A network meta-analysis of the association between patient traits and response to regular dosing with ICS plus short-acting ß2-agonist reliever or ICS/formoterol reliever only in mild asthma.

INTRODUCTION/BACKGROUND: Mild asthma treatment recommendations include intermittent inhaled corticosteroid (ICS)/formoterol dosing or regular ICS dosing with short-acting ß2-agonist reliever. Due to the heterogeneity of asthma, identification of traits associated with improved outcomes to specific treatments would be clinically beneficial. AIMS/OBJECTIVES: To assess the impact of patient traits on treatment outcomes of regular ICS dosing compared with intermittent ICS/formoterol dosing, a systematic literature review (SLR) and network meta-analysis (NMA) was conducted. Searches identified randomised controlled trials (RCTs) of patients with asthma aged ≥12 years, containing ≥1 regular ICS dosing or intermittent ICS/formoterol dosing treatment arm, reporting traits and outcomes of interest. RESULTS: The SLR identified 11 RCTs of mild asthma, of 14,516 patients. A total of 11 traits and 11 outcomes of interest were identified. Of these, a feasibility assessment indicated possible assessment of three traits (age, baseline lung function, smoking history) and two outcomes (exacerbation rate, change in lung function). The NMA found no significant association of any trait with any outcome with regular ICS dosing relative to intermittent ICS/formoterol dosing. Inconsistent reporting of traits and outcomes between RCTs limited analysis. CONCLUSIONS: This is the first systematic analysis of associations between patient traits and differential treatment outcomes in mild asthma. Although the traits analysed were not found to significantly interact with relative treatment response, inconsistent reporting from the RCTs prevented assessment of some of the most clinically relevant traits and outcomes, such as adherence. More consistent reporting of respiratory RCTs would provide more comparable data and aid future analyses.

Systematic literature review of traits and outcomes reported in randomised controlled trials of asthma with regular dosing of inhaled corticosteroids with short-acting ß2-agonist reliever, as-needed ICS/formoterol, or ICS/formoterol maintenance and reliever therapy.

INTRODUCTION: Asthma treatments based solely on diagnostic label do not benefit patients equally. To identify patient traits that may be associated with improved treatment response to regular inhaled corticosteroid (ICSs) dosing with short-acting ß2-agonist reliever or ICS/formoterol-containing therapy, a systematic literature review (SLR) was conducted. METHODS: Searches of databases including MEDLINE and Embase identified randomised controlled trials (RCTs) of patients with asthma, aged ≥12 years, published 1998-2022, containing ≥1 regular ICS dosing or ICS/formoterol-containing treatment arm, and reporting patient traits and outcomes of interest. Relevant data was extracted and underwent a feasibility assessment to determine suitability for meta-analysis. RESULTS: The SLR identified 39 RCTs of 72,740 patients and 90 treatment arms, reporting 11 traits and 11 outcomes. Five patient traits (age, body mass index, FEV1, smoking history, asthma control) and five outcomes (exacerbation rate, lung function, asthma control, adherence, time to first exacerbation) were deemed feasible for inclusion in meta-analyses due to sufficient comparable reporting. Subgroups of clinical outcomes stratified by levels of patient traits were reported in 16 RCTs. CONCLUSION: A systematic review of studies of regular ICS dosing with SABA or ICS/formoterol-containing treatment strategies in asthma identified consistent reporting of five traits and outcomes, allowing exploration of associations with treatment response. Conversely, many other traits and outcomes, although being potentially relevant, were inconsistently reported and limited subgroup reporting meant analyses of treatment response for subgroups of traits was not possible. We recommend more consistent measurement and reporting of clinically relevant patient traits and outcomes in respiratory RCTs.

Overprescription of short-acting β2 agonists: reflections from the SABINA study in Brazil / Prescrição excessiva de β2-agonistas de curta duração: reflexões a partir do estudo SABINA no Brasil

ABSTRACT Objective: To assess prescription patterns for short-acting b2 agonists (SABAs) and other asthma medications in asthma patients treated by specialists and participating in the SABA use IN Asthma (SABINA) study in Brazil. Methods: This was an observational, cross-sectional study conducted at five sites in different regions of Brazil. The primary endpoints were to record SABA prescriptions and obtain data on over-the-counter (OTC) SABA purchases at the pharmacy. Results: Data on 218 asthma patients were analyzed. Of those 218 patients, 80.3% were prescribed SABAs in addition to their maintenance therapy, with a mean of 11.2 SABA canisters in the previous 12 months. Of those patients, 71.4% were prescribed ≥ 3 canisters and 42.2% were prescribed ≥ 10 canisters. None of the patients were prescribed SABA monotherapy. A total of 14.2% of the patients reported purchasing SABAs OTC at a pharmacy without a prescription. Of those, 48.4% purchased ≥ 3 SABA canisters. A fixed-dose combination of an inhaled corticosteroid and a long-acting b2 agonist was prescribed to 95.0% of the patients. In the year before the study visit, 45.0% of the patients received at least one course of oral corticosteroid burst treatment. Asthma was well controlled in 43.1% of the patients, partly controlled in 34.9%, and uncontrolled in 22.0%. Patients reported a mean of 1.1 severe asthma exacerbations, with 49.1% experiencing 1 or more severe exacerbations. Conclusions: Overprescription and OTC purchases of SABAs are common in Brazil, possibly leading to the need for courses of oral corticosteroids. The health care community should collaborate to implement evidence-based recommendations and promote health education to improve asthma management in Brazil.

