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Purpose: The aims of this study were to analyze and characterize the irrintzi (a folkloric shout emitted in a single breath used by the Basque people) acoustically and to describe the mechanism by which it is emitted. Method: Thirty-six sound samples of 12 female volunteers were analyzed. Acoustic analysis included primarily fundamental frequency ( f o ), spectral analysis in the time domain with a narrowband filter, and the use of linear predictive coding (LPC). Laryngeal and pharyngeal movements while emitting an irrintzi were studied by fiberoptic nasal endoscopy. Postural and mandible movements were observed and video recorded. Movements of the larynx and the vocal tract were also studied by lateral pharyngo-laryngeal radioscopy. Results: The central part of an irrintzi spectrogram contains a peculiar, repeated M-shaped motif unseen in the spectrogram of any other human vocal emission, and intensity was over 90 dB SPL in all cases. f o was very high (1487 Hz) especially at the end of the irrintzi. Fiberoptic nasal endoscopy consistently revealed considerable elevation of the glottis, with the larynx swinging forward and retraction of the ventricular bands. Lateral radioscopy showed a very high larynx and a high tongue dorsum. Conclusions: The irrintzi is a sound emitted in a single breath and characterized by its shrillness and loudness, qualities that make it audible in noisy environments and over large distances and the vocal technique observed when it is produced can be explained by the Estill voice model (Steinhauer et al., 2017). The use of this technique may help in the treatment of voice disorders and improve efficiency in singers, teachers, actors, and people who use their voice at high volume or at high frequency. Supplemental Material: https://doi.org/10.23641/asha.20779405

In various cultures there are vocal sounds and cries associated with the folk tradition. All these cries are emitted in a single breath, have a high frequency and are loud. They are consequently audible over long distances and cut through other vocal expressions or other sounds generated by instruments.The objective of this work is to acoustically analyze some of these folkloric cries and study elements common to all of them.In this study, Irrintzi, Aturuxo, Tzagrit, ululation Darfur and Kurava cries were subjected to descriptive acoustic spectrographic analysis, and the resulting descriptions were compared both quantitatively, in terms of various acoustic parameters, and qualitatively, in terms of spectrographic characteristics and the way the cries sound.All of the cries contained high frequencies. Spectrograms of the cries revealed that they had a common pattern: a lower initial frequency ascends rapidly (the attack) and is then maintained throughout a stable phase of the emission (the body) before a final drop in frequency (the ending or coda). The body is the longest phase.This initial study of five sounds of folk tradition has opened up a wealth of acoustic and cultural discoveries. Broader studies are now needed to determine if the characteristics we have reported are common to other cries, to look for other similarities, and to delve into meanings, implications and possible applications. In-depth understanding of the mechanism of emission of traditional cries could provide tools for voice re-education in patients with dysphonia due to vocal strain (muscle tension dysphonia, vocal nodules, etc.), for improving voice quality, and for increasing the efficiency of vocal performance.

Rationale Idiopathic pulmonary fibrosis (IPF) has a dismal prognosis. Mesenchymal stromal cells (MSCs) have shown benefit in other inflammatory diseases. Objectives To evaluate the safety and feasibility of endobronchial administration of bone marrow autologous MSCs (BM-MSC) in patients with mild-to-moderate IPF. Methods A phase I multicentre clinical trial (ClinicalTrials.gov NCT01919827) with a single endobronchial administration of autologous adult BM-MSCs in patients diagnosed with mild-to-moderate IPF. In a first escalating-dose phase, three patients were included sequentially in three dose cohorts (10×106, 50×106 and 100×106 cells). In a second phase, nine patients received the highest tolerated dose. Follow-up with pulmonary function testing, 6-min walk test and St George's Respiratory Questionnaire was done at 1, 2, 3, 6 and 12 months, and with computed tomography at 3, 6 and 12 months. Results 21 bone marrow samples were obtained from 17 patients. Three patients were excluded from treatment due to chromosome aberrations detected in MSCs after culture, and one patient died before treatment. Finally, 13 patients received the BM-MSC infusion. No treatment-related severe adverse events were observed during follow-up. Compared to baseline, the mean forced vital capacity showed an initial decline of 8.1% at 3 months. The number of patients without functional progression was six (46%) at 3 months and three (23%) at 12 months. Conclusions The endobronchial infusion of BM-MSCs did not cause immediate serious adverse events in IPF patients, but a relevant proportion of patients suffered clinical and/or functional progression. Genomic instability of BM-MSCs during culture found in three patients may be troublesome for the use of autologous MSCs in IPF patients., Endobronchial autologous mesenchymal stromal cells (MSCs) did not cause direct serious adverse events in IPF patients. However, significant progression was seen in seven out of 13 patients. Genomic instability of autologous MSCs may limit use in IPF. https://bit.ly/39akv7z

