Inhaler technique education in elderly patients with asthma or COPD: impact on disease exacerbations-a protocol for a single-blinded randomised controlled trial

Chronic Obstructive Pulmonary Disease (COPD)and asthma affect more than 10% of the population. Most patients use their inhaler incorrectly, mainly the elderly, thereby becoming more susceptible to poor clinical control and exacerbations. Placebo device training is regarded as one of the best teaching methods, but there is scarce evidence to support it as the most effective one to improve major clinical outcomes. Our objective is to perform a single-blinded RCT to assess the impact of this education tool in these patients. Introduction Chronic Obstructive Pulmonary Disease (COPD)and asthma affect more than 10% of the population. Most patients use their inhaler incorrectly, mainly the elderly, thereby becoming more susceptible to poor clinical control and exacerbations. Placebo device training is regarded as one of the best teaching methods, but there is scarce evidence to support it as the most effective one to improve major clinical outcomes. Our objective is to perform a single-blinded RCT to assess the impact of this education tool in these patients. Methods and analysis A multicentre single-blinded Randomised Controlled Trial (RCT) will be set up, comparing an inhaler education programme with a teach-to-goal placebo-device training versus usual care, with a 1-year follow-up, in patients above 65 years of age with asthma or COPD. Intervention will be provided at baseline, and after 3 and 6 months, with interim analysis at an intermediate time point. Exacerbation rates were set as primary outcomes, and quality of life, adherence rates, clinical control and respiratory function were chosen as secondary outcomes. A sample size of 146 participants (73 in each arm) was estimated as adequate to detect a 50% reduction in event rates. Two-sample proportions χ² test will be used to study primary outcome and subgroup analysis will be carried out according to major baseline characteristicsFaculty of Health Sciences at the University of Beira Interior and Life and Health Sciences Research Institute (ICVS)/3B’s at University of Minho in Portugal. This work was prepared with scientific support from Harvard Medical School, in accordance with the Portuguese Clinical Scholarship Research Training Program

Socio-epidemiological Aspects of Respiratory Allergic Diseases in Southern Africa

The prevalence of respiratory allergic diseases has been increasing in Southern Africa both in urban and in rural environments. Various factors may contribute toward this situation, namely, exposure to aeroallergens, such as grass pollens and house dust mites. However, other irritant environmental triggers, such as exposure to tobacco smoke and certain indoor and outdoor fumes, may also play a relevant part. Furthermore, certain parasitic and mycobacterial infections may act as allergic disease risk modifiers, although such an influence should be confirmed. Finally, certain cultural and socioeconomic factors may also influence accessibility to healthcare and adherence to treatment of these diseases

Changes in Glycolytic Pathway in SARS-COV 2 Infection and Their Importance in Understanding the Severity of COVID-19

Publisher Copyright: © Copyright © 2021 Santos, Póvoa, Paixão, Mendonça and Taborda-Barata.COVID-19 is an infectious disease caused by Coronavirus 2 (SARS-CoV-2) that may lead to a severe acute respiratory syndrome. Such syndrome is thought to be related, at least in part, to a dysregulation of the immune system which involves three main components: hyperactivity of the innate immune system; decreased production of type 1 Interferons (IFN) by SARS-CoV-2-infected cells, namely respiratory epithelial cells and macrophages; and decreased numbers of both CD4+ and particularly CD8+ T cells. Herein, we describe how excessive activation of the innate immune system and the need for viral replication in several cells of the infected organism promote significant alterations in cells’ energy metabolism (glucose metabolism), which may underlie the poor prognosis of the disease in severe situations. When activated, cells of the innate immune system reprogram their metabolism, and increase glucose uptake to ensure secretion of pro-inflammatory cytokines. Changes in glucose metabolism are also observed in pulmonary epithelial cells, contributing to dysregulation of cytokine synthesis and inflammation of the pulmonary epithelium. Controlling hyperglycolysis in critically ill patients may help to reduce the exaggerated production of pro-inflammatory cytokines and optimise the actions of the adaptive immune system. In this review, we suggest that the administration of non-toxic concentrations of 2-deoxy-D-glucose, the use of GLUT 1 inhibitors, of antioxidants such as vitamin C in high doses, as well as the administration of N-acetylcysteine in high doses, may be useful complementary therapeutic strategies for these patients, as suggested by some clinical trials and/ or reports. Overall, understanding changes in the glycolytic pathway associated with COVID-19 infection can help to find new forms of treatment for this disease.publishersversionpublishe

Relationship with inflammatory and clinical phenotypes and prognostic implications