RESUMO Objetivo: Avaliar os padrões de prescrição de short-acting b2 agonists (SABAs, b2-agonistas de curta duração) e outros medicamentos para asma em pacientes tratados por especialistas e participantes do estudo SABA use IN Asthma (SABINA) no Brasil. Métodos: Trata-se de um estudo transversal observacional realizado em cinco locais em diferentes regiões do Brasil. Os desfechos primários foram registrar as prescrições de SABAs e obter dados a respeito da compra de SABAs sem receita médica na farmácia. Resultados: Foram analisados dados a respeito de 218 pacientes com asma. Dos 218 pacientes, 80,3% receberam prescrição de SABA além da terapia de manutenção, com uma média de 11,2 frascos de SABA nos 12 meses anteriores. Destes, 71,4% receberam prescrição de ≥ 3 frascos e 42,2% receberam prescrição de ≥ 10 frascos. Nenhum dos pacientes recebeu prescrição de monoterapia com SABA. Do total de pacientes, 14,2% relataram que compraram SABAs sem receita médica na farmácia. Destes, 48,4% compraram ≥ 3 frascos de SABA. Foram prescritas doses fixas combinadas de corticosteroide inalatório e b2-agonista de longa duração para 95,0% dos pacientes. No ano anterior à visita do estudo, 45,0% dos pacientes receberam pelo menos um ciclo de tratamento de curta duração com corticosteroide oral. A asma estava bem controlada em 43,1% dos pacientes, parcialmente controlada em 34,9% e não controlada em 22,0%. Os pacientes relataram uma média de 1,1 exacerbações graves da asma, sendo que 49,1% apresentaram uma ou mais exacerbações graves. Conclusões: A prescrição excessiva e a compra de SABAs sem receita médica são comuns no Brasil e possivelmente levam à necessidade de uso de corticosteroides orais. A comunidade de profissionais de saúde deve colaborar para implantar recomendações baseadas em evidências e promover a educação em saúde para melhorar o manejo da asma no Brasil.

The rs2601796 variant in ADCY9 gene is associated with severe asthma and less bronchodilator response.

Asthma is a respiratory disease caused by the interaction of genetic and environmental factors. The adenylyl cyclase type 9 (ADCY9) enzyme produces the cyclic-adenosinemonophosphate (cAMP), important mediator involved in bronchodilation and immunomodulatory response. The aim of this study was to investigate if rs2601796 and rs2532019 variants in the ADCY9 gene are associated with asthma and lung function. The study comprised 1,052 subjects. Logistic regressions were done using PLINK 1.9 adjusted by sex, age, BMI, smoke and principal components. Bronchodilator responsiveness was assessed using the percentage of difference in FEV1 before and after the bronchodilator use. The in silico analysis for gene expression was performed in the GTEx Portal. The variant rs2601796 (AA/AG genotype) was positively associated with asthma severity (OR: 1.60 IC95%: 1.08-2.39) and with obstruction in individuals with severe asthma (OR: 3.10, IC95%: 1.11-8.62). Individuals with severe asthma and the AA/AG genotype of rs2601796 had less responsiveness to bronchodilators and also a lower expression of ADCY9 in lung and whole blood. The variant rs2532019 (TT/GT genotype) also downregulated the ADCY9 gene expression, but no significant association with the studied phenotypes was found. Thus, the variant in ADCY9 was associated with worse asthma outcomes, including a lower response to bronchodilators, likely due to the impact on its gene expression rate. This variant may be useful in the future to assist in personalized management of patients with asthma.

A network meta-analysis of the association between patient traits and response to regular dosing with ICS/long-acting ß2-agonist plus short-acting ß2 agonist reliever or maintenance and reliever therapy for asthma.

INTRODUCTION: Current treatment for moderate-severe asthma with inhaled corticosteroid (ICS)-based therapy can follow two strategies: a single inhaler maintenance and reliever therapy (MART) regimen, or regular dosing with ICS/long-acting ß2-agonist used as maintenance therapy plus a separate short acting ß2-agonist reliever inhaler. It would be clinically useful to understand the potential of patient traits to influence regular dosing or MART treatment outcomes. OBJECTIVES: A systematic literature review (SLR) and meta-analysis was conducted to identify specific patient traits that may predict improved clinical outcomes with regular dosing or MART. RESULTS: The SLR identified 28 studies in patients with moderate-severe asthma assessing regular dosing or MART treatments and reporting the traits and outcomes of interest. Network meta-regressions found no significant difference in the relative efficacy of regular dosing as compared with MART on any of the clinical outcomes (exacerbation rate, time to first exacerbation, FEV1, reliever use and adherence) for any of the patient traits (baseline lung function, baseline ACQ, age, BMI, and smoking history) evaluated. However, some trends towards traits influencing treatment efficacy were identified. Inconsistent reporting of traits and outcomes was observed between trials. CONCLUSIONS: The analysed patient traits evaluated in this study were associated with similar efficacy for the analysed outcomes to either regular dosing or MART; however, trends from the data observed encourage future analyses for possible identification of additional traits, or a combination of traits, that may be of interest. More comparable reporting of clinically important traits and outcomes would improve future analyses.

Single nucleotide variants in the IL33 and IL1RL1 (ST2) genes are associated with periodontitis and with Aggregatibacter actinomycetemcomitans in the dental plaque biofilm: A putative role in understanding the host immune response in periodontitis.

