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Objective: Digital interventions such as remote monitoring of symptoms and physiological measurements have the potential to reduce the economic burden of asthma and chronic obstructive pulmonary disease (COPD) but their cost-effectiveness remains unclear. This systematic review of randomised controlled trials (RCT) aims to assess whether digital health interventions can be cost-effective in these patients., Design: Systematic review of RCTs. Study quality was assessed using RoB2 tool., Data Sources: Systematic search in three databases: PubMed, Scopus and Web of Science., Eligibility Criteria: Studies were eligible if they were RCTs with health economic evaluations assessing participants with asthma and/or COPD and comparing a digital health intervention to standard of care., Results: We included 35 RCTs, of which 21 were related to COPD, 13 to asthma and one to both diseases. Overall, studies assessed four categories of digital health interventions: (i) Electronic patient diaries (n = 4), (ii) real-time monitoring (n = 19), (iii) teleconsultations (n = 6) and (iv) others (n = 6). Eleven studies performed a full economic evaluation analysis, while 24 studies performed a partial economic analysis. Most studies involving real-time monitoring or teleconsultations presented economic results in favour of digital health interventions (indicating them to be cost-effective or less expensive than the standard of care). Mixed results were obtained for electronic patient diaries. In the studies that conducted a full economic analysis, the incremental cost-effectiveness ratio (ICER) ranged from 3530,93€/QALY and 286,369,28€/QALY. In the studies that conducted a partial economic analysis, the cost differences between the intervention group and the control group ranged from 0,12€ and 85,217,86€. Half studies with low risk of bias concluded that the intervention was economically favourable., Conclusion: Although costs varied based on intervention type, follow-up period and country, most studies report digital health interventions to be affordable or associated with decreased costs., Trial Registration: PROSPERO: CRD42023439195., (© 2024 John Wiley & Sons Ltd.)

Introduction: Patient and public involvement (PPI) initiatives involving patients with chronic respiratory disease (CRD) are rare. Therefore, this study aimed to explore the perspectives of patients with CRD, carers and interested citizens regarding the relevance and need for a PPI network and suggestions for its implementation., Methods: A qualitative study based on focus groups was conducted. Recruitment occurred through invitations on social media platforms and to patients who have participated in previous asthma studies of the team. Three focus groups were conducted, via video conference, using a semi-structured guide. Thematic analysis was performed by two independent researchers and discussed with the extended team., Results: Fifteen patients with CRD, one carer and one interested citizen (13 females, median 36 (range: 18-72) years) participated. All participants acknowledged the importance of implementing a collaborative network and demonstrated interest in being integrated. Participants acknowledged the importance of their involvement in several phases of the research cycle. The main aim identified for this network was to facilitate communication between patients and researchers. Participants regarded the integration of patients, carers, researchers and healthcare professionals from different scientific areas as relevant. The use of digital platforms to attract members and support the work, together with group dynamics and regular meetings, were some of the most relevant practical considerations for implementing the network. The identified facilitators for their engagement were sharing experiences, researchers' and healthcare professionals' support and feedback and schedule flexibility. The identified barriers included the amount of time dedicated, low health/digital literacy and the potential detachment of nondiagnosed patients or those with low symptom impact in daily life., Conclusion: Patients, carers and citizens acknowledged the relevance of implementing a collaborative network and demonstrated interest in active participation in every stage of the health research cycle. A deeper knowledge of the barriers and facilitators identified in this study could support implementing these initiatives in Portugal., Patient or Public Contribution: This study was designed by a research team that included one patient with asthma and one carer. They were specifically involved in building the study protocol and the interview guide. They also gave feedback regarding the electronic consent form and the short sociodemographic questionnaire created, namely by removing noncontributing words or phrases and rewording expressions. The lay summary was written by another patient with asthma. All participants of this study were invited to implement and integrate the ConectAR network-a collaborative network of research in respiratory health., Public Summary: In Portugal, chronic respiratory patients do not have an active role as 'coinvestigators'. This study aimed to acknowledge if patients and citizens considered a patient and public involvement network useful, whose main purpose would be to facilitate communication between patients and researchers. A study based on online group interviews was carried out with patients with chronic respiratory diseases and interested citizens, both recruited on social media platforms. Participants considered that bringing together patients, carers, researchers and healthcare professionals is valuable because sharing different experiences and perspectives may help patients to improve their daily lives and increase research quality. In conclusion, patients agree that implementing a collaborative network with researchers and healthcare professionals and participating in the health research cycle is quite preponderant. Acknowledging what can help and deter this network may be beneficial to implementing this type of initiative in Portugal., (© 2023 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Background: EQ-5D-5L (EuroQOL, 5 Domains, 5 Levels) is a widely used health-related quality-of-life instrument, comprising 5 domains. However, it is not known how each domain is impacted by rhinitis or asthma control., Objective: To assess the association between rhinitis or asthma control and the different EQ-5D-5L domains using data from the MASK-air mHealth app., Methods: In