Usefulness of the LCOPD, CAFS and CASIS scales in understanding the impact of COPD on patients.

BACKGROUND: The Living with COPD (LCOPD), COPD and Asthma Fatigue Scale (CAFS), and COPD and Asthma Sleep Impact Scale (CASIS) are instruments developed to assess the overall impact of chronic obstructive pulmonary disease (COPD) on daily life, fatigue, and sleep impairment, respectively. OBJECTIVES: To assess the usefulness of these instruments and to identify factors associated with the concepts they measure. METHOD: The questionnaires were administered to patients with moderate to severe COPD. Descriptive analyses of sociodemographic and clinical data were performed, and bivariate and multivariate analyses were used to identify factors associated with the overall impact of COPD on patients' lives, fatigue, and sleep impairment. RESULTS: A total of 408 patients was included (mostly males, 91.2%), with an average age of 68 years (SD = 9.3). Statistically significant differences were observed in the scores of the three questionnaires with regard to level of education, presence of chronic cough or expectoration, level of dyspnea, number of exacerbations, physical activity level, presence of depression and anxiety, and number of treatments indicated for COPD. The LCOPD and CAFS questionnaires also discriminated between different levels of airflow obstruction and, in the case of CAFS, age and gender. Linear regression showed that level of dyspnea, physical activity, and presence of anxiety were significantly related to the LCOPD, CAFS and CASIS scores. The presence of depression was significant in the LCOPD and CAFS questionnaires and chronic cough was significant in the CAFS questionnaire. CONCLUSIONS: The LCOPD, CAFS, and CASIS instruments are valid and useful in understanding the overall impact of COPD on daily life, fatigue, and sleep impairment in patients with moderate to severe COPD.

Endobronchial autologous bone marrow-mesenchymal stromal cells in idiopathic pulmonary fibrosis: a phase I trial.

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.

[The cinema as a vector of expansion of the smoking epidemic]. / El cine como vector de expansión de la epidemia tabáquica.

For many years the film industry has been a loyal contributor to the tobacco industry by showing actors smoking cigarettes onscreen and hence encouraging young people to become nicotine addicts. The Prevention of Nicotine Addiction movement in the United States has adequately documented this phenomenon and there is now sufficient scientific evidence to demonstrate the close relationship between smoking in films and the onset of smoking in adolescents and young adults. To encourage social debate, working groups have been created to put pressure on the film industry through the use of commercials in mainstream media in the hope of making Hollywood accept its responsibility and change its attitude. Smoke Free Movies, an initiative led by the University of California, is making substantial progress toward limiting the appearance of cigarettes in American movies. In Europe, and particularly in Spain, these kinds of initiatives are still fairly new. The Prevention of Nicotine Addiction Movement in Spain should learn from the United States in order to promote similar policies. Some of the proven measures include the following: certification in credits stating no payment was received for the appearance of tobacco in the film, projection of anti-tobacco advertisements before any film that contains scenes with smoking, no brand identification and no subsidies for films that encourage smoking.

[Benefit of brief interventions and pharmacotherapies for smoking cessation in teenagers]. / Valor de la intervención breve y los tratamientos farmacológicos para dejar de fumar en adolescentes.

Management of smoking includes approaches such as health advice against smoking, brief or intensive interventions, and pharmacotherapy. However, we do not have enough information on the use of such approaches in teenagers. School programs aimed at children and adolescents are perhaps the most widely used intervention and the one for which we have the most experience. Such programs should meet a series of well-defined criteria, but in recent years their effectiveness has been questioned. Currently, information is lacking on how effective these interventions are in young smokers who wish to stop. Several clinical guidelines recommend advice and a brief intervention in adolescents but are less specific regarding pharmacotherapy. By integrating advice and a brief intervention into existing smoking prevention and control programs in schools, such approaches could be used to combat smoking in children and adolescents. However, the information available on the use of such interventions in children and adolescents is insufficient and more research needs to be done, particularly by health care professionals specialized in the identification of susceptible individuals and treatment of smoking.

[Genetic basis of tobacco dependence]. / Bases genéticas del hábito tabáquico.

Dependence on tobacco is one of the most important health problems in our society due to the direct relationship with lung cancer. Early studies in twins revealed that genetic factors modify the susceptibility to develop tobacco dependence. Different studies are underway to try to find an association between polymorphisms of genes involved either in nicotine metabolization or in neural transmission and the initiation and maintenance of the dependence on tobacco. Here we review the studies performed so far and discuss new perspectives for future studies.

Endobronchial valves in the treatment of persistent air leak, an alternative to surgery.

