Pilar de Lucas Ramos

Respiratory complications of obesity.

Educational aims To make readers aware of the importance of obesity in respiratory medicine. To outline the mechanisms of breathing problems in obesity. To explain strategies for management of breathing problems in obesity. Summary Obesity has become a public health problem because of its epidemic proportions in the population. There are many associated respiratory problems with sleep apnoea, obesity hypoventilation and obesity-associated asthma. The mechanisms of diminished breathing in the obese are complex and involve central control, peripheral drive, airway calibre and probably metabolic pathways. All pulmonologists need to know how to manage obesity-related problems and make informed choices about modalities of treatment.

‘Smoking Genes’: A Genetic Association Study

Some controversy exists on the specific genetic variants that are associated with nicotine dependence and smoking-related phenotypes. The purpose of this study was to analyse the association of smoking status and smoking-related phenotypes (included nicotine dependence) with 17 candidate genetic variants: CYP2A6*1×2, CYP2A6*2 (1799T>A) [rs1801272], CYP2A6*9 (−48T>G) [rs28399433], CYP2A6*12, CYP2A13*2 (3375C>T) [rs8192789], CYP2A13*3 (7520C>G), CYP2A13*4 (579G>A), CYP2A13*7 (578C>T) [rs72552266], CYP2B6*4 (785A>G), CYP2B6*9 (516G>T), CHRNA3 546C>T [rs578776], CHRNA5 1192G>A [rs16969968], CNR1 3764C>G [rs6928499], DRD2-ANKK1 2137G>A (Taq1A) [rs1800497], 5HTT LPR, HTR2A −1438A>G [rs6311] and OPRM1 118A>G [rs1799971]. We studied the genotypes of the aforementioned polymorphisms in a cohort of Spanish smokers (cases, N = 126) and ethnically matched never smokers (controls, N = 80). The results showed significant between-group differences for CYP2A6*2 and CYP2A6*12 (both P<0.001). Compared with carriers of variant alleles, the odds ratio (OR) for being a non-smoker in individuals with the wild-type genotype of CYP2A6*12 and DRD2-ANKK1 2137G>A (Taq1A) polymorphisms was 3.60 (95%CI: 1.75, 7.44) and 2.63 (95%CI: 1.41, 4.89) respectively. Compared with the wild-type genotype, the OR for being a non-smoker in carriers of the minor CYP2A6*2 allele was 1.80 (95%CI: 1.24, 2.65). We found a significant genotype effect (all P≤0.017) for the following smoking-related phenotypes: (i) cigarettes smoked per day and CYP2A13*3; (ii) pack years smoked and CYP2A6*2, CYP2A6*1×2, CYP2A13*7, CYP2B6*4 and DRD2-ANKK1 2137G>A (Taq1A); (iii) nicotine dependence (assessed with the Fagestrom test) and CYP2A6*9. Overall, our results suggest that genetic variants potentially involved in nicotine metabolization (mainly, CYP2A6 polymorphisms) are those showing the strongest association with smoking-related phenotypes, as opposed to genetic variants influencing the brain effects of nicotine, e.g., through nicotinic acetylcholine (CHRNA5), serotoninergic (HTR2A), opioid (OPRM1) or cannabinoid receptors (CNR1).

Complicaciones respiratorias de la obesidad

Obesity, well known as a cardiovascular risk factor, can also lead to significant respiratory complications. The respiratory changes associated with obesity extend from a simple change in respiratory function, with no effect on gas exchange, to the more serious condition of hypercapnic respiratory failure, characteristic of obesity hypoventilation syndrome. More recently, it has been reported that there is an increased prevalence of asthma which is probably multifactorial in origin, but in which inflammation may play an important role. Hypoventilation in the obese subject is the result of complex interactions that involve changes in the ventilatory mechanics and anomalies in breathing control. Two other conditions (COPD and sleep apnea-hypopnea syndrome [SAHS], often present in obese patients, can trigger or aggravate it. The prevalence of hypoventilation in the obese is under-estimated and the diagnosis is usually established during an exacerbation, or when the patient is studied due to suspicion of SAHS. Ventilatory management of these patients includes either CPAP or NIV. The choice of one or another will depend on the underlying clinical condition and whether or not there is another comorbidity. Both NIV and CPAP have demonstrated their effectiveness, not only in the control of gas exchange, but also in improving the quality of life and survival of these patients.

