Smart Bioimpedance Device for the Assessment of Peripheral Muscles in Patients with COPD.

Muscle dysfunction and muscle atrophy are common complications resulting from Chronic Obstructive Pulmonary Disease (COPD). The evaluation of the peripheral muscles can be carried out through the assessment of their structural components from ultrasound images or their functional components through isometric and isotonic strength tests. This evaluation, performed mainly on the quadriceps muscle, is not only of great interest for diagnosis, prognosis and monitoring of COPD, but also for the evaluation of the benefits of therapeutic interventions. In this work, bioimpedance spectroscopy technology is proposed as a low-cost and easy-to-use alternative for the evaluation of peripheral muscles, becoming a feasible alternative to ultrasound images and strength tests for their application in routine clinical practice. For this purpose, a laboratory prototype of a bioimpedance device has been adapted to perform segmental measurements in the quadriceps region. The validation results obtained in a pseudo-randomized study in patients with COPD in a controlled clinical environment which involved 33 volunteers confirm the correlation and correspondence of the bioimpedance parameters with respect to the structural and functional parameters of the quadriceps muscle, making it possible to propose a set of prediction equations. The main contribution of this manuscript is the discovery of a linear relationship between quadriceps muscle properties and the bioimpedance Cole model parameters, reaching a correlation of 0.69 and an average error of less than 0.2 cm regarding the thickness of the quadriceps estimations from ultrasound images, and a correlation of 0.77 and an average error of 3.9 kg regarding the isometric strength of the quadriceps muscle.

[National Survey on the Activity of Lung Function Laboratories. Effects During the SARS-COV-2 Pandemic]. / Encuesta sobre la actividad de los laboratorios de función pulmonar. Efectos durante la pandemia por SARS-CoV-2.

Introduction: Following the SARS-CoV-2 pandemic in March 2020, pulmonary function testing (PFT) laboratories underwent a transformation, with a reduction in the number of tests or closure in some cases. The aim of this work was to know the activity of PFT in Spain and the modification of this activity due to the pandemic. Material and methods: A protocolised survey was carried out to members of the PFT laboratories through the Spanish Society of Pneumology and Thoracic Surgery (SEPAR). Results: Thirty-nine hospitals in Spain responded. The pulmonary function tests most frequently performed in the PFT laboratories were forced spirometry with bronchodilator test (100%), body plethysmography (97.4%), CO transfer capacity (97.4%), respiratory muscle strength measured in the mouth (97.4%), 6-minute walking test (94.7%), measurement of exhaled fraction of nitric oxide (92.3%) and incremental exercise test (71.8%).The pandemic led to a significant decrease in the number of tests (35.4%) during 2020 with subsequent recovery in 2021, without reaching pre-pandemic values.The most important changes were increased examination times, working with personal protective equipment and ventilation of the rooms. The performance of the nasopharyngeal swab for SARS-CoV2 testing prior to the tests was not homogeneous in the PFT laboratories. Conclusions: Most hospitals are sufficiently equipped to perform the most common pulmonary function tests. The pandemic resulted in a loss of activity in all hospitals.

[Results of the Implementation of a Case-Finding Program for Alpha-1 Antitrypsin Deficiency in COPD Patients]. / Resultados de la implementación de un programa de detección de casos de déficit de alfa-1 antitripsina en pacientes con EPOC.

Objectives: Currently, the identification of new cases of alpha-1 antitrypsin deficiency (AATD) continues to be one of the great challenges facing the disease. The present study aims to perform an analysis of the results of the implementation of a systematic case detection program of AATD for patients with chronic obstructive pulmonary disease. Material and methods: Cross-sectional observational study in which the results of AAT screening until December 2022 were analyzed. The cases studied were divided into three periods: (1) no systematic case detection until 2013; (2) systematic case detection of S and Z alleles for cases with AAT < 90 mg/dL until 2018, and (3) systematic case detection of 14 mutations for cases with AAT < 120 mg/dL since 2018. Results: A total of 471 cases were studied, of which 306 (65.0%) were carriers of some mutation related to HAD. The number of detected cases of all mutations with their percentage against those studied in each period was respectively: 6 (100%), 48 (88.8%) and 253 (61.5%). If we limit to severe mutations (AAT < 57.2 mg/dL), the distribution by periods was respectively: 3 (50.0), 10 (18.5%) and 17 (4.1%). Conclusions: The present study describes the changes in the detection of patients carrying DAAT-related alleles with three different case identification policies. The data support the use of systematic case detection system in the COPD patient population.