The Interleukin (IL)-33 is important in several inflammatory diseases and its cellular receptor is the Interleukin 1 receptor-like 1 (IL1RL1), also called suppression of tumorigenicity 2 ligand (ST2L). This study investigated associations between single nucleotide variants (SNVs) in the IL33 gene and in the IL1RL1 (ST2) gene with periodontitis. Additionally, aimed to determine the role of Aggregatibacter actinomycetemcomitans (Aa) relative amount in the subgingival biofilm in these associations. A cross-sectional study was carried out with 506 individuals that answered a structured questionnaire used to collect their health status, socioeconomic-demographic, and behavioral characteristics. Periodontal examination was performed to determine the presence and severity of periodontitis, and subgingival biofilm samples were collected to quantify the relative amount of Aa by real time polymerase chain reaction. Human genomic DNA was extracted from whole blood cells and SNV genotyping was performed. Logistic regression estimated the association measurements, odds ratio (OR), and 95% confidence interval (95%CI), between the IL33 and ST2 genes with periodontitis, and subgroup analyses assessed the relative amount of Aa in these associations. 23% of individuals had periodontitis. Adjusted measurements showed a statistically significant inverse association between two SNVs of the ST2; rs148548829 (C allele) and rs10206753 (G allele). These two alleles together with a third SNV, the rs11693204 (A allele), were inversely associated with moderate periodontitis. One SNV of the IL33 gene also showed a statistically significant inverse association with moderate periodontitis. Nine SNVs of the ST2 gene were inversely associated with the relative amount of Aa. In the high Aa subgroup, there was a direct association between 11 SNVs of the ST2 gene and moderate periodontitis and two SNVs of the ST2 gene and severe periodontitis, and eight SNVs of the ST2 gene and periodontitis. These exploratory findings of genetic variants in IL-33/ST2 axis support the concept that the different tissue responses among individuals with periodontitis may be modulated by the host's genetics, influencing the physiopathology of the disease.

Variants in interferon gamma inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) genes that modulate inflammatory response are associated with periodontitis.

OBJECTIVE: Evaluate the association of genetic variants of the interferon gamma inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) genes with periodontitis. METHODS: The study involved 117 individuals with periodontitis and 389 without periodontitis, all Brazilians, miscegenated. Individuals with periodontitis presented at least 4 teeth with ≥ 1 site with probing depth ≥ 4 mm; clinical attachment level ≥ 3 mm on the same site and bleeding upon stimulus. Genotyping was performed using the Infinium Multi-Ethnic AMR/AFR-8 Bead Chip focused on Hispanic and African American populations with approximately 2 million markers of the human genome. Multivariate logistic regression was performed to identify associations in additive, dominant and recessive models adjusted for covariates age, obesity, mouth breathing, flossing, asthma, and ancestry. RESULTS: In IFI16, the rs75985579-A is positively associated with periodontitis in the additive (Odds Ratio adjusted (ORadjusted) 2.65, 95% confidence interval (CI):1.25-5.60, p value: 0.007) and dominant models (ORadjusted 2.56, 95%CI:1.13-5.81, p value: 0.017). In AIM2, the rs76457189-G, is associated negatively with periodontitis in two genetic models evaluated, additive (ORadjusted 0.21, 95%CI:0.05-0.94, p value: 0.022) and dominant (ORadjusted 0.21, 95%CI:0.05-0.94, p value: 0.022). CONCLUSIONS: These results have shown that variants in the IFI16 and AIM2 genes are associated with periodontitis. Individuals with at least one A (adenine) allele of the rs75985579 (IFI16) are more than twice as likely to have periodontitis, while individuals with the G (guanine) allele of rs76457189 (AIM2) are less likely to be diagnosed with periodontitis, providing a negative association with periodontitis.

Handgrip strength as a diagnostic tool for frailty risk in elderly patients with moderate to severe asthma / Força de preensão manual como ferramenta diagnóstica de risco de fragilidade em pacientes idosos com asma moderada a grave

ABSTRACT Objective: To evaluate handgrip strength (HGS) as a diagnostic tool for frailty risk in elderly patients with asthma, as well as to investigate the prevalence of frailty in this population. Methods: This was a cross-sectional study including 96 patients ≥ 60 years of age diagnosed with moderate to severe asthma and treated at a tertiary referral center in Brazil. We measured HGS using a calibrated hydraulic hand dynamometer. We used a frailty scale and the AUC to assess the diagnostic accuracy of the HGS test. Results: The median age of participants was 67 years. Most (78%) were women and non-White (91%) of low socioeconomic status. HGS identified those at risk for frailty, with an AUC of 71.6% (61.5-80.4%; p < 0.002), as well as a sensitivity of 73.58% and a specificity of 67.53%, on the basis of a cutoff of ≤ 19 kgf. Conclusions: HGS appears to be a simple, reliable tool for clinicians to determine frailty risk in older asthma patients in a point-of-care setting.

RESUMO Objetivo: Avaliar a força de preensão manual (FPM) como ferramenta diagnóstica de risco de fragilidade em pacientes idosos com asma e investigar a prevalência de fragilidade nessa população. Métodos: Estudo transversal com 96 pacientes com idade ≥ 60 anos e diagnóstico de asma moderada a grave, atendidos em um centro terciário de referência no Brasil. Medimos a FPM com um dinamômetro hidráulico manual calibrado. Usamos uma escala de fragilidade e a ASC para avaliar a precisão diagnóstica do teste de FPM. Resultados: A mediana da idade dos participantes foi de 67 anos. A maioria eram mulheres (78%) não brancas (91%) cujo nível socioeconômico era baixo. O ponto de corte de FPM ≤ 19 kgf identificou os participantes que apresentavam risco de fragilidade, com ASC = 71,6% (61,5-80,4%; p < 0,002), sensibilidade = 73,58% e especificidade = 67,53%. Conclusões: A FPM parece ser uma ferramenta simples e confiável para determinar, no próprio local de atendimento médico, o risco de fragilidade em pacientes idosos com asma.

