Non-eosinophilic Exacerbations Research Articles

Mucus Plugs as Precursors to Exacerbation and Lung Function Decline in COPD Patients

BackgroundMucus plugs identified through chest computed tomography (CT) scans have emerged as potential prognostic factors in chronic obstructive pulmonary disease (COPD). This 5-year longitudinal study investigated their impact on exacerbations and FEV1 decline. MethodsCOPD patients with baseline chest CT and spirometric assessments were categorized based on mucus plug presence. Propensity-score matching yielded balanced groups. Exacerbation rates, time to exacerbation events, hazard ratio (HR) for exacerbations, and annual rates of FEV1 decline were evaluated. Sensitivity analysis was performed with stratification according to mucus plug scores of 0, 1–2, and ≥3. ResultsAmong 623 eligible patients, the mucus plug group was 44.3%. Through 1:1 propensity-score matching, each group was comprised of 187 individuals with balanced covariates. The mucus plug group showed higher rates of moderate-to-severe (0.51/year vs. 0.58/year, P=0.035), severe exacerbations (0.21/year vs. 0.24/year, P=0.032), and non-eosinophilic exacerbations (0.45/year vs. 0.52/year, P=0.008). Mucus plugs were associated with increased hazard of moderate-to-severe (adjusted HR=1.502 [95% CI 1.116–2.020]), severe (adjusted HR=2.106 [95% CI, 1.429–3.103]), and non-eosinophilic exacerbations (adjusted HR=1.551 [95% CI, 1.132–2.125]). Annual FEV1 decline was accelerated in the mucus plug group (β-coefficient=−62 [95% CI, −120 to −5], P=0.035). Sensitivity analysis showed higher risk of exacerbations and accelerated FEV1 decline in mucus plug score ≥3 compared to score 0. ConclusionsMucus plugs are associated with increased risks of exacerbations, particularly non-eosinophilic, and accelerated FEV1 declines over 5 years. Our study identified the potential prognostic value of mucus plugs on future exacerbation risks and lung function decline trajectories.

Exploring the Interaction between Fractional Exhaled Nitric Oxide and Biologic Treatment in Severe Asthma: A Systematic Review.

Fractional exhaled nitric oxide (FeNO) is a biomarker of airway inflammation associated with airway hyper-responsiveness and type-2 inflammation. Its role in the management of severe asthmatic patients undergoing biologic treatment, as well as FeNO dynamics during biologic treatment, is largely unexplored. The aim was to evaluate published data contributing to the following areas: (1) FeNO as a predictive biomarker of response to biologic treatment; (2) the influence of biologic treatment in FeNO values; (3) FeNO as a biomarker for the prediction of exacerbations in patients treated with biologics. The systematic search was conducted on the Medline database through the Pubmed search engine, including all studies from 2009 to the present. Higher baseline values of FeNO are associated with better clinical control in patients treated with omalizumab, dupilumab, and tezepelumab. FeNO dynamics during biologic treatment highlights a clear reduction in FeNO values in patients treated with anti-IL4/13 and anti-IL13, as well as in patients treated with tezepelumab. During the treatment, FeNO may help to predict clinical worsening and to differentiate eosinophilic from non-eosinophilic exacerbations. Higher baseline FeNO levels appear to be associated with a greater benefit in terms of clinical control and reduction of exacerbation rate, while FeNO dynamics during biologic treatment remains a largely unexplored issue since few studies have investigated it as a primary outcome. FeNO remains detectable during biologic treatment, but its potential utility as a biomarker of clinical control is still unclear and represents an interesting research area to be developed.

Predictors of Influenza PCR Positivity in Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

