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Monitoring is a major component of asthma management in children. Regular monitoring allows for diagnosis confirmation, treatment optimization, and natural history review. Numerous factors that may affect disease activity and patient well-being need to be monitored: response and adherence to treatment, disease control, disease progression, comorbidities, quality of life, medication side-effects, allergen and irritant exposures, diet and more. However, the prioritization of such factors and the selection of relevant assessment tools is an unmet need. Furthermore, rapidly developing technologies promise new opportunities for closer, or even "real-time," monitoring between visits. Following an approach that included needs assessment, evidence appraisal, and Delphi consensus, the PeARL Think Tank, in collaboration with major international professional and patient organizations, has developed a set of 24 recommendations on pediatric asthma monitoring, to support healthcare professionals in decision-making and care pathway design., (© 2024 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Introduction: Even though increased use of reliever medication, including short-acting beta agonists (SABA), provides an indirect measure of symptom worsening, there have been limited efforts to assess how different patterns of reliever use correlate with symptom control and future risk of exacerbations. Here, we evaluate the effect of individual baseline characteristics on reliever use in patients with moderate-severe asthma on regular maintenance therapy with fluticasone propionate (FP) or combination therapy with fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR)., Methods: A drug-disease model describing the number of 24-h puffs and overnight occasions was developed with data from five clinical studies (N = 6212). The model was implemented using a nonlinear mixed effects approach and a Poisson function, considering clinical and demographic baseline characteristics. Goodness of fit and model predictive performance were assessed. Heatmaps were created to summarise the effect of concurrent baseline factors on reliever utilisation., Results: The final model accurately described individual patterns of reliever use, which is significantly increased with time since diagnosis, smoking, higher Asthma Control Questionnaire (ACQ-5) score and higher body mass index (BMI) at baseline. Whilst the number of puffs decreases slowly after an initial drop relative to the start of treatment, exacerbating patients utilise significantly more reliever than those who do not exacerbate. The mean effect of FP/SAL (median dose: 250/50 μg BID) on reliever use was slightly higher than that of BUD/FOR (median dose: 160/4.5 μg BID), i.e. a 75.3% vs 69.3% reduction in reliever use, respectively., Conclusions: The availability of individual-level patient data in conjunction with a parametric approach enabled the characterisation of interindividual differences in the patterns of reliever use in patients with moderate-severe asthma. Taken together, individual demographic and clinical characteristics, as well as exacerbation history, can be considered an indicator of the degree of asthma control. High SABA reliever use suggests suboptimal clinical management of patients on maintenance therapy., (© 2024. The Author(s).)

The emergence of biologic therapies for the management of asthma has been a revolutionary change in our capacity to manage this disease. Since the launch of omalizumab, several other biologics have been marketed or are close to being marketed, suggesting that a plethora of monoclonal antibodies can be expected in the coming years. This will facilitate the transition to the paradigm of personalized medicine, but on the other hand will decisively further complicate the choice of the most appropriate treatment, in the absence of reliable enough biological markers. For these reasons, along with the relatively short time of use with these treatments, there are recurrently arising questions for which there are not even moderately documented answers, and for which the only solution must be based, with all reservations, on the combination of indirect evidence and expertise. In this paper, we attempt to address such questions, providing relevant commentaries and considering the whole width of the evidence base., Competing Interests: None to declare related to this work., (© 2023 The Authors.)