this cross-sectional study, we assessed data from all MASK-air users (2015-2021; 24 countries). For the levels of each EQ-5D-5L domain, we assessed rhinitis and asthma visual analog scales (VASs) and the combined symptom-medication score (CSMS). We built ordinal multivariable models assessing the adjusted association between VAS/CSMS values and the levels of each EQ-5D-5L domain. Finally, we compared EQ-5D-5L data from users with rhinitis and self-reported asthma with data from users with rhinitis alone., Results: We assessed 5354 days from 3092 users. We observed an association between worse control of rhinitis or asthma (higher VASs and CSMS) and worse EQ-5D-5L levels. In multivariable models, all VASs and the CSMS were associated with higher levels of pain/discomfort and daily activities. For anxiety/depression, the association was mostly observed for rhinitis-related tools (VAS nose, VAS global, and CSMS), although the presence of self-reported asthma was also associated with worse anxiety/depression. Worse mobility ("walking around") was particularly associated with VAS asthma and with the presence of asthma., Conclusions: A worse rhinitis control and a worse asthma control are associated with higher EQ-5D-5L levels, particularly regarding pain/discomfort and activity impairment. Worse rhinitis control is associated with worse anxiety/depression, and poor asthma control with worse mobility., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objectives: Anxiety and depression are relevant comorbidities in asthma, but, in Portugal and Spain, data on this topic are scarce. We assessed, in patients with asthma, the frequency of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) and the European Quality of Life Five Dimension Questionnaire (EQ-5D); the level of agreement between these questionnaires, and the factors associated with these symptoms., Methods: This is a secondary analysis of the INSPIRERS studies. A total of 614 adolescents and adults with persistent asthma (32.6±16.9 years, 64.7% female) were recruited from 30 primary care centres and 32 allergy, pulmonology and paediatric clinics. Demographic and clinical characteristics, HADS and EQ-5D were collected. A score ≥8 on Hospital Anxiety and Depression Scale-Anxiety/Hospital Anxiety and Depression Scale-Depression or a positive answer to EQ-5D item 5 indicated the presence of these symptoms. Agreement was determined by Cohen's kappa. Two multivariable logistic regressions were built., Results: According to HADS, 36% of the participants had symptoms of anxiety and 12% of depression. According to EQ-5D, 36% of the participants had anxiety/depression. The agreement between questionnaires in identifying anxiety/depression was moderate (k=0.55, 95% CI 0.48 to 0.62). Late asthma diagnosis, comorbidities and female gender were predictors of anxiety/depression, while better asthma control, health-related quality of life and perception of health were associated with lower odds for anxiety/depression., Conclusion: At least 1/3 of the patients with persistent asthma experience symptoms of anxiety/depression, showing the relevance of screening these disorders in patients with asthma. EQ-5D and HADS questionnaires showed a moderate agreement in the identification of anxiety/depression symptoms. The identified associated factors need to be further investigated in long-term studies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Currently available European Alpine Altitude Climate Treatment (AACT) programs combine the physical characteristics of altitude with the avoidance of environmental triggers in the alpine climate and a personalized multidisciplinary pulmonary rehabilitation approach. The reduced barometric pressure, oxygen pressure, and air density, the relatively low temperature and humidity, and the increased UV radiation at moderate altitude induce several physiological and immunological adaptation responses. The environmental characteristics of the alpine climate include reduced aeroallergens such as house dust mites (HDM), pollen, fungi, and less air pollution. These combined factors seem to have immunomodulatory effects controlling pathogenic inflammatory responses and favoring less neuro-immune stress in patients with different asthma phenotypes. The extensive multidisciplinary treatment program may further contribute to the observed clinical improvement by AACT in asthma control and quality of life, fewer exacerbations and hospitalizations, reduced need for oral corticosteroids (OCS), improved lung function, decreased airway hyperresponsiveness (AHR), improved exercise tolerance, and improved sinonasal outcomes. Based on observational studies and expert opinion, AACT represents a valuable therapy for those patients irrespective of their asthma phenotype, who cannot achieve optimal control of their complex condition despite all the advances in medical science and treatment according to guidelines, and therefore run the risk of falling into a downward spiral of loss of physical and mental health. In the light of the observed rapid decrease in inflammation and immunomodulatory effects, AACT can be considered as a natural treatment that targets biological pathways., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Inhaled medication used for treatment of chronic obstructive lung diseases (asthma, chronic obstructive pulmonary disease-COPD, and Asthma-COPD overlap) may be associated with adverse drug reactions (ADRs). The aim of this study was to characterise spontaneous reports (SRs) of suspected ADRs received by the Portuguese Pharmacovigilance System (PPS), from 2007 to 2017., Methods: Retrospective observational study of SRs associated with single substance and combination inhalers, analysed in terms of pharmacological class of the involved drugs, sex and age range of the involved patients, and seriousness and type of ADRs., Results: 230 SRs were analysed, accounting for a total of 599 suspected ADRs. Inhaled corticosteroid/long-acting beta-2 agonist combination had the highest frequency in SRs (32.2%) and in ADRs (32.7%). There was a slight predominance in men (51.3%) and non-elderly adults were the most affected age group (39.1%). Most SRs were serious (70.4%). In total, "respiratory, thoracic and mediastinal diseases" ADRs were the most reported (19.5%), with "dyspnea" being the most frequent (4.8%)., Conclusions: Most SRs were associated with controller medications and were expected. Most ADRs involved non-elderly adults, were serious and of respiratory nature and many were due to overuse of reliever medication.

