A decade of urban fires: Portuguese events between 2013 and 2022.

This study describes a dataset containing urban fire events that took place in mainland Portugal between 2013 and 2022. The Regulation n.º3317-A/2018, established by the Portuguese National Emergency and Civil Protection Authority (Autoridade Nacional de Emergência e Proteção Civil, ANEPC), defines the Operations Management System (Sistema de Gestão de Operações, SGO). Among other attributions, this system allows to manage the lyfe-cycle of the urban fire events, from ignition to extinction, through the Operations Decision Support System (Sistema de Apoio à Decisão Operacional, SADO). This system supports the systematic collection of a minimum set of data on each event. All instances included in the dataset were retrieved from SADO. To make the data suitable for analytic purposes, several pre-processing actions were taken, including the steps of data transformation and cleaning. The dataset was further validated by a set of technical procedures aiming to verify both data correctness and utility. The final dataset provides the most recent multi-year record of Portuguese urban fires including 27 variables on 72641 events.

Robust, maintainable, emergency invasive mechanical ventilator. / Ventilador mecânico invasivo de emergência resistente e de fácil manutenção.

OBJECTIVE: To develop a simple, robust, safe and efficient invasive mechanical ventilator that can be used in remote areas of the world or war zones where the practical utility of more sophisticated equipment is limited by considerations of maintainability, availability of parts, transportation and/or cost. METHODS: The device implements the pressure-controlled continuous mandatory ventilation mode, complemented by a simple assist-control mode. Continuous positive airway pressure is also possible. The consumption of compressed gases is minimized by avoiding a continuous flow of oxygen or air. Respiratory rates and inspiration/expiration time ratios are electronically determined, and an apnea/power loss alarm is provided. RESULTS: The pressure profiles were measured for a range of conditions and found to be adjustable within a ± 2.5cmH2O error margin and stable well within this range over a 41-hour period. Respiratory cycle timing parameters were precise within a few percentage points over the same period. The device was tested for durability for an equivalent period of four months. Chemical and biological tests failed to identify any contamination of the gas by volatile organic compounds or microorganisms. A ventilation test on a large animal, in comparison with a well established ventilator, showed that the animal could be adequately ventilated over a period of 60 minutes, without any noticeable negative aftereffects during the subsequent 24-hour period. CONCLUSION: This ventilator design may be viable, after further animal tests and formal approval by the competent authorities, for clinical application in the abovementioned atypical circumstances.

OBJETIVO: Desenvolver um ventilador mecânico invasivo simples, resistente, seguro e eficiente que possa ser utilizado em áreas remotas do mundo ou zonas de guerra, em que a utilidade prática de equipamentos mais sofisticados é limitada por questões de manutenção, disponibilidade de peças, transporte e/ou custo. MÉTODOS: O dispositivo implementa o modo de ventilação mandatória contínua com pressão controlada, complementado por um simples modo assisto-controlado. Pode-se também utilizar a pressão positiva contínua nas vias aéreas. Ao se evitar o fluxo contínuo de oxigênio ou ar, minimiza-se o consumo de gases comprimidos. As taxas respiratórias e as relações de tempo de inspiração e expiração são determinadas eletronicamente. Além disso, conta com um alarme de apneia/falta de energia. RESULTADOS: Os perfis de pressão foram medidos para uma série de condições, sendo considerados ajustáveis dentro de uma margem de erro de ± 2,5cmH2O, e foram considerados bem estáveis dentro dessa variação durante um período de 41 horas. Os parâmetros de tempo do ciclo respiratório foram precisos dentro de alguns pontos percentuais durante o mesmo período. O dispositivo foi testado quanto à durabilidade por um período equivalente a 4 meses. Os testes químicos e biológicos não conseguiram identificar qualquer contaminação do gás por compostos orgânicos voláteis ou micro-organismos. Em comparação com um ventilador bem estabelecido, o teste de ventilação em um animal de grande porte mostrou que este poderia ser ventilado adequadamente durante um período de 60 minutos, sem quaisquer efeitos negativos perceptíveis durante o período subsequente de 24 horas. CONCLUSÃO: Este projeto de ventilador pode ser viável após novos testes em animais e aprovação formal pelas autoridades competentes, para aplicação clínica nas circunstâncias atípicas anteriormente mencionadas.