Aims: There is limited understanding of how clinical and demographic characteristics are associated with exacerbation risk in patients with moderate-to-severe asthma, and how these factors correlate with symptom control and treatment response. Here we assess the relationship between baseline characteristics and exacerbation risk during regular dosing with inhaled corticosteroids (ICS) monotherapy or in combination with long-acting beta2-agonists (ICS/LABA) in clinical trial patients with varying levels of symptom control, as assessed by the asthma control questionnaire (ACQ-5)., Methods: A time-to-event model was developed using pooled patient data (N = 16 282) from nine clinical studies [Correction added on 26 July 2023, after first online publication: The N value in the preceding sentence has been corrected in this version.]. A parametric hazard function was used to describe the time-to-first exacerbation. Covariate analysis included the assessment of the effect of seasonal variation, clinical and demographic baseline characteristics on baseline hazard. Predictive performance was evaluated by standard graphical and statistical methods., Results: An exponential hazard model best described the time-to-first exacerbation in moderate-to-severe asthma patients. Body mass index, smoking status, sex, ACQ-5, % predicted forced expiratory volume over 1 s (FEV 1 p) and season were identified as statistically significant covariates affecting baseline hazard irrespective of ICS or ICS/LABA use. Fluticasone propionate/salmeterol (FP/SAL) combination therapy resulted in a significant reduction in the baseline hazard (30.8%) relative to FP monotherapy., Conclusions: Interindividual differences at baseline and seasonal variation affect the exacerbation risk independently from drug treatment. Moreover, it appears that even when a comparable level of symptom control is achieved in a group of patients, each individual may have a different exacerbation risk, depending on their baseline characteristics and time of the year. These findings highlight the importance of personalized interventions in moderate-to-severe asthma patients., (© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Fluticasone propionate/salmeterol xinafoate (FP/SAL) is an inhaled corticosteroid (ICS) and long-acting β 2 -agonist (LABA) combination, indicated for the regular treatment of children (aged >4 years) with asthma that is inadequately controlled with ICS monotherapy plus as-needed short-acting β 2 -agonists, or already adequately controlled with ICS/LABA., Objective: Compared with the adult population, fewer clinical studies have investigated the efficacy of FP/SAL in paediatric patients with moderate and moderate-to-severe asthma. In this review, we synthesise the available evidence for the efficacy and safety of FP/SAL in the paediatric population, compared with other available therapies indicated for asthma in children., Eligibility Criteria: A literature review identified randomised controlled trials and observational studies of FP/SAL in the paediatric population with moderate-to-severe asthma., Sources of Evidence: The Medline database was searched using PubMed (https://pubmed.ncbi.nlm.nih.gov/), with no publication date restrictions. Search strategies were developed and refined by authors., Charting Methods: Selected articles were screened for clinical outcome data (exacerbation reduction, nocturnal awakenings, lung function, symptom control, rescue medication use and safety) and a table of key parameters developed., Results: Improvements in asthma outcomes with FP/SAL include reduced risk of asthma-related emergency department visits and hospitalisations, protection against exercise-induced asthma and improvements in measures of lung function. Compared with FP monotherapy, greater improvements in measures of lung function and asthma control are reported. In addition, reduced incidence of exacerbations, hospitalisations and rescue medication use is observed with FP/SAL compared with ICS and leukotriene receptor antagonist therapy. Furthermore, FP/SAL therapy can reduce exposure to both inhaled and oral corticosteroids., Conclusions: FP/SAL is a reliable treatment option in patients not achieving control with ICS monotherapy or a different ICS/LABA combination. Evidence shows that FP/SAL is well tolerated and has a similar safety profile to FP monotherapy. Thus, FP/SAL provides an effective option for the management of moderate-to-severe asthma in the paediatric population., Competing Interests: Competing interests: PMP has acted as a speaker/consultant for AstraZeneca, GSK, Novartis, Boehringer Ingelheim and Sanofi. SN has acted as a speaker/consultant for AstraZeneca, GSK, Novartis, Boehringer Ingelheim and Sanofi. APMC has acted as a speaker/consultant for Danone, Nutricia, AbbVie and Sanofi. CT and APG are full-time employees of GSK and hold shares in GSK., (© 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.)

The Global Initiative for Asthma (GINA) was established in 1993 by the World Health Organization and the US National Heart Lung and Blood Institute to improve asthma awareness, prevention and management worldwide. GINA develops and publishes evidence-based, annually updated resources for clinicians. GINA guidance is adopted by national asthma guidelines in many countries, adapted to fit local healthcare systems, practices, and resource availability. GINA is independent of industry, funded by the sale and licensing of its materials. This review summarizes key practical guidance for primary care from the 2022 GINA strategy report. It provides guidance on confirming the diagnosis of asthma using spirometry or peak expiratory flow. GINA recommends that all adults, adolescents and most children with asthma should receive inhaled corticosteroid (ICS)-containing therapy to reduce the risk of severe exacerbations, either taken regularly, or (for adults and adolescents with "mild" asthma) as combination ICS-formoterol taken as needed for symptom relief. For patients with moderate-severe asthma, the preferred regimen is maintenance-and-reliever therapy (MART) with ICS-formoterol. Asthma treatment is not "one size fits all"; GINA recommends individualized assessment, adjustment, and review of treatment. As many patients with difficult-to-treat or severe asthma are not referred early for specialist review, we provide updated guidance for primary care on diagnosis, further investigation, optimization and treatment of severe asthma across secondary and tertiary care. While the GINA strategy has global relevance, we recognize that there are special considerations for its adoption in low- and middle-income countries, particularly the current poor access to inhaled medications., (© 2023. The Author(s).)

