalization). The multivariable-adjusted incidence rate ratios (IRRs) were 1.28 (95% CI, 1.06-1.55) for moderate exacerbations and 1.55 (1.20-2.00) for severe exacerbations for individuals with blood eosinophil counts >0.29 × 109/L (highest tertile) vs individuals with blood eosinophil counts <0.18 × 109/L (lowest tertile). For blood neutrophils, the multivariable-adjusted IRRs were 2.14 (1.74-2.63) for moderate exacerbations and 1.18 (0.89-1.55) for severe exacerbations for individuals with blood neutrophil counts >4.85 × 109/L (highest tertile) vs individuals with blood neutrophil counts <3.77 × 109/L (lowest tertile). Blood eosinophil and neutrophil counts interacted on moderate exacerbations (P = 3 × 10-4), but not on severe exacerbations. High blood eosinophil counts are associated with an increased risk of both moderate and severe asthma exacerbations, while high blood neutrophil counts are associated with an increased risk of moderate, but not severe exacerbations.

Serum cytokine profiles as predictors of asthma control in adults from the EGEA study

BackgroundTo which extent serum cytokines may predict asthma control in adults remains understudied. ObjectivesWe investigated cross-sectional and longitudinal associations between cytokine profiles and asthma outcomes. MethodsSerum interleukin (IL)-1Ra, IL-5, IL-7, IL-8, IL-10, IL-13 and TNF-α levels were determined in 283 adults with current asthma from the 2nd survey of the Epidemiological Study on the Genetics and Environment of Asthma (EGEA2). Participants were followed-up seven years later. Asthma symptom control was assessed according to GINA 2015 guidelines. Cytokine profiles were identified by principal component (PC) analyses, and expressed as above/below the median. ResultsThe first two PCs captured 82.5% of the variability. While all seven cytokines scored high on PC1, only IL-1Ra and IL-10 scored high on PC2. At EGEA2, neither PC1 nor PC2 were related to exacerbations, asthma attacks, asthma symptom control, lung function, or allergic diseases. High level of PC1 (above the median) was associated with higher blood neutrophil counts (P = 0.02), while high level of PC2 was associated with lower IgE levels (P = 0.04). High level of PC2 at EGEA2 was associated with lower bronchial hyperresponsiveness (adjusted(a) OR[95%CI] = 0.46[0.23; 0.91]) and with subsequent lower risk of worsening asthma control and attacks (aOR[95%CI] = 0.24[0.09; 0.60]; 0.31[0.11; 0.85] respectively). ConclusionsSerum cytokine profiles with high levels of IL-1Ra and IL-10 were associated with lower subsequent risks of worsening asthma control and attacks in adults. This study adds new findings for the role of serum cytokine profiles to help identifying adults with subsequent risk of asthma burden that could be targeted for specific therapies.

Prognostic value of a quantitative analysis of lipoarabinomannan in urine from patients with HIV-associated tuberculosis.

BackgroundDetection of the mycobacterial cell wall antigen lipoarabinomannan (LAM) in urine can be used to diagnose HIV-associated tuberculosis (TB) using a qualitative (positive/negative) read-out. However, it is not known whether the quantity of LAM present in urine provides additional prognostic information.Methods/FindingsConsecutively recruited adult outpatients initiating antiretroviral therapy (ART) in South Africa were investigated for TB regardless of clinical symptoms using sputum smear microscopy and liquid culture (reference standard). Urine samples were tested using the Clearview TB-ELISA for LAM and the Xpert MTB/RIF assay. The ELISA optical densities (OD) were used as a quantitative assessment of urine LAM. Among 514 patients with complete sputum and urine LAM OD results, culture-confirmed TB was diagnosed in 84 patients. Twenty-three (27.3%) were LAM-positive with a median LAM OD of 0.68 (IQR 0.16–2.43; range, 0.10–3.29) and 61 (72.6%) were LAM negative (LAM OD <0.1 above background). Higher LAM ODs were associated with a range of prognostic indices, including lower CD4 cell counts, lower haemoglobin levels, higher blood neutrophil counts and higher mycobacterial load as assessed using both sputum and urine samples. The median LAM OD among patients who died was more than 6.8-fold higher than that of patients who remained alive at 3 months (P<0.001). The small number of deaths, however, precluded adequate assessment of mortality risk stratified according to urine LAM OD.ConclusionsIn patients with HIV-associated TB, concentrations of LAM in urine were strongly associated with a range of poor prognostic characteristics known to be associated with mortality risk. Urine LAM assays with a semi-quantitative (negative vs. low-positive vs. high-positive) read-out may have improved clinical utility over assays with a simple binary result.

Neutrophil Count for the Identification of Postmenopausal Hypertensive Women at Increased Cardiovascular Risk

High white blood cell and neutrophil counts identify patients at increased cardiovascular risk in various clinical settings. However, the prognostic value of white blood cell and neutrophil counts in hypertensive postmenopausal women is unknown. We tested the independent prognostic value of total white blood cell and neutrophil counts for cardiovascular events in hypertensive postmenopausal women. We examined 298 initially untreated postmenopausal women with essential hypertension who were part of Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA). Mean duration of follow-up was 8 years (range 1-20 years). Treatment was tailored to each individual. Mean age at entry was 59 years. Diabetic women comprised 9.1% of the group, and current smokers comprised 17.5% of the group. During follow-up, 31 new major cardiovascular events occurred. In univariable analyses, age, diabetes, serum creatinine, blood pressure, left ventricular hypertrophy, and neutrophil count showed an association with the risk of events (all P<.05). In a multivariable Cox analysis, after adjustment for traditional cardiovascular risk factors, for each 1.25x10 (1 standard deviation) increase in neutrophil count there was a 67% higher risk of cardiovascular events (hazard ratio 1.67, 95% confidence interval 1.32-2.07; P<.001). Furthermore, neutrophil count showed robust incremental predictive value for cardiovascular events, in addition to traditional risk factors. Total white blood cell count did not show any association with cardiovascular events. A high peripheral neutrophil count identifies postmenopausal hypertensive women at increased risk of cardiovascular disease. Such relation appears to be independent of traditional risk factors. III.