Evaluation of Different Doses in Inhaled Therapy: A Comprehensive Analysis.

BACKGROUND: Currently, there is a considerable degree of confusion over the dosage of inhaled medications. Here, we carried out a review of all the doses used for the devices used in inhalation therapy. METHODS: We first performed a systematic search of the different inhalation devices included on the July 2023 Spanish Ministry of Health Billing List. We then consulted the Spanish Agency for Medicines and Health Products to find the updated official label and to obtain the information on the exact composition. RESULTS: We identified 90 unique products, of which 22 were long-acting bronchodilators (and combinations thereof) and 68 were products containing inhaled corticosteroids (ICS). Overall, 10 products with bronchodilators and 40 with ICS were marketed with the metered dose, while 11 with bronchodilators and 28 with ICS were marketed with the delivered dose. In addition, in some bronchodilators, the drug was referred to as a type of salt, whereas in others the information referred to the drug itself. CONCLUSIONS: Our data show that for each inhaled drug there may be up to four different doses and that the marketed name may refer to any of these. Clinicians must be aware of these different dosages when prescribing inhaled medications.

Inflammatory response in human lung cells stimulated with plasma from COPD patients.

Background: Chronic obstructive pulmonary disease (COPD) is a condition resulting from a persistent inflammatory state in the airways even after smoking cessation. Intriguingly, the reasons behind this persistence of the inflammatory influx without smoking exposure have not been fully unraveled. We aimed to explore the hypothesis that systemic inflammation in COPD patients influences lung cell inflammatory response. Methods: We cultured human lung fibroblast and human airway epithelial cell lines with plasma from COPD patients (four emphysematous-COPD, four asthma-COPD overlap, four chronic bronchitis-COPD, and four bronchiectasis- COPD), and four smokers or ex-smokers without COPD as controls. Non-stimulated cells were used as controls. We measured Interleukine-8 (IL-8), C-reactive protein (CRP) and matrix metalloproteinase-9 (MMP-9) in plasma and culture supernatants by ELISA. Results: Cells stimulated with plasma from COPD patients and non-COPD smoker subjects produced higher CRP, IL- 8 and MMP-9 levels, an increase for COPD in CRP (p=0.029) in epithelial cells and IL-8 (p=0.039) in fibroblasts and decrease for MMP-9 (p=0.039) in fibroblasts, compared with non-stimulated cells. The response was higher in epithelial cells for IL-8 (p=0.003) and in fibroblasts for MMP-9 (p=0.063). The plasma from chronic bronchitis and bronchiectasis phenotypes induced higher IL-8 in fibroblasts. Conclusions: Plasma from COPD patients increases the inflammatory response in lung epithelial cells and lung fibroblasts, with a different response depending on the cell type and clinical phenotype.

Effects of genetics and altitude on lung function.

OBJECTIVES: The aim of this work is to present a review on the impact of genetics and altitude on lung function from classic and recent studies. DATA SOURCE: A systematic search has been carried out in different databases of scientific studies, using keywords related to lung volumes, spirometry, altitude and genetics. RESULTS: The results of this work have been structured into three parts. First, the relationship between genes and lung function. Next, a review of the genetic predispositions related to respiratory adaptation of people who inhabit high-altitude regions for millennia. Finally, temporary effects and long-term acclimatisation on respiratory physiology at high altitude are presented. CONCLUSIONS: The works focused on the influence of genetics and altitude on lung function are currently of interest in terms of studying the interactions between genetic, epigenetic and environmental factors in the configuration of the pathophysiological adaptation patterns.

A Mobile Health Solution Complementing Psychopharmacology-Supported Smoking Cessation: Randomized Controlled Trial.