Bronchial asthma is a chronic disease that affects individuals of all ages. It has a high prevalence and is associated with high morbidity and considerable levels of mortality. However, asthma is not a single disease, and multiple subtypes or phenotypes (clinical, inflammatory or combinations thereof) can be detected, namely in aggregated clusters. Most studies have characterised asthma phenotypes and clusters of phenotypes using mainly clinical and inflammatory parameters. These studies are important because they may have clinical and prognostic implications and may also help to tailor personalised treatment approaches. In addition, various metabolomics studies have helped to further define the metabolic features of asthma, using electronic noses or targeted and untargeted approaches. Besides discriminating between asthma and a healthy state, metabolomics can detect the metabolic signatures associated with some asthma subtypes, namely eosinophilic and non-eosinophilic phenotypes or the obese asthma phenotype, and this may prove very useful in point-of-care application. Furthermore, metabolomics also discriminates between asthma and other “phenotypes” of chronic obstructive airway diseases, such as chronic obstructive pulmonary disease (COPD) or Asthma–COPD Overlap (ACO). However, there are still various aspects that need to be more thoroughly investigated in the context of asthma phenotypes in adequately designed, homogeneous, multicentre studies, using adequate tools and integrating metabolomics into a multiple-level approach.publishersversionpublishe

Development of a screening questionnaire for the study of food allergy in adults

Background & aims: As far as we know, no screening questionnaire has been developed and validated for identification of adverse food reactions in Portuguese-speaking adults, as an initial approach towards the investigation of cases of possible food allergy. Thus, the objective of this study was to develop and validate a screening questionnaire of food allergy in adult Portuguesespeaking patients. Methods: This was a multicentre, cross-sectional study using a simple random sample of 186 adults between 18 and 82 years old from various parts of the centre of Portugal. Intelligibility of the questionnaire was first assessed in 24 patients with confirmed IgE- or non-IgE-mediated food allergy, and in 24 volunteers without food allergies. The 17-item questionnaire was subsequently applied by phone to 78 food allergic patients (66 IgE-mediated and 12 non-IgE mediated) and to 60 non-food allergic volunteers, with subsequent reassessment (re-test). Face and content validity, intelligibility, construct validity, and test-retest reliability (temporal stability) were analysed. Results: Face and content validity allowed item reduction from 30 to 17 items with adequate content validity index >0.78. Construct validity was confirmed in the 66 confirmed IgE-mediated food allergic patients, 12 non-IgE-mediated food allergic patients, and 60 non-allergic patients. Test-Retest Reliability (general temporal stability) of the test had a Spearman correlation coefficient value of 0.845 for the retest. Cohen's Kappa values for the relevant questions were greater than 0.890 for almost all items. No differences were found when sex, age, and volunteers' recruitment origin were analysed. An inverse relationship was found between reliability and retest time interval. Conclusions: Due to the quick and easy implementation, confirmation of face, content and construct validity as well as high temporal reproducibility, this screening questionnaire may be a useful study tool for an initial approach to detection of food allergies in adults.info:eu-repo/semantics/publishedVersio

Biological effects of thermal water-associated hydrogen sulfide on human airways and associated immune cells: Implications for respiratory diseases

Natural mineral (thermal) waters have been used for centuries as treatment for various diseases. However, the scientific background of such therapeutic action is mostly empiric and based on knowledge acquired over time. Among the various types of natural mineral waters, sulfurous thermal waters (STWs) are the most common type in the center of Portugal. STWs are characterized by high pH, poor mineralization, and the presence of several ions and salts, such as bicarbonate, sodium, fluoride, silica, and carbonate. Furthermore, these waters are indicated as a good option for the treatment of various illnesses, namely respiratory diseases (e.g., allergic rhinitis, asthma, and chronic obstructive pulmonary disease). From the sulfide species present in these waters, hydrogen sulfide (H2S) stands out due to its abundance. In healthy conditions, H2S-related enzymes (e.g., cystathionine β-synthase and cystathionine γ-lyase) are expressed in human lungs, where they have mucolytic, antioxidant, anti-inflammatory, and antibacterial roles, thus contributing to airway epithelium homeostasis. These roles occur mainly through S-sulfhydration, a post-translational modification through which H2S is able to change the activity of several targets, such as ion channels, second messengers, proteins, among others. However, in respiratory diseases the metabolism of H2S is altered, which seems to contribute somehow to the respiratory deterioration. Moreover, H2S has been regarded as a good biomarker of airway dysfunction and severity, and can be measured in serum, sputum, and exhaled air. Hence, in this review we will recapitulate the effects of STWs on lung epithelial-immune crosstalk through the action of its main component, H2S

Prevalence and clinical features of adverse food reactions in Portuguese adolescents

Background & aims: The objective of the present study was to determine, for the first time, the prevalence and clinical features of food allergy in Portuguese adolescents. Methods: Cross-sectional study performed in various secondary schools in central Portugal. Randomly selected adolescents replied to a validated food allergy questionnaire. Those who reported an adverse food reaction were seen at participating hospitals, where clinical history was taken, skin prick (SPT) and prick-prick skin (SPPT) tests were performed, and food allergen-specific IgE levels (sIgE) were determined. An open oral challenge was performed in selected cases. Cases of positive clinical history of immediate (up to 2 h after ingestion) reaction in association with positive food sIgE levels and/or SPT were classified as IgE-associated probable food allergy and as confirmed IgE-mediated food allergy if food challenges were positive. Cases of positive clinical history of delayed (more than 2 h after ingestion) and negative food sIgE levels independently of positive SPT or SPPT results, were classified as non-IgE associated probable food allergy. Results: The prevalence of probable food allergy in Portuguese adolescents was 1.41% (95% CI: 0.90–2.03%), with fresh fruits, shellfish, nuts, and peanut as the most frequently implicated foods. IgE-mediated probable food allergy occurred in 1.23% (95% CI: 0.67–1.72%) of cases, with fresh fruits, shellfish, and nuts mainly involved. Cutaneous symptoms were most frequently reported. Conclusions: The prevalence of probable food allergies in Portuguese adolescents is low, is mostly related to fresh fruits, shellfish, nuts, and peanut, and most frequently involves cutaneous symptoms.info:eu-repo/semantics/publishedVersio