Background: Health and fitness apps have potential benefits to improve self-management and disease control among patients with asthma. However, inconsistent use rates have been reported across studies, regions, and health systems. A better understanding of the characteristics of users and nonusers is critical to design solutions that are effectively integrated in patients' daily lives, and to ensure that these equitably reach out to different groups of patients, thus improving rather than entrenching health inequities., Objective: This study aimed to evaluate the use of general health and fitness apps by patients with asthma and to identify determinants of usage., Methods: A secondary analysis of the INSPIRERS observational studies was conducted using data from face-to-face visits. Patients with a diagnosis of asthma were included between November 2017 and August 2020. Individual-level data were collected, including age, gender, marital status, educational level, health status, presence of anxiety and depression, postcode, socioeconomic level, digital literacy, use of health services, and use of health and fitness apps. Multivariate logistic regression was used to model the probability of being a health and fitness app user. Statistical analysis was performed in R., Results: A total of 526 patients attended a face-to-face visit in the 49 recruiting centers and 514 had complete data. Most participants were ≤40 years old (66.4%), had at least 10 years of education (57.4%), and were in the 3 higher quintiles of the socioeconomic deprivation index (70.1%). The majority reported an overall good health status (visual analogue scale [VAS] score>70 in 93.1%) and the prevalence of anxiety and depression was 34.3% and 11.9%, respectively. The proportion of participants who reported using health and fitness mobile apps was 41.1% (n=211). Multivariate models revealed that single individuals and those with more than 10 years of education are more likely to use health and fitness mobile apps (adjusted odds ratio [aOR] 2.22, 95%CI 1.05-4.75 and aOR 1.95, 95%CI 1.12-3.45, respectively). Higher digital literacy scores were also associated with higher odds of being a user of health and fitness apps, with participants in the second, third, and fourth quartiles reporting aORs of 6.74 (95%CI 2.90-17.40), 10.30 (95%CI 4.28-27.56), and 11.52 (95%CI 4.78-30.87), respectively. Participants with depression symptoms had lower odds of using health and fitness apps (aOR 0.32, 95%CI 0.12-0.83)., Conclusions: A better understanding of the barriers and enhancers of app use among patients with lower education, lower digital literacy, or depressive symptoms is key to design tailored interventions to ensure a sustained and equitable use of these technologies. Future studies should also assess users' general health-seeking behavior and their interest and concerns specifically about digital tools. These factors may impact both initial engagement and sustained use., (©Ana Luísa Neves, Cristina Jácome, Tiago Taveira-Gomes, Ana Margarida Pereira, Rute Almeida, Rita Amaral, Magna Alves-Correia, Sandra Mendes, Cláudia Chaves-Loureiro, Margarida Valério, Cristina Lopes, Joana Carvalho, Ana Mendes, Carmelita Ribeiro, Sara Prates, José Alberto Ferreira, Maria Fernanda Teixeira, Joana Branco, Marta Santalha, Maria João Vasconcelos, Carlos Lozoya, Natacha Santos, Francisca Cardia, Ana Sofia Moreira, Luís Taborda-Barata, Cláudia Sofia Pinto, Rosário Ferreira, Pedro Morais Silva, Tania Monteiro Ferreira, Raquel Câmara, Rui Lobo, Diana Bordalo, Cristina Guimarães, Maria Espírito Santo, José Ferraz de Oliveira, Maria José Cálix Augusto, Ricardo Gomes, Inês Vieira, Sofia da Silva, Maria Marques, João Cardoso, Ana Morete, Margarida Aroso, Ana Margarida Cruz, Carlos Nunes, Rita Câmara, Natalina Rodrigues, Carmo Abreu, Ana Luísa Albuquerque, Claúdia Vieira, Carlos Santos, Rosália Páscoa, Carla Chaves-Loureiro, Adelaide Alves, Ângela Neves, José Varanda Marques, Bruno Reis, Manuel Ferreira-Magalhães, João Almeida Fonseca. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 22.09.2021.)