Asthma imposes a heavy morbidity burden during childhood; it affects over 10% of children in Europe and North America and it is estimated to exceed 400 million people worldwide by the year 2025. In clinical practice, diagnosis of asthma in children is mostly based on clinical criteria; nevertheless, assessment of both physiological and pathological processes through biomarkers, support asthma diagnosis, aid monitoring, and further lead to better treatment outcomes and reduced morbidity. Recently, identification and validation of biomarkers in pediatric asthma has emerged as a top priority across leading experts, researchers, and clinicians. Moreover, the implementation of non-invasive biomarkers for the assessment and monitoring of paediatric patients with asthma, has been prioritized; however, only a proportion of them are currently included in the clinical practise. Although, the use of non-invasive biomarkers is highly supported in recent asthma guidelines for documenting diagnosis and supporting monitoring of asthmatic patients, data on the Pediatric population are limited. In the present report, the Pediatric Asthma Committee of the World Allergy Organization (WAO), aims to summarize and discuss available data for the implementation of non-invasive biomarkers in the diagnosis and monitoring in children with asthma. Information on the most studied biomarkers, including spirometry, oscillometry, markers of allergic sensitization, fractional exhaled nitric oxide, and the most recent exhaled breath markers and "omic" approaches, will be reviewed. Practical limitations and considerations based on both experts' opinion and critical review of the literature, on the utility of all "well-known" and newly introduced non-invasive biomarkers will be presented. A critical commentary on biomarkers' use in diagnosing and monitoring asthma during the COVID-19 pandemic, cost and availability of biomarkers in different settings and in developing countries, the differences on the biomarkers use between Primary Practitioners, Pediatricians, and Specialists and their role on the longitudinal aspect of asthma is provided., (© 2022 The Authors.)

Asthma is the most common noncommunicable disease in children, and among the most common in adults. The great majority of people with asthma live in low and middle income countries (LMICs), which have disproportionately high asthma-related morbidity and mortality. Essential inhaled medications, particularly those containing inhaled corticosteroids (ICS), are often unavailable or unaffordable, and this explains much of the global burden of preventable asthma morbidity and mortality. Guidelines developed for LMICs are generally based on the outdated assumption that patients with asthma symptoms <1-3 times per week do not need (or benefit from) ICS. Even when ICS are prescribed, many patients manage their asthma with oral or inhaled short-acting β 2 -agonists (SABA) alone, owing to issues of availability and affordability. A single ICS-formoterol inhaler-based approach to asthma management for all severities of asthma, from mild to severe, starting at diagnosis, might overcome SABA overuse/over-reliance and reduce the burden of symptoms and severe exacerbations. However, ICS-formoterol inhalers are currently very poorly available or unaffordable in LMICs. There is a pressing need for pragmatic clinical trial evidence of the feasibility and cost-effectiveness of this and other strategies to improve asthma care in these countries. The global health inequality in asthma care that deprives so many children, adolescents and adults of healthy lives and puts them at increased risk of death, despite the availability of highly effective therapeutic approaches, is unacceptable. A World Health Assembly Resolution on universal access to affordable and effective asthma care is needed to focus attention and investment on addressing this need., Competing Interests: Conflict of interest: The Global Initiative for Asthma (GINA) provided writing assistance during the course of the present manuscript. K. Mortimer additionally reports consulting fees from AstraZeneca, outside the submitted work, and is a member of the science committee for GINA. H.K. Reddel reports grants from AstraZeneca, GlaxoSmithKline and Novartis; consulting fees from Novartis; lecture honoraria from AstraZeneca, GlaxoSmithKline, Teva, Boehringer Ingelheim, Sanofi and Chiesi; and participation on advisory boards for AstraZeneca, GlaxoSmithKline, Novartis, Chiesi and Sanofi, outside the submitted work; and is also Chair of Scientific Committee and Member of Board of Directors for GINA, and Member of Australian Asthma Guidelines Committee for National Asthma Council. P.M. Pitrez reports consulting fees from AstraZeneca, Novartis, GSK, Boehringer Ingelheim and Sanofi; lecture honoraria from AstraZeneca, Novartis, GSK, Boehringer Ingelheim and Sanofi; and travel support from GSK and Boehringer Ingelheim, outside the submitted work. E.D. Bateman reports consulting fees from AstraZeneca, Sanofi Genzyme, Regeneron, Novartis and ALK; and lecture honoraria from AstraZeneca, Orion, Menarini, Novartis, Sanofi Genzyme and Regeneron, outside the submitted work; and is also a member of the Board and Science Committee of GINA., (Copyright ©The authors 2022.)