Pharmacology Versus Convenience: A Benefit/Risk Analysis of Regular Maintenance Versus Infrequent or As-Needed Inhaled Corticosteroid Use in Mild Asthma.

INTRODUCTION: This study compared the bronchoprotective and benefit/risk profiles of various inhaled corticosteroid (ICS) dosing regimens in mild asthma. METHODS: A pharmacokinetic/pharmacodynamic model was developed and validated describing the relationship between ICS dose and time-course for airway bronchoprotection, [provocative concentration of adenosine monophosphate (AMP) causing ≥ 20% decline in forced expiratory volume in 1 s (FEV1) (AMP PC20)], for fluticasone furoate (FF), fluticasone propionate (FP) and budesonide (BUD). For regular ICS maintenance therapy (100% and 50% adherence) and infrequent or as-needed use (dosing 3-4 times per week), treatment effectiveness was expressed as percent time during 28 days when bronchoprotection exceeded either the threshold for a treatment-related bronchoprotective effect (AMP PC20 ≥ 0.25 doubling dose) or the threshold for a clinically significant bronchoprotective effect (AMP PC20 ≥ 1.0 doubling dose). This value was divided by the total ICS dose administered expressed in prednisolone equivalents to give a therapeutic index (TI). RESULTS: The model-predicted time course of ICS-induced bronchoprotection with regular daily maintenance dosing and 100% adherence showed that all ICS at the highest recommended doses for mild asthma exceeded the threshold for clinically significant bronchoprotective effect for all or most of the 28-day dosing period, mean (90% CI); 100% (96.1-100), 99.9% (8.0-100) and 100% (58.2-100) with TI values of 16.9, 6.6 and 5.4 for FF 100 µg OD, FP 200 µg BID and BUD 200 µg BID, respectively. For simulated poor adherence (50%) to regular daily maintenance therapy, corresponding mean (90% CI) values were; 75.7% (39.4-89.1), 52.3% (0.7-69.2) and 51.3% (28.6-58.3) with TI values of 25.7, 6.9 and 5.6. For simulated infrequent/as needed use the corresponding values were; 77.0% (37.6-87.0), 25.5% (0.0-38.0) and 26.2% (14.3-31.5) with TI values of 26.1, 6.7 and 5.7. For all regimen/scenarios, FF had the most sustained efficacy and favourable TI followed by FP and BUD. CONCLUSIONS: At doses recommended for mild asthma, all ICS regimens provide sustained bronchoprotective efficacy when dosed regularly with high adherence. With poor adherence or use 3-4 times per week (infrequent/as needed), longer-acting ICS molecules will more likely provide sustained protection and a better TI versus shorter duration of action molecules (FF > FP ≥ BUD). These data highlight the benefits of using ICS as regular daily maintenance dosing in mild asthma and the potential risks of under-treatment with ICS (which may occur with ICS/formoterol as-needed approach in mild persistent asthma) associated with reduced levels of bronchoprotection.

Ecocardiografia e Análise de Doenças Cardiovasculares Subclínicas em Povos Indígenas que Vivem em Diferentes Graus de Urbanização: Projeto de Aterosclerose nas Populações Indígenas (Pai) / Echocardiography and Analysis of Subclinical Cardiovascular Diseases in Indigenous People Living in Different Degrees of Urbanization: Project of Atherosclerosis Among Indigenous Populations (Pai

Fundamento: O processo de urbanização tem impacto na carga de doenças cardiovasculares. As populações indígenas podem sofrer uma transição epidemiológica devastadora. Objetivos: Descrever o protocolo de estudo do Projeto de Aterosclerose nas Populações Indígenas (PAI) para avaliar a análise ecocardiográfica e as doenças cardiovasculares (CV) subclínicas em populações indígenas de acordo com o grau de urbanização e mostrar resultados preliminares do estudo piloto. Métodos: O PAI é um estudo transversal, com voluntários com idade entre 30 e 70 anos, em grupos indígenas brasileiros expostos a estágios baixos e avançados de urbanização (Fulni-ô e Truká, respectivamente) e um grupo controle urbano, excluindo indivíduos com doenças CV conhecidas ou em hemodiálise. O estudo piloto começou no território de Fulni-ô em setembro de 2016. Os participantes foram submetidos a avaliação clínica e laboratorial, eletrocardiograma (ECG), ultrassonografia de carótidas e um protocolo ecocardiográfico abrangente, incluindo strain longitudinal global (SLG) avaliado por speckle tracking. Os resultados preliminares são descritos de acordo com o sexo em uma análise univariada. Resultados: O estudo piloto avaliou o protocolo descrito em 55 indivíduos do grupo indígena Fulni-ô (48,7 ± 12,0 anos, 80% mulheres). Foram encontrados fatores de risco tradicionais como hipertensão, diabetes e dislipidemia em 40%, 36% e 54%, respectivamente, sem diferenças estatísticas significativas entre os sexos. O uso de tabaco mostrou-se extremamente prevalente, referido em 91% dos participantes. Os parâmetros derivados da ecocardiografia estavam, em média, dentro da faixa normal. No entanto, a média do SLG foi de 17,3 ± 3,4% (p 0,73 por sexo). Conclusão: Descrevemos o protocolo do estudo PAI para avaliar doenças cardiovasculares subclínicas e fatores de risco em populações indígenas de acordo com o estágio de urbanização. Resultados preliminares sugerem alta prevalência desses na população indígena em menor grau de urbanização.