Introduction: Identification and characterisation of single allergens at molecular level is important. Component-resolved diagnosis offers the possibility of higher diagnostic precision, thereby allowing better patient management. House dust mites (HDM) have a worldwide distribution. Studies from different countries have shown that IgE-mediated allergy to storage mites (SM) is important in rural and urban populations. With the availability of HDM and SM molecular allergen components, studies have investigated whether different molecular sensitisation profiles are associated with clinical disease outcomes. However, no previous systematic review has synthesised the underlying evidence., Methods and Analysis: We will search Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Methodology Register), MEDLINE, EMBASE, CINAHL, AMED, ISI Web of Science (Science and Social Science Index) from inception to March 2020. Unpublished and ongoing work, as well as research in progress will be searched in www.ClinicalTrials.gov; www.controlledtrials.com and wwwanzctrorgau. We will contact an international panel of experts in this field. No language restrictions will apply; translations will be undertaken where necessary. The Critical Appraisal Skills Programme quality assessment tool will be used to appraise the methodological quality of included studies. A descriptive summary with data tables will be constructed, and if adequate, meta-analysis using random effects will be performed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist will be followed for reporting., Ethics and Dissemination: Since this systematic review will be only based on published and retrievable literature, no ethics approval is required. We will publish the systematic review in an international peer-reviewed journal., Trial Registration Number: reviewregistry959., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Poor medication adherence is a major challenge in asthma, and objective assessment of inhaler adherence is needed. The InspirerMundi app aims to monitor adherence while providing a positive experience through gamification and social support., Objective: This study aimed to evaluate the feasibility and acceptability of the InspirerMundi app to monitor medication adherence in adolescents and adults with persistent asthma (treated with daily inhaled medication)., Methods: A 1-month mixed method multicenter observational study was conducted in 26 secondary care centers from Portugal and Spain. During an initial face-to-face visit, physicians reported patients' asthma therapeutic plan in a structured questionnaire. During the visits, patients were invited to use the app daily to register their asthma medication intakes. A scheduled intake was considered taken when patients registered the intake (inhaler, blister, or other drug formulation) by using the image-based medication detection tool. At 1 month, patients were interviewed by phone, and app satisfaction was assessed on a 1 (low) to 5 (high) scale. Patients were also asked to point out the most and least preferred app features and make suggestions for future app improvements., Results: A total of 107 patients (median 27 [P25-P75 14-40] years) were invited, 92.5% (99/107) installed the app, and 73.8% (79/107) completed the 1-month interview. Patients interacted with the app a median of 9 (P25-P75 1-24) days. At least one medication was registered in the app by 78% (77/99) of patients. A total of 53% (52/99) of participants registered all prescribed inhalers, and 34% (34/99) registered the complete asthma therapeutic plan. Median medication adherence was 75% (P25-P75 25%-90%) for inhalers and 82% (P25-P75 50%-94%) for other drug formulations. Patients were globally satisfied with the app, with 75% (59/79) scoring ≥4,; adherence monitoring, symptom monitoring, and gamification features being the most highly scored components; and the medication detection tool among the lowest scored. A total of 53% (42/79) of the patients stated that the app had motivated them to improve adherence to inhaled medication and 77% (61/79) would recommend the app to other patients. Patient feedback was reflected in 4 major themes: medication-related features (67/79, 85%), gamification and social network (33/79, 42%), symptom monitoring and physician communication (21/79, 27%), and other aspects (16/79, 20%)., Conclusions: The InspirerMundi app was feasible and acceptable to monitor medication adherence in patients with asthma. Based on patient feedback and to increase the registering of medications, the therapeutic plan registration and medication detection tool were redesigned. Our results highlight the importance of patient participation to produce a patient-centered and engaging mHealth asthma app., (©Cristina Jácome, Rute Almeida, Ana Margarida Pereira, Rita Amaral, Sandra Mendes, Magna Alves-Correia, Carmen Vidal, Sara López Freire, Paula Méndez Brea, Luís Araújo, Mariana Couto, Darío Antolín-Amérigo, Belén de la Hoz Caballer, Alicia Barra Castro, David Gonzalez-De-Olano, Ana Todo Bom, João Azevedo, Paula Leiria Pinto, Nicole Pinto, Ana Castro Neves, Ana Palhinha, Filipa Todo Bom, Alberto Costa, Cláudia Chaves Loureiro, Lilia Maia Santos, Ana Arrobas, Margarida Valério, João Cardoso, Madalena Emiliano, Rita Gerardo, José Carlos Cidrais Rodrigues, Georgeta Oliveira, Joana Carvalho, Ana Mendes, Carlos Lozoya, Natacha Santos, Fernando Menezes, Ricardo Gomes, Rita Câmara, Rodrigo Rodrigues Alves, Ana Sofia Moreira, Diana Bordalo, Carlos Alves, José Alberto Ferreira, Cristina Lopes, Diana Silva, Maria João Vasconcelos, Maria Fernanda Teixeira, Manuel Ferreira-Magalhães, Luís Taborda-Barata, Maria José Cálix, Adelaide Alves, João Almeida Fonseca. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 25.05.2021.)

