The clinical context for using blood eosinophil (EOS) counts as treatment-response biomarkers in asthma and COPD requires better understanding of EOS distributions and ranges. We describe EOS ...distributions and ranges published in asthma, COPD, control (non-asthma/COPD) and general populations.
We conducted a comprehensive literature review and meta-analysis of observational studies (January 2008 to November 2018) that included EOS counts in asthma, severe asthma, COPD, control and general populations. Excluded studies had total sample sizes <200, EOS as inclusion criterion, hospitalised population only and exclusively paediatric participants.
Overall, 91 eligible studies were identified, most had total-population-level data available: asthma (39 studies), severe asthma (12 studies), COPD (23 studies), control (seven studies) and general populations (14 studies); some articles reported data for multiple populations. Reported EOS distributions were right-skewed (seven studies). Reported median EOS counts ranged from 157-280 cells·µL
(asthma, 22 studies); 200-400 cells·µL
(severe asthma, eight studies); 150-183 cells·µL
(COPD, six studies); and 100-160 cells·µL
(controls, three studies); and 100-200 cells·µL
(general populations, six studies). The meta-analysis showed that observed variability was mostly between studies rather than within studies. Factors reportedly associated with higher blood EOS counts included current smoking, positive skin-prick test, elevated total IgE, comorbid allergic rhinitis, age ≤18 years, male sex, spirometric asthma/COPD diagnosis, metabolic syndrome and adiposity.
EOS distribution and range varied by study population, and were affected by clinical factors including age, smoking history and comorbidities, which, regardless of severity, should be considered during treatment decision-making.
There is growing interest in blood eosinophil counts in the management of chronic respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD). Despite this, typical blood ...eosinophil levels in the general population, and the impact of potential confounders on these levels have not been clearly defined.We measured blood eosinophil counts in a random sample of 11 042 subjects recruited from the general population in Austria. We then: 1) identified factors associated with high blood eosinophil counts (>75th percentile); and 2) excluded subjects with these factors to estimate median blood eosinophil counts in a "healthy" sub-population (n=3641).We found that: 1) in the entire cohort, age ≤18 years (OR 2.41), asthma (OR 2.05), current smoking (OR 1.72), positive skin prick test (OR 1.64), COPD (OR 1.56), metabolic syndrome (OR 1.41), male sex (OR 1.36) and obesity (OR 1.16) were significantly (p<0.05) associated with high blood eosinophil counts (binary multivariable logistic regression analysis), and had an additive effect; and 2) after excluding these factors, in those older than 18 years, blood eosinophil counts were higher in males than in females (median 120 (5%-95% CI: 30-330)
100 (30-310) cells·µL
, respectively) and did not change with age.Median blood eosinophil counts in adults are considerably lower than those currently regarded as normal, do not change with age beyond puberty, but are significantly influenced by a variety of factors which have an additive effect. These observations will contribute to the interpretation of blood eosinophil levels in clinical practice.
Background: The Lung, hEart, sociAl, boDy (LEAD) Study (ClinicalTrials.gov; NCT01727518; http://clinicaltrials.gov) is a longitudinal, observational, population-based Austrian cohort that aims to ...investigate the relationship between genetic, environmental, social, developmental and ageing factors influencing respiratory health and comorbidities through life. The general working hypothesis of LEAD is the interaction of these genetic, environmental and socioeconomic factors influences lung development and ageing, the risk of occurrence of several non-communicable diseases (respiratory, cardiovascular, metabolic and neurologic), as well as their phenotypic (ie, clinical) presentation. Methods: LEAD invited from 2011–2016 a random sample (stratified by age, gender, residential area) of Vienna inhabitants (urban cohort) and all the inhabitants of six villages from Lower Austria (rural cohort). Participants will be followed-up every four years. A number of investigations and measurements were obtained in each of the four domains of the study (Lung, hEart, sociAl, boDy) including data to screen for lung, cardiovascular and metabolic diseases, osteoporosis, and cognitive function. Blood and urine samples are stored in a biobank for future investigations. Results: A total of 11.423 males (47.6%) and females (52.4%), aged 6–80 years have been included in the cohort. Compared to governmental statistics, the external validity of LEAD with respect to age, gender, citizenship, and smoking status was high. Conclusions: In conclusion, the LEAD cohort has been established following high quality standards; it is representative of the Austrian population and offers a platform to understand lung development and ageing as a key mechanism of human health both in early and late adulthood.