Background: The urbanization process impacts the burden of cardiovascular disease (CVD). Indigenous populations can undergo a devastating epidemiological transition. Objective: The present study aimed to describe the Project of Atherosclerosis among Indigenous Populations (PAI) study protocol for assessing echocardiographic images and subclinical CVD in indigenous populations according to the degree of urbanization and report its preliminary results. Methods: The PAI is a cross-sectional study that includes volunteers aged 30­70 years among Brazilian indigenous groups exposed to low and advanced stages of urbanization (Fulni-ô and Truká, respectively) and an urban control group. Individuals with known CVD or who were on hemodialysis were excluded. The pilot study began in Fulni-ô territory in September 2016. The participants underwent clinical and laboratory

Factors that affect blood eosinophil counts in a non-asthmatic population: Post hoc analysis of data from Brazil.

BACKGROUND: Improved understanding of the normal range of blood eosinophil counts (BEC) and conditions that influence them in non-asthmatic individuals should allow more accurate estimation of the threshold at which eosinophilic disease should be considered, diagnosed, and treated. This analysis investigated the impact of atopy, smoking, and parasitic infection on BEC. METHODS: This was a post hoc analysis of non-asthmatic subjects from a case-control study (CONEP 450/10) conducted at the Program for Control of Asthma in Bahia (ProAR). Participant BECs were measured at baseline; correlations between predefined risk factors and BEC were assessed via univariate and stratified analysis. RESULTS: Of the 454 participants included, 3% were helminth parasite-positive, 18% were non-helminth parasite-positive; and 450 had BEC data. The median (interquartile range [IQR]) BEC was 152 (96, 252) cells/µL. Any positive skin prick test, elevated total immunoglobulin E, allergic rhinitis, and being a current smoker were all individually associated with higher BEC (p < 0.05) compared with BEC in participants without these factors, but having a non-helminthic parasitic infection was not. Participants with all 4 risk factors that were associated with higher BEC had a median (IQR) BEC of 192 cells/µL (94, 416) versus 106 cells/µL (70, 164) for those with no risk factors. CONCLUSIONS: In non-asthmatic subjects, atopy, allergic rhinitis, and current smoking status were associated with higher BEC compared with subjects without these factors, but BEC values were well below the threshold commonly accepted as normal. Therefore, BEC should be interpreted in the context of an individual's medical conditions and other BEC-influencing factors.

Asthma similarities across ProAR (Brazil) and U-BIOPRED (Europe) adult cohorts of contrasting locations, ethnicity and socioeconomic status.

BACKGROUND: Asthma prevalence is 339 million globally. 'Severe asthma' (SA) comprises subjects with uncontrolled asthma despite proper management. OBJECTIVES: To compare asthma from diverse ethnicities and environments. METHODS: A cross-sectional analysis of two adult cohorts, a Brazilian (ProAR) and a European (U-BIOPRED). U-BIOPRED comprised of 311 non-smoking with Severe Asthma (SAn), 110 smokers or ex-smokers with SA (SAs) and 88 mild to moderate asthmatics (MMA) while ProAR included 544 SA and 452 MMA. Although these projects were independent, there were similarities in objectives and methodology, with ProAR adopting operating procedures of U-BIOPRED. RESULTS: Among SA subjects, age, weight, proportion of former smokers and FEV1 pre-bronchodilator were similar. The proportion of SA with a positive skin prick tests (SPT) to aeroallergens, the scores of sino-nasal symptoms and quality of life were comparable. In addition, blood eosinophil counts (EOS) and the % of subjects with EOS > 300 cells/µl were not different. The Europeans with SA however, were more severe with a greater proportion of continuous oral corticosteroids (OCS), worse symptoms and more frequent exacerbations. FEV1/FVC pre- and post-bronchodilator were lower among the Europeans. The MMA cohorts were less comparable in control and treatment, but similar in the proportion of allergic rhinitis, gastroesophageal reflux disease and EOS >3%. CONCLUSIONS: ProAR and U-BIOPRED cohorts, with varying severity, ethnicity and environment have similarities, which provide the basis for global external validation of asthma phenotypes. This should stimulate collaboration between asthma consortia with the aim of understanding SA, which will lead to better management.

Effects of PACK guide training on the management of asthma and chronic obstructive pulmonary disease by primary care clinicians: a pragmatic cluster randomised controlled trial in Florianópolis, Brazil.

INTRODUCTION: The Practical Approach to Care Kit (PACK) guide was localised for Brazil, where primary care doctors and nurses were trained to use it. METHODS: Twenty-four municipal clinics in Florianópolis were randomly allocated to receive outreach training and the guide, and 24 were allocated to receive only the guide. 6666 adult patients with asthma or chronic obstructive pulmonary disease (COPD) were enrolled, and trial outcomes were measured over 12 months, using electronic medical records. The primary outcomes were composite scores of treatment changes and spirometry, and new asthma and COPD diagnosis rates. RESULTS: Asthma scores in 2437 intervention group participants were higher (74.8%, 20.4% and 4.8% with scores of 0, 1 and 2, respectively) than in 2633 control group participants (80.0%, 16.8% and 3.2%) (OR for higher score 1.32, 95% CI 1.08 to 1.61, p=0.006). Adjusted for asthma scores recorded in each clinic before training started, the OR was 1.24 (95% CI 1.03 to 1.50, p=0.022). COPD scores in 1371 intervention group participants (77.7%, 17.9% and 4.3% with scores of 0, 1 and 2) did not differ from those in 1181 control group participants (80.5%, 15.8% and 3.7%) (OR 1.21, 95% CI 0.94 to 1.55, p=0.142). Rates of new asthma and COPD diagnoses, and hospital admission, and indicators of investigation, diagnosis and treatment of comorbid cardiovascular disease, diabetes and depression, and tobacco cessation did not differ between trial arms. CONCLUSION: PACK training increased guideline-based treatment and spirometry for asthma but did not affect COPD or comorbid conditions, or diagnosis rates. TRIAL REGISTRATION: NCT02786030 (https://clinicaltrials.gov/).

