Arantza Campo

Hyperleptinaemia, respiratory drive and hypercapnic response in obese patients

Leptin is a powerful stimulant of ventilation in rodents. In humans, resistance to leptin has been consistently associated with obesity. Raised leptin levels have been reported in subjects with sleep apnoea or obesity–hypoventilation syndrome. The aim of the present study was to assess, by multivariate analysis, the possible association between respiratory centre impairment and levels of serum leptin. In total, 364 obese subjects (body mass index ≥30 kg·m−2) underwent the following tests: sleep studies, respiratory function tests, baseline and hypercapnic response (mouth occlusion pressure (P0.1), minute ventilation), fasting leptin levels, body composition and anthropometric measures. Subjects with airways obstruction on spirometry were excluded. Out of the 346 subjects undergoing testing, 245 were included in the current analysis. Lung volumes, age, log leptin levels, end-tidal carbon dioxide tension, percentage body fat and minimal nocturnal saturation were predictors for baseline P0.1. The hypercapnic response test was performed by 186 subjects; log leptin levels were predictors for hypercapnic response in males, but not in females. Hyperleptinaemia is associated with a reduction in respiratory drive and hypercapnic response, irrespective of the amount of body fat. These data suggest the extension of leptin resistance to the respiratory centre.

Gender and Chronic Obstructive Pulmonary Disease in High-Risk Smokers

Background: Data suggest that women are more susceptible to develop airway obstruction compared to men for the same number of cigarettes smoked. Objectives: To compare the prevalence of chronic obstructive lung disease (COPD) and the effect of smoking on the risk of developing COPD according to gender, in a population of high-risk smokers. Methods: In 795 smokers, spirometry was performed using the criteria of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) to determine airflow obstruction. COPD prevalence was determined in smokers grouped according to the number of cigarettes smoked per year [<20 (I), 20–40 (II), 40–60 (III) and >60 pack-years (IV)] and age. Results: Men were older, smoked more and for a longer period. Age at smoking initiation and the number of packs smoked per day did not differ. COPD was diagnosed in 26% of the subjects (30.5% men and 22.3% women, p < 0.001) with similar degree of obstruction (forced expiratory volume in 1 s: 78% of predicted in men vs. 75% in women). COPD prevalence was lower in women in all categories irrespective of the pack-year history (I: 9 vs. 19%; II: 16 vs. 28%; III: 28 vs. 39%, and IV: 25 vs. 42%, respectively, p < 0.001). In those older than 50 years, 34% men and 17% women (p < .001) had COPD. Conclusions: Using the GOLD criteria, the prevalence of COPD in smokers was higher than previous reports. In this self-selected sample of high-risk smokers having the same smoking history, prevalence was lower in women than in men, suggesting a lower susceptibility for the development of airway obstruction.

Comparing algorithms for automated vessel segmentation in computed tomography scans of the lung: the VESSEL12 study

The VESSEL12 (VESsel SEgmentation in the Lung) challenge objectively compares the performance of different algorithms to identify vessels in thoracic computed tomography (CT) scans. Vessel segmentation is fundamental in computer aided processing of data generated by 3D imaging modalities. As manual vessel segmentation is prohibitively time consuming, any real world application requires some form of automation. Several approaches exist for automated vessel segmentation, but judging their relative merits is difficult due to a lack of standardized evaluation. We present an annotated reference dataset containing 20 CT scans and propose nine categories to perform a comprehensive evaluation of vessel segmentation algorithms from both academia and industry. Twenty algorithms participated in the VESSEL12 challenge, held at International Symposium on Biomedical Imaging (ISBI) 2012. All results have been published at the VESSEL12 website http://vessel12.grand-challenge.org. The challenge remains ongoing and open to new participants. Our three contributions are: (1) an annotated reference dataset available online for evaluation of new algorithms; (2) a quantitative scoring system for objective comparison of algorithms; and (3) performance analysis of the strengths and weaknesses of the various vessel segmentation methods in the presence of various lung diseases.

Emphysema Presence, Severity, and Distribution Has Little Impact on the Clinical Presentation of a Cohort of Patients With Mild to Moderate COPD

BACKGROUND Phenotypic characterization of patients with COPD may have potential prognostic and therapeutic implications. Available information on the relationship between emphysema and the clinical presentation in patients with COPD is limited to advanced stages of the disease. The objective of this study was to describe emphysema presence, severity, and distribution and its impact on clinical presentation of patients with mild to moderate COPD. METHODS One hundred fifteen patients with COPD underwent clinical and chest CT scan evaluation for the presence, severity, and distribution of emphysema. Patients with and without emphysema and with different forms of emphysema distribution (upper/lower/core/peel) were compared. The impact of emphysema severity and distribution on clinical presentation was determined. RESULTS Fifty percent of the patients had mild homogeneously distributed emphysema (1.84; 0.76%-4.77%). Upper and core zones had the more severe degree of emphysema. Patients with emphysema were older, more frequently men, and had lower FEV(1)%, higher total lung capacity percentage, and lower diffusing capacity of the lung for carbon monoxide. No differences were found between the clinical or physiologic parameters of the different emphysema distributions. CONCLUSIONS In patients with mild to moderate COPD, although the presence of emphysema has an impact on physiologic presentation, its severity and distribution seem to have little impact on clinical presentation.

