The influence of BMI in asthma. Which traits are due to obesity and which to asthma and obesity phenotype?

BACKGROUND AND OBJECTIVES: Characteristics of the asthma and obesity phenotype have been described by cluster studies, but they have not been subsequently confirmed. Specific characteristics of this phenotype have not been differentiated from those inherent to the patient's body mass index (BMI). This study aims to assess the effect of BMI on asthma. This will allow to identify which traits could define the asthma and obesity phenotype, and which are inherent to the patient´s BMI. METHODS: A real-life retrospective observational study was conducted with a 2,514 patients database. Data was collected on the first visit to the Allergy clinic of all patients who underwent a correct spirometry maneuver due to suspected asthma between November 2014 and November 2017. All BMI, sex and age groups were represented. RESULTS: BMI influence over asthma differed in different age groups and genders. All spirometric results and FeNO were influenced by BMI. Concerning asthma characteristics only a later asthma onset with higher BMI values was observed. No other differences were found between different BMI groups. CONCLUSIONS: The effect of BMI on asthma is age dependent, so it should be corrected for age. The most important variations are on FeNO and spirometric results. The specific characteristics of the asthma and obesity phenotype are a greater perception of symptoms with fewer alterations in respiratory function tests and a lower prevalence of atopy, rhinitis and allergy, including allergic asthma. Other characteristics of this phenotype, such as a higher women prevalence or being late-onset or non-eosinophilic asthma, are non-specific for this phenotype.

Functional Examination of the Upper and Lower Airways in Asthma and Respiratory Allergic Diseases: Considerations in the Post-SARS-CoV-2 Era.

Airway examination procedures can potentially transmit infectious diseases to patients and to the health care professionals who perform them via various mechanisms. The COVID-19 pandemic has halted most of the activity of the clinics and laboratories involved in assessment of lung and nasal function, and clear recommendations in this regard have been made. Today, we still do not know for sure what its consequences will be in the short or long term, since important gaps remain in our knowledge of aspects as fundamental as virus transmission mechanisms, pathophysiology, immune response, and diagnosis. In this review, we study the examination techniques used to assess patients with respiratory allergy, asthma, and associated diseases during this period and highlight their possible advantages and disadvantages. Therefore, we focus on exploring the entire upper and lower airways, from the perspective of the safety of both health professionals and patients and their specific characteristics. We also analyze the intrinsic value of these interventions in terms of diagnosis and patient management. The changing situation of COVID-19 may mean that some of the assertions presented in this review will have to be modified in the future. While we seek to ensure a consistently broad approach, some differences in operational details may apply owing to local regulations.

Correction to: Cost-effectiveness analysis of umeclidinium bromide/vilanterol 62.5/25 mcg versus tiotropium/olodaterol 5/5 mcg in symptomatic patients with chronic obstructive pulmonary disease: a Spanish National Healthcare System perspective.

Following publication of the original article [1], we have been notified of the below corrections to the 5th paragraph in the Discussion section.

Obesity and Asthma: Key Clinical Questions.

Obesity is a common comorbidity of asthma that is associated not only with development of the disease, but also with poorer disease control and greater severity. Recent prospective evidence supports the idea that body weight gain precedes the development of asthma, although the debate is far from over. The objective of this document is to conduct a systematic review of 3 clinical questions related to asthma and obesity: (a) Obesity and asthma: the chicken or the egg? Clinical insights from epidemiological and phenotyping studies. (b) Is obesity a confounding factor in the diagnosis and management of asthma, especially in severe or difficult-to-control asthma? (c) How do obese asthma patients respond to pharmacological treatments and to biological drugs? Do we have effective specific interventions? Revised epidemiological, pathological, and mechanistic evidence combined with data from interventional clinical trials prevent us from clearly stating that obesity causes asthma. However, the complexity and heterogeneity of both illnesses make several clinical scenarios possible. Furthermore, asthma represents an additional clinical challenge in the obese patient. Physicians need to be aware of the confounding effects created by the more marked perception of symptoms, alterations in lung function, and the various comorbidities that obese persons present. Exhaustive phenotyping of the obese asthma patient should enable us to develop a rational therapeutic plan, including both the pharmacological approach and specific antiobesity therapies such as combining diet and exercise and, in extreme cases, bariatric surgery.