Evidence is weak for the ability of long-term non-invasive positive pressure ventilation (NPPV) to improve survival in patients with stable hypercapnic chronic obstructive pulmonary disease (COPD). ...Previous prospective studies did not target a reduction in hypercapnia when adjusting ventilator settings. This study investigated the effect of long-term NPPV, targeted to markedly reduce hypercapnia, on survival in patients with advanced, stable hypercapnic COPD.
This investigator-initiated, prospective, multicentre, randomised, controlled clinical trial enrolled patients with stable GOLD stage IV COPD and a partial carbon dioxide pressure (PaCO2) of 7 kPa (51.9 mm Hg) or higher and pH higher than 7.35. NPPV was targeted to reduce baseline PaCO2 by at least 20% or to achieve PaCO2 values lower than 6.5 kPa (48.1 mm Hg). Patients were randomly assigned (in a 1:1 ratio) via a computer-generated randomisation sequence with a block size of four, to continue optimised standard treatment (control group) or to receive additional NPPV for at least 12 months (intervention group). The primary outcome was 1-year all-cause mortality. Analysis was by intention to treat. The intervention was unblinded, but outcome assessment was blinded to treatment assignment. This study is registered with ClinicalTrials.gov, number NCT00710541.
Patients were recruited from 36 respiratory units in Germany and Austria, starting on Oct 29, 2004, and terminated with a record of the vital status on July 31, 2011. 195 patients were randomly assigned to the NPPV group (n=102) or to the control group (n=93). All patients from the control group and the NPPV group were included in the primary analysis. 1-year mortality was 12% (12 of 102 patients) in the intervention group and 33% (31 of 93 patients) in the control group; hazard ratio 0.24 (95% CI 0.11-0.49; p=0.0004). 14 (14%) patients reported facial skin rash, which could be managed by changing the type of the mask. No other intervention-related adverse events were reported.
The addition of long-term NPPV to standard treatment improves survival of patients with hypercapnic, stable COPD when NPPV is targeted to greatly reduce hypercapnia.
German Lung Foundation; ResMed, Germany; Tyco Healthcare, Germany; and Weinmann, Germany.
•Long-term air pollution (PM10) exposure was associated with higher fat mass index and lower lean mass index in children and adolescents.•Estimates from longitudinal analyses investigating ...associations between environmental exposures and changes in body composition over an average of 4 years, were positive for PM10 for certain conditions but not for other exposures.•Railway and road-traffic noise exposures were not associated with body composition, both in cross-sectional and longitudinal analyses.
While long-term air pollution and noise exposure has been linked to increasing cardiometabolic disease risk, potential effects on body composition remains unclear. This study aimed to investigate the associations of long-term air pollution, noise and body composition.
We used repeated data from the LEAD (Lung, hEart, sociAl, boDy) study conducted in Vienna, Austria. Body mass index (BMI; kg/m2), fat mass index (FMI; z-score), and lean mass index (LMI; z-score) were measured using dual-energy x-ray absorptiometry at the first (t0; 2011-ongoing) and second (t1; 2017-ongoing) examinations. Annual particulate matter (PM10) and nitrogen dioxide (NO2) concentrations were estimated with the GRAMM/GRAL model (2015–2021). Day-evening-night (Lden) and night-time (Lnight) noise levels from transportation were modeled for 2017 following the European Union Directive 2002/49/EC. Exposures were assigned to residential addresses. We performed analyses separately in children/adolescents and adults, using linear mixed-effects models with random participant intercepts and linear regression models for cross-sectional and longitudinal associations, respectively. Models were adjusted for co-exposure, lifestyle and sociodemographics.
