Chronic heart failure (CHF) is characterized by an ongoing nonresolving inflammatory status, where T lymphocytes seem critical. It has been recently recognized that transition from acute to chronic inflammation could be caused by defects in resolving inflammation, the resolution of which is mediated by a novel family of ω‐3‐derived specialized proresolving lipid mediators such as resolvins. We analyzed 27 elderly patients with CHF and 23 healthy age‐matched control subjects, and we reported significantly lower levels of D‐series resolvin (RvD)l in plasma of patients with CHF that were associated with a reduced ability of their leukocytes to produce this lipid via its biosynthetic enzyme 15‐lipoxygenase and that correlated with gas exchange dysfunction. Furthermore, when pretreating ex vivo peripheral blood mononuclear cells of patients with CHF with RvD1 or RvD2, we found that neither of them was able to modulate the immune response of CD8 ⁺ and CD4 ⁺ T cells in terms of proinflammatory cytokine production, namely TNF‐α, IFN‐γ, IL‐17, and IL‐2. Such impaired T‐cell responsiveness in patients with CHF was associated with a significant reduction in mRNA and protein expression of RvD1 receptor GPR32, suggesting a defective signaling in the proresolving pathway. We conclude that patients with CHF show alterations in producing proresolving mediator RvD1 and a failure of adaptive immune cells in responding to the anti‐inflammatory actions of RvDs that may contribute to the progression of chronic inflammation. Thus, the proresolution pathway might be a potential candidate to design better treatments for CHF aimed at reducing T cell‐mediated chronic inflammation.—Chiurchiù, V., Leuti, A., Saracini, S., Fontana, D., Finamore, P., Giua, R., Padovini, L., Incalzi, R. A., Maccarrone, M. Resolution of inflammation is altered in chronic heart failure and entails a dysfunctional responsiveness of T lymphocytes. FASEB J. 33, 909–916 (2019). www.fasebj.org

Introduction: The vast majority of respiratory diseases are associated with the production of volatile organic compounds (VOCs), the analysis of which might improve our knowledge about these disorders and their clinical management. The aim of this narrative review is to provide a comprehensive summary of current evidence supporting the application of breath analysis in the field of respiratory diseases, as well as suggesting potential applications available in the near future. Areas covered: A computerized literature search was performed to identify relevant articles reporting original data on the clinical use of breath analysis in respiratory diseases. Papers focusing on diseases other than respiratory, technical issues of VOC sampling and analysis, in vitro experiments or exogenous compounds were excluded. Expert commentary: Currently available evidence on the application of breath analysis in respiratory diseases is encouraging; however, it is mostly based on single center studies without external validation. The standardization of the technique, together with multicenter clinical trials with external validation, will ensure it is ready for clinical use. Current and new applications in respiratory diseases may represent a major breakthrough in the field, so much so as to deserve further efforts in outlining the most effective way to apply VOC analysis for clinical purposes.

Aim: Six-minute walking test distance (6MWD) and body mass index, obstruction, dyspnea and exercise (BODE) index are measures of functional status in COPD patients, but require space, time and patient’s compliance. Exhaled volatile organic compounds (VOCs) analysis via electronic nose is a quick and easy method that has already been used to discriminate COPD phenotypes. The aim of this study is to evaluate whether VOCs analysis can predict functional status and its variation over time in COPD patients. Methods: A monocentric prospective study with 1 year of follow-up was carried out. All patients underwent pulmonary function tests, arterial gas analysis, bioimpedance analysis, 6-minute walking test, and VOCs collection. Exhaled breath was collected with Pneumopipe^® and analyzed using BIONOTE electronic nose. Outcomes prediction was performed by k-fold cross-validated partial least square discriminant analysis: accuracy, sensitivity and specificity as well as Cohen’s kappa for agreement were calculated. Results: We enrolled 63 patients, 60.3% men, with a mean age of 71 (SD: 8) years, median BODE index of 1 (interquartile range: 0–3) and mean 6MWD normalized by squared height (n6MWD) of 133.5 (SD: 42) m/m². The BIONOTE predicted baseline BODE score (dichotomized as BODE score <3 or ≥3) with an accuracy of 86% and quartiles of n6MWD with an accuracy of 79%. n6MWD decline more than the median value after 1 year was predicted with an accuracy of 86% by BIONOTE, 52% by Global Initiative for Chronic Obstructive Lung Disease (GOLD) class and 78% by combined BIONOTE and GOLD class. Conclusion: Exhaled VOCs analysis identifies classes of BODE and n6MWD quartiles, and outperforms GOLD classification in predicting n6MWD variation.