Cost-effectiveness analysis of umeclidinium bromide/vilanterol 62.5/25 mcg versus tiotropium/olodaterol 5/5 mcg in symptomatic patients with chronic obstructive pulmonary disease: a Spanish National Healthcare System perspective.

BACKGROUND: A head-to-head study demonstrated the superiority of once-daily umeclidinium bromide/vilanterol (UMEC/VI) 62.5/25 mcg on trough forced expiratory volume in 1 s (FEV1) versus once-daily tiotropium/olodaterol (TIO/OLO) 5/5 mcg in symptomatic patients with chronic obstructive pulmonary disease (COPD). This analysis evaluated the cost effectiveness of UMEC/VI versus TIO/OLO from a Spanish National Healthcare System perspective, using data from this study and Spanish literature. METHODS: This analysis was conducted from the perspective of the Spanish National Healthcare System with a 3-year horizon as base case. A disease progression model using a linked risk equation approach was used to estimate disease progression and associated healthcare costs, and quality-adjusted life years (QALYs). The Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study was used to develop the statistical risk equations for clinical endpoints, and costs were calculated using a health state approach (by dyspnea severity). Utilities for QALY calculation were estimated using patient baseline characteristics within a regression fit to Spanish observational data. Treatment effect, expressed as change from baseline in FEV1 was obtained from the head-to-head study and used in the model (UMEC/VI minus TIO/OLO difference: + 52 mL [95% confidence interval: 28, 77]). Baseline patient characteristics were sourced from Spanish literature or the head-to-head study if unavailable. A scenario analysis using only the intent-to-treat (ITT) population from the head-to-head study, and sensitivity analyses (including probabilistic sensitivity analyses), were conducted. Direct healthcare costs (2017 Euro) were obtained from Spanish sources and costs and benefits were discounted at 3% per annum. RESULTS: UMEC/VI was associated with small improvements in QALYs (+ 0.029) over a 3-year time horizon, compared with TIO/OLO, alongside cost savings of €393/patient. The ITT scenario analysis and sensitivity analyses had similar results. All probabilistic simulations resulted in UMEC/VI being less costly and more effective than TIO/OLO. CONCLUSION: UMEC/VI dominated TIO/OLO (more effective and less expensive). These results may aid payers and decision-makers in Spain when making judgements on which long-acting muscarinic antagonist/long-acting ß2-agonist (LAMA/LABA) treatments can be considered cost effective in Spain.

Does airway hyperresponsiveness monitoring lead to improved asthma control?

The current guidelines recommend an approach to asthma management based on asthma control, rather than asthma severity. Although several specific questionnaires have been developed and control criteria have been established based on clinical guidelines, the evaluation of asthma control is still not optimal. In general, these indicators provide adequate assessment of current control, but they are more limited when estimating future risk. There is much evidence demonstrating the persistence of airway inflammation and airway hyperresponsiveness (AHR) in patients with total control. Therefore, the objective of this review was to analyse the possible role of AHR monitoring as an instrument for assessing asthma control. We will evaluate its capacity as an indicator for future risk, both for estimating the possibility of clinical deterioration and loss of lung function or exacerbations. Furthermore, its relationship with inhaled corticosteroid treatment will be analysed, while emphasizing its capacity for predicting response and adjusting dosage, as well as information about the capability of AHR for monitoring treatment. Last of all, we will discuss the main limitations and emerging opportunities of AHR as an assessment instrument for asthma control.

Asthma diagnosis is not associated with obesity in a population of adults from Madrid.