A total of 19,202 observations (nt0 = 12,717, nt1 = 6,485) from participants aged 6–86 years (mean age at t0 = 41.0 years; 52.9 % female; mean PM10 = 21 µg/m3; mean follow-up time = 4.1 years) were analyzed. Among children and adolescents (age ≤ 18 years at first visit), higher PM10exposure was cross-sectionally associated with higher FMI z-scores (0.09 95 % Confidence Interval (CI): 0.03, 0.16) and lower LMI z-scores (−0.05 95 % CI: −0.10, −0.002) per 1.8 µg/m3. Adults showed similar trends in cross-sectional associations as children, though not reaching statistical significance. We observed no associations for noise exposures. Longitudinal analyses on body composition changes over time yielded positive associations for PM10, but not for other exposures.
Air pollution exposure, mainly PM10, was cross-sectionally and longitudinally associated with body composition in children/adolescents and adults. Railway/road-traffic noise exposures showed no associations in both cross-sectional and longitudinal analyses.
Reference values for lung volumes are necessary to identify and diagnose restrictive lung diseases and hyperinflation, but the values have to be validated in the relevant population. Our aim was to ...investigate the Global Lung Function Initiative (GLI) reference equations in a representative healthy Austrian population and create population-derived reference equations if poor fit was observed.
We analysed spirometry and body plethysmography data from 5371 respiratory healthy subjects (6-80 years) from the Austrian LEAD Study. Fit with the GLI equations was examined using z-scores and distributions within the limits of normality. LEAD reference equations were then created using the LMS method and the generalized additive model of location shape and scale package according to GLI models.
Good fit, defined as mean z-scores between + 0.5 and -0.5,was not observed for the GLI static lung volume equations, with mean z-scores > 0.5 for residual volume (RV), RV/TLC (total lung capacity) and TLC in both sexes, and for expiratory reserve volume (ERV) and inspiratory capacity in females. Distribution within the limits of normality were shifted to the upper limit except for ERV. Population-derived reference equations from the LEAD cohort showed superior fit for lung volumes and provided reproducible results.
GLI lung volume reference equations demonstrated a poor fit for our cohort, especially in females. Therefore a new set of Austrian reference equations for static lung volumes was developed, that can be applied to both children and adults (6-80 years of age).
We analyzed SARS-CoV-2 seroprevalence in a large, well-described representative Viennese cohort after an early governmental lockdown with respect to the occurrence of symptoms and household ...transmission. Participants of the LEAD Study, a population-based cohort study from Vienna, Austria, were invited along with their household members (April 20th to May20th 2020). Sera were analyzed using anti-SARS-CoV-2 immunoassay including a neutralization test as a confirmatory assay. A total of 12,419 individuals participated (5984 LEAD participants; 6435 household members), 163 (1.31%; 59 LEAD cohort members) of whom were SARS-CoV-2 antibody positive. The estimated number of COVID-19 cases projected from our findings by age and sex for Vienna was 21,504 (1.13%). Cumulative number of positively tested cases in Vienna until May 20th 2020 was 3020, hence 7.1 times (95% confidence interval 5.5-9.1) lower than projected. Relative risk (RR) of seropositivity by age was highest for children aged 6-9 years RR compared to age group 20-49: 1.21 (CI 0.37-4.01), lowest for ≥ 65 years RR 0.47 (CI 0.21-1.03). Half of the positive individuals developed no or mild symptoms. In a multivariate analysis, taste and smell disturbances were most strongly related to SARS-CoV-2 positivity. Infection probability within households with one confirmed SARS-CoV-2-specific antibody-positive person was 31%. Although seroprevalence was very low (1.13%) for a central European capital city, due to an early governmental lockdown, SARS-CoV-2 infections were more prevalent than officially reported polymerase chain reaction-positive cases. Of note, seroprevalence was highest in young children. Half of SARS-CoV-2 antibody-positive subjects had no or only mild symptoms. Taste and smell disturbances were most prominent, possibly guiding clinicians in diagnosing SARS-CoV-2 infection.
Appropriate use of antibiotics in the management of hospitalised patients with COPD exacerbations is defined within the GOLD strategy. This paper analyses the factors associated with antibiotic ...prescribing in patients to better understand how prescribing may be improved.
