- Novel non-invasive early detection of lung cancer using liquid immunobiopsy metabolic activity profiles -
Cancer Immunol Immunother, 2018
Lung cancer is the leading cause of cancer death worldwide. Survival is largely dependent on the stage of diagnosis: the localized disease has a 5-year survival greater than 55%, whereas, for spread tumors, this rate is only 4%. Therefore, the early detection of lung cancer is key for improving prognosis. In this study, we present an innovative, non-invasive, cancer detection approach based on measurements of the metabolic activity profiles of immune system cells. For each Liquid ImmunoBiopsy test, a 384 multi-well plate is loaded with freshly separated PBMCs, and each well contains 1 of the 16 selected stimulants in several increasing concentrations. The extracellular acidity is measured in both air-open and hermetically-sealed states, using a commercial fluorescence plate reader, for approximately 1.5 h. Both states enable the measurement of real-time accumulation of 'soluble' versus 'volatile' metabolic products, thereby ifferentiating between oxidative phosphorylation and aerobic glycolysis. The metabolic activity profiles are analyzed for cancer diagnosis by machine-learning tools. We present a diagnostic accuracy study, using a multivariable prediction model to differentiate between lung cancer and control blood samples. The model was developed and tested using a cohort of 200 subjects (100 lung cancer and 100 control subjects), yielding 91% sensitivity and 80% specificity in a 20-fold cross-validation. Our results clearly indicate that the proposed clinical model is suitable for non-invasive early lung cancer diagnosis, and is indifferent to lung cancer stage and histological type.
- Pulmonary hemodynamics in heart failure patients with reduced or preserved ejection fraction and pulmonary hypertension: Similarities and disparities. -
Am Heart J. 2017
OBJECTIVE: The current understanding of pulmonary hypertension (PH) due to left ventricular diseases does not distinguish heart failure (HF) with reduced ejection fraction (HFrEF) from HF and preserved ejection fraction (HFpEF), in terms of pulmonary hemodynamics. The value of pulmonary vascular compliance (PCa) and diastolic pulmonary gradient (DPG) as predictors of survival in either HF syndrome is controversial. The aims of our study were to compare the pulmonary hemodynamics in the two HF phenotypes, given similar values of pulmonary artery wedge pressure (PAWP), and to evaluate the impact of PCa and DPG on survival.
METHODS: We retrospectively reviewed the charts of 168 PH-HFrEF and 86 PH-HFpEF patients. The independent association of PCa and DPG with prognosis was assessed by means of a Cox proportional hazard model. All cause survival was analyzed over an average follow-up period of 50 months.
RESULTS: PH-HFpEF patients had a significantly higher DPG than PH-HFrEF patients (6.1±7.1 vs 1.8±4.5 mmHg, adjusted P=.025). PCa was similar in PH-HFpEF and PH-HFrEF. PCa was a significant predictor of survival, according to previously described preset cutoffs (2.15 mL/mmHg in HFrEF and 1.1 mL/mmHg in HFpEF) and based on a continuous scale; whereas DPG had no impact on survival in both patients groups.
CONCLUSION: Our findings suggest that for similar levels of PAWP, pulmonary circulation may be stiffer in patients with HFpEF-PH than patients with HFrEF-PH, leading to higher DPGs. Nonetheless, PCa rather than DPG emerged as the stronger predictor of survival in both left-sided PH phenotypes.
- Circulating eosinophil levels do not predict severe exacerbations in COPD: a retrospective study -
ERJ Open Res. 2018 Aug
Whether the level of circulating eosinophils in chronic obstructive pulmonary disease (COPD) patients can predict the risk of exacerbations of COPD (ECOPD) or response to treatment is debated. Here, we evaluate the prevalence of elevated eosinophils in COPD patients and its relationship with severe ECOPD requiring hospitalisation. We retrospectively reviewed the charts of COPD patients hospitalised in our centre between January 1, 2005 and November 30, 2015 because of ECOPD or other reasons (controls). In a second analysis, the ECOPD patients were divided into two subgroups based on having ECOPD in the next year after the index event or not. Circulating eosinophils, both during clinical stability and hospitalisation, as well as clinical and functional data and the relation to recurrent exacerbations were analysed. We studied 992 COPD patients (318 ECOPD patients and 674 controls). Among ECOPD patients, 121 had one or more ECOPD during the year after the index event. The prevalence of eosinophils ≥2% was 72% in ECOPD patients and 71% in controls (p=0.93). Among ECOPD patients, eosinophil levels ≥2%, ≥4% or ≥300 cells·μL-1, either when clinically stable or during hospitalisation, did not show a significant association with the rate of recurrent severe exacerbations. The severity of airflow limitation was associated with recurrent exacerbations, but inhaled corticosteroid treatment was not. The majority of COPD patients have circulating eosinophils >2% and a significant association with the risk of severe ECOPD or response to inhaled corticosteroids was not demonstrated.
- Can asthmatic subjects dive? -
Eur Respir, Rev. 2016
Recreational diving with self-contained underwater breathing apparatus (scuba) has grown in popularity. Asthma is a common disease with a similar prevalence in divers as in the general population. Due to theoretical concern about an increased risk for pulmonary barotrauma and decompression sickness in asthmatic divers, in the past the approach to asthmatic diver candidates was very conservative, with scuba disallowed. However, experience in the field and data in the current literature do not support this dogmatic approach. In this review the theoretical risk factors of diving with asthma, the epidemiological data and the recommended approach to the asthmatic diver candidate will be described.