BACKGROUND: Smoking cessation is a persistent leading public health challenge. Mobile health (mHealth) solutions are emerging to improve smoking cessation treatments. Previous approaches have proposed supporting cessation with tailored motivational messages. Some managed to provide short-term improvements in smoking cessation. Yet, these approaches were either static in terms of personalization or human-based nonscalable solutions. Additionally, long-term effects were neither presented nor assessed in combination with existing psychopharmacological therapies. OBJECTIVE: This study aimed to analyze the long-term efficacy of a mobile app supporting psychopharmacological therapy for smoking cessation and complementarily assess the involved innovative technology. METHODS: A 12-month, randomized, open-label, parallel-group trial comparing smoking cessation rates was performed at Virgen del Rocío University Hospital in Seville (Spain). Smokers were randomly allocated to a control group (CG) receiving usual care (psychopharmacological treatment, n=120) or an intervention group (IG) receiving psychopharmacological treatment and using a mobile app providing artificial intelligence-generated and tailored smoking cessation support messages (n=120). The secondary objectives were to analyze health-related quality of life and monitor healthy lifestyle and physical exercise habits. Safety was assessed according to the presence of adverse events related to the pharmacological therapy. Per-protocol and intention-to-treat analyses were performed. Incomplete data and multinomial regression analyses were performed to assess the variables influencing participant cessation probability. The technical solution was assessed according to the precision of the tailored motivational smoking cessation messages and user engagement. Cessation and no cessation subgroups were compared using t tests. A voluntary satisfaction questionnaire was administered at the end of the intervention to all participants who completed the trial. RESULTS: In the IG, abstinence was 2.75 times higher (adjusted OR 3.45, P=.01) in the per-protocol analysis and 2.15 times higher (adjusted OR 3.13, P=.002) in the intention-to-treat analysis. Lost data analysis and multinomial logistic models showed different patterns in participants who dropped out. Regarding safety, 14 of 120 (11.7%) IG participants and 13 of 120 (10.8%) CG participants had 19 and 23 adverse events, respectively (P=.84). None of the clinical secondary objective measures showed relevant differences between the groups. The system was able to learn and tailor messages for improved effectiveness in supporting smoking cessation but was unable to reduce the time between a message being sent and opened. In either case, there was no relevant difference between the cessation and no cessation subgroups. However, a significant difference was found in system engagement at 6 months (P=.04) but not in all subsequent months. High system appreciation was reported at the end of the study. CONCLUSIONS: The proposed mHealth solution complementing psychopharmacological therapy showed greater efficacy for achieving 1-year tobacco abstinence as compared with psychopharmacological therapy alone. It provides a basis for artificial intelligence-based future approaches. TRIAL REGISTRATION: ClinicalTrials.gov NCT03553173; https://clinicaltrials.gov/ct2/show/NCT03553173. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/12464.

Diagnostic Performance of a Lateral Flow Assay for the Detection of Alpha-1-Antitrypsin Deficiency / Rendimiento diagnóstico de un ensayo de flujo lateral para la detección de la deficiencia de alfa-1 antitripsina

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Smart Bioimpedance Spectroscopy Device for Body Composition Estimation.

The purpose of this work is to describe a first approach to a smart bioimpedance spectroscopy device for its application to the estimation of body composition. The proposed device is capable of carrying out bioimpedance measurements in multiple configurable frequencies, processing the data to obtain the modulus and the bioimpedance phase in each of the frequencies, and transmitting the processed information wirelessly. Another novelty of this work is a new algorithm for the identification of Cole model parameters, which is the basis of body composition estimation through bioimpedance spectroscopy analysis. Against other proposals, the main advantages of the proposed method are its robustness against parasitic effects by employing an extended version of Cole model with phase delay and three dispersions, its simplicity and low computational load. The results obtained in a validation study with respiratory patients show the accuracy and feasibility of the proposed technology for bioimpedance measurements. The precision and validity of the algorithm was also proven in a validation study with peritoneal dialysis patients. The proposed method was the most accurate compared with other existing algorithms. Moreover, in those cases affected by parasitic effects the proposed algorithm provided better approximations to the bioimpedance values than a reference device.