Ventilación mecánica no invasiva en pacientes con síndrome de obesidad-hipoventilación. Evolución a largo plazo y factores pronósticos

INTRODUCTION Obesity is associated with 2 closely related respiratory diseases: obesity hypoventilation syndrome (OHS) and obstructive sleep apnea-hypopnea syndrome (OSAHS). It has been shown that noninvasive ventilation during sleep produces clinical and functional improvement in these patients. The long-term survival rate with this treatment, and the difference in clinical progress in OHS patients with and without OSAHS are analyzed. METHODOLOGY Longitudinal, observational study with a cohort of patients diagnosed with OHS, included in a home ventilation program over a period of 12 years, divided into 2 groups: pure OHS and OSAHS-associated OHS. Bi-level positive airway pressure ventilation was administered. During the follow-up period, symptoms, exacerbations and hospitalizations, blood gas tests and pulmonary function tests, and survival rates were monitored and compared. RESULTS Eighty-three patients were eligible for analysis, 60 women (72.3%) and 23 men (27.7%), with a mean survival time of 8.47 years. Fifty patients (60.2%) were included in the group without OSAHS (OHS) and 33 (39.8%) in the OSAHS-associated OHS group (OHS-OSAHS). PaCO₂ in the OHS group was significantly higher than in the OHS-OSAHS group (P<.01). OHS patients also had a higher hospitalization rate (P<.05). There was a significant improvement in both groups in FEV₁ and FVC, and no differences between groups in PaCO₂ and PaO₂ values. There were no differences in mortality between the 2 groups, but low FVC values were predictive of mortality. CONCLUSIONS The use of mechanical ventilation in patients with OHS, with or without OSAHS, is an effective treatment for the correction of blood gases and functional alterations and can achieve prolonged survival rates.

Neumonía varicelosa en adultos: revisión de 13 casos

La neumonia varicelosa es una complicacion de la varice la que aparece casi exclusivamente en adultos. El cuadro cli nico oscila entre formas poco sintomaticas a insuficiencia respiratoria grave. Estudio retrospectivo de los casos de neumonia varicelosa en adultos, ingresados en nuestro hospital durante un perio do de 7 anos. Se incluyen 13 pacientes adultos (nueve varo nes y cuatro mujeres) cuyo diagnostico de neumonia varicelosa se establecio mediante criterios clinicorradiologicos en el curso de una varicela. Tres de ellos tenian inmunodepresion (dos infectados por el VIH y un lupus sistemico) y una paciente estaba en el tercer trimestre del embarazo. El 77% de los pacientes eran fumadores activos. Los sintomas mas frecuentes fueron la tos y la disnea ademas de la erupcion cutanea y la fiebre. Todos los pacientes tenian patron nodu lar bilateral extenso en la radiografia de torax, sin afecta cion pleural ni adenopatias mediastinicas. Todos recibieron tratamiento con aciclovir intravenoso y la evolucion fue fa vorable en todos excepto en un paciente infectado por el VIH, que fallecio. La paciente gestante necesito atencion en la unidad de cuidados intensivos.

El uso del límite inferior de la normalidad como criterio de EPOC excluye pacientes con elevada morbilidad y alto consumo de recursos sanitarios

The objective of this study is to analyze the clinical characteristics of two COPD patient populations: one diagnosed using the lower limit of normal (LLN) and another diagnosed by the GOLD criteria. We also compared the population excluded by the LLN criterion with a non-COPD control population. The COPD patients determined with the LLN criterion presented significantly lower levels of FEV1/FVC at 0.55 (0.8) vs. 0.66 (0.2), P=.000; FEV1 44.9% (14) vs. 53.8% (13), P=.000, and FVC 64.7% (17) vs. 70.4% p 0.04. The two COPD groups presented more frequent ER visits in the last year (57% and 52% of the patients, respectively, compared with 11.9% of the control group), without any statistically significant differences between the two. This same pattern was observed in the number of ER visits in the last year: 1.98 (1.6), 1.84 (1.5) and 1.18 (0.7), respectively. When we analyzed the prevalence of the comorbidities that are most frequently associated COPD, there was a clear increase in the percentage of patients who presented associated disorders compared with the control group. Nevertheless, these differences were not very relevant between the two COPD groups. The differences also were not relevant between both COPD groups in the pharmacological prescription profile. In conclusion, the use of the LLN as a criterion for establishing the diagnosis of COPD, compared with the GOLD criteria, excludes a population with important clinical manifestations and with a high consumption of health-care resources. Before its implementation, the relevance of applying this criterion in clinical practice should be analyzed.