SARS-CoV-2, the COVID-19 causative agent, has infected millions of people and killed over 1.6 million worldwide. A small percentage of cases persist with prolonged positive RT-PCR on nasopharyngeal swabs. The aim of this study was to determine risk factors for prolonged viral shedding amongst patient's basal clinical conditions.We have evaluated all 513 patients attended in our hospital between 1 March and 1 July. We have selected all 18 patients with prolonged viral shedding and compared them with 36 sex-matched randomly selected controls. Demographic, treatment and clinical data were systematically collected.Global median duration of viral clearance was 25.5 days (n = 54; IQR, 22-39.3 days), 48.5 days in cases (IQR 38.7-54.9 days) and 23 days in controls (IQR 20.2-25.7), respectively. There were not observed differences in demographic, symptoms or treatment data between groups. Chronic rhinosinusitis and atopy were more common in patients with prolonged viral shedding (67%) compared with controls (11% and 25% respectively) (P 0.001 and P = 0.003). The use of inhaled corticosteroids was also more frequent in case group (P = 0.007). Multivariate analysis indicated that CRS (odds ratio [OR], 18.78; 95% confidence interval [95%CI], 3.89-90.59; P 0.001) was independently associated with prolonged SARS-CoV-2 RNA shedding in URT samples, after adjusting for initial PCR Ct values.We found that chronic rhinosinusitis and atopy might be associated with increased risk of prolonged viral shedding. If confirmed in prospective trials, this finding might have clinical implications for quarantine duration due to increased risk of pandemic spread.

Introduction The prevalence of bronchiectasis in the general population and in individuals undergoing lung cancer screening with low dose computed tomography (LDCT) is unknown. The aim of this study is to estimate the prevalence and impact of bronchiectasis in a screening lung cancer program. Methods 3028 individuals participating in an international multicenter lung cancer screening consortium (I-ELCAP) were selected from 2000 to 2012. Patients with bronchiectasis on baseline CT were identified and compared to selected controls. Detection of nodules, need for additional studies and incidence of cancer were analyzed over the follow-up period. Results The prevalence of bronchiectasis was 11.6%(354/3028). On the baseline LDCT, the number of subjects with nodules identified was 189(53.4%) in patients with bronchiectasis compared to 63(17.8%) in controls (p

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 >10 mm 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 9–42 mm, 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.

Rationale: Smoking has been associated with osteoporosis. Little is known about the combined role of clinical, spirometric, radiological and biochemical markers in the identification of osteoporosis in this high-risk population. Methods: 135 smokers were consecutively recruited. Clinical and demographic data was registered, presence and degree of airway limitation identified, presence of emphysema detected in a low-dose chest computed tomography, blood bone turnover markers (BTM) measured and their fracture risk assessment tool (FRAX) score calculated. Bone densitometry was performed on all patients, classifying their bone as healthy, with osteopenia or osteoporosis. Results: One hundred and six (78.5%) patients had an abnormal densitometry and 37 (27%) had osteoporosis. A multivariable analysis showed that emphysema presence (odds ratio [OR]: 3.90; 95% confidence interval [CI]: 1.43-10.64), a FRAX for a hip fracture 10-year risk>3% (OR: 5.29; 95% CI: 1.59-17.63) and a beta-crosslaps (β–CTX) level>0.20 ng/mL (OR: 3.16; 95% CI: 1.10-9.08) were independently associated with osteoporosis. Using their OR, the Score for Identification of Osteoporosis in Smokers (SIOS) was constructed that goes from 0 to 3.7. A SIOS> 2 points was associated a high risk of osteoporosis (OR: 5.6; 95% CI: 2.4-12.9). Conclusions: The present study demonstrated that radiological emphysema, a FRAX score for hip fracture >3%, and a β–CTX level>0.20 ng/mL were the best predictors of the presence of osteoporosis. A SIOS>2 could be use as a screening tool to help clinicians identify smokers at high risk of osteoporosis.