Background: In 2020, a unique social experience was provided by the pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2. Interventions to tackle the pandemic may affect the burden of other respiratory diseases., Objective: This study aims to assess the impact of the COVID-19 mitigation strategies on hospitalizations for asthma in children aged between 1 and 14 years, adults aged between 20 and 59 years, and elderly older than 60 years., Methods: Data from hospital admissions for asthma were obtained from the Department of Informatics of Brazilian Public Health System database in the period between January 2016 and December 2020 and analyzed by age groups. To evaluate the effect of containment measures on the incidence of asthma and respiratory system diseases (total), the absolute reduction and relative reduction were calculated by analyzing the subsets from 2016 to 2019 versus 2020., Results: There was a significant reduction in the average incidence of hospitalizations in 2020, with numbers ranging from -59% (incidence rate ratio, 0.41 [0.37-0.45]) for age 1 to 14 years (prepandemic 1,393.2/100,000 vs pandemic 574.9/100.000), -37% (incidence rate ratio, 0.63 [0.49-0.80]) for age 20 to 59 years (prepandemic 160.2/100,000 vs pandemic 101.1/100,000), and -60% (incidence rate ratio, 0.40 [0.33-0.47]) for older than 60 years (prepandemic 460.6/100,000 vs pandemic 185.3/100,000)., Conclusions: Ashtma hospitalizations decreased in 2020, especially in the pediatric group and the older group during the COVID-19 pandemic, which may be associated with the reduction in the incidence of many respiratory viral infections., (© 2022 The Author(s).)