Ventilador mecânico invasivo de emergência resistente e de fácil manutenção / Robust, maintainable, emergency invasive mechanical ventilator

RESUMO Objetivo: Desenvolver um ventilador mecânico invasivo simples, resistente, seguro e eficiente que possa ser utilizado em áreas remotas do mundo ou zonas de guerra, em que a utilidade prática de equipamentos mais sofisticados é limitada por questões de manutenção, disponibilidade de peças, transporte e/ou custo. Métodos: O dispositivo implementa o modo de ventilação mandatória contínua com pressão controlada, complementado por um simples modo assisto-controlado. Pode-se também utilizar a pressão positiva contínua nas vias aéreas. Ao se evitar o fluxo contínuo de oxigênio ou ar, minimiza-se o consumo de gases comprimidos. As taxas respiratórias e as relações de tempo de inspiração e expiração são determinadas eletronicamente. Além disso, conta com um alarme de apneia/falta de energia. Resultados: Os perfis de pressão foram medidos para uma série de condições, sendo considerados ajustáveis dentro de uma margem de erro de ± 2,5cmH2O, e foram considerados bem estáveis dentro dessa variação durante um período de 41 horas. Os parâmetros de tempo do ciclo respiratório foram precisos dentro de alguns pontos percentuais durante o mesmo período. O dispositivo foi testado quanto à durabilidade por um período equivalente a 4 meses. Os testes químicos e biológicos não conseguiram identificar qualquer contaminação do gás por compostos orgânicos voláteis ou micro-organismos. Em comparação com um ventilador bem estabelecido, o teste de ventilação em um animal de grande porte mostrou que este poderia ser ventilado adequadamente durante um período de 60 minutos, sem quaisquer efeitos negativos perceptíveis durante o período subsequente de 24 horas. Conclusão: Este projeto de ventilador pode ser viável após novos testes em animais e aprovação formal pelas autoridades competentes, para aplicação clínica nas circunstâncias atípicas anteriormente mencionadas.

ABSTRACT Objective: To develop a simple, robust, safe and efficient invasive mechanical ventilator that can be used in remote areas of the world or war zones where the practical utility of more sophisticated equipment is limited by considerations of maintainability, availability of parts, transportation and/or cost. Methods: The device implements the pressure-controlled continuous mandatory ventilation mode, complemented by a simple assist-control mode. Continuous positive airway pressure is also possible. The consumption of compressed gases is minimized by avoiding a continuous flow of oxygen or air. Respiratory rates and inspiration/expiration time ratios are electronically determined, and an apnea/power loss alarm is provided. Results: The pressure profiles were measured for a range of conditions and found to be adjustable within a ± 2.5cmH2O error margin and stable well within this range over a 41-hour period. Respiratory cycle timing parameters were precise within a few percentage points over the same period. The device was tested for durability for an equivalent period of four months. Chemical and biological tests failed to identify any contamination of the gas by volatile organic compounds or microorganisms. A ventilation test on a large animal, in comparison with a well established ventilator, showed that the animal could be adequately ventilated over a period of 60 minutes, without any noticeable negative aftereffects during the subsequent 24-hour period. Conclusion: This ventilator design may be viable, after further animal tests and formal approval by the competent authorities, for clinical application in the abovementioned atypical circumstances.

Days Needed for the Disappearance of a Cough Due to the Use of an Angiotensin-Converting Enzyme Inhibitor and Identification of Predisposing Factors Associated With Its Appearance in a Clinical Cohort of Hypertensive Patients.

Our main objective was to investigate the numbers of days necessary for the disappearance of the cough caused by an angiotensin-converting enzyme inhibitor (ACEI) subsequent to the discontinuation of treatment, and to identify the associated factors that contribute to the appearance of said cough and angioneurotic edema. We studied 1101 patients with hypertension treated with an ACEI for 15 years. A multivariate analysis of binary logistic regression was performed to identify predisposing cough factors. In the 1101 patients treated with ACEI, 270 were diagnosed as having a cough caused by an ACEI (24.5%). The average numbers of days until the cough disappeared was 6.06 ± 1.58 days. The significant predisposing factors of the cough were female sex (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.31-2.39), previous diagnosis of obstructive sleep apnea (OR, 1.85; 95% CI, 1.31-2.61), and concomitant use of thiazides (OR, 1.50; 95% CI, 1.11-2.04). Statins were shown as a protective factor (OR, 0.69; 95% CI, 0.51-0.93). In the case of angioneurotic edema, 25 patients (2.3%) were diagnosed, without significant determinants. Our analysis showed that the cough disappeared in a period of ≤10 days for 96.7% of patients diagnosed with a cough, subsequent to the discontinuation of ACEI treatment. The risk factors identified for the appearance of a cough include female sex, previous obstructive sleep apnea, and concomitant use of thiazides. The use of statins was found to be a protective factor. The incidence of angioneurotic edema in our cohort is greater than that described in the literature.

