Effects of anti-IL5 biological treatments on blood IgE levels in severe asthmatic patients: A real-life multicentre study (BIONIGE)

Background: Mepolizumab and benralizumab are clinically effective biological treatments for severe eosinophilic asthmatic patients by hampering eosinophilic inflammation. The effects of these compound on the immunoglobulin (Ig)E T2 component are virtually unknown. Objectives: To evaluate the change in total IgE levels at 4 ± 2 months after initiation of the mepolizumab (primary outcome) or benralizumab. When available, the changes of blood inflammatory cell counts, lung function and asthma control test (ACT) were also assessed and correlated with changes in total IgE levels. Methods: Observational, retrospective, multicentre, cohort study. Severe eosinophilic atopic asthmatic patients treated with mepolizumab or benralizumab were included in the analysis. Results: Three-month treatment (on average) with mepolizumab (n = 104) or benralizumab (n = 82) resulted in significantly higher reduction of blood eosinophil and basophil levels in patients treated with benralizumab compared to mepolizumab. Mepolizumab did not significantly modified the levels of blood total IgE during the study period, whereas benralizumab significantly reduced (−35%, p < 0.001) total blood IgE levels. In patients treated with benralizumab the reduction of blood total Ig-E levels correlated with the reduction of blood basophils (but not eosinophils) and weakly with the improvement of asthma control. Conclusion: Benralizumab but not mepolizumab, treatment led to a significant reduction of circulating IgE level. The study provides different and specific mechanisms of action for anti-IL5-pathway treatments

[Pathology of chronic obstructive pulmonary disease]

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder of the lung characterized by poorly reversible airflow limitation. It is not a unique disease entity but rather a complex of conditions which include emphysema, chronic bronchitis and, sometimes, asthma. Moreover, COPD is a progressive disease often associated with exacerbations. Cigarette smoking, which is the most important risk factor for the development of COPD, induces pathological changes involving lung parenchyma, peripheral airways and central airways. Since lung parenchyma and peripheral airways are the sites responsible for airflow limitation and central airways are the main site of mucus hypersecretion, pathological changes in these compartments may be relevant in the development of COPD

Metabolic-Associated Fatty Liver Disease Is Highly Prevalent in the Postacute COVID Syndrome.

Background: A proposal has recently been advanced to change the traditional definition of nonalcoholic fatty liver disease to metabolic-associated fatty liver disease (MAFLD), to reflect the cluster of metabolic abnormalities that may be more closely associated with cardiovascular risk. Long coronavirus disease 2019 (COVID-19) is a smoldering inflammatory condition, characterized by several symptom clusters. This study aims to determine the prevalence of MAFLD in patients with postacute COVID syndrome (PACS) and its association with other PACS-cluster phenotypes. Methods: We included 235 patients observed at a single university outpatient clinic. The diagnosis of PACS was based on ≥1 cluster of symptoms: respiratory, neurocognitive, musculoskeletal, psychological, sensory, and dermatological. The outcome was prevalence of MAFLD detected by transient elastography during the first postdischarge follow-up outpatient visit. The prevalence of MAFLD at the time of hospital admission was calculated retrospectively using the hepatic steatosis index. Results: Of 235 patients, 162 (69%) were men (median age 61). The prevalence of MAFLD was 55.3% at follow-up and 37.3% on admission (P < .001). Insulin resistance (odds ratio [OR] = 1.5; 95% confidence interval [CI], 1.14-1.96), body mass index (OR = 1.14; 95% CI, 1.04-1.24), and the metabolic syndrome (OR = 2.54; 95% CI, 1.13-5.68) were independent predictors of MAFLD. The number of PACS clusters was inversely associated with MAFLD (OR = 0.86; 95% CI, .76-0.97). Thirty-one patients (13.2%) had MAFLD with no other associated PACS clusters. All correlations between MAFLD and other PACS clusters were weak. Conclusions: Metabolic-associated fatty liver disease was highly prevalent after hospital discharge and may represent a specific PACS-cluster phenotype, with potential long-term metabolic and cardiovascular health implications

Core outcome set for the management of acute exacerbations of chronic obstructive pulmonary disease: the COS-AECOPD ERS Task Force study protocol.