BACKGROUND: Several studies have suggested a relationship between asthma and obesity; however, this relationship is unclear when obesity is compared with bronchial hyperresponsiveness to methacholine. AIM: To determine whether obesity is associated with a diagnosis of asthma. METHODS: We conducted a cross-sectional study in a population of Spanish adults in the north of Madrid, Spain between 2003 and 2007. The patients included had experienced asthma symptoms during the previous year, but had a ratio of forced expiratory volume in the first second of expiration (FEV1) to forced vital capacity (FVC) of > 70%. Diagnosis was confirmed by the presence of symptoms and demonstration of bronchial hyperresponsiveness to methacholine. Obesity was measured by body mass index (BMI). Adjusted odd ratios (OR) were obtained by logistic regression. RESULTS: Of a total of 1424 patients included, 251 (17.6%) were diagnosed with asthma. These patients were younger (P < .001) and had lower BMI (P < .001) and lung function parameters (FEV1 and FEV1/FVC ratio) than individuals without asthma (P < .001). After adjusting the model for age, gender, baseline FEV1, and FEV1/FVC ratio, patients with overweight or obesity were not more frequently diagnosed with asthma than those with normal weight (OR, 0.848 [95% confidence interval (CI), 0.59-1.20]; and OR, 0.616 [95% CI, 0.38-0.99], respectively). In addition, obese males were more frequently diagnosed with asthma than obese females (P < .041). CONCLUSIONS: In this study, obesity and overweight were not associated with a diagnosis of asthma based on the presence of consistent symptoms and demonstration of airway responsiveness to methacholine.

Changing patterns in tobacco consumption among Spanish military personnel under stressful conditions.

OBJECTIVE: A study is made to determine the prevalence of smoking and its variation over time in a group of Spanish military personnel (MP) under stressful conditions. METHODS: A questionnaire specifically designed for this study was administered to the entire MP contingent assigned to Banghis province (Afghanistan) between July and October 2009. A descriptive analysis was made (p < 0.05, 95%CI). RESULTS: The study sample comprised 254 MP (males 239; mean age 32 years (SD 9)). A total of 39.8% (95%CI; 33.7 - 45.8) were smokers, while 3.1% (95%CI; 1.0 - 5.3%) were former smokers. Regarding smoking habit before and at the end of deployment, one-half (50.5%) of the smokers declared that they smoked the same as before, 20.8% more than before, and 18.8% less than before. In turn, 5.9% of the smokers claimed to have started to smoke in the course of deployment, while 4% of the former smokers declared that they had quit smoking. The MP who quit smoking were younger than those who began to smoke (24 +/- 5 vs 39 +/- 9 years, p = 0.038). Moreover, the heavy smokers (> or = 15 cigarettes/day) reduced tobacco consumption, while the less heavy smokers increased the habit (p < 0.0001). CONCLUSIONS: The prevalence of daily smokers is high among MP. The majority of smokers smoke the same at the end of deployment. Those who quit smoking during the mission are significantly younger than those who begin to smoke. In turn, heavy smokers reduced their habit, while less heavy smokers increased smoking.

Recent trends in COPD prevalence in Spain: a repeated cross-sectional survey 1997-2007.

We aimed to describe changes in the prevalence of chronic obstructive pulmonary disease (COPD) in Spain by means of a repeated cross-sectional design comparing two population-based studies conducted 10 yrs apart. We compared participants from IBERPOC (Estudio epidemiológico de EPOC en España) (n = 4,030), conducted in 1997, with those of EPI-SCAN (Epidemiologic Study of COPD in Spain) (n = 3,802), conducted in 2007. Poorly reversible airflow obstruction compatible with COPD was defined according to the old European Respiratory Society definitions. COPD prevalence in the population between 40 to 69 yrs of age dropped from 9.1% (95% CI 8.1-10.2%) in 1997 to 4.5% (95% CI 2.4-6.6%), a 50.4% decline. The distribution of COPD prevalence by severity also changed from 38.3% mild, 39.7% moderate and 22.0% severe in 1997, to 85.6% mild, 13.0% moderate and 1.4% severe in 2007, and in the 40-69 yr EPI-SCAN sub-sample to 84.3% mild, 15.0% moderate and 0.7% severe. Overall, underdiagnosis was reduced from 78% to 73% (not a significant difference) and undertreatment from 81% to 54% (p<0.05) within this 10-yr frame. The finding of a substantial reduction in the prevalence of COPD in Spain is unexpected, as were the observed changes in the severity distribution, and highlights the difficulties in comparisons between repeated cross-sectional surveys of spirometry in the population.