Low-dose volumetric computed tomography for quantification of emphysema in asymptomatic smokers participating in an early lung cancer detection trial.

Purpose High-resolution computed tomography (CT) is a validated method to quantify the extent of pulmonary emphysema. In this study, we assessed the reliability of low-dose volumetric CT (LDCT) for the quantification of emphysema and its correlation with spirometric indices of airway obstruction. Materials and Methods The study population consisted of 102 consecutive current and former smokers participating in a lung cancer screening trial. All subjects underwent spirometry testing and LDCT at entry and a LDCT after 12 months. The extent of emphysema was estimated by 2 techniques; by using the lung attenuation threshold analysis and by visual assessment of the 2 independent radiologists. The reproducibility of these determinations was assessed using test-retest reliability and κ coefficient of agreement. The correlation of LDCT-based emphysema determinations with indices of airway obstruction on spirometry was also calculated. Results Eighty percent of the participants were male, with a mean (standard deviation) age of 54.5 (7.5) years, and median pack-years (interquartile range) of 20 (24). Test-retest reliability of all LDCT-based emphysema determinations was very good (intraclass correlation coefficient of 0.92 for the volume of emphysema, and 0.93 for the emphysema index or emphysema volume/total lung volume). Similarly, there was an excellent interrater agreement for visual assessment of emphysema (κ coefficient=0.91). Higher volumes of emphysema measured quantitatively or visually significantly correlated with spirometric markers of airway obstruction. Conclusions Volumetric LDCT is a reliable and valid technique for the quantification of emphysema in asymptomatic smokers.

Clinical Features of Smokers With Radiological Emphysema But Without Airway Limitation

Background: The clinical characteristics of patients with emphysema but without airway limitations remain unknown. The goal of this study was to compare the clinical features of current and former smokers without airflow limitation who have radiologic emphysema on chest CT scans vs a control group of current and ex‐smokers without emphysema. Methods: Subjects enrolled had anthropometric characteristics recorded, provided a medical history, and underwent low‐dose chest CT scanning. The following parameters were also evaluated: pulmonary function tests including diffusion capacity for carbon monoxide (Dlco), the modified Medical Research Council dyspnea score, COPD assessment test (CAT), and 6‐min walk test (6MWT). A comparison was conducted between those with and without CT‐confirmed emphysema. Results: Of the 203 subjects, 154 had emphysema, and 49 did not. Adjusted group comparisons revealed that a higher proportion of patients with emphysema according to low‐dose chest CT scanning had an abnormal Dlco value (< 80%) (46% vs 19%; P = .02), a decrease in percentage of oxygen saturation > 4% during the 6MWT (8.5% vs 0; P = .04), and an altered quality of life (CAT score ≥ 10) (32% vs 14%; P = .01). A detailed analysis of the CAT questionnaire items revealed that more patients with emphysema had a score ≥ 1 in the “chest tightness” (P = .05) and “limitation when doing activities at home” (P < .01) items compared with those with no emphysema. They also experienced significantly more exacerbations in the previous year (0.19 vs 0.04; P = .02). Conclusions: A significant proportion of smokers with emphysema according to low‐dose chest CT scanning but without airway limitation had alterations in their quality of life, number of exacerbations, Dlco values, and oxygen saturation during the 6MWT test.

Assessment of indeterminate pulmonary nodules detected in lung cancer screening: Diagnostic accuracy of FDG PET/CT

BACKGROUND A major drawback of lung cancer screening programs is the high frequency of false-positive findings on computed tomography (CT). We investigated the accuracy of selective 2-[fluorine-18]-fluoro-2-deoxy-d-glucose (FDG) Positron Emission Tomography/Computed Tomography (PET/CT) scan in assessing radiologically indeterminate lung nodules detected in lung cancer screening. METHODS FDG PET/CT was performed to characterize 64 baseline lung nodules >10mm and 36 incidence nodules detected on low-dose CT screening in asymptomatic current or former smokers (83 men, age range 40-83 years) at high risk for lung cancer. CT images were acquired without intravenous contrast. Nodules were analyzed by size, density, and metabolic activity and visual scored on a 5-point scale for FDG uptake. Nodules were classified as negative for malignancy when no FDG uptake was observed, or positive when focal uptake was observed in the visual analysis, and the maximum standardized uptake value (SUVmax) was measured. Final diagnosis was based on histopathological evaluation or at least 24 months of follow-up. RESULTS A total of 100 nodules were included. The prevalence of lung cancer was 1%. The sensitivity, specificity, NPV and PPV of visual analysis to detect malignancy were 84%, 95%, 91%, and 91%, respectively, with an accuracy of 91% (AUC 0.893). FDG PET/CT accurately detected 31 malignant tumors (diameters 9-42mm, SUVmax range 0.6-14.2) and was falsely negative in 6 patients. With SUVmax thresholds for malignancy of 1.5, 2, and 2.5, specificity was 97% but sensitivity decreased to 65%, 49%, and 46% respectively, and accuracy decreased to 85%, 79%, and 78% respectively (AUC 0.872). CONCLUSIONS The visual analysis of FDG PET/CT scan is highly accurate in characterizing indeterminate pulmonary nodules detected in lung cancer screening with low-dose CT. Semi-quantitative analysis does not improve the accuracy of FDG PET/CT over that obtained with a qualitative method for lung nodule characterization.