Triple therapy for COPD: a crude analysis from a systematic review of the evidence.

We systematically reviewed the current knowledge on fixed-dose triple therapies for the treatment of chronic obstructive pulmonary disease (COPD), with a specific focus on its efficacy versus single bronchodilation, double fixed dose combinations, and open triple therapies. Articles were retrieved from PubMed, Embase, and Scopus up to 3 August 2018. We selected articles with randomized controlled or crossover design conducted in patients with COPD and published as full-length articles or scientific letters, evaluating triple therapy combinations in a single or different inhaler, and with efficacy data versus monocomponents, double combinations, or open triple therapies. Our systematic search reported 108 articles, of which 24 trials were finally selected for the analysis. A total of 7 studies with fixed dose triple therapy combinations, and 17 studies with open triple therapies combinations. Triple therapy showed improvements in lung function [trough forced expiratory volume (FEV1) ranging from not significant (NS) to 147 ml], health status using the St. George's Respiratory Questionnaire [(SGRQ) from NS to 8.8 points], and exacerbations [risk ratio (RR) from NS to 0.59 for all exacerbations] versus single or double therapies with a variability in the response, depending the specific combination, and the comparison group. The proportion of adverse effects was similar between study groups, the exception being the increase in pneumonia for some inhaled corticosteroid (ICS) containing groups. The reviews of this paper are available via the supplementary material section.

Evaluación del grado de acuerdo transversal y el pronóstico longitudinal de la nueva clasificación GOLD 2017: un análisis de la cohorte TRACE / Evaluation of the level of transversal agreement and longitudinal prognosis of the new GOLD 2017 classification: a TRACE cohort analysis

Objetivo: evaluar la clasificación de los pacientes con EPOC según la versión 2016 y 2017 del documento GOLD, estudiar su grado de acuerdo y valorar el impacto pronóstico de su utilización. Método: el estudio "Registro y análisis en el tiempo de resultados clínicos en EPOC" (Proyecto TRACE: Timebased Register and Analysis of COPD Endpoints) es una cohorte de pacientes prospectiva que tiene por objetivo la descripción de la evolución clínica de los pacientes con EPOC con las herramientas básicas del clínico, en la que se recoge sistemáticamente los síntomas, la función pulmonar y las agudizaciones. En la visita basal se clasificaron a los pacientes según las versiones 2016 y 2017 de la GOLD y se estudió su grado de acuerdo mediante el coeficiente kappa. Durante 4 años de visita anuales, se siguieron a los pacientes y se estudió la capacidad pronóstica de cada clasificación mediante curvas de Kaplan-Meier. Resultados: la cohorte inicial estaba compuesta por 391 pacientes en la visita basal de los que se seleccionaron 357 para el análisis. La distribución de los pacientes según los tipos GOLD de la versión 2016 y 2017 mostraba un coeficiente kappa de 0,665 (p < 0,001), sugiriendo un grado de acuerdo bueno. El análisis de la supervivencia aportó curvas similares entre las dos clasificaciones con diferencias significativas del nuevo grupo D frente al A y B, pero sin diferencias entre los grupos más leves. Conclusiones: el presente estudio evalúa el grado de acuerdo y la capacidad pronóstica de los dos documentos GOLD más recientes. Los resultados indican un comportamiento similar tanto en la valoración transversal como en la longitudinal a largo plazo

Objective: To evaluate the classification of patients with COPD according to the 2016 and 2017 versions of the GOLD document, to study the level of agreement and to evaluate the prognostic impact of their use. Methods: The "Time-based Register and Analysis of COPD Endpoints" (TRACE Project) is a prospective patient cohort whose objective is to describe the clinical evolution of patients with COPD using the basic tools for the disease, which systematically records symptoms, lung function and exacerbations. Patients were classified during the baseline visit according to the 2016 and 2017 versions of GOLD and the level of agreement was studied using Cohen's kappa coefficient. Patients were monitored throughout four years of annual visits and the prognostic capacity of each classification was studied using Kaplan-Meier curves. Results: The initial cohort consisted of 391 patients at the baseline visit, of which 357 were selected for the analysis. The distribution of patients according to GOLD group in the 2016 and 2017 versions showed a kappa coefficient of 0.665 (p < 0.001), suggesting a good level of agreement. The survival analysis provided similar curves between the two classifications with significant differences in the new group D compared to groups A and B, but without differences between the milder groups. Conclusion: This study evaluates the level of agreement and the prognostic ability of the most recent GOLD documents. The results indicate similar behavior in both the transversal and long-term longitudinal evaluation