Dual exposure to smoking and household air pollution is associated with an increased risk of severe asthma in adults in Brazil.

BACKGROUND: The relationship between smoking, household pollution, dual exposure and severity of asthma in adults has not been sufficiently studied. We examined and compared the effects of cigarette smoking, domestic wood burning pollution and dual exposure (tobacco and wood burning) upon asthma severity in adults. METHODS: This was a cross-sectional study performed with 452 individuals with mild to moderate asthma and 544 patients with severe asthma (previously untreated). Smoking and exposure to wood smoke were identified and quantified through questionnaires to evaluate current and/or previous exposure; objective determination of cigarette exposure was obtained through the measurement of urinary cotinine. Asthma control was evaluated through Asthma Control Questionnaire; and severity was classified according to the Global Initiative for Asthma criteria. Subjects were grouped according to exposure type into 4 groups: smokers, household pollution, dual-exposure and no-exposure. Chi square, Mann-Whitney, and Kruskal-Wallis tests were used for comparisons between groups. RESULTS: Out of 996 included individuals, 78 (7.8%) were exposed to cigarette smoking alone, 358 (35.9%) to household pollution alone, 155 (15.6%) to the two exposures combined and 405 (40.7%) were not exposed. Compared to unexposed individuals, exposure to household pollution resulted in poorer asthma control, higher proportion of severe asthma, and worse indicators of lung function. The double-exposed individuals were worse off in all the evaluated parameters, and they were significantly worse than subjects with single exposure to household air pollution in relation to asthma severity and lung function. These subjects were predominantly females, older, with longer residence time in rural areas, lower income and lower schooling levels. Multivariate analysis showed that exposure to household pollution and double exposure were predictive factors associated with lack of control and increased severity of asthma. CONCLUSIONS: Exposure to household pollution is associated with poorer control, greater severity, and poorer pulmonary function; double-exposed individuals have a greater risk of severe asthma and decreased lung function than those exposed only to household pollution.

A proposed scheme to cope with comorbidities in asthma.

The prevalence of non-communicable chronic diseases has been on the rise and the co-occurrence of morbidities is becoming more common. Multimorbidities are found more frequently among women, those with a history of mental disorders, lower level of schooling, and unfavorable socioeconomic condition. Physical inactivity, smoking and obesity are also associated with multimorbidities. Its occurrence is directly related to the age, affecting the majority of the individuals with more than 50 years old. It is important to consider the possibility of comorbid conditions that aggravate, complicate or simulate the symptoms of the disease in the face of a patient with asthma and poor response to treatment. Among subjects with asthma, some conditions stand out as the most frequent: chronic rhinitis or rhinosinusitis, gastroesophageal reflux disease, obstructive sleep apnea syndrome, obesity, and cardiovascular disorders. Comorbidities reduce the chances of optimal asthma control. It is essential to assess and manage properly these complex situations, choosing wisely preventive strategies and treatment options to avoid adverse events and optimize outcomes. Medications for asthma have the potential to worsen cardiovascular conditions, while beta-adrenergic receptor blockers and angiotensin conversion enzyme inhibitors used for cardiovascular conditions, can worsen asthma. Handling properly these cases will save lives and resources. However, there are multiple gaps in knowledge requiring investigation in this field to inform integrated care pathways and policies. It is likely information may be obtained from real life studies and electronic medical databases. Communications between the providers and patients may be facilitated by electronic technology, opening a large window for guided self-management.

Curricular intervention increases adolescents' knowledge about asthma: a randomized trial / Intervenção curricular eleva o conhecimento dos adolescentes sobre a asma: um ensaio randomizado

Abstract Objectives To evaluate the impact of a curricular intervention concerning the knowledge about asthma among adolescents from a public school. Methods This was a randomized, controlled trial study on a curricular intervention in asthma, carried out with asthmatic and non-asthmatic adolescents. The study participants were divided into a curricular intervention group for asthma (IG), and a control group with traditional curriculum (CG). Topics related to asthma were included in the curriculum, such as the disease concept, triggering factors, treatment, symptoms, action plan, and beliefs in popular myths about the disease. These topics were evaluated through a questionnaire with scores ranging from 0 to 20 points, expressed by the mean score. The acquisition of knowledge was evaluated 90 days and 540 days after the start of the intervention (baseline), by applying the mixed linear model for analysis of associations. Results 181 students participated in the study (IG = 101 and CG = 80). As shown by their scores before the intervention; the students were unaware about asthma (IG: x=10.7±2.9 vs. CG: x=11.5±2.7 points), its treatment (IG: x=1.6±0.9 vs. CG: x=1.6±0.8 points), and reported beliefs in popular myths about the disease (IG: x=1.5±1.1 vs. CG: x=1.7±1.1 points). After the intervention, the IG showed higher overall knowledge (GI: x=15.5±3.1 points), as well as knowledge about the treatment (GI: x=2.5±1.0 points), and two times more knowledge in the field "beliefs in popular myths about the disease" when compared to the CG. A greater probability of achieving satisfactory knowledge about asthma was noted in the IG (RR = 3.5), with NTT = 2.0. Conclusion The inclusion of the asthma topic in the curriculum improved knowledge about the disease in a subgroup of students.