Rationale Pulmonary artery enlargement (PAE) is associated with exacerbations in Chronic Obstructive Pulmonary Disease (COPD) and with survival in moderate to severe patients. The potential role of PAE in survival prediction has not been compared with other clinical and physiological prognostic markers. Methods In 188 patients with COPD, PA diameter was measured on a chest CT and the following clinical and physiological parameters registered: age, gender, smoking status, pack-years history, dyspnea, lung function, exercise capacity, Body Mass Index, BODE index and history of exacerbations in year prior to enrolment. Proportional Cox regression analysis determined the best predictor of all cause survival. Results During 83 months (±42), 43 patients died. Age, pack-years history, smoking status, BMI, FEV1%, six minute walking distance, Modified Medical Research Council dyspnea scale, BODE index, exacerbation rate prior to enrollment, PA diameter and PAE (diameter≥30mm) were associated with survival. In the multivariable analysis, age (HR: 1.08; 95%CI: 1.03–1.12, p

Background The International Classification of Sleep Disorders – Third Edition (ICSD-3) classifies catathrenia among the respiratory disorders and not as a parasomnia as in ICSD-2. Few patients have been reported during these years, and the clinical description of the sound is different from group to group. In fact, there is no full agreement about its nature, origin, meaning, and treatment. Methods and results In this paper we review the literature on catathrenia focusing on the characteristics of the sound, demographics of the patients, aetiology, response to treatment, etc., in order to support its classification as a respiratory disorder or a parasomnia. We also discuss the possibility of Catathrenia being not one disorder but two variants or two different disorders.

Background Chronic Obstructive Pulmonary Disease (COPD) is an independent risk factor for cardiovascular (CV) disease, one of the most frequent causes of death in COPD patients. The goal of the present study was to evaluate the prognostic value of non-invasive CV risk markers in COPD patients. Methods CV risk was prospectively evaluated in 287 COPD patients using non-invasive markers including the Framingham score, the Systematic Coronary Risk Evaluation (SCORE) charts, coronary arterial calcium (CAC), epicardial adipose tissue (EAT), as well as clinical, biochemical and physiological variables. The predictive power of each parameter was explored using CV events as the main outcome. Results During a median follow up of 65 months (ICR: 36–100), 44 CV events were recorded, 12 acute myocardial infarctions (27.3%), 10 ischemic heart disease/angina (22.7%), 12 peripheral artery disease events requiring surgery (27.3%) and 10 strokes (22.7%). A total of 35 CV deaths occurred during that period. Univariable analysis determined that age, hypertension, CRP, total Cholesterol, LDL-Cholesterol, Framingham score and CAC were independently associated with CV events. Multivariable analysis identified CAC as the best predictor of CV events (HR; 95%CI: 1.32; 1.19–1.46, p

Contains fulltext : 137671.pdf (Publisher’s version ) (Open Access) The {VESSEL12} ({VES}sel {SE}mentation in the {L}ung) 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.

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.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.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).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.