PurposeInfluenza infection is an important cause of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Clinical features predicting influenza PCR positivity are unknown. We aim to identify predictors of influenza PCR positivity in AECOPD.Patients and MethodsA retrospective study of AECOPD cases admitted between 1st January 2016 to 30 June 2017 with combined nasal/throat swabs sent for influenza PCR (Xpert Xpress Flu/RSV) within 24 hours of admission was performed. Clinical parameters and investigations within 24 hours of admission were retrieved from electronic medical records.ResultsInfluenza PCR were sent for 925 AECOPD cases (mean age 75 years, 87.9% male). There were 90 PCR positive cases (68 Influenza A, 22 Influenza B). Influenza PCR positive cases had higher temperatures, higher heart rates, lower white cell and lower eosinophil counts. Age, gender, COPD severity, comorbidities and smoking status were similar in both groups. There were no differences in blood pressure, oxygen status, neutrophil or lymphocyte counts, C reactive protein, procalcitonin or chest X-ray consolidation between groups. Higher temperature, higher heart rate, white cell count in the lowest quartile (Q1 < 8.1 x109/L) and non-eosinophilic exacerbations predicted influenza PCR positivity on univariate logistic regression and these factors remained significant after multivariate adjustment (temperature adjusted odds ratio [adj OR] 1.324 [1.009–1.737], p = 0.043; heart rate adj OR 1.017 [1.004–1.030], p = 0.011; white cell count Q1 adj OR 3.330 [1.690–6.562], p = 0.001; eosinophilic exacerbations adj OR 0.390 [0.202–0.756], p = 0.005).ConclusionHigher temperature, higher heart rate, low white cell count (especially when < 8.1 x109/L) and non-eosinophilic exacerbations are independent predictors of influenza PCR positivity in AECOPD cases.

High eosinophil blood counts are associated with a shorter length of hospital stay in exacerbated COPD patients \u2013 a retrospective analysis

BackgroundIn 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 methodsWe 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%).ResultsPatients 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.ConclusionThe 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.

Year in review 2017: Chronic obstructive pulmonary disease and asthma.

Year in review 2017: Chronic obstructive pulmonary disease and asthma.

Does eosinophilia and neutrophil to lymphocyte ratio affect hospital re-admission in cases of COPD exacerbation?

We aimed to assess the relationship between peripheral eosinophilia and neutrophil/lymphocyte ratio with hospital admissions and re-admissions with chronic obstructive pulmonary disease (COPD) exacerbations. An observational cohort study was carried out in a tertiary teaching hospital. Subjects with previously diagnosed COPD and who were admitted as outpatients with acute exacerbations were included. The subjects' characteristics, complete blood count (CBC) parameters, neutrophil to lymphocyte rate (NLR), C-reactive protein (CRP), mean platelet volume (MPV) on admission and re-admission within the first 28 days. Patients were grouped according to their peripheral blood eosinophilia levels; group 1, > 2% (eosinophilic), group 2, ≤ 2% (non-eosinophilic or neutrophilic). The recorded data from the two groups were compared. 1490 eligible COPD subjects were enrolled. Approximately 42% were classified as eosinophilic. The non-eosinophilic group had a significantly higher leukocyte count, neutrophil percentage, and NLR than the eosinophilic group. The NLR value in patients with repeat re-admissions was higher than the average, i.e., 4.50 (p= 0.001). MPV and CRP measured on admission and re-admission were similar in both groups. The rate of hospital re-admission within 28 days was significantly higher in patients with a non-eosinophilic attack. When a patient is admitted to outpatients with a NLR greater than 4.50 and with a non-eosinophilic exacerbation they have an increased risk of re-admission in the first month. Higher NLR values and non-eosinophilic exacerbations may be helpful for the early detection of potential acute attacks in COPD patients, and may be indicators for antibiotic management.

Clinical characteristics of eosinophilic asthma exacerbations.

ABSTRACTBackground and objectiveAirway eosinophilia is associated with an increased risk of asthma exacerbations; however, the impact on the severity of exacerbations is largely unknown. We describe the sputum inflammatory phenotype during asthma exacerbation and correlate it with severity and treatment response.MethodsPatients presenting to hospital with an asthma exacerbation were recruited during a 12‐month period and followed up after 4 weeks. Induced sputum was collected at both visits. Patients underwent spirometry, arterial blood gas analysis, fractional exhaled nitric oxide analysis, white blood cell counts and a screening for common respiratory viruses and bacteria. An eosinophilic exacerbation (EE) was defined as having sputum eosinophils ≥ 3% and a non‐eosinophilic exacerbation as < 3% (NEE).ResultsA total of 47 patients were enrolled; 37 (79%) had successful sputum induction at baseline, of whom 43% had sputum eosinophils ≥3% (EE). Patients with EE had a significantly lower forced expiratory volume in 1 s (FEV1) % predicted (70.8%, P = 0.03) than patients with NEE (83.6%). Furthermore, EE patients were more likely to require supplemental oxygen during admission (63% vs 14%, P = 0.002). The prevalence of respiratory viruses was the same in EE and NEE patients (44% vs 52%, P = 0.60), as was bacterial infection (6% vs 14%, P = 0.44). Fractional expiratory nitric oxide (FeNO) correlated with sputum %‐eosinophils (ρ = 0.57, P < 0.001), and predicted airway eosinophilia with a sensitivity of 86% and a specificity of 70%.ConclusionOur findings suggest that eosinophilic asthma exacerbations may be clinically more severe than NEEs, supporting the identification of these higher risk patients for specific interventions.