A Predictive Mathematical Model of Cell Cycle, Metabolism, and Apoptosis of Monoclonal Antibody-Producing GS-NS0 Cells.

The monoclonal antibody (mAb) industry is witnessing unprecedented growth, with an increasing range of new molecules and biosimilars as well as disease targets approved than ever before. Competition necessitates pharmaceutical companies to reduce development/production costs and time-to-market. To this aim, mathematical modeling can aid traditional experiment-only-based process development by reducing the design space, integrating scales, and assisting in identifying optimal operating conditions in less time and with lower expense. Mathematical models have been employed by other industries for control and optimization purposes and are important decisional tools for testing scenarios, process configurations, operating conditions, etc. Herein, a predictive, experimentally validated mathematical model that captures cellular metabolism and growth with cell cycle, cell death (apoptosis), and mAb production in GS-NS0 cells is presented. The model utilizes cellular, metabolic, and gene expression data, highlighting how multiple data sources can be integrated in one tool with the aim of optimizing mammalian cell bioprocessing.

Apoptosis: A mammalian cell bioprocessing perspective.

Apoptosis is a form of programmed and controlled cell death that accounts for the majority of cellular death in bioprocesses. Cell death affects culture longevity and product quality; it is instigated by several stresses experienced by the cells within a bioreactor. Understanding the factors that cause apoptosis as well as developing strategies that can protect cells is crucial for robust bioprocess development. This review aims to a) address apoptosis from a bioprocess perspective; b) describe the significant apoptotic mechanisms linking them to the most relevant stresses encountered in bioreactors; c) discuss the design of operating conditions in order to avoid cell death; d) focus on industrially relevant cell lines; and e) present anti-apoptosis strategies including cell engineering and model-based optimization of bioprocesses. In addition, the importance of apoptosis in quality-by-design bioprocess development from clone screening to production scale are highlighted.

The Increasingly Human and Profitable Monoclonal Antibody Market.

The monoclonal antibody (mAb) market has changed rapidly in the past 5 years: it has doubled in size, becoming dominated by fully human molecules, launched bispecific molecules, and faced competition from biosimilars. We summarize the market in terms of therapeutic applications, type and structure of mAbs, dominant companies, manufacturing locations, and emerging markets.

Centralized Unmanned Aerial Vehicle Mesh Network Placement Scheme: A Multi-Objective Evolutionary Algorithm Approach.

In the past, Unmanned Aerial Vehicles (UAVs) were mostly used in military operations to prevent pilot losses. Nowadays, the fast technological evolution has enabled the production of a class of cost-effective UAVs that can service a plethora of public and civilian applications, especially when configured to work cooperatively to accomplish a task. However, designing a communication network among the UAVs is a challenging task. In this article, we propose a centralized UAV placement strategy, where UAVs are used as flying access points forming a mesh network, providing connectivity to ground nodes deployed in a target area. The geographical placement of UAVs is optimized based on a Multi-Objective Evolutionary Algorithm (MOEA). The goal of the proposed scheme is to cover all ground nodes using a minimum number of UAVs, while maximizing the fulfillment of their data rate requirements. The UAVs can employ different data rates depending on the channel conditions, which are expressed by the Signal-to-Noise-Ratio (SNR). In this work, the elitist Non-Dominated Sorting Genetic Algorithm II (NSGA-II) is used to find a set of optimal positions to place UAVs, given the positions of the ground nodes. We evaluate the trade-off between the number of UAVs used to cover the target area and the data rate requirement of the ground nodes. Simulation results show that the proposed algorithm can optimize the UAV placement given the requirement and the positions of the ground nodes in the geographical area.

Mobile Exergaming in Adolescents' Everyday Life-Contextual Design of Where, When, with Whom, and How: The SmartLife Case.