The European COPD audit was a study of clinical care in 384 hospitals from 13 European countries between 2010 and 2011 enrolling 16018 patients. Those admitted to hospital due to a clinician-made diagnosis of exacerbation of COPD at the time of discharge were audited. We defined antibiotic prescribing compliance as consistent with the GOLD 2010 recommendations. Two different multivariate models were used to evaluate factors associated with the prescription of antibiotics and the guideline-compliant prescriptions.
Overall 86% of admissions were given antibiotics but only 61.4% cases met the GOLD recommendations. Antibiotics were more likely to be given in hospital and at discharge if received prior to admission. Antibiotic prescription was more likely in patients who met the GOLD recommendations and in those with radiological consolidation but there was also a significant use of antibiotics in patients who did not meet either criterion. Patients cared for on a Respiratory Ward were more likely to receive GOLD compliant antibiotic management.
The present study describes the audited in-hospital antibiotic prescription for COPD exacerbation across different European countries. In general, there is an apparent overuse of antibiotics likely to be associated with both patient and practice-related variables.
There is controversy regarding the significance of radiological consolidation in the context of COPD exacerbation (eCOPD). While some studies into eCOPD exclude these cases, consolidation is a common ...feature of eCOPD admissions in real practice. This study aims to address the question of whether consolidation in eCOPD is a distinct clinical phenotype with implications for management decisions and outcomes.
The European COPD Audit was carried out in 384 hospitals from 13 European countries between 2010 and 2011 to analyze guideline adherence in eCOPD. In this analysis, admissions were split according to the presence or not of consolidation on the admission chest radiograph. Groups were compared in terms of clinical and epidemiological features, existing treatment, clinical care utilized and mortality.
14,111 cases were included comprising 2,714 (19.2%) with consolidation and 11,397 (80.8%) without. The risk of radiographic consolidation increased with age, female gender, cardiovascular diseases, having had two or more admissions in the previous year, and sputum color change. Previous treatment with inhaled steroids was not associated. Patients with radiographic consolidation were significantly more likely to receive antibiotics, oxygen and non-invasive ventilation during the admission and had a lower survival from admission to 90-day follow-up.
Patients admitted for COPD exacerbation who have radiological consolidation have a more severe illness course, are treated more intensively by clinicians and have a poorer prognosis. We recommend that these patients be considered a distinct subset in COPD exacerbation.
Abstract Background Physical exercise training is an evidence-based treatment in chronic obstructive pulmonary disease, and patients' peak work rate is associated with reduced chronic obstructive ...pulmonary disease mortality. We assessed whether supplemental oxygen during exercise training in nonhypoxemic patients with chronic obstructive pulmonary disease might lead to superior training outcomes, including improved peak work rate. Methods This was a randomized, double-blind, controlled, crossover trial. Twenty-nine patients with chronic obstructive pulmonary disease (aged 63.5 ± 5.9 years; forced expiratory volume in 1 second percent predicted, 46.4 ± 8.6) completed 2 consecutive 6-week periods of endurance and strength training with progressive intensity, which was performed 3 times per week with supplemental oxygen or compressed medical air (flow via nasal cannula: 10 L/min). Each session of electrocardiography-controlled interval cycling lasted 31 minutes and consisted of a warm-up, 7 cycles of 1-minute intervals at 70% to 80% of peak work rate alternating with 2 minutes of active recovery, and final cooldown. Thereafter, patients completed 8 strength-training exercises of 1 set each with 8 to 15 repetitions to failure. Change in peak work rate was the primary study end point. Results The increase in peak work rate was more than twice as high when patients exercised with supplemental oxygen compared with medical air (0.16 ± 0.02 W/kg vs 0.07 ± 0.02 W/kg; P < .001), which was consistent with all other secondary study end points related to exercise capacity. The impact of oxygen on peak work rate was 39.1% of the overall training effect, whereas it had no influence on strength gain ( P > .1 for all exercises). Conclusions We report that supplemental oxygen in nonhypoxemic chronic obstructive pulmonary disease doubled the effect of endurance training but had no effect on strength gain.
PDF