Blood Eosinophils and Outcomes in Severe Hospitalized Exacerbations of COPD

Patients with moderate exacerbations of COPD and the eosinophilic phenotype have better outcomes with prednisolone. Whether this outcome is similar in patients hospitalized with a severe exacerbation of COPD is unclear. We investigated the rate of recovery of eosinophilic and noneosinophilic exacerbations in patients participating in a multicenter randomized controlled trial assessing health outcomes in hospitalized exacerbations. Patients were recruited at presentation to the hospital with an exacerbation of COPD. They were stratified into groups according to eosinophilic exacerbations if the peripheral blood eosinophil count on admission was≥ 200 cells/μL and/or≥ 2%of the total leukocyte count. Admission details, serum C-reactive protein levels, length of stay, and subsequent rehospitalization data were compared between groups. A total of 243 patients with COPD (117 men) with a mean age of 71 years (range, 45-93 years) were recruited. The inpatient mortality rate was 3%(median time to death, 12days; range, 9-16days). The median absolute eosinophil count was 100 cells/μL (range, 10-1,500 cells/μL), and 25%met our criteria for an eosinophilic exacerbation; in this population, the mean length of stay (in days) was shorter than in patients with noneosinophilic exacerbations (5.0 [range, 1-19] vs6.5 [range, 1-33]; P= .015) following treatment with oral corticosteroids and independent of treatment prior to admission. Readmission rates at 12months were similar between groups. The study patients presenting to the hospital with a severe eosinophilic exacerbation of COPD had a shorter length of stay. The exacerbations were usually not associated with elevated C-reactive protein levels, suggesting that better treatment stratification of exacerbations can be used. http://www.isrctn.com/ISRCTN05557928.

S26 Severe hospitalised exacerbations of COPD with an eosinophilic phenotype have favourable outcomes with prednisolone therapy: sub-analysis from a prospective multi-centre randomised control trial

IntroductionIn moderate exacerbations of COPD, patients with the eosinophilic phenotype (>2% of the total leukocyte count) have better outcomes with prednisolone. However, it remains unclear whether patients with severe exacerbations...

Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations

One important goal of asthma treatment is to reduce exacerbations. The current authors investigated if the use of sputum cell counts to guide treatment would achieve this goal. A total of 117 adults with asthma were entered into a multicentre, randomised, parallel group-effectiveness study for two treatment strategies over a 2-yr period. In one strategy (the clinical strategy: CS) treatment was based on symptoms and spirometry. In the other (the sputum strategy: SS) sputum cell counts were used to guide corticosteroid therapy to keep eosinophils<or=2%; symptoms and spirometry were used to identify clinical control, exacerbations and other treatments. Patients were blind to sputum cell counts in both strategies and physicians were blind in the CS, thus removing bias. First, the minimum treatment to maintain control was identified in 107 patients (Phase 1) and then this treatment was continued (Phase 2) for the remaining of the 2 yrs. The primary outcomes were the relative risk reduction for the occurrence of the first exacerbation in Phase 2 and the length of time without exacerbation. The current authors also examined the type and severity of exacerbations and the cumulative dose of inhaled steroid needed. The duration and number of exacerbations in Phase 1 were similar in both groups. In Phase 2 there were a 126 exacerbations of which 79 occurred in the CS (62.7%) and 47 (37.3%) in the SS groups. The majority of the 126 exacerbations (101; 80.1%) were mild. The majority of the 102 exacerbations, where sputum examination was performed before any treatment (n=70), were noneosinophilic. In the SS patients, the time to the first exacerbation was longer (by 213 days) especially in those considered to need treatment with a long acting beta2-agonist (by 490 days), the relative risk ratio was lower (by 49%), and the number of exacerbations needing prednisone was reduced (5 versus 15). This benefit was seen mainly in patients needing treatment with inhaled steroid in a daily dose equivalent to fluticasone>250 microg, and was due to fewer eosinophilic exacerbations. The cumulative dose of corticosteroid during the trial was similar in both groups. Monitoring sputum cell counts was found to benefit patients with moderate-to-severe asthma by reducing the number of eosinophilic exacerbations and by reducing the severity of both eosinophilic and noneosinophilic exacerbations without increasing the total corticosteroid dose. It had no influence on the frequency of noneosinophilic exacerbations, which were the most common exacerbations.