Resumo Objetivo Avaliar o impacto de uma intervenção curricular sobre o conhecimento em asma dos adolescentes de um colégio público. Métodos Ensaio controlado e randomizado de uma intervenção curricular em asma, conduzido com adolescentes, asmáticos e não asmáticos, alocados em: grupo intervenção curricular em asma (GI) e grupo controle com currículo tradicional (GC). Foram inseridos no currículo tópicos relacionados à asma, tais como conceito, fatores desencadeantes, tratamento, sintomas, plano de ação e crenças em mitos populares sobre a doença, avaliados por meio de um questionário com escore de 0-20, expressos em média de acertos. Avaliou-se a apreensão do conhecimento 90 dias e 540 dias após o início da intervenção (baseline), aplicou-se o modelo linear misto para análise das associações. Resultados 181 estudantes participaram do estudo (GI = 101 e GC = 80). Os estudantes desconheciam a asma, como revelam os seus escores anteriores à intervenção (GI: x= 10,7±2,9 vs. GC: x= 11,5±2,7 acertos), seu tratamento (GI: x= 1,6±0,9 vs. GC: x= 1,6±0,8 acertos) e relataram crenças em mitos populares sobre a doença (GI: x=1,5±1,1 vs. GC: x=1,7±1,1 acertos). Após a intervenção, o GI apresentou maior conhecimento geral (GI: x= 15,5±3,1 acertos); sobre o tratamento (GI: x= 2,5±1,0 acertos) e duas vezes mais conhecimento no domínio "crenças em mitos populares sobre a doença" comparado com o GC. Maior probabilidade de alcançar conhecimento satisfatório sobre a asma foi observado no GI (RR = 3,5), com NNT = 2,0. Conclusão A inserção do tema asma no currículo é capaz de elevar o conhecimento sobre a doença em um subgrupo de estudantes.

Conhecimento de farmacêuticos sobre rinite alérgica e seu impacto na asma (guia ARIA para farmacêuticos): um estudo piloto comparativo entre Brasil e Paraguai / Knowledge of allergic rhinitis and its impact on asthma among pharmacists (ARIA guidelines for pharmacists): a comparative pilot study in Brazil and Paraguay

Introdução: Os farmacêuticos, geralmente, são os primeiros profissionais a atenderem pacientes com rinite alérgica (RA). A guia ARIA (Rinite Alérgica e seu Impacto na Asma) estabelece padrões de melhores práticas para o manejo de pacientes com RA. Objetivo: Avaliar o nível de conhecimento sobre RA e a guia ARIA entre farmacêuticos do Brasil (BR) e Paraguai (PY). Método: 205 farmacêuticos (BR = 78, PY = 127) responderam ao questionário online autoaplicável (ARIA One Airways) sobre dados pessoais, profissionais e conhecimento sobre RA e guia ARIA, empregando o Google Forms. Resultados: A mediana de idade foi 32 anos, 35% BR e 52% PY referiam terem tido mais de quatro anos de treinamento. Embora reconheçam os principais sintomas de RA, 26% BR e 100% PY nunca perguntaram se o paciente tinha diagnóstico médico de RA; 20,5% BR e 100,0% PY se os sintomas ocorreram quando perto de animais ou alérgenos; 55% BR e 76% PY se o paciente tinha diagnóstico médico de asma; 59% BR e 70% PY se a rinite piora os sintomas de asma. Anti-histamínicos sedantes foram recomendados por 34,6% BR e 26,8% PY, e corticosteroides intranasais por 59% BR e 52% PY. Embora 85% BR e 100% PY desconheçam as diretrizes ARIA, 94,9% BR e 60,6% PY encaminhariam o paciente a um especialista. Conclusão: Embora os farmacêuticos sejam os primeiros profissionais procurados pelo paciente com RA para alívio de sintomas, o seu nível de conhecimento sobre RA e a guia ARIA é baixo. O seu treinamento para atingir melhor abordagem clínica é primordial.

Introduction: Pharmacists are usually the first professionals to see patients with allergic rhinitis (AR). The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines establish best practice standards for the management of patients with AR. Objective: To evaluate the level of knowledge of AR and ARIA guideline recommendations among pharmacists in Brazil (BR) and Paraguay (PY). Method: A total of 205 pharmacists (BR = 78, PY = 127) answered a self-administered online questionnaire (ARIA One Airways), using the Google Forms tool, containing questions covering personal data, professional data, and knowledge of AR and ARIA guidelines. Results: Median age was 32 years; 35% BR and 52% PY reported having had more than four years of training. Although they recognized the main symptoms of AR, 26% BR and 100% PY never asked whether the patient had a medical diagnosis of AR; 20.5% BR and 100.0% PY if symptoms occurred when close to animals or allergens; 55% BR and 76% PY if the patient had a medical diagnosis of asthma; 59% BR and 70% PY if rhinitis worsened asthma symptoms. Sedating antihistamines were recommended by 34.6% BR and 26.8% PY, and intranasal corticosteroids by 59% BR and 52% PY. Although 85% BR and 100% PY were unaware of ARIA guidelines, 94.9% BR and 60.6% PY would refer the patient to a specialist. Conclusion: Even though pharmacists are the first professionals sought by patients with AR for symptom relief, their level of knowledge of AR and ARIA guidelines is very low. Training is paramount to improve clinical management of AR among pharmacists.