Exergames, more specifically console-based exergames, are generally enjoyed by adolescents and known to increase physical activity. Nevertheless, they have a reduced usage over time and demonstrate little effectiveness over the long term. In order to increase playing time, mobile exergames may increase potential playing time, but need to be engaging and integrated in everyday life. The goal of the present study was to examine the context of gameplay for mobile exergaming in adolescents’ everyday life to inform game design and the integration of gameplay into everyday life. Eight focus groups were conducted with 49 Flemish adolescents (11 to 17 years of age). The focus groups were audiotaped, transcribed, and analyzed by means of thematic analysis via Nvivo 11 software (QSR International Pty Ltd., Victoria, Australia). The adolescents indicated leisure time and travel time to and from school as suitable timeframes for playing a mobile exergame. Outdoor gameplay should be restricted to the personal living environment of adolescents. Besides outdoor locations, the game should also be adaptable to at-home activities. Activities could vary from running outside to fitness exercises inside. Furthermore, the social context of the game was important, e.g., playing in teams or meeting at (virtual) meeting points. Physical activity tracking via smart clothing was identified as a motivator for gameplay. By means of this study, game developers may be better equipped to develop mobile exergames that embed gameplay in adolescents’ everyday life.

Hepatopulmonary syndrome: which blood gas analysis criteria and position should we use for diagnosis?

Introduction: Different blood gas criteria have been used in the diagnosis of hepatopulmonary syndrome (HPS). Patients and methods: Arterial blood gases were prospectively evaluated in 194 cirrhotic candidates for liver transplantation (LT) in the supine and seated position. Three blood gas criteria were analyzed: classic (partial pressure of oxygen [PaO2] < 70 mmHg and/or alveolar-arterial gradient of oxygen [A-a PO2] ≥ 20 mmHg), modern (A-a PO2 ≥ 15 mmHg or ≥ 20 mmHg in patients over 64) and the A-a PO2 ≥ threshold value adjusted for age. Results: The prevalence of HPS in the supine and seated position was 27.8% and 23.2% (classic), 34% and 25.3% (modern) and 22.2% and 19% (adjusted for age), respectively. The proportion of severe and very severe cases increased in a seated position (11/49 [22.4%] vs 5/66 [7.6%], p = 0.02). No difference was observed in the pre-LT, post-LT and overall mortality in patients with HPS, regardless of the criteria used. Conclusion: Obtaining blood gas measurements in the supine position and the use of modern criteria are more sensitive for the diagnosis of HPS. Blood gas analysis with the patient seated detects a greater number of severe and very severe cases. The presence of HPS was not associated with an increase in mortality regardless of blood gas criterion used (AU)

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Hepatopulmonary syndrome: which blood gas analysis criteria and position should we use for diagnosis?

INTRODUCTION: Different blood gas criteria have been used in the diagnosis of hepatopulmonary syndrome (HPS). PATIENTS AND METHODS: Arterial blood gases were prospectively evaluated in 194 cirrhotic candidates for liver transplantation (LT) in the supine and seated position. Three blood gas criteria were analyzed: classic (partial pressure of oxygen [PaO2] < 70 mmHg and/or alveolar-arterial gradient of oxygen [A-a PO2] ≥ 20 mmHg), modern (A-a PO2 ≥ 15 mmHg or ≥ 20 mmHg in patients over 64) and the A-a PO2 ≥ threshold value adjusted for age. RESULTS: The prevalence of HPS in the supine and seated position was 27.8% and 23.2% (classic), 34% and 25.3% (modern) and 22.2% and 19% (adjusted for age), respectively. The proportion of severe and very severe cases increased in a seated position (11/49 [22.4%] vs 5/66 [7.6%], p = 0.02). No difference was observed in the pre-LT, post-LT and overall mortality in patients with HPS, regardless of the criteria used. CONCLUSION: Obtaining blood gas measurements in the supine position and the use of modern criteria are more sensitive for the diagnosis of HPS. Blood gas analysis with the patient seated detects a greater number of severe and very severe cases. The presence of HPS was not associated with an increase in mortality regardless of blood gas criterion used.

Monoclonal Antibodies Production Platforms: An Opportunity Study of a Non-Protein-A Chromatographic Platform Based on Process Economics.

Monoclonal antibodies currently dominate the biopharmaceutical market with growing sales having reached 80 billion USD in 2016. As most top-selling mAbs are approaching the end of their patent life, biopharmaceutical companies compete fiercely in the biosimilars market. These two factors present a strong motivation for alternative process strategies and process optimization. In this work a novel purification strategy for monoclonal antibodies comprising phenylboronic acid multimodal chromatography for capture followed by polishing by ion-exchange monolithic chromatography and packed bed hydrophobic interaction chromatography is presented and compared to the traditional protein-A-based process. Although the capital investment is similar for both processes, the operation cost is 20% lower for the novel strategy. This study shows that the new process is worthwhile investing in and could present a viable alternative to the platform process used by most industrial players.