Using the Social-Local-Mobile App for Smoking Cessation in the SmokeFreeBrain Project: Protocol for a Randomized Controlled Trial.

BACKGROUND: Smoking is considered the main cause of preventable illness and early deaths worldwide. The treatment usually prescribed to people who wish to quit smoking is a multidisciplinary intervention, combining both psychological advice and pharmacological therapy, since the application of both strategies significantly increases the chance of success in a quit attempt. OBJECTIVE: We present a study protocol of a 12-month randomized open-label parallel-group trial whose primary objective is to analyze the efficacy and efficiency of usual psychopharmacological therapy plus the Social-Local-Mobile app (intervention group) applied to the smoking cessation process compared with usual psychopharmacological therapy alone (control group). METHODS: The target population consists of adult smokers (both male and female) attending the Smoking Cessation Unit at Virgen del Rocío University Hospital, Seville, Spain. Social-Local-Mobile is an innovative intervention based on mobile technologies and their capacity to trigger behavioral changes. The app is a complement to pharmacological therapies to quit smoking by providing personalized motivational messages, physical activity monitoring, lifestyle advice, and distractions (minigames) to help overcome cravings. Usual pharmacological therapy consists of bupropion (Zyntabac 150 mg) or varenicline (Champix 0.5 mg or 1 mg). The main outcomes will be (1) the smoking abstinence rate at 1 year measured by means of exhaled carbon monoxide and urinary cotinine tests, and (2) the result of the cost-effectiveness analysis, which will be expressed in terms of an incremental cost-effectiveness ratio. Secondary outcome measures will be (1) analysis of the safety of pharmacological therapy, (2) analysis of the health-related quality of life of patients, and (3) monitoring of healthy lifestyle and physical exercise habits. RESULTS: Of 548 patients identified using the hospital's electronic records system, we excluded 308 patients: 188 declined to participate and 120 did not meet the inclusion criteria. A total of 240 patients were enrolled: the control group (n=120) will receive usual psychopharmacological therapy, while the intervention group (n=120) will receive usual psychopharmacological therapy plus the So-Lo-Mo app. The project was approved for funding in June 2015. Enrollment started in October 2016 and was completed in October 2017. Data gathering was completed in November 2018, and data analysis is under way. The first results are expected to be submitted for publication in early 2019. CONCLUSIONS: Social networks and mobile technologies influence our daily lives and, therefore, may influence our smoking habits as well. As part of the SmokeFreeBrain H2020 European Commission project, this study aims at elucidating the potential role of these technologies when used as an extra aid to quit smoking. TRIAL REGISTRATION: ClinicalTrials.gov NCT03553173; https://clinicaltrials.gov/ct2/show/record/NCT03553173 (Archived by WebCite at http://www.webcitation.org/74DuHypOW). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/12464.

Smart Vest for Respiratory Rate Monitoring of COPD Patients Based on Non-Contact Capacitive Sensing.

In this paper, a first approach to the design of a portable device for non-contact monitoring of respiratory rate by capacitive sensing is presented. The sensing system is integrated into a smart vest for an untethered, low-cost and comfortable breathing monitoring of Chronic Obstructive Pulmonary Disease (COPD) patients during the rest period between respiratory rehabilitation exercises at home. To provide an extensible solution to the remote monitoring using this sensor and other devices, the design and preliminary development of an e-Health platform based on the Internet of Medical Things (IoMT) paradigm is also presented. In order to validate the proposed solution, two quasi-experimental studies have been developed, comparing the estimations with respect to the golden standard. In a first study with healthy subjects, the mean value of the respiratory rate error, the standard deviation of the error and the correlation coefficient were 0.01 breaths per minute (bpm), 0.97 bpm and 0.995 (p < 0.00001), respectively. In a second study with COPD patients, the values were −0.14 bpm, 0.28 bpm and 0.9988 (p < 0.0000001), respectively. The results for the rest period show the technical and functional feasibility of the prototype and serve as a preliminary validation of the device for respiratory rate monitoring of patients with COPD.