Prevalence of COPD in Spain: impact of undiagnosed COPD on quality of life and daily life activities.

AIMS: This study aimed to determine the prevalence of chronic obstructive pulmonary disease (COPD) in Spain and identify the level of undiagnosed disease and its impact on health-related quality of life (HRQL) and activities of daily living (ADL). METHODS: A population-based sample of 4274 adults aged 40-80 years was surveyed. They were invited to answer a questionnaire and undergo prebrochodilator and postbronchodilator spirometry. COPD was defined as a postbronchodilator FEV(1)/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio of <0.70. RESULTS: For 3802 participants with good-quality postbronchodilator spirometry, the overall prevalence of COPD was 10.2% (95% CI 9.2% to 11.1%) and was higher in men (15.1%) than in women (5.6%). The prevalence of COPD stage II or higher was 4.4% (95%CI; 3.8%-5.1%). The prevalence of COPD increased with age and with cigarette smoking and was higher in those with a low educational level. A previous diagnosis of COPD was reported by only 27% of those with COPD. Diagnosed patients had more severe disease, higher cumulative tobacco consumption and more severely impaired HRQL compared with undiagnosed subjects. However, even patients with undiagnosed COPD stage I+ already showed impairment in HRQL and in some aspects of ADL compared with participants without COPD. CONCLUSIONS: The prevalence of COPD in individuals between 40 and 80 years of age in Spain is 10.2% and increases with age, tobacco consumption and lower educational levels. The rate of diagnosised COPD is very high and undiagnosed individuals with COPD already have a significant impairment in HRQL and ADL.

Effects of CPAP on oxidative stress and nitrate efficiency in sleep apnoea: a randomised trial.

BACKGROUND: Previous studies have presented contradictory data concerning obstructive sleep apnoea syndrome (OSAS), lipid oxidation and nitric oxide (NO) bioavailability. This study was undertaken to (1) compare the concentration of 8-isoprostane and total nitrate and nitrite (NOx) in plasma of middle-aged men with OSAS and no other known co-morbidity and healthy controls of the same age, gender and body mass index; and (2) test the hypothesis that nasal continuous positive airway pressure (CPAP) therapy attenuates oxidative stress and nitrate deficiency. METHODS: A prospective, randomised, placebo controlled, double-blind, crossover study was performed in 31 consecutive middle-aged men with newly diagnosed OSAS and 15 healthy control subjects. Patients with OSAS were randomised to receive sham CPAP or effective CPAP for 12 weeks. Blood pressure, urinary catecholamine levels and plasma 8-isoprostane and NOx concentrations were obtained before and after both treatment modalities. RESULTS: Patients with OSAS had significantly higher 8-isoprostane levels (median (IQR) 42.5 (29.2-78.2) vs 20.0 (12.5-52.5) pg/ml, p = 0.041, Mann-Whitney test) and lower NOx levels (264 (165-650) vs 590 (251-1465) micromol/l, p = 0.022) than healthy subjects. Body mass index, blood pressure and urinary catecholamines were unchanged by CPAP therapy, but 8-isoprostane concentrations decreased (38.5 (24.2-58.7) pg/ml at baseline vs 22.5 (16.2-35.3) pg/ml on CPAP, p = 0.0001) and NOx levels increased (280 (177-707) vs 1373 (981-1517) micromol/l, p = 0.0001) after CPAP. CONCLUSIONS: OSAS is associated with an increase in oxidative stress and a decrease in NOx that is normalised by CPAP therapy.

Nutritional state during COPD exacerbation: clinical and prognostic implications.