The utility of the macro-aggregated albumin lung perfusion scan in the diagnosis and prognosis of hepatopulmonary syndrome in cirrhotic patients candidates for liver transplantation

Background: The macro-aggregated albumin lung perfusion scan (99mTc-MAA) is a diagnostic method for hepatopulmonary syndrome (HPS). Aim: To determine the sensitivity of 99mTc-MAA in diagnosing HPS, to establish the utility of 99mTc-MAA in determining the influence of HPS on hypoxemia in patients with concomitant pulmonary disease and to determine the correlation between 99mTc-MAA values and other respiratory parameters. Methods: Data from 115 cirrhotic patients who were eligible for liver transplantation (LT) were prospectively analyzed. A transthoracic contrast echocardiography and 99mTc-MAA were performed in 85 patients, and 74 patients were diagnosed with HPS. Results: The overall sensitivity of 99mTc-MAA for the diagnosis of HPS was 18.9% (14/74) in all of the HPS cases and 66.7% (4/6) in the severe to very severe cases. In HPS patients who did not have lung disease, the degree of brain uptake of 99mTc-MAA was correlated with the alveolar-arterial oxygen gradient (A-a PO2) (r = 0.32, p < 0.05) and estimated oxygen shunt (r = 0.41, p < 0.05) and inversely correlated with partial pressure of arterial oxygen (PaO2) while breathing 100% O2 (r = -0.43, p < 0.05). The 99mTc-MAA was positive in 20.6% (7/36) of the patients with HPS and lung disease. The brain uptake of 99mTc-MAA was not associated with mortality and normalized in all cases six months after LT. Conclusions: The 99mTc-MAA is a low sensitivity test for the diagnosis of HPS that can be useful in patients who have concomitant lung disease and in severe to very severe cases of HPS. It was not related to mortality, and brain uptake normalized after LT (AU)

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BIM-Based E-Procurement: An Innovative Approach to Construction E-Procurement.

This paper presents an innovative approach to e-procurement in construction, which uses building information models (BIM) to support the construction procurement process. The result is an integrated and electronic instrument connected to a rich knowledge base capable of advanced operations and able to strengthen transaction relationships and collaboration throughout the supply chain. The BIM-based e-procurement prototype has been developed using distinct existing electronic solutions and an IFC server and was tested in a pilot case study, which supported further discussions of the results of the research.

Genetic analysis of candidate SNPs for metabolic syndrome in obstructive sleep apnea (OSA).

Obstructive sleep apnea (OSA) is a common disorder characterized by the reduction or complete cessation in airflow resulting from an obstruction of the upper airway. Several studies have observed an increased risk for cardiovascular morbidity and mortality among OSA patients. Metabolic syndrome (MetS), a cluster of cardiovascular risk factors characterized by the presence of insulin resistance, is often found in patients with OSA, but the complex interplay between these two syndromes is not well understood. In this study, we present the results of a genetic association analysis of 373 candidate SNPs for MetS selected in a previous genome wide association analysis (GWAS). The 384 selected SNPs were genotyped using the Illumina VeraCode Technology in 387 subjects retrospectively assessed at the Internal Medicine Unit of the "Virgen de Valme" University Hospital (Seville, Spain). In order to increase the power of this study and to validate our findings in an independent population, we used data from the Framingham Sleep Study which comprises 368 individuals. Only the rs11211631 polymorphism was associated with OSA in both populations, with an estimated OR=0.57 (0.42-0.79) in the joint analysis (p=7.21×10(-4)). This SNP was selected in the previous GWAS for MetS components using a digenic approach, but was not significant in the monogenic study. We have also identified two SNPs (rs2687855 and rs4299396) with a protective effect from OSA only in the subpopulation with abdominal obesity. As a whole, our study does not support the idea that OSA and MetS share major genetic determinants, although both syndromes share common epidemiological and clinical features.

Oxidative stress responses to carboxylic acid functionalized single wall carbon nanotubes on the human intestinal cell line Caco-2.