Rationale: Little is known about the impact of an abnormal DLco ( Objective: To compare clinical and functional characteristics of active or former smokers without airway obstruction with or without emphysema and/or abnormal DLco. Methods: This is an observational study of active or former smokers that underwent a low dose CT scan (LDCT), pulmonary function tests, COPD assessment test (CAT) and 6 minute walking distance test (6MWD) . Patients were classified in 3 groups depending on the presence of visually detected radiological emphysema and DLco values (no-emphysema; emphysema with DLco>80%; emphysema with DLco Results: 168 patients were analyzed. Patients with emphysema had a higher CAT score (7.96 vs 5.95 p=0.002) and a greater fall in SpO2% post-6MWD (22.7% vs 4.2%, p=0,004) . In those with an abnormal DLco, CAT score are even higher (4.78 vs 9.36, p=0.01) and a greater % having a fall in the SpO2% (96.3% vs 94.4%, p=0.007). In this group there were more active smokers (69% vs. 50%, p=0.025), with lower mean predicted FEV1 (96.7 vs 105.2%, p=0.004) and higher residual volume/total lung capacity ratio (37.05 vs 32.44, p:0.05). Conclusion: In active or former smokers with emphysema, the presence of an abnormal DLco determine a worse clinical and physiological presentation. The present findings gives value to the determination of DLco in smokers without airway obstruction.

Introduction: Chronic Obstructive Pulmonary Disease (COPD) has been associated with osteoporosis. Little is known about the potential role of radiological emphysema on the presence of osteoporosis. Objective: Our objective was to determine the putative role of emphysema in the presence of osteoporosis in active and former smokers. Methods: Data from 120 active and former smokers, followed at a Pulmonary Service from 2013 to 2015 were prospectively registered: age, sex, body mass index (BMI), pack-years history, smoking status, spirometric diagnosis of COPD and the presence of emphysema (chest computed tomography- documented). Bone densitometry (BD) was performed on all patients, and classified according to WHO criteria as healthy, osteopenia or osteoporotic. Results: The characteristics of patients with and without osteoporosis are described in Table 1. Patients with osteoporosis were mainly women, with lower BMI, and higher percentage of them with radiological emphysema. Adjusted analyses showed that only the presence of emphysema (odds ratio [OR]: 4.49; 95% confidence interval [CI]:1.81-11.15, p

Introduction: Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of osteoporosis. In these patients, the relationship between osteoporosis measured by bone density in chest computed tomography (CT) and dual-energy X-ray absorptiometry (DXA) is not well established. Objectives: To determine the association between the bone mineral density (BMD) measured in the first lumbar vertebra (L1) of a low dose chest CT (LDCT) with the one measured in a bone DXA. We also aim at exploring the possible association of this measurement with the severity of radiological emphysema. Methods: 43 COPD patients with emphysema were evaluated. In a LDCT we determined BMD in the central part of L1 body. DXA was in all patients. The quantification of emphysema in CT was performed using a specific software (Volume, Siemens Healthcar) considering 3 different thresholds: -900, -950 and -960 Hounsfield Units (HU), and the emphysema index (EI) was calculated. Spearman correlation coefficient was used for the statistical analysis. Results: The correlation between the BMD in L1 by CT and the lumbar spine (L1-L4) density by DXA was 0.40 (p Conclusions: There is a weak correlation between BMD measured in CT and DXA. In the same way, there is a weak inverse correlation between IE and BMD determined by CT. Further studies are needed to establish the relationship between these two diseases processes.

Telomeres are DNA–protein structures that protect chromosome ends from degradation and shorten progressively with each cell division [1]. Telomere length measured in peripheral leukocytes has been used to determine an individual's “biological age”, and previous reports have demonstrated that patients with chronic obstructive pulmonary disease (COPD) and/or emphysema have shorter peripheral leukocyte telomere length [2–5]. The presence of COPD and emphysema are independent risk factors for the ultimate development of lung cancer [6, 7]. Leukocyte telomere length should be included among the independent risk factors associated with lung cancer J.P. de-Torres, G. Bastarrika, J.J. Zulueta, P. Sanchez-Salcedo, B.R. Celli (conception and design, analysis and interpretation, and drafting the manuscript for important intellectual content); A.B. Alcaide, J. Berto, A. Campo, M. del Mar Ocon, C. Monente, R. Pio, M.J. Pajares, L. Montuenga (analysis and interpretation).