Background/objectives: Older patients with asthma or chronic obstructive pulmonary disease (COPD) are particularly susceptible to inhaler technique errors and poor clinical outcomes. Several factors may influence their risk, but most studies are inconsistent and contradictory. We developed a tool for the major predictors of individual risk in these patients., Design, Setting and Participants: In this multicentre, cross-sectional study, several demographic, socioeconomic and clinical characteristics were collected as potential predictors. Clinical features and inhaler technique performance were the main outcomes. Linear and logistic regression models were set up to identify significant variables. Subgroup analysis was performed according to age, cognitive performance and different types of inhalers., Results: We included 130 participants, mean age of 74.4 (± 6.4) years. Mean years of device use were 5.8 (± 7.3). Inhaler errors affected 71.6% (95% CI 64-78.5) and critical mistakes 31.1% (95% CI 24-38.8). There were respiratory comorbidities in 82.3% of participants, and 56.2% had moderate to severe disease. A predictive score of misuse probability was developed for clinical practice, including points attributable to cognitive score, adherence and having received previous education on a placebo device. Other significant variables of individual risk were having respiratory allergies or comorbidities, smoking status, depression and educational level. Worse performance was detected in cognitively impaired patients older than 75 years who were using dry powder inhalers (DPI). Lung function was associated with smoking load, incorrect dose activation and absent end pause after inhalation., Conclusions: Individual risk assessment in older individuals should focus on inhaler technique performance (mainly on dose activation and end pause) and adherence, smoking, respiratory comorbidities and cognitive impairment. Placebo device training provided by doctors seems to best suit these patients.

Introduction: Childhood infections, particularly those caused by helminths are considered to be important environmental exposures influencing the development of allergic diseases. However, epidemiological studies focusing on the relationship between helminth infections and risk of allergic diseases, performed worldwide, show inconsistent findings. Previous systematic reviews of observational studies published 10 or more years ago showed conflicting findings for effects of helminths on allergic diseases. Over the past 10 years there has been growing literature addressing this research area and these need to be considered in order to appreciate the most contemporary evidence. The objective of the current systematic review will be to provide an up-to-date synthesis of findings of observational studies investigating the influence of helminth infections on atopy, and allergic diseases., Methods and Analysis: This systematic review protocol was registered at PROSPERO. We will search Cochrane Library, MEDLINE, EMBASE, CINAHL, AMED, ISI Web of Science, WHO Global Health Library, Scielo, IndMed, PakMediNet, KoreaMed, Ichushi for published studies from 1970 to January 2020. Bibliographies of all eligible studies will be reviewed to identify additional studies. Unpublished and ongoing research will also be searched in key databases. There will be no language or geographical restrictions regarding publications. Critical Appraisal Skills Programme quality assessment tool will be used to appraise methodological quality of included studies. A descriptive summary with data tables will be constructed, and if adequate, meta-analysis using random-effects will be performed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist will be followed for reporting of the systematic review., Ethics and Dissemination: Since this systematic review will be only based on published and retrievable literature, no ethics approval will be sought. The multidisciplinary team performing this systematic review will participate in relevant dissemination activities. Findings will be presented at scientific meetings and publish the systematic review in international, peer-reviewed, open-access journals., Prospero Registration Number: CRD42020167249., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Incorrect inhaler usage is frequent, particularly in elderly asthmatic patients. This study aimed at comparing inhaler technique errors and their determinants, as well inhaler technique self-perception versus real performance, between elderly and non-elderly asthmatics. Methods: Cross-sectional assessment of 92 elderly and 100 non-elderly asthmatics followed at specialty clinics. A standardized questionnaire was applied and inhaler technique demonstration was requested. Errors were assessed using checklists based on manufacturers' instructions and inhaler technique was graded as correct, acceptable or incorrect. Chi-Square Test and Fischer's Exact Test were used for comparative analysis of nominal variables. A p value equal to or less than 0.05 was considered statistically significant. Results: Inhaler technique was correct in a minority of elderly and young patients, without significant differences between study groups. Only 11.1% of the elderly who classified their inhaler as easy and 12.7% who stated their technique was correct had no errors. Previous regular inhaler training was associated with better actual performance in young but not in elderly patients. Conclusion: Our study showed that in spite of regular follow up at specialized outpatient clinics, inhaler devices are associated with a high frequency of errors in elderly and non-elderly asthmatics. In addition, most patients tend to overestimate their technique as correct. Finally, previous, frequent training was associated with a significantly higher percentage of patients showing correct or acceptable technique but only in non-elderly asthmatics, which suggests that elderly asthmatics may need specifically tailored inhaler education programs.