AIMS: To estimate the prevalence of malnutrition in chronic obstructive pulmonary disease (COPD) patients hospitalized for exacerbation and to evaluate its clinical and prognostic influence on the exacerbation. SUBJECTS/METHODS: The subjects were 78 consecutive patients with moderate-to-severe COPD who were admitted to hospital with a diagnosis of exacerbation. Nutritional status was assessed by means of body mass index (BMI), bioelectric impedance analysis and levels of plasmatic albumin. Previous spirometry, 6-min walk test, severity of the exacerbation, days of hospitalization and readmission in the following 3 months were also evaluated. RESULTS: Malnutrition [BMI <20 or fat-free mass (FFM) index

[The EPI-SCAN survey to assess the prevalence of chronic obstructive pulmonary disease in Spanish 40-to-80-year-olds: protocol summary]. / Estudio EPI-SCAN: resumen del protocolo de un estudio para estimar la prevalencia de EPOC en personas de 40 a 80 años en España.

BACKGROUND AND OBJECTIVES: Chronic obstructive pulmonary disease (COPD) causes considerable morbidity and mortality in Spain. The 1997 IBERPOC study, applying the old criteria of the European Respiratory Society, reported a COPD prevalence of 9.1% in the adult population of Spain. The Epidemiologic Study of COPD in Spain (EPI-SCAN) aims to determine the current prevalence of COPD in residents of Spain aged 40-80 years and to estimate changes over the past 10 years. Secondary objectives are, among others, to describe the current prevalence of smoking and changes in COPD prevalence relative to previous studies; to describe treatments received by patients, quality of life, and the BODE index (body mass index, obstruction of airflow, dyspnea, and exercise tolerance); and to measure inflammatory markers in blood and exhaled-breath condensate. PATIENTS AND METHODS: EPI-SCAN is a population-based, cross-sectional epidemiologic study targeting the general population of Spain aged between 40 and 80 years. Participating centers were located in Barcelona, Burgos, Cordoba, Huesca, Madrid, Oviedo, Seville, Valencia, Vic, and Vigo. All subjects filled in an extensive questionnaire to collect social, demographic, and clinical information. Slow and forced spirometry tests before and after a bronchodilator test were also undertaken. Additionally, selected subjects performed a 6-minute walk test and answered generic and specific quality-of-life questionnaires, as well as an activities-of-daily-living questionnaire. Exhaled-breath condensate and blood samples were also collected from these subjects for measurement of inflammatory and other biomarkers.

CPAP decreases plasma levels of soluble tumour necrosis factor-alpha receptor 1 in obstructive sleep apnoea.

There is increasing evidence that inflammation plays an important role in the development of cardiovascular complications in patients with obstructive sleep apnoea (OSA). No previous works have studied levels of soluble tumour necrosis factor-alpha receptor (sTNFR)-1 in patients with OSA. The aims of the present study were to examine serum levels of sTNFR-1 and the effect of nasal continuous positive airway pressure (CPAP) in patients with OSA. A prospective, randomised, placebo-controlled crossover study was performed. In total, 30 consecutive newly diagnosed OSA patients (apnoea/hypopnoea index 43.8+/-27.0 events x h(-1)) and 15 healthy obese patients were selected. Urinary levels of norepinephrine and epinephrine, as well as plasma sTNFR-1, tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and leukotriene (LT)B(4) levels were obtained at baseline and after 3 months of CPAP or sham CPAP. Nocturnal urinary levels of norepinephrine, epinephrine and sTNFR-1 (1,053+/-269 versus 820+/-166 pg x mL(-1)) were significantly higher in OSA patients. There were no significant differences in plasma levels of IL-6, LTB(4), or TNF-alpha between the two study groups. There were no significant differences in blood pressure, urinary catecholamine levels, or plasma IL-6, LTB(4) and TNF-alpha levels after both treatment modalities. However, after 3 months of effective CPAP usage, sTNFR-1 levels were significantly reduced (1,053+/-269 versus 899+/-254 pg x mL(-1)). Obstructive sleep apnoea patients have higher levels of soluble tumour necrosis factor-alpha receptor 1 than individuals without OSA; soluble tumour necrosis factor-alpha receptor 1 levels are lowered by continuous positive airway pressure therapy. These findings further corroborate a potential role of inflammation in the natural history of obstructive sleep apnoea.