Background: In older and multimorbid patients, chronic conditions may affect the prognostic validity of computed tomography (CT) findings in COVID-19. This study aims at assessing to which extent CT findings have prognostic implications in COVID-19 older patients. Methods: Hospitalized COVID-19 patients aged 60 years or more enrolled in the multicenter, observational and longitudinal GeroCovid study who underwent chest CT were included. Patients were stratified by tertiles of age and pneumonia severity to compare CT findings. Hierarchical clustering based on CT findings was performed to identify CT-related classificatory constructs, if any. The hazard ratio (HR) of mortality was calculated for individual CT findings and for clusters, after adjusting for potential confounders. Results: 380 hospitalized COVID-19 patients, with a mean age of 78 (SD:9) years, underwent chest CT scan. Ground glass opacity (GGO), consolidation, and pleural effusion were the three most common CT findings, with GGO prevalence decreasing from younger to older patients and pleural effusion increasing. More severe the pneumonia more prevalent were GGO, consolidation and pleural effusion. HR of mortality was 1.94 (95%CI 1.24–3.06) for pleural effusion and 13 (95%CI 6.41–27) for cluster with a low prevalence of GGO and a high prevalence of pleural effusion (“LH”), respectively. Out of the three CT based clusters, “LH” was the only independent predictor in the multivariable model. Conclusions: Pleural effusion qualifies as a distinctive prognostic marker in older COVID-19 patients. Research is needed to verify whether pleural effusion reflects COVID-19 severity or a coexisting chronic condition making the patient at special risk of death. Trial registration: ClinicalTrials.gov: NCT04379440

Background and Objectives: Obstructive sleep apnea syndrome (OSAS) represents an independent risk factor for cardiovascular, metabolic and neurological events. Polysomnography is the gold-standard for the diagnosis, however is expensive and time-consuming and not suitable for widespread use. Breath analysis is an innovative, non-invasive technique, able to provide clinically relevant information about OSAS. This systematic review was aimed to outline available evidence on the role of exhaled breath analysis in OSAS, taking into account the techniques’ level of adherence to the recently proposed technical standards. Materials and Methods: Articles reporting original data on exhaled breath analysis in OSAS were identified through a computerized and manual literature search and screened. Duplicate publications, case reports, case series, conference papers, expert opinions, comments, reviews and meta-analysis were excluded. Results: Fractional exhaled Nitric Oxide (FeNO) is higher in OSAS patients than controls, however its absolute value is within reported normal ranges. FeNO association with AHI is controversial, as well as its change after continuous positive airway pressure (C-PAP) therapy. Exhaled breath condensate (EBC) is acid in OSAS, cytokines and oxidative stress markers are elevated, they positively correlate with AHI and normalize after treatment. The analysis of volatile organic compounds (VOCs) by spectrometry or electronic nose is able to discriminate OSAS from healthy controls. The main technical issues regards the dilution of EBC and the lack of external validation in VOCs studies. Conclusions: Exhaled breath analysis has a promising role in the understanding of mechanisms underpinning OSAS and has demonstrated a clinical relevance in identifying individuals affected by the disease, in assessing the response to treatment and, potentially, to monitor patient’s adherence to mechanical ventilation. Albeit the majority of the technical standards proposed by the ERS committee have been followed by existing papers, further work is needed to uniform the methodology.