Objectives : Biological drugs have been successfully tested in asthma, especially in the most severe forms of the disease. The goal of this study was to characterize the safety profile of biologicals used in asthma. Methods : Retrospective and descriptive analysis of spontaneous reports (SRs) involving omalizumab and mepolizumab, sent to the Portuguese Pharmacovigilance System, since market launch until October 2018. Results : A total of 127 SRs for omalizumab and 10 SRs mepolizumab were found. Most patients were female (75.6% omalizumab and 90.0% mepolizumab), and aged 18-64 years (61.4% and 50.0%, respectively). 71.7% of the reports for omalizumab were serious, with 2 cases of anaphylaxis, 12 malignant neoplasms and 2 abortions. Only 20.0% of the reports for mepolizumab were considered serious. A total of 391 adverse drug reactions (ADRs) for omalizumab and 20 ADRs for mepolizumab were found. Most reported ADRs belonged to System organ class (SOC) groups: 'respiratory, thoracic and mediastinal disorders' and 'investigations', for omalizumab; 'musculoskeletal and connective tissue disorders' and 'general disorders and administration site conditions' for mepolizumab. Conclusion : Over the years, there was an increasing trend of SRs with these biological drugs. However, it is necessary to continue to develop educational programs in order to get a better reporting system.

Objective: We aimed to compare patient's and physician's ratings of inhaled medication adherence and to identify predictors of patient-physician discordance., Design: Baseline data from two prospective multicentre observational studies., Setting: 29 allergy, pulmonology and paediatric secondary care outpatient clinics in Portugal., Participants: 395 patients (≥13 years old) with persistent asthma., Measures: Data on demographics, patient-physician relationship, upper airway control, asthma control, asthma treatment, forced expiratory volume in one second (FEV 1 ) and healthcare use were collected. Patients and physicians independently assessed adherence to inhaled controller medication during the previous week using a 100 mm Visual Analogue Scale (VAS). Discordance was defined as classification in distinct VAS categories (low 0-50; medium 51-80; high 81-100) or as an absolute difference in VAS scores ≥10 mm. Correlation between patients' and physicians' VAS scores/categories was explored. A multinomial logistic regression identified the predictors of physician overestimation and underestimation., Results: High inhaler adherence was reported both by patients (median (percentile 25 to percentile 75) 85 (65-95) mm; 53% VAS>80) and by physicians (84 (68-95) mm; 53% VAS>80). Correlation between patient and physician VAS scores was moderate (r s =0.580; p<0.001). Discordance occurred in 56% of cases: in 28% physicians overestimated adherence and in 27% underestimated. Low adherence as assessed by the physician (OR=27.35 (9.85 to 75.95)), FEV 1 ≥80% (OR=2.59 (1.08 to 6.20)) and a first appointment (OR=5.63 (1.24 to 25.56)) were predictors of underestimation. An uncontrolled asthma (OR=2.33 (1.25 to 4.34)), uncontrolled upper airway disease (OR=2.86 (1.35 to 6.04)) and prescription of short-acting beta-agonists alone (OR=3.05 (1.15 to 8.08)) were associated with overestimation. Medium adherence as assessed by the physician was significantly associated with higher risk of discordance, both for overestimation and underestimation of adherence (OR=14.50 (6.04 to 34.81); OR=2.21 (1.07 to 4.58)), while having a written action plan decreased the likelihood of discordance (OR=0.25 (0.12 to 0.52); OR=0.41 (0.22 to 0.78)) (R 2 =44%)., Conclusion: Although both patients and physicians report high inhaler adherence, discordance occurred in half of cases. Implementation of objective adherence measures and effective communication are needed to improve patient-physician agreement., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Older patients with asthma or chronic obstructive pulmonary disease are particularly susceptible to exacerbations that may be associated with incorrect use of inhalers. Educational programs with inhaler technique review seem to be effective, but no studies have addressed their cost-effectiveness in older adult patients. The objective was to perform a cost-effectiveness analysis of education programs in older patients and estimate the cost benefit of applying such a program in Portugal., Design: We developed a decision tree analysis from a healthcare perspective, according to intervention costs and the exacerbation rates and costs described in a previous meta-analysis. A sensitivity analysis of worst and best case scenarios was performed to estimate thresholds for intervention affordable limits, as well as cost-saving estimations and incremental cost-effectiveness ratios (ICERs) for a Portuguese scenario., Setting and Participants: We estimated cost-effectiveness thresholds applicable in all settings and performed a sensitivity analysis of a theoretical intervention model in all patients including an inhaler technique review at an annual appointment with a doctor and a nurse., Results: In the best case scenario, the intervention affordable budget could be up to almost 1800€ (US $1585.24) per patient per year. Mean intervention-associated savings in Portugal would be 311.88€ (US $274.68) per patient per year, representing annual savings up to €131 million (US $150 million) for the whole health system, already including intervention costs. ICERs for Portugal vary between 93.73€ (US $82.55) and 437.43€ (US $385.25) per exacerbation avoided., Conclusion: A model of an intervention program with an inhaler technique review in older adult patients suggests that this intervention is cost-effective and can generate significant savings. J Am Geriatr Soc 1-7, 2019., (© 2019 The American Geriatrics Society.)