OBJECTIVE Impaired lung function and innate immunity have both attracted growing interest as a potentially novel risk factor for glucose intolerance, insulin resistance, and type 2 diabetes. We aimed to evaluate whether surfactant protein D (SP-D), a lung-derived innate immune protein, was behind these associations. RESEARCH DESIGN AND METHODS Serum SP-D was evaluated in four different cohorts. The cross-sectional associations between SP-D and metabolic and inflammatory parameters were evaluated in two cohorts, the cross-sectional relationship with lung function in one cohort, and the longitudinal effects of weight loss on fasting and circadian rhythm of serum SP-D and cortisol concentrations in one prospective cohort. RESULTS In the cross-sectional studies, serum SP-D concentration was significantly decreased in subjects with obesity and type 2 diabetes (P = 0.005) and was negatively associated with fasting and postload serum glucose. SP-D was also associated with A1C, serum lipids, insulin sensitivity, inflammatory parameters, and plasma insulinase activity. Smoking subjects with normal glucose tolerance, but not smoking patients with type 2 diabetes, showed significantly higher serum SP-D concentration than nonsmokers. Serum SP-D concentration correlated positively with end-tidal carbon dioxide tension (r = 0.54, P = 0.034). In the longitudinal study, fasting serum SP-D concentration decreased significantly after weight loss (P = 0.02). Moreover, the main components of cortisol and SP-D rhythms became synchronous after weight loss. CONCLUSIONS These findings suggest that lung innate immunity, as inferred from circulating SP-D concentrations, is at the cross-roads of inflammation, obesity, and insulin resistance.

N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of neurohormonal activation that is useful in the diagnosis and prognosis of various forms of pulmonary arterial hypertension (PAH). We sought to characterise and compare NT-proBNP in a cohort of PAH related to systemic sclerosis (PAH-SSc) and idiopathic PAH (IPAH) patients. NT-proBNP levels, collected from PAH-SSc and IPAH patients followed prospectively, were compared and correlated with haemodynamic variables. Cox proportional hazard models were created to assess the predictive value of NT-proBNP. 98 patients (55 PAH-SSc, 43 IPAH) were included. Haemodynamics were similar, except for lower mean pulmonary arterial pressure in PAH-SSc. NT-proBNP levels were significantly higher in PAH-SSc (3,419+/-3,784 versus 1,393+/-1,633 pg x mL(-1); p0.01) and were more closely related to haemodynamics in PAH-SSc than IPAH. 28 patients died. NT-proBNP predicted survival (hazard ratio (HR) 3.18; p0.01) in the overall cohort; however, when stratified by group, predicted survival only in PAH-SSc (HR 3.07, p0.01 versus 2.02, p = 0.29 in IPAH). This is the first description showing NT-proBNP levels are 1) significantly higher in PAH-SSc than IPAH despite less severe haemodynamic perturbations, and 2) stronger predictors of survival in PAH-SSc, suggesting that neurohormonal regulation may differ between PAH-SSc and IPAH. Future studies to define pertinent mechanisms are warranted.

Lung cancer screening using computed tomography (CT) is effective in detecting early stage disease. However, concerns regarding adherence have been raised. The current authors conducted a retrospective observational study of 641 asymptomatic smokers enrolled in a lung cancer screening programme between 2000 and 2003. Adherent subjects were compared with nonadherent subjects with regard to lung function, sex, age, motivation for enrollment, smoking status, distance to the referral centre, family history of lung cancer, asbestos exposure, education, the presence and type of nodule(s) seen on initial CT, and exposure to a nursing intervention designed to improve adherence. Overall, early adherence to the study protocol was 65%. Multivariate analysis confirmed the importance of sex, proximity to the referral centre, the presence of noncalcified nodules, and the nursing intervention as factors conditioning adherence to the study protocol. Patients encouraged to participate in the study were more adherent, as were former smokers. Sex interactions were observed in multivariate analysis. The nursing intervention was significant for females, while abnormal lung function improved male adherence. Adherence to lung cancer screening is particularly good among females and subjects living near the referral centre. The present study suggests the need to develop new strategies, especially those targeting males and subjects with low risk perception, in order to improve adherence.

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 >or=30 kg.m(-2)) underwent the following tests: sleep studies, respiratory function tests, baseline and hypercapnic response (mouth occlusion pressure (P(0.1)), 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 P(0.1). 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.