INTRODUCTION: Persistent air leak is frustrating for both patients and physicians, above all leaks with a high risk of surgery. Insertion of endobronchial valves could be an alternative to surgery. The aim of this study is to describe our experience in these valves and analyse their efficacy in a series of patients with persistent air leaks. MATERIAL AND METHODS: The valves are inserted by means of flexible bronchoscopy under conscious sedation and local anesthesia. A preliminary bronchoscopy identifies the air leak by bronchial occlusion using a balloon catheter. A successful outcome is defined as complete disappearance of the leak following removal of the chest drain, without the need for further surgery. RESULTS: From November 2010 to December 2013, 8 patients with persistent air leaks were treated with endobronchial valves. The number of valves used ranged from 1 to 4 (median 2), with a median duration of air leak prior to placement of 15.5 days. There were no complications and the resolution of the leak was complete in 6 of 8 patients (75%). The median duration of drainage after insertion of the valves was 13 days and the median time to removal of 52.5 days. CONCLUSIONS: Insertion of endobronchial valves is a safe and effective method for treating persistent air leaks, and a valid alternative to surgery.

Budgetary impact analysis on funding smoking-cessation drugs in patients with COPD in Spain.

The aim of the study was to assess the budgetary impact of funding smoking-cessation drugs in COPD patients in Spain. A hybrid model (cohort and Markov) was developed for a 5-year time horizon. Only approved cessation drugs (varenicline, bupropion, and nicotine replacement therapy) were considered. Irrespective of the drug, the model allowed for an initial cessation attempt, and up to three additional attempts in case of failure or smoking relapse during a 5-year period. Drug effectiveness was based on controlled clinical trials. National Health System perspective was applied; therefore, only medical resources were included. The pharmaceutical costs for smoking-cessation drugs, extra medical follow-up as a consequence of public reimbursement, and annual savings for health costs avoided due to stopping smoking were considered. The model estimated that 17,756 COPD patients would stop smoking if public funding was available, compared with 1,303 without reimbursement. In the reimbursement scenario, the savings accounted for a total of €48.0 million, compensating for expenditures on drugs and medical visits (€40.4 million). Accumulated total additional savings in 5 years (€4.3 million) compared with the scenario without reimbursement was shown. Sensitivity analyses supported the results robustness. Funding smoking-cessation drugs in COPD patients seems to be an efficient option and a National Health System drug reimbursement scheme would represent a cost-saving policy in Spain.

Association of a novel polymorphism of the ß2-chimaerin gene (CHN2) with smoking.

OBJECTIVE: The CHN2 gene encodes the ß2-chimaerin, a Rac-specific guanosine-5'-triphosphatase activating protein with an important role in the establishment of functional brain circuitry by controlling axon pruning. Genetic studies suggest that the CHN2 gene harbors variants that contribute to addiction vulnerability and smoking behavior. To further evaluate the role of ß2-chimaerin in nicotine addiction, we investigated the association of 3 individual polymorphisms of the CHN2 gene with smoking dependence. METHODS: Three hundred sixty-one healthy volunteers, 173 smokers (mean ± SD age, 60.4 ± 1.4 years) and 188 control subjects (mean ± SD age, 45.9 ± 1.4 years) were genotyped for 3 single-nucleotide polymorphisms in the CHN2 gene (rs3750103, rs12112301, and rs186911567). The association of these polymorphisms with smoking habits was analyzed. RESULTS: There was no significant association of polymorphisms rs12112301 and rs3750103 with smoking. However, there was a significant difference in the frequency of the rs186911567 polymorphism between the smokers and the controls (P = 0.003). CONCLUSIONS: We report for the first time a significant association of the novel rs186911567 polymorphism of the CHN2 gene with smoking.

Adverse effects of pharmacological therapy for nicotine addiction in smokers following a smoking cessation program.

This multicenter, community-based, prospective, longitudinal study evaluated the safety of nicotine replacement therapy (NRT), bupropion, and combined therapy of NRT and bupropion for smokers seeking to quit, when these therapies were used under real-world conditions following a smoking cessation program. Participants were smokers aged 18 years or older who attended five smoking cessation clinics. Evaluations were made at 15, 30, 60, and 90 days. We investigated the possible existence of adverse effects as well as the severity of each adverse effect and its influence on the treatment course. The study included 904 smokers: 370 received NRT, 413 received bupropion, and 121 received combined therapy. At 15, 30, 60, and 90 days, adverse effects were reported by 43.8%, 33.1%, 22.3%, and 5.7% of subjects, respectively. Adverse effects were significantly more frequent in subjects receiving combined therapy or bupropion alone than in NRT-treated subjects at the 15-, 30-, and 60-day follow-ups. A total of 83 smokers (9.3%) withdrew from treatment and 116 (12.8%) stopped temporarily because of adverse effects. No differences were found in the percentages of discontinuation among the different treatment options. Adverse effects rarely were severe (n=10). Nevertheless, 41 subjects (4.5%) discontinued drug therapy indefinitely and 55 (6.1%) discontinued it temporarily because of mild adverse effects. Pharmacological therapies for smoking cessation are safe as long as they are appropriately prescribed and supervised by clinicians according to clinical practice guidelines. Adverse effects are primarily mild. Nonetheless, mild adverse effects may be perceived by patients as a serious enough problem to cause them to discontinue treatment.