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 characteristics., Ethics and Dissemination: Every participant will sign a written consent form. A Data Safety Monitoring Board will be set up to evaluate data throughout the study and to monitor early stopping criteria. Identity of all participants will be protected. This protocol was approved on 22 November 2017 by the local Ethics Committee of University of Beira Interior, with the reference number CE-UBI-Pj-2017-025. Results will be presented in scientific meetings and published in peer-reviewed journals., Trial Registration Number: NCT03449316; Pre-Results., Competing Interests: Competing interests: JC-d-S reports competing interests from Harvard Medical School, during the conduct of the study, as scientific support. He also reports from Boheringer Ingelheim and from AstraZeneca outside the submitted work, and all these fees were received by a non-profit organisation to be used in CME and research. The remaining authors declare only from Harvard Medical School, during the conduct of the study, as scientific support., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate the effect of inhaler education programs on clinical outcomes and exacerbation rates in older adults with asthma or chronic obstructive pulmonary disease (COPD)., Design: Systematic review and meta-analysis., Setting and Participants: Older adults with asthma or COPD, either in primary or secondary health care and pharmacy setting., Measurements: We searched the Medline, Embase, and Central databases according to the main eligibility criteria for inclusion: systematic reviews, meta-analysis, clinical trials and quasi-experimental studies; participants aged 65 and older; education on inhaler technique and reporting of disease control and exacerbation rates. We used the Grading of Recommendations, Assessment, Development and Evaluations scale for quality assessment and used a random-effect model with Mantel-Haenszel adjustment to perform a meta-analysis., Results: We included 8 studies (4 randomized, 4 quasi-experimental) with a total of 1,812 participants. The most frequent type of intervention was physical demonstration of inhaler technique, training with placebo devices. Five studies showed significant reduction in exacerbation rates (pooled risk ratio=0.71, 95% confidence interval=0.59-0.86; p < .001), although effect on disease control and quality of life showed high discrepancy in the reported results, and all randomized studies revealed uncertainty in their risk of bias assessment., Conclusion: All interventions seemed to improve inhaler performance and clinically relevant outcomes, but a placebo device could be the most effective. There is evidence that interventions reduce exacerbation risk in older adults, although to an overall moderate degree. J Am Geriatr Soc 67:57-66, 2019., (© 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.)

Objective: Asthma is usually misdiagnosed and under-treated in the elderly population, resulting in complications and increased severity to the patient. In this review, we describe some of the most important serum markers of asthma studied so far, reporting their outcomes and possible prediction of asthma in the elderly population., Methods: The PubMed electronic database was used to search for promising serum biomarkers of asthma studied in original articles published in peer-reviewed journals from 2000 to January 2013., Results: A total of 13 relevant serum biomarkers were selected, including IgE, CRP, high sensitive CRP, IL-6, IL-8, IL-17, TNF-α, neopterin, serum amyloid A, eosinophil cationic protein, leukolysin, YKL-40 and soluble CD86., Conclusions: Although the major focus of treatment and research has been on allergic asthma, several forms of the disease are recognized, such as neutrophilic asthma, which is characteristic of older patients. Different phenotypes imply different treatments and so it becomes important to correctly determine which type of asthma the patient is suffering from. Serum markers capable of supporting a diagnosis of asthma are needed in order to counter mistreatment and misdiagnosis with other obstructive airways disease (OAD) in elderly patients. As convenient as serum markers may seem to be, a marker capable of accurately identifying asthma with sufficient specificity is yet to be found.