Chronic Obstructive Pulmonary Disease (COPD) is associated with numerous extrapulmonary diseases including osteoporosis. The incidence of osteoporosis in COPD patients is high and its early detection would prevent significant associated morbidity. To determine the utility of Fracture Risk Assessment Tool (FRAX) index and bone turnover markers (BTM) for the diagnosis of osteoporosis in COPD patients. This is a pilot study of 50 COPD patients followed at a Pulmonary Service. Age, sex, pack-years of smoking status, lung function, FRAX index and BTM (betacrosslap, osteocalcin and N-terminal propeptide of type 1 procollagen [P1NP]) were recorded. Bone densitometry was performed on all patients, and was classified as healthy or osteoporotic according to WHO criteria. The potential utility of FRAX index and BTM was explored by ROC analysis. Patient characteristics are described in Table 1. Excluding densitometric values, the area under the curve (AUC) for major fracture and hip fracture was 0.72 and 0.73, respectively; and the AUC for betacrosslap, osteocalcin and P1NP were 0.70, 0.74 and 0.63, respectively (Figure 1). The FRAX index and BTM have potential value in the screening for the early diagnosis of osteoporosis in COPD patients. The completion of our study will allow the identification of a useful cutoff point for early screening.

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 [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.

El manejo hospitalario del derrame pleural maligno incluye la colocacion de un tubo de toracostomia convencional, drenaje y esclerosis mediante talcaje, y/o el abordaje quirurgico mediante videotoracoscopia. Ambas tecnicas requieren ingresos prolongados, de hasta una semana de duracion. Lamentablemente, la esperanza de vida en pacientes con esta enfermedad no suele superar los 6 meses, motivo por el que toda intervencion paliativa destinada a mejorar la calidad de vida debe tener como objetivo primordial el evitar, en la medida de lo posible, el ingreso hospitalario y aliviar el dolor. Hay pocas alternativas ambulatorias al manejo hospitalario. De ellas, la toracocentesis de repeticion es la mas frecuentemente utilizada. Describimos el uso de un cateter tunelizado en el manejo ambulatorio del derrame pleural maligno de un paciente con adenocarcinoma de pulmon en estadio IIIB. Consideramos que este cateter ofrece una alternativa viable y mejor tolerada que el tratamiento convencional.

RationaleEpicardial 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.ObjectivesTo assess EAT volume in COPD and explore its association with clinical and physiological variables of disease severity.MethodsWe 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.ResultsCOPD patients had a higher EAT volume [143.7 (P25-75, 108.3-196.6) vs 129.1 (P25-75, 91.3-170.8) cm(3), p = 0.02)] and the EAT volume was significantly associated with CAC (r = 0.38, pConclusionsEAT 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.

RationaleLow-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.ObjectiveTO 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.MethodsSubjects 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.Results160 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.ConclusionsCurrent 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.

The aim of this study was to examine the causes and outcomes of hospitalisation in patients with pulmonary arterial hypertension (PAH). 205 consecutive hospitalisations occurring between 2000 and 2009 in 90 PAH patients were studied. The leading causes for hospitalisation were right heart failure (RHF; 56%), infection (16%) and bleeding disorders (8%). For patients with RHF, in-hospital mortality was 14% overall, 46% for patients receiving inotropes and 48% for those admitted to the intensive care unit. The predictors for in-hospital mortality were the presence of connective tissue disease (CTD) (OR 4.92), systolic blood pressure

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.

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.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 kappa coefficient of agreement. The correlation of LDCT-based emphysema determinations with indices of airway obstruction on spirometry was also calculated.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 (kappa coefficient=0.91). Higher volumes of emphysema measured quantitatively or visually significantly correlated with spirometric markers of airway obstruction.Volumetric LDCT is a reliable and valid technique for the quantification of emphysema in asymptomatic smokers.