[Risk of exposure to cross-transmission of infections in a dialysis unit: structural analysis of a simulated epidemic model]. / Riesgo de exposición a la transmisión cruzada de infecciones en una unidad de diálisis: análisis estructural de un modelo epidémico simulado.

UNLABELLED: Several studies show that cross-transmission of germs among patients under dialysis can occur as a consequence of processes in which the dialysis machine participates. The need of vascular access and lengthy periods of extracorporeal circulation increases the vulnerability to infection from nearby microorganisms. This study is intended to analyze the structural and dynamic features of the cross-transmission network generated by the propagation of germs which are capable of contaminating the hemodialyzers. METHODS: The simulation was carried out in a Dialysis Unit equipped with 19 machines for 62 patients. One of these patients was randomly chosen and considered as a carrier of an infectious agent capable of being transmitted to other patients, by means of the shared use of the same dialysis machine. For 10 days, the patient-machine allocation couples were registered. Co-occurrence matrices were elaborated and processed with the program UCINET 6.1 for social network analysis. Graphs were designed to visualize the networks of contagion, the centrality measures were calculated and the dynamic performance of the network generated by the chaining of the successive exposures of machines and patients was studied. RESULTS: The simulation let us visualize a rapid expansion of the risk of contagion of patients and contamination of machines. In 10 days, 87,09% of patients could have been exposed to the infection, and 68,42% of the machines could have been contaminated. These figures supposes that 5,4 new patients and 1,3 new machines could be potentially exposed every day. Along the first 5 days, the daily rate of exposure for patients and machines remains relatively low (3 new exposed patients and 1,2 new exposed machines every day). But the speed with witch the risk of contagion spreads, increases drastically in the last 5 days (7,8 new exposed patients every day). The fact that each patient requires at least 3 weekly sessions of dialysis and that a different machine can be allocated to him in each session explains that the risk of exposure can spread in some few days to a lot of patients and machines. It can also explain the difficulties found by the researches in identifying the responsible source of the origin of the sero-conversion outbreaks studied by the moment. CONCLUSIONS: If a germ can be transmitted from patient to patient by means of the incidental contamination of a dialysis machine, the appearance of an infected patient in a dialysis unit generates a risk of exposition that spreads quickly among other patients. Few days after an infected patient gets a dialysis session, it cannot be ruled out that most of the patients have been exposed to contagion and most of the machines exposed to contamination.

New screening method for lung cancer by detecting volatile organic compounds in breath.

Lung cancer is a frequent cause of cancer-related deaths in the world. There is no valid screening process and this limits its detection to the late stages, with consequently high mortality rates. Volatile organic compounds (VOC) are chemical compounds (mainly the products of cell catabolism) found as gases in the human breath. Different methods have been developed to analyse VOCs and to compare them in healthy subjects and lung cancer patients. In this review, we summarise the different techniques used to analyse VOC. Many reports have been published with promising results similar to those achieved with accepted screening methods such as mammography. These methods show good perspectives on lung cancer screening.

[Determining cardiac output by carbon dioxide rebreathing in patients with sleep apnea-hypopnea syndrome]. / Determinación del gasto cardíaco mediante reinhalación de CO2 en pacientes con síndrome de apneas-hipopneas durante el sueño.

The objective of the present study was to determine the relation between resting cardiac output in patients with sleep apnea-hypopnea syndrome but without arterial hypertension or heart failure as measured indirectly by the carbon dioxide rebreathing method and left ventricular function evaluated by transthoracic echocardiography. We also compared the variability and reproducibility of the measurements obtained by the equilibrium and exponential methods. In patients with sleep apnea-hypopnea syndrome there was a modest but significant association between resting cardiac output and left ventricular shortening fraction (r=0.690; P<.001) and left ventricular ejection fraction (r=0.690; P<.001). In addition, mean (SD) cardiac output obtained by the equilibrium method showed a lower coefficient of variability (0.21 [0.08]) than that of the exponential method (0.16 [0.09]) (P<.01) as well as a narrower reproducibility interval.