IV Brazilian Consensus on Rhinitis - an update on allergic rhinitis, / IV Consenso Brasileiro sobre Rinite - atualização em rinite alérgica,

Abstract Introduction The guidelines on allergic rhinitis aim to update knowledge about the disease and care for affected patients. The initiative called "Allergic Rhinitis and its Impact on Asthma", initially published in 2001 and updated in 2008 and 2010, has been very successful in disseminating information and evidence, as well as providing a classification of severity and proposing a systemized treatment protocol. In order to include the participation of other medical professionals in the treatment of allergic rhinitis, it is important to develop algorithms that accurately indicate what should and can be done regionally. Objective To update the III Brazilian Consensus on Rhinitis - 2012, with the creation of an algorithm for allergic rhinitis management. Methods We invited 24 experts nominated by the Brazilian Association of Allergy and Immunology, Brazilian Association of Otorhinolaryngology and Head and Neck Surgery and Brazilian Society of Pediatrics to update the 2012 document. Results The update of the last Brazilian Consensus on Rhinitis incorporated and adapted the relevant information published in all "Allergic Rhinitis and its Impact on Asthma" Initiative documents to the Brazilian scenario, bringing new concepts such as local allergic rhinitis, new drugs and treatment evaluation methods. Conclusion A flowchart for allergic rhinitis treatment has been proposed.

Resumo Introdução As diretrizes sobre rinite alergica visam atualizar os conhecimentos sobre a doença e os cuidados para com esses pacientes. A iniciativa designada "Rinite Alergica e seu Impacto na Asma", cujo relatorio inicial foi publicado em 2001 e atualizada em 2008 e 2010, tem sido muito bem sucedida na disseminaçao de informaçoes e evidencias, bem como na formulaçao da classificaçao de gravidade e proposta de sistematizaçao do tratamento. Entretanto, visando a participaçao de outros profissionais medicos no atendimento da rinite alergica, e importante o desenvolvimento de algoritmos que indiquem com precisao o que deve e pode ser feito regionalmente. Objetivo Atualizar o III Consenso Brasileiro sobre Rinites-2012, com elaboraçao de algoritmo para conduta da rinite alergica. Método Foram convidados 24 especialistas indicados pelas Associaçao Brasileira de Alergia e Imunologia, Associaçao Brasileira de Otorrinolaringologia e Cirurgia Cervico-Facial e Sociedade Brasileira de Pediatria para atualizaçao do documento de 2012. Resultados A atualizaçao do ultimo Consenso Brasileiro sobre Rinites, incorporou e adaptou para a realidade brasileira as informaçoes relevantes publicadas em todos os documentos da Iniciativa "Rinite Alergica e seu Impacto na Asma", trazendo novos conceitos como a rinite alergica local, novos medicamentos e metodos de avaliaçao de tratamento. Conclusão Proposto um fluxograma de tratamento para a rinite alergica.

IV Brazilian Consensus on Rhinitis - an update on allergic rhinitis.

INTRODUCTION: The guidelines on allergic rhinitis aim to update knowledge about the disease and care for affected patients. The initiative called "Allergic Rhinitis and its Impact on Asthma", initially published in 2001 and updated in 2008 and 2010, has been very successful in disseminating information and evidence, as well as providing a classification of severity and proposing a systemized treatment protocol. In order to include the participation of other medical professionals in the treatment of allergic rhinitis, it is important to develop algorithms that accurately indicate what should and can be done regionally. OBJECTIVE: To update the III Brazilian Consensus on Rhinitis - 2012, with the creation of an algorithm for allergic rhinitis management. METHODS: We invited 24 experts nominated by the Brazilian Association of Allergy and Immunology, Brazilian Association of Otorhinolaryngology and Head and Neck Surgery and Brazilian Society of Pediatrics to update the 2012 document. RESULTS: The update of the last Brazilian Consensus on Rhinitis incorporated and adapted the relevant information published in all "Allergic Rhinitis and its Impact on Asthma" Initiative documents to the Brazilian scenario, bringing new concepts such as local allergic rhinitis, new drugs and treatment evaluation methods. CONCLUSION: A flowchart for allergic rhinitis treatment has been proposed.

O atendimento médico de pacientes com doenças imunoalérgicas no Brasil: reflexões e propostas para a melhoria ­ Carta de Belo Horizonte / Caring for patients with immunoallergic diseases in Brazil: reflections and proposals for improvement ­ The Belo Horizonte Charter

Apesar do aumento na prevalência e gravidade das doenças imunoalérgicas no Brasil, como em todo o mundo, o acesso a atendimento especializado, exames complementares e terapias que possibilitam o controle adequado delas, especialmente as com potencial fatal, é restrito a poucos centros no Brasil, e muitas dessas condições e terapias não estão contempladas nos Protocolos Clínicos e Diretrizes Terapêuticas do Ministério da Saúde. No presente trabalho, analisamos a realidade atual e carências na assistência a pacientes com doenças alérgicas como anafilaxia, alergia ao leite de vaca, asma, dermatite atópica e urticária crônica e com imunodeficiências primárias. São apresentadas, também, propostas de ações em que a Associação Brasileira de Alergia e Imunologia poderia trabalhar em parceria com o Ministério da Saúde para reduzir o impacto médico, social e financeiro dessas doenças.

Despite the increase observed in the prevalence and severity of immunoallergic diseases, both in Brazil and worldwide, access to specialized care and to complementary tests and therapies that allow adequate disease control, especially in potentially fatal cases, is restricted to a few centers in Brazil. In addition, many of these conditions and therapies are not included in the Brazilian Ministry of Health's Clinical Protocols and Therapeutic Guidelines. In the present study, we analyze the current situation and weaknesses in the care of patients with allergic diseases such as anaphylaxis, cow's milk allergy, asthma, atopic dermatitis, and chronic urticaria, as well as those with primary immunodeficiencies. Possible actions that could be undertaken by the Brazilian Association of Allergy and Immunology in partnership with the Brazilian Ministry of Health are proposed, with the aim of reducing the medical, social, and financial impact associated with these diseases.