Rationale: Identification of risk factors for lung cancer can help in selecting patients who may benefit the most from smoking cessation interventions, early detection, or chemoprevention. Objective To evaluate whether the presence of emphysema on low-radiation-dose CT (LDCT) of the chest is an independent risk factor for lung cancer. Methods The study used data from a prospective cohort of 1,166 former and current smokers participating in a lung cancer screening study. All individuals underwent a baseline LDCT and spirometry followed by yearly repeat LDCT studies. The incidence density of lung cancer among patients with and without emphysema on LDCT was estimated. Stratified and multiple regression analyses were used to assess whether emphysema is an independent risk factor for lung cancer after adjusting for age, gender, smoking history, and the presence of airway obstruction on spirometry. Results On univariate analysis, the incidence density of lung cancer among individuals with and without emphysema on LDCT was 25.0 per 1,000 person-years and 7.5 per 1,000 person-years, respectively (risk ratio [RR], 3.33; 95% confidence interval [CI], 1.41 to 7.85). Emphysema was also associated with increased risk of lung cancer when the analysis was limited to individuals without airway obstruction on spirometry (RR, 4.33; 95% CI, 1.04 to 18.16). Multivariate analysis showed that the presence of emphysema (RR, 2.51; 95% CI, 1.01 to 6.23) on LDCT but not airway obstruction (RR, 2.10; 95% CI, 0.79 to 5.58) was associated with increased risk of lung cancer after adjusting for potential cofounders. Conclusions Results suggest that the presence of emphysema on LDCT is an independent risk factor for lung cancer.

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.

RATIONALE: Lung cancer screening using computed tomography (CT) is effective in detecting lung cancer in early stages. Concerns regarding false-positive rates and unnecessary invasive procedures have been raised. OBJECTIVE: To study the efficiency of a lung cancer protocol using spiral CT and F-18-fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: High-risk individuals underwent screening with annual spiral CTs. Follow-up CTs were done for noncalcified nodules of 5 mm or greater, and FDG-PET was done for nodules 10 mm or larger or smaller (> 7 mm), growing nodules. RESULTS: A total of 911 individuals completed a baseline CT study and 424 had at least one annual follow-up study. Of the former, 14% had noncalcified nodules of 5 mm or larger, and 3.6% had nodules of 10 mm or larger. Eleven non-small cell lung cancers (NSCLC) and one small cell lung cancer (SCLC) were diagnosed in the baseline study (prevalence rate, 1.32%), and two NSCLCs in the annual study (incidence rate, 0.47%). All NSCLCs (92% of prevalence cancers) were diagnosed in stage I (12 stage IA, 1 stage IB). FDG-PET was helpful for the correct diagnosis in 19 of 25 indeterminate nodules. The sensitivity, specificity, positive predictive value, and negative predictive value of FDG-PET for the diagnosis of malignancy were 69, 91, 90, and 71%, respectively. However, the sensitivity and negative predictive value of the screening algorithm, which included a 3-month follow-up CT for nodules with a negative FDG-PET, was 100%. CONCLUSION: A protocol for early lung cancer detection using spiral CT and FDG-PET is useful and may minimize unnecessary invasive procedures for benign lesions.

SummaryBackgroundCOPD is an independent risk factor for lung cancer, especially in patients with mild to moderate disease.ObjectiveTo determine if performing lung cancer screening in GOLD 1 and 2 COPD patients, results in reduced lung cancer mortality.MethodsThis study compared patients with mild to moderate COPD from 2 cohorts matched for age, gender, BMI, FEV1%, pack-yrs history and smoking status. The screening group (SG) had an annual low dose computed tomography (LDCT). The control group (CG) was prospectively followed with usual care. Lung cancer incidence and mortality densities were compared between groups.ResultsFrom an initial sample of 410 (SG) and 735 (CG) patients we were able to match 333 patients from each group. At the same follow-up time lung cancer incidence density was 1.79/100 person-years in the SG and 4.14/100 person-years in the CG (p = 0.004). The most frequent histological type was adenocarcinoma in both SG and CG (65% and 46%, respectively), followed by squamous cell carcinoma (25% and 37%, respectively). Eighty percent of lung cancers in the SG (16/20) were diagnosed in stage I, and all of CG cancers (35/35) were in stage III or IV. Mortality incidence density from lung cancer (0.08 vs. 2.48/100 person-years, p