Serum uric acid is increased in respiratory disease, especially in the presence of hypoxia and systemic inflammation. We evaluated serum uric acid as a biomarker for prediction of mortality and future acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Serum uric acid was measured in 314 eligible consecutive patients on admission for AECOPD. Patients were evaluated monthly for 1 year.Uric acid levels were higher in patients with more severe airflow limitation and in those experiencing frequent exacerbations. High uric acid levels (o6.9 mg?dL -1 ) were an independent predictor of 30-day mortality in multivariate Cox regression analysis (HR 1.317, 95% CI 1.011-1.736; p50.044), but not of 1-year mortality. Patients with high serum uric acid required more prolonged hospitalisation, and more often needed noninvasive ventilation and admission to the intensive care unit within 30 days. In addition, high uric acid levels were associated with increased risk and hospitalisation for AECOPD in 1 year in multivariate Poisson regression analysis (incidence rate ratio 1.184 (95% CI 1.125-1.246) and 1.190 (95% CI 1.105-1.282), respectively; both p,0.001).Serum uric acid is associated with increased 30-day mortality and risk for AECOPD and hospitalisations in 1-year follow-up. This low-cost biomarker may be useful in the identification of high-risk chronic obstructive pulmonary disease patients that could benefit from intensive management. @ERSpublications Serum uric acid was linked with airflow limitation in COPD and predicted mortality and future exacerbations

The impact of depressive symptoms on outcomes of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) has not been thoroughly evaluated in prospective studies.We prospectively enrolled 230 consecutive patients hospitalised for AECOPD, without previous diagnosis of depression. Depressive symptoms were evaluated with Beck's depression inventory. Pulmonary function tests, arterial blood gases, COPD assessment test (CAT) and Borg dyspnoea scale were recorded on admission and on days 3, 10 and 40. Patients were evaluated monthly for 1 year.Patients with depressive symptoms required longer hospitalisation (mean¡SD 11.6¡3.7 versus 5.6¡4.1 days, p,0.001). Clinical variables improved during the course of AECOPD, but depressive symptoms on admission had a significant impact on dyspnoea (p,0.001) and CAT score (p50.012) improvement. Patients with depressive symptoms presented more AECOPD (p,0.001) and more hospitalisations for AECOPD (p,0.001) in 1 year. In multivariate analysis, depressive symptoms were an independent predictor of mortality (hazard ratio 3.568, 95% CI 1.302-9.780) and risk for AECOPD (incidence rate ratio (IRR) 2.221, 95% CI 1.573-3.135) and AECOPD hospitalisations (IRR 3.589, 95% CI 2.319-5.556) in 1 year.The presence of depressive symptoms in patients admitted for AECOPD has a significant impact on recovery and is related to worse survival and increased risk for subsequent COPD exacerbations and hospitalisations in 1 year.

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Currently, and based on the development of relevant biologic therapies, T2-high is the most well-defined endotype of asthma. Although much progress has been made in elucidating T2-high inflammation pathways, no specific clinically applicable biomarkers for T2-low asthma have been identified. The therapeutic approach of T2-low asthma is a problem urgently needing solution, firstly because these patients have poor response to steroids, and secondly because they are not candidates for the newer targeted biologic agents. There is, thus, an unmet need for the identification of biomarkers that can help the diagnosis and endotyping of T2-low asthmaOngoing investigation is focusing on neutrophilic airway inflammation mediators as therapeutic targets, including IL-8, IL-17, IL-1, IL-6, IL-23, TNF-a; molecules that target to restore corticosteroid sensitivity, mainly mitogen-activated protein kinase inhibitors, tyrosine kinase inhibitors and phosphatidylinositol 3-kinase inhibitors; PDE3 inhibitors that act as bronchodilators and PDE4 inhibitors that have an anti-inflammatory effect; and airway smooth muscle mass attenuation therapies, mainly for patients with paucigranulocytic inflammationThis manuscript aims to review the evidence for non-eosinophilic inflammation being a target for therapy in asthma, discuss current and potential future therapeutic approaches, such as novel molecules and biologic agents, and assess clinical trials of licensed drugs in the treatment of T2-low asthma.

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 prioritized for inclusion in the core outcome set through a two-round Delphi survey that was completed by 1,063 participants (256 patients, 488 health professionals and 319 clinical academics) from 88 countries in 5 continents. Two global, multi-stakeholder, virtual consensus meetings were conducted to (i) finalize the core outcome set and (ii) prioritize a single measurement instrument to be used for evaluating each of the prioritized outcomes. Consensus was informed by rigorous methodological systematic reviews. The views of patients with COPD were accounted for in all stages of the project. Survival, treatment success, breathlessness, quality of life, activities of daily living, need for 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 optimize some of the selected measurement instruments. The panel did not consider the prioritized set of outcomes and associated measurement instruments burdensome for patients and health professionals to use.