Smokers with CT Detected Emphysema and No Airway Obstruction Have Decreased Plasma Levels of EGF, IL-15, IL-8 and IL-1ra

Rationale Low-grade inflammation and emphysema have been shown to be associated with an increased risk of lung cancer. However, the systemic inflammatory response in patients with emphysema is still unknown. Objective To compare the plasma cytokine profiles in two groups of current or former smokers without airway obstruction: a control group of individuals without computed tomography (CT) detected emphysema vs. a study group of individuals with CT detected emphysema. Methods Subjects underwent a chest CT, spirometry, and determination of EGF, IL-15, IL-1ra, IL-8, MCP-1, MIP-1β, TGFα, TNFα, and VEGF levels in plasma. Cytokine levels in each group were compared adjusting for confounding factors. Results 160 current smokers and former smokers without airway obstruction participated in the study: 80 without emphysema and 80 subjects with emphysema. Adjusted group comparisons revealed significant reductions in EGF (−0.317, p = 0.01), IL-15 (−0.21, p = 0.01), IL-8 (−0.180, p = 0.02) and IL-1ra (−0.220, p = 0.03) in subjects with emphysema and normal spirometry. Conclusions Current or former smokers expressing a well-defined disease characteristic such as emphysema, has a specific plasma cytokine profile. This includes a decrease of cytokines mainly implicated in activation of apoptosis or decrease of immunosurveillance. This information should be taken into account when evaluated patients with tobacco respiratory diseases.

Epicardial Adipose Tissue in Patients with Chronic Obstructive Pulmonary Disease

Rationale Epicardial Adipose Tissue (EAT) volume as determined by chest computed tomography (CT) is an independent marker of cardiovascular events in the general population. COPD patients have an increased risk of cardiovascular disease, however nothing is known about the EAT volume in this population. Objectives To assess EAT volume in COPD and explore its association with clinical and physiological variables of disease severity. Methods We measured EAT using low-dose CT in 171 stable COPD patients and 70 controls matched by age, smoking history and BMI. We determined blood pressure, cholesterol, glucose and HbA1c levels, microalbuminuria, lung function, BODE index, co-morbidity index and coronary artery calcium score (CAC). EAT volume were compared between groups. Uni and multivariate analyses explored the relationship between EAT volume and the COPD related variables. Results COPD patients had a higher EAT volume [143.7 (P25–75, 108.3–196.6) vs 129.1 (P25–75, 91.3–170.8) cm3, p = 0.02)] and the EAT volume was significantly associated with CAC (r = 0.38, p<0.001) and CRP (r = 0.32, p<0.001) but not with microalbuminuria (r = 0.12, p = 0.13). In COPD patients, EAT volume was associated with: age, pack-years, BMI, gender, FEV1%, 6 MWD, MMRC and HTN. Multivariate analysis showed that only pack-years (B = 0.6, 95% CI: 0.5–1.3), BMI (B = 7.8, 95% CI: 5.7–9.9) and 6 MWD (B = −0.2, 95% CI: −0.3–−0.1), predicted EAT volume. Conclusions EAT volume is increased in COPD patients and is independently associated with smoking history, BMI and exercise capacity, all modifiable risk factors of future cardiovascular events. EAT volume could be a non-invasive marker of COPD patients at high risk for future cardiovascular events.

Outpatient Management of Malignant Pleural Effusion Using a Tunneled Pleural Catheter: Preliminary Experience

Inpatient management of malignant pleural effusion includes the placement of a conventional thoracostomy tube for drainage and talc slurry pleurodesis and/or a surgical approach consisting of video-assisted thoracoscopic talc insufflation. Both techniques require prolonged hospital stays of up to 1 week. Unfortunately, life expectancy in patients with this disease does not usually exceed 6 months, and so the primary aim of any palliative intervention intended to improve quality of life should be to avoid hospital admissions and to relieve pain as far as possible. Of the few outpatient alternatives to hospital management the most frequently used is repeated thoracentesis. We describe the outpatient management of malignant pleural effusion by placement of a tunneled pleural catheter in a patient with stage IIIB lung adenocarcinoma. In our opinion, the use of this catheter offers a viable alternative to conventional therapy and is better tolerated.