Mercury levels in biological matrices from inhabitants of Estarreja, Portugal

Humans are exposed to mercury trough several pathways including the consumption of contaminated seafood and ingestion of contaminated house dust. We have previously demonstrated that mercury levels in house dust samples from Estarreja region are amongst the highest reported in Portugal. Here we report the levels of total mercury in different biological matrices from 88 adult individuals from Estarreja (age: 37-83, median: 68). Mercury was detected in all samples analysed, with the highest levels being found in hair (range: 560-4540 ng/g, median: 1680 ng/g), followed by fingernails (range: 215-1740 ng/g, median: 844 ng/g), toenails (range: 144-1850 ng/g, median: 555 ng/g), blood (range: 0.97-18.4 ng/g, median: 6.70 ng/g) and urine (range: 0.15-5.14 ng/g, median: 0.61 ng/g). The hair to blood ratio (H:B) varied between 147 and 616, with a median value of 274, which is only 9% higher than the H:B ratio proposed by the Word Health Organization . The concentrations of mercury in hair were very strongly correlated with the concentrations in blood (p0.001). Such results suggest that a urine levels reflect the exposure to a different species of mercury, reinforcing previous studies that propose urine as a suitable matrix for inorganic mercury whereas blood, hair and nails are suitable matrices for methylmercury exposure.Ana C Sousa acknowledges the financial support from University of Aveiro, in the scope of the framework contract foreseen in the numbers 4, 5 and 6 of the article 23, of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19 (A.C.A. Sousa)publishe

Endocrine Disrupting Chemicals in Patients with Chronic Obstructive Pulmonary Diseases

The study of indoor environmental quality as well as the development and progression of chronic respiratory diseases have received a great deal of attention in the past few years. However, most of those surveys focus on the effects of particulate matter (PM) and biological contaminants (fungi and bacteria) and evidences on the effects of endocrine disrupting chemicals (EDCs) in these pathologies are limited. Hence, RESPIRA project aims to contribute towards a better understanding of the role of multiple stressors in respiratory diseases by providing data on the levels and effects of EDCs in patients with Chronic Obstructive Pulmonary Disease (COPD) and control individuals from Estarreja region (NW Portugal). Here we will summarize the results obtained for phenolic compounds (parabens, triclosan and triclocarban) in matched human and indoor environmental samples (house dust) from COPD patients. Overall, the concentrations in dust samples are one to two orders of magnitude higher that the concentrations in human urine. Triclosan was detected in all the dust samples, triclocarban was detected in 82% of the dust samples and parabens in 90% to 100% of the samples. In urine samples, triclosan was detected in 56% of the samples, triclocarban was always bellow detection limit (0.25 ng/mL) and parabens detection frequency varied widely (23-84%). Interestingly, the highest level reported in dust for triclosan (1200 ng/g) corresponded to the house of the patient with the highest triclosan concentration in urine (140 ng/mL).publishe

Urinary neonicotinoids profiles in adults from Aveiro district, NW Portugal

Neonicotinoid insecticides (Neonics - NNs) are systemic insecticides widely used in agriculture to control insects. Due to their broad-spectrum insecticide activity, they are also used in the domestic environment and on animals, including household pets. Owing to their toxicity towards non-target organisms, particu-larly honeybees, the agricultural outdoor use of some neonics was already banned. Nevertheless, they can still be used in indoor activities. Neonics’ residues have been detected in food, water and indoor dust and, consequently, humans are exposed to these insecticides. However, human biomonitoring data is limited to a few studies worldwide, with no data for Portugal. In this study, levels of neonicotinoids namely ace-tamiprid (and its metabolite dm-acetamiprid), clothianidin, dinotefuran, imidacloprid, nitenpyran, thi-acloprid and thiamethoxan, were quantified in spot urine samples provided by 46 volunteers from Aveiro district. The volunteers were recruited from RESPIRA project, an ongoing study that aims to evaluate the role of environmental contaminants in the progression of respiratory diseases. Overall, the obtained re-sults disclose that 81.4% of the individuals were exposed to at least one neonicotinoid. Dinotefuran and dm-acetamiprid showed the highest detection frequencies (46.5%), followed by imidacloprid (41.9%), whereas nitenpyran and thiacloprid were never detected (bellow detection limit). The neonics with the highest concentrations were dm-acetamiprid (max: 1443 ug/g creatinine, average: 39.1 ug/g creatinine) and thiamethoxan (max: 152 ug/g creatinine, average: 6.9 ug/g creatinine). These results are in general accordance with previous reports that disclosed dm-acetamiprid as one of the most frequently detected NN in human urine samples.publishe