Estudio de la prevalencia y actitudes sobre tabaquismo en pacientes sometidos a oxigenoterapia crónica domiciliaria. Estudio toma

INTRODUCTION The objective of this study is to analyse the prevalence, attitudes and characteristics of smoking in the population of patients subjected to Long Term Domiciliary Oxygen Therapy (LTDOT) in the Community of Madrid. PATIENT AND METHODS A representative sample of 845 subjects (of which 461 (46%) were male) was obtained from a total of 11,174 who fulfilled the inclusion criteria. The mean age was 78.25 years (95% Confidence Interval (CI): 77.55-78.95; SD=10.36). A descriptive cross-sectional study was conducted based on questionnaires as well as cooximetry. RESULTS Forty-eight subjects (5.7%; 95%CI: 4.3%-7.5%) were smokers and 438 (51.8%; 95%CI: 48.5%-55.2%) were ex-smokers. The percentage of active smokers was higher in the 60 years or less subject group (χ(2); P<0.001). The large majority (75%) of smokers were men, their proportion being significantly higher than that of current non-smokers (χ(2); P<0.003). The mean score in the Fagerström Test was 3.6. More than 65% of smokers had their first cigarette up to 30 min from getting up in the morning, and 45% of these were in a preparation phase. Seventeen percent of these subjects said that they had not received advice on quitting smoking. CONCLUSIONS There is a high rate of smoking in patients on LTDOT, with a higher probability of males and younger subjects continuing to smoke. There is a high level of physical dependency for nicotine.

El cigarrillo electrónico. Declaración oficial de la Sociedad Española de Neumología y Cirugía Torácica (SEPAR) sobre la eficacia, seguridad y regulación de los cigarrillos electrónicos

The electronic cigarette (EC) is a device formed by three basic elements: battery, atomizer and cartridge. When assembled, it looks like a cigarette. The cartridge contains different substances: propylene glycol, glycerine and, sometimes, nicotine. When the user “vapes”, the battery is activated, the atomizer is heated and the liquid is drawn in and vaporized. The smoker inhales the mist produced. Various substances have been detected in this mist: formaldehyde, acetaldehyde and acrolein and some heavy metals. Although these are found in lower concentrations than in cigarettes, they may still be harmful for the human body. Several surveys show that 3-10% of smokers regularly use e-cigarettes. A randomized study has shown that the efficacy of e-cigarettes for helping smokers to quit is similar to nicotine patches. Nevertheless, the study has relevant methodological limitations and reliable conclusions cannot be deduced. This report sets down the Position Statement of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) on the efficacy and safety of e-cigarettes. This statement declares that e-cigarettes should be regulated as medicinal products.

Impact of Legislation on Passive Smoking in Spain

Background: In 2005, the Spanish government approved Law 28/2005 on health measures against smoking; this was amended in 2010 by Law 42/2010. Objective: The purpose of this study was to assess the impact of these laws on passive smoking. Methods: Three epidemiological studies were conducted on a representative sample of the population via telephone surveys. The first was conducted prior to the first law coming into force, the second a year after its approval and the third a year after the approval of the second.Results: Six thousand eight hundred people were surveyed in 2005, 3,289 in 2007 and 3,298 in 2011. The first survey showed that 49.5% of nonsmokers were exposed to second-hand smoke (SHS) while by 2007, following the introduction of Law 28/2005, this exposure had been reduced to 37.9% (results previously published in 2008). The 2011 survey, conducted following the introduction of Law 42/2010, showed that just 21% of people were exposed. These data indicate that overall exposure to SHS was reduced by 22% between 2005 and 2007 and by a further 16.9% between 2007 and 2011. The overall impact of Law 42/2010 is estimated to be around 44% and Law 28/2005 around 22%. Conclusion: Legislation introduced in Spain has markedly reduced the exposure of nonsmokers to SHS.

Chronic obstructive pulmonary disease History Assessment in Spain: una valoración multidimensional de la enfermedad pulmonar obstructiva crónica. Método y organización del trabajo

INTRODUCTION This present paper describes the method and the organization of the study known as the COPD History Assessment In SpaiN (CHAIN), whose main objective is to evaluate the long-term natural history of a chronic obstructive pulmonary disease (COPD) patient cohort from a multidimensional standpoint and to identify clinical phenotypes, in comparison with another non-COPD control cohort. PATIENTS AND METHODS CHAIN is a multicenter, observational study of prospective cohorts carried out at 36 Spanish hospitals. Both cohorts will be followed-up during a 5-year study period with complete office visits every 12 months and telephone interviews every 6 months in order to evaluate exacerbations and the vital state of the subjects. The recruitment period for cases was between 15 January 2010 and 31 March 2012. At each annual visit, information will be collected on: (i) clinical aspects (socio-economic situation, anthropometric data, comorbidities, smoking, respiratory symptoms, exacerbations, quality of life, anxiety-depression scale, daily life activities, treatments); (ii) respiratory function (spirometry, blood gases, hyperinflation, diffusion, respiratory pressures); (iii) BODE index (main study variable); (iv) peripheral muscle function, and (v) blood work-up (including IgE and cardiovascular risk factors). In addition, a serum bank will be created for the future determination of biomarkers. The data of the patients are anonymized in a database with a hierarchical access control in order to guarantee secure information access. The CHAIN study will provide information about the progression of COPD and it will establish a network of researchers for future projects related with COPD.