Randomised controlled trials (RCTs) on the management of COPD exacerbations evaluate heterogeneous outcomes, often omitting those that are clinically important and patient relevant. This limits their usability and comparability. A core outcome set (COS) is a consensus-based minimum set of clinically important outcomes that should be evaluated in all RCTs in specific areas of health care. We present the study protocol of the COS-AECOPD ERS Task Force, aiming to develop a COS for COPD exacerbation management, that could remedy these limitations. For the development of this COS we follow standard methodology recommended by the COMET initiative. A comprehensive list of outcomes is assembled through a methodological systematic review of the outcomes reported in relevant RCTs. Qualitative research with patients with COPD will also be conducted, aiming to identify additional outcomes that may be important to patients, but are not currently addressed in clinical research studies. Prioritisation of the core outcomes will be facilitated through an extensive, multi-stakeholder Delphi survey with a global reach. Selection will be finalised in an international, multi-stakeholder meeting. For every core outcome, we will recommend a specific measurement instrument and standardised time points for evaluation. Selection of instruments will be based on evidence-informed consensus. Our work will improve the quality, usability and comparability of future RCTs on the management of COPD exacerbations and, ultimately, the care of patients with COPD. Multi-stakeholder engagement and societal support by the European Respiratory Society will raise awareness and promote implementation of the COS

ERS statement: A core outcome set for clinical trials evaluating the management of COPD exacerbations

Clinical trials evaluating the management of acute exacerbations of COPD assess heterogeneous outcomes, often omitting those that are clinically relevant or more important to patients. We have developed a core outcome set, a consensus-based minimum set of important outcomes that we recommend are evaluated in all future clinical trials on exacerbations management, to improve their quality and comparability. COPD exacerbations outcomes were identified through methodological systematic reviews and qualitative interviews with 86 patients from 11 countries globally. The most critical outcomes were prioritised for inclusion in the core outcome set through a two-round Delphi survey completed by 1063 participants (256 patients, 488 health professionals and 319 clinical academics) from 88 countries in five continents. Two global, multi-stakeholder, virtual consensus meetings were conducted to 1) finalise the core outcome set and 2) prioritise a single measurement instrument to be used for evaluating each of the prioritised outcomes. Consensus was informed by rigorous methodological systematic reviews. The views of patients with COPD were accounted for at all stages of the project. Survival, treatment success, breathlessness, quality of life, activities of daily living, the need for a higher level of care, arterial blood gases, disease progression, future exacerbations and hospital admissions, treatment safety and adherence were all included in the core outcome set. Focused methodological research was recommended to further validate and optimise some of the selected measurement instruments. The panel did not consider the prioritised set of outcomes and associated measurement instruments to be burdensome for patients and health professionals to use

Exhaled and arterial levels of endothelin-1 are increased and correlate with pulmonary systolic pressure in COPD with pulmonary hypertension

BACKGROUND: Endothelin-1 (ET-1) and Nitric Oxide (NO) are crucial mediators for establishing pulmonary artery hypertension (PAH). We tested the hypothesis that their imbalance might also occur in COPD patients with PAH. METHODS: The aims of the study were to measure exhaled breath condensate (EBC) and circulating levels of ET-1, as well as exhaled NO (FENO) levels by, respectively, a specific enzyme immunoassay kit, and by chemiluminescence analysis in 3 groups of subjects: COPD with PAH (12), COPD only (36), and healthy individuals (15). In order to evaluate pulmonary-artery systolic pressure (PaPs), all COPD patients underwent Echo-Doppler assessment. RESULTS: Significantly increased exhaled and circulating levels of ET-1 were found in COPD with PAH compared to both COPD (p < 0.0001) only, and healthy controls (p < 0.0001). In COPD with PAH, linear regression analysis showed good correlation between ET-1 in EBC and PaPs (r = 0.621; p = 0.031), and between arterial levels of ET-1 and PaPs (r = 0.648; p = 0.022), while arterial levels of ET-1 inversely correlated with FEV1%, (r = -0.59, p = 0.043), and PaPs negatively correlated to PaO2 (r = -0.618; p = 0.032). Significantly reduced levels of FENO were found in COPD associated with PAH, compared to COPD only (22.92 +/- 11.38 vs.35.07 +/- 17.53 ppb; p = 0.03). Thus, we observed an imbalanced output in the breath between ET-1 and NO, as expression of pulmonary endothelium and epithelium impairment, in COPD with PAH compared to COPD only. Whether this imbalance is an early cause or result of PAH due to COPD is still unknown and deserves further investigations