Factores que afectan a la función pulmonar: una revisión bibliográfica / Factors Affecting Lung Function: A Review of the Literature

Los valores de referencia de las pruebas de función pulmonar están basados históricamente en factores antropométricos como el peso, la altura, el género y la edad. La FVC y el FEV1 disminuyen con la edad y, en contraposición, volúmenes y capacidades como el RV y la FRC se incrementan. La TLC, CV, RV, FVC y FEV1 se ven afectados por la altura, puesto que son proporcionales al tamaño corporal. Esto significa que un individuo alto sufrirá un mayor decremento de sus volúmenes pulmonares a medida que aumente su edad. Algunas variables decrecen exponencialmente con el incremento del peso, como la FRC y el ERV, de tal forma que los sujetos con obesidad mórbida pueden llegar a alcanzar un volumen corriente cercano al RV. Los hombres poseen vías aéreas de conducción más largas que las mujeres, dando lugar a una mayor resistencia específica de las vías respiratorias. El mayor trabajo respiratorio en mujeres para aumentar la ventilación provoca que, en condiciones con la misma intensidad física, el consumo de oxígeno sea más alto que en hombres. En posición vertical los volúmenes pulmonares son más altos que en el resto de las posturas. La DLCO es significativamente mayor en posiciones supinas que en posición sentada y vertical, no existiendo diferencias significativas en posición sentada y de pie. Las características antropométricas no son suficientes para explicar las diferencias existentes en la función pulmonar entre diferentes etnias y ponen de manifiesto la importancia de considerar otros factores adicionales a los clásicos antropométricos para su medición

Lung function reference values are traditionally based on anthropometric factors, such as weight, height, sex, and age. FVC and FEV1 decline with age, while volumes and capacities, such as RV and FRC, increase. TLC, VC, RV, FVC and FEV1 are affected by height, since they are proportional to body size. This means that a tall individual will experience greater decrease in lung volumes as they get older. Some variables, such as FRC and ERV, decline exponentially with an increase in weight, to the extent that tidal volume in morbidly obese patients can be close to that of RV. Men have longer airways than women, causing greater specific resistance in the respiratory tract. The increased work of breathing to increase ventilation among women means that their consumption of oxygen is higher than men under similar conditions of physical intensity. Lung volumes are higher when the subject is standing than in other positions. DLCO is significantly higher in supine positions than in sitting or standing positions, but the difference between sitting and standing positions is not significant. Anthropometric characteristics are insufficient to explain differences in lung function between different ethnic groups, underlining the importance of considering other factors in addition to the conventional anthropometric measurements

Factors Affecting Lung Function: A Review of the Literature. / Factores que afectan a la función pulmonar: una revisión bibliográfica.

Lung function reference values are traditionally based on anthropometric factors, such as weight, height, sex, and age. FVC and FEV1 decline with age, while volumes and capacities, such as RV and FRC, increase. TLC, VC, RV, FVC and FEV1 are affected by height, since they are proportional to body size. This means that a tall individual will experience greater decrease in lung volumes as they get older. Some variables, such as FRC and ERV, decline exponentially with an increase in weight, to the extent that tidal volume in morbidly obese patients can be close to that of RV. Men have longer airways than women, causing greater specific resistance in the respiratory tract. The increased work of breathing to increase ventilation among women means that their consumption of oxygen is higher than men under similar conditions of physical intensity. Lung volumes are higher when the subject is standing than in other positions. DLCO is significantly higher in supine positions than in sitting or standing positions, but the difference between sitting and standing positions is not significant. Anthropometric characteristics are insufficient to explain differences in lung function between different ethnic groups, underlining the importance of considering other factors in addition to the conventional anthropometric measurements.