Carbon nanotubes (CNT) are among the more promising nanomaterials due to their potential applications. In this sense, the adverse effects that CNT can induce are of concern. In particular, carboxylic acid functionalized single wall carbon nanotubes (COOH-SWCNT) have shown to reduce cell viability and induce morphological effects on the human intestinal cell line Caco-2, but little is known about the toxic mechanisms involved. The aim of the present study was to investigate the oxidative stress responses of this cell line after 24h exposure to COOH-SWCNT. Biomarkers assayed included lipid peroxidation (LPO), reactive oxygen species (ROS) generation, and enzymatic and non-enzymatic antioxidant defences. Results showed an increase in ROS from 100µg/mL reaching 5.2-fold the basal value at the highest concentration assayed. An induction of catalase, superoxide dismutase and glutathione peroxidase activities was also observed, meanwhile glutathione reductase showed a reduced activity at 1000µg/mL. Glutathione (GSH) levels also decreased (2.5-fold) at the highest level of exposure. Therefore, the antioxidant defences could not overwhelm the oxidative insult caused by COOH-SWCNT and LPO products increased in a concentration-dependent manner. We can conclude that oxidative stress plays a role in the pathogenicity induced by COOH-SWCNT on Caco-2 cells at the concentrations assayed.

Influence of carboxylic acid functionalization on the cytotoxic effects induced by single wall carbon nanotubes on human endothelial cells (HUVEC).

A vast variety of nanomaterials have been developed in the recent years, being carbon nanotubes (CNTs) the ones that have attracted more attention, due to its unique properties which make them suitable for numerous applications. Consequently, it is predicted that tons of CNTs will be produced worldwide every year, being its exposure of toxicological concern. Nanomaterials, once into the body, can translocate from the uptake sites to the blood circulation or the lymphatic system, resulting in distribution throughout the body. Thus, the vascular endothelium can be in contact with them and can suffer from their toxic effects. In this regard, the aim of this work was to investigate the cytotoxicity of single-walled carbon nanotubes (SWCNTs) on human endothelial cells evaluating the influence of acid carboxylic functionalization and also the exposure time (24 and 48 h). Biomarkers assessed were neutral red uptake, protein content, a tetrazolium salt metabolization and cell viability by means of the Trypan blue exclusion test. Cells were exposed to concentrations between 0 and 800 µg/mL SWCNTs for 24 and 48 h. Results have shown that both SWCNTs and carboxylic acid functionalized single-walled carbon nanotubes (COOH-SWCNTs) induce toxic effects in HUVEC cells in a concentration- and time-dependent way. Moreover, the carboxylic acid functionalization results in a higher toxicity compared to the SWCNTs.

Identification of genetic factors associated with susceptibility to angiotensin-converting enzyme inhibitors-induced cough.

BACKGROUND AND OBJECTIVE: Angiotensin-converting enzyme inhibitors (ACEi) are the first selected drugs for hypertensive patients because of its protective properties against heart and kidney diseases. Persistent cough is a common adverse reaction associated with ACEi, which can bind to the treatment cessation, but its etiology remains an unresolved issue. The most accepted mechanism is that the inhibition of ACEi increases kinins levels, resulting in the activation of proinflammatory mechanisms and nitric oxide generation. However, relatively little is known about the genetic susceptibility to ACEi-induced cough in hypertensive patients. METHODS: We carried out a monogenic association analysis of 39 polymorphisms and haplotypes in genes encoding key proteins related to ACEi activity with the occurrence of ACEi-induced cough. We also carried out a digenic association analysis and investigated the existence of epistatic interactions between the analyzed polymorphisms using a logistic regression procedure. Finally, we investigated the predictive value of the identified associations for ACEi-induced cough. RESULTS: We found that genetic polymorphisms in MME [rs2016848, P=0.002, odds ratio (OR)=1.795], BDKRB2 (rs8012552, P=0.012, OR=1.609), PTGER3 (rs11209716, P=0.002, OR=0.565), and ACE (rs4344) genes are associated with ACEi-related cough. For the latter, the effect is sex specific, having a protective effect in males (P=0.027, OR=0.560) and increasing the risk in females (P=0.031, OR=1.847). In addition, genetic interactions between peptidases involved in kinins levels (CPN1 and XPNPEP1) and proteins related to prostaglandin metabolism (PTGIS and PTGIR) strongly modify the risk of ACEi-induced cough presentation (0.102≤OR≤0.384 for protective combinations and 2.732≤OR≤7.216 for risk combinations). CONCLUSION: These results are consistent with the hypothesis that the mechanism of cough is related to the accumulation of bradykinin, substance P, and prostaglandins.