Associations of IL-4, IL-4R, and IL-13 Gene Polymorphisms in Coal Workers' Pneumoconiosis in China: A Case-Control Study

Background: The IL-4, IL-4 receptor (IL4R), and IL-13 genes are crucial immune factors and may influence the course of various diseases. In the present study, we investigated the association between the potential functional polymorphisms in IL-4, IL-4R, and IL-13 and coal workers ’ pneumoconiosis (CWP) risk in a Chinese population. Methods: Six polymorphisms (C-590T in IL-4, Ile50Val, Ser478Pro, and Gln551Arg in IL-4R, C-1055T and Arg130Gln in IL-13) were genotyped and analyzed in a case-control study of 556 CWP and 541 control subjects. Results: Our results revealed that the IL-4 CT/CC genotypes were associated with a significantly decreased risk of CWP (odd

Prevalence of anaemia in older persons: systematic review

<p>Abstract</p> <p>Background</p> <p>Ageing populations will impact on healthcare provision, especially since extra years are not necessarily spent in good health. It is important to identify and understand the significance of common medical problems in older people. Anaemia may be one such problem. We report on the prevalence of anaemia in cohorts of elderly people in the general population. The presence of anaemia is associated with a worse prognosis for both morbidity and mortality.</p> <p>Methods</p> <p>Electronic searching and reference lists of published reports were used to identify studies that reported on prevalence of anaemia in cohorts of at least 100 individuals predominantly aged 65 years and over living in developed countries, together with criteria used to define anaemia. Studies of anaemia prevalence in specific disease groups or published before 1980 were excluded. Prevalence data for the entire cohort, for men and women separately and for different age bands were extracted.</p> <p>Results</p> <p>Forty-five studies contributed data. Thirty-four studies (n = 85,409) used WHO criteria to define anaemia. The weighted mean prevalence was 17% (3–50%) overall, and 12% (3–25%) in studies based in the community (27, n = 69,975), 47% (31–50%) in nursing homes (3, n = 1481), and 40% (40–72%) in hospital admissions (4, n = 13,953). Anaemia prevalence increased with age, was slightly higher in men than women, and was higher in black people than white. Most individuals classified as anaemic using WHO criteria were only mildly anaemic.</p> <p>Conclusion</p> <p>Anaemia, as defined by WHO criteria, is common in older people living in the community and particularly common in nursing home residents and hospital admissions. Predicted demographic changes underline the need to understand more about anaemia in older people.</p

Early incidence of occupational asthma among young bakers, pastry-makers and hairdressers: design of a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Occupational exposures are thought to be responsible for 10-15% of new-onset asthma cases in adults, with disparities across sectors. Because most of the data are derived from registries and cross-sectional studies, little is known about incidence of occupational asthma (OA) during the first years after inception of exposure. This paper describes the design of a study that focuses on this early asthma onset period among young workers in the bakery, pastry making and hairdressing sectors in order to assess early incidence of OA in these "at risk" occupations according to exposure duration, and to identify risk factors of OA incidence.</p> <p>Methods/Design</p> <p>The study population is composed of subjects who graduated between 2001 and 2006 in these sectors where they experience exposure to organic or inorganic allergenic or irritant compounds (with an objective of 150 subjects by year) and 250 young workers with no specific occupational exposure. A phone interview focusing on respiratory and 'Ear-Nose-Throat' (ENT) work-related symptoms screen subjects considered as "possibly OA cases". Subjects are invited to participate in a medical visit to complete clinical and lung function investigations, including fractional exhaled nitric oxide (FE_NO) and carbon monoxide (CO) measurements, and to collect blood samples for IgE (Immunoglobulin E) measurements (total IgE and IgE for work-related and common allergens). Markers of oxidative stress and genetic polymorphisms exploration are also assessed. A random sample of 200 "non-cases" (controls) is also visited, following a nested case-control design.</p> <p>Discussion</p> <p>This study may allow to describ a latent period between inception of exposure and the rise of the prevalence of asthma symptoms, an information that would be useful for the prevention of OA. Such a time frame would be suited for conducting screening campaigns of this emergent asthma at a stage when occupational hygiene measures and adapted therapeutic interventions might be effective.</p> <p>Trial registration</p> <p>Clinical trial registration number is NCT01096537.</p