Background: Rhinitis prevalence is increasing worldwide and is frequently associated with asthma, for which it is a risk factor. The aims of the study were to characterise the adult population with rhinitis attending the Cova da Beira Hospital Allergy Clinic, and to assess the relationship between rhinitis and asthma., Methods: In total, 686 patients were characterised by clinical history and anterior rhinoscopy, and classified according to international guidelines. Atopy was determined by skin prick testing to aeroallergens and quantification of specific IgE., Results: Seventy two percent of patients had allergic rhinitis (AR), and 28% had non-allergic rhinitis (NAR). NAR was more frequently associated with older age, perennial symptoms and female gender. NAR patients more frequently had bronchial asthma. In addition, more NAR than AR patients also had drug allergy, pharyngitis, sinusitis and urticaria. AR patients with nasal polyps more frequently had asthma. Grass pollen and mites were the major sensitisers for AR patients. Sensitisation profiles were not significantly different between urban- and rural-based AR patients., Conclusions: Asthma was more frequently associated with non-allergic than with allergic rhinitis. The two types of rhinitis did not differ in clinical severity. Although sensitisation profiles were not different between the urban and rural patients, allergic rhinitis prevalence was higher in urban patients.

Background: Asthma presents a significant health challenge, imposing a considerable burden on healthcare services. Discrepancies in asthma‐related hospitalisations may reflect underlying health disparities. We aimed to analyse inequities in asthma hospital admissions in mainland Portugal and Spain, from a regional perspective and considering sex and age. Methods: We conducted a retrospective study using data from the Spanish and Portuguese national hospitalisations databases. We calculated crude national and regional yearly hospitalisation rates according per Nomenclature of Territorial Units for Statistics region. Additionally, we calculated hospitalisation rates adjusted for asthma prevalence and the female‐to‐male ratio in asthma hospital admissions per age group, considering the female‐to‐male ratio in the overall population. Results: Between 2012 and 2016, there were 92,084 asthma hospital admissions in mainland Spain and 7717 in mainland Portugal. There was a trend for a higher‐than‐average rate of asthma‐related hospitalisations in the Northern regions of both countries. Women had a hospitalisation rate that was 3.2 times higher than men. Age was associated with higher risk for asthma hospitalisation, with individuals aged 65 and older displaying a hospitalisation rate 4.5 times higher than those under 65. Additionally, while hospitalisations in women aged <65 years were 2.3 times more likely than in men of the same age, hospitalisations in women aged ≥65 years were 3.5 times higher than in men aged ≥65 years. Conclusion: This study suggests that marked regional inequities in asthma hospital admissions exist in Spain and Portugal. Additionally, women are particularly at risk of hospitalisation due to asthma, and such risk increases with age. [ABSTRACT FROM AUTHOR]

Chronic respiratory diseases are a dealing cause of death and disability worldwide. Their prevalence is steadily increasing and the exposure to environmental contaminants, including Flame Retardants (FRs), is being considered as a possible risk factor. Despite the widespread and continuous exposure to FRs, the role of these contaminants in chronic respiratory diseases is yet not clear. This study aims to systematically review the association between the exposure to FRs and chronic respiratory diseases. Searches were performed using the Cochrane Library, MEDLINE, EMBASE, PUBMED, SCOPUS, ISI Web of Science (Science and Social Science Index), WHO Global Health Library and CINAHL EBSCO. Among the initial 353 articles found, only 9 fulfilled the inclusion criteria and were included. No statistically significant increase in the risk for chronic respiratory diseases with exposure to FRs was found and therefore there is not enough evidence to support that FRs pose a significantly higher risk for the development or worsening of respiratory diseases. However, a non-significant trend for potential hazard was found for asthma and rhinitis/rhinoconjunctivitis, particularly considering urinary organophosphate esters (OPEs) including TNBP, TPHP, TCEP and TCIPP congeners/compounds. Most studies showed a predominance of moderate risk of bias, therefore the global strength of the evidence is low. The limitations of the studies here reviewed, and the potential hazardous effects herein identified highlights the need for good quality large-scale cohort studies in which biomarkers of exposure should be quantified in biological samples. Flame retardants and the risk for chronic respiratory diseases – A Systematic review of observational studies. [Display omitted] • There is a potential risk for asthma with exposure to TNBP and TPHP. • There is a potential risk for wheezing with exposure to EHDPHP (measured as urinary metabolite 5-OH-EHDPHP). • There is a potential risk for rhinoconjunctivitis with exposure to TCEP and TCIPP. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]