Background: Regulatory bodies have approved five biologics for severe asthma. However, regional differences in accessibility may limit the global potential for personalized medicine., Objective: To compare global differences in ease of access to biologics., Methods: In April 2021, national prescription criteria for omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab were reviewed by severe asthma experts collaborating in the International Severe Asthma Registry. Outcomes (per country, per biologic) were (1) country-specific prescription criteria and (2) development of the Biologic Accessibility Score (BACS). The BACS composite score incorporates 10 prescription criteria, each with a maximum score of 10 points. Referenced to European Medicines Agency marketing authorization specifications, a higher score reflects easier access., Results: Biologic prescription criteria differed substantially across 28 countries from five continents. Blood eosinophil count thresholds (usually ≥300 cells/μL) and exacerbations were key requirements for anti-IgE/anti-IL-5/5R prescriptions in around 80% of licensed countries. Most countries (40% for dupilumab to 54% for mepolizumab) require two or more moderate or severe exacerbations, whereas numbers ranged from none to four. Moreover, 0% (for reslizumab) to 21% (for omalizumab) of countries required long-term oral corticosteroid use. The BACS highlighted marked between-country differences in ease of access. For omalizumab, mepolizumab, benralizumab, and dupilumab, only two, one, four, and seven countries, respectively, scored equal or higher than the European Medicines Agency reference BACS. For reslizumab, all countries scored lower., Conclusions: Although some differences were expected in country-specific biologic prescription criteria and ease of access, the substantial differences found in the current study present a challenge to implementing precision medicine across the world., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Allergic asthma is characterized by chronic airway inflammation and is constantly associated with anxiety disorder. Recent studies showed bidirectional interaction between the brain and the lung tissue. However, where and how the brain is affected in allergic asthma remains unclear. We aimed to investigate the neuroinflammatory, neurochemical, and neurometabolic alterations that lead to anxiety-like behavior in an experimental model of allergic asthma. Mice were submitted to an allergic asthma model induced by ovalbumin (OVA) and the control group received only Dulbecco's phosphate-buffered saline (DPBS). Our findings indicate that airway inflammation increases interleukin (IL) -9, IL-13, eotaxin, and IL-1β release and changes acetylcholinesterase (AChE) and Na + ,K + -ATPase activities in the brain of mice. Furthermore, we demonstrate that a higher reactive oxygen species (ROS) formation and antioxidant defense alteration that leads to protein damage and mitochondrial dysfunction. Therefore, airway inflammation promotes a pro-inflammatory environment with an increase of BDNF expression in the brain of allergic asthma mice. These pro-inflammatory environments lead to an increase in glucose uptake in the limbic regions and to anxiety-like behavior that was observed through the elevated plus maze (EPM) test and downregulation of glucocorticoid receptor (GR). In conclusion, the present study revealed for the first time that airway inflammation induces neuroinflammatory, neurochemical, and neurometabolic changes within the brain that leads to anxiety-like behavior. Knowledge about mechanisms that lead to anxiety phenotype in asthma is a beneficial tool that can be used for the complete management and treatment of the disease., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: to evaluate the accuracy of an antibody point-of-care lateral flow immunoassay (LFI - Wondfo Biotech Co., Guangzhou, China) in a pediatric population., Methods: children and adolescents (2 months to 18 years) with signs and symptoms suggestive of acute SARS-CoV-2 infection were prospectively investigated with nasopharyngeal RT-PCR and LFI at the emergency room. RT-PCR was performed at baseline, and LFI at the same time or scheduled for those with less than 7 days of the clinical picture. Overall accuracy, sensitivity and specificity were assessed, as well as according to the onset of symptoms (7-13 or ≥14 days) at the time of the LFI test., Results: In 175 children included, RT-PCR and LFI were positive in 51 (29.14%) and 36 (20.57%), respectively. The overall sensitivity, specificity, positive and negative predictive value was 70.6% (95%CI 56.2-82.5), 96.8% (95%CI 91.9-99.1), 90.0% (95%CI 77.2-96.0), and 88.9% (95%CI 83.9-92.5), respectively. At 7-13 and ≥14 days after the onset of symptoms, sensitivity was 60.0% (95%CI 26.2-87.8) and 73.2% (95%CI 57.1-85.8) and specificity was 97.9% (95%CI 88.7-99.9) and 96.1% (95%CI 89.0-99.2), respectively., Conclusion: Despite its high specificity, in the present study the sensitivity of LFI in children was lower (around 70%) than most reports in adults. Although a positive result is informative, a negative LFI test cannot rule out COVID-19 in children., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2021. Published by Elsevier Editora Ltda.)

Point-of-care serological tests for SARS-CoV-2 have been used for COVID-19 diagnosis. However, their accuracy over time regarding the onset of symptoms is not fully understood. We aimed to assess the accuracy of a point-of-care lateral flow immunoassay (LFI). Subjects, aged over 18 years, presenting clinical symptoms suggestive of acute SARS-CoV-2 infection were tested once by both nasopharyngeal and oropharyngeal RT-PCR and LFI. The accuracy of LFI was assessed in periodic intervals of three days in relation to the onset of symptoms. The optimal cut-off point was defined as the number of days required to achieve the best sensitivity and specificity. This cut-off point was also used to compare LFI accuracy according to participants' status: outpatient or hospitalized. In total, 959 patients were included, 379 (39.52%) tested positive for SARS-CoV-2 with RT-PCR, and 272 (28.36%) tested positive with LFI. LFI best performance was achieved after 10 days of the onset of symptoms, with sensitivity and specificity of 84.9% (95%CI: 79.8-89.1) and 94.4% (95%CI: 91.0-96.8), respectively. Although the specificity was similar (94.6% vs. 88.9%, p = 0.051), the sensitivity was higher in hospitalized patients than in outpatients (91.7% vs. 82.1%, p = 0.032) after 10 days of the onset of symptoms. Best sensitivity of point-of-care LFI was found 10 days after the onset of symptoms which may limit its use in acute care. Specificity remained high regardless of the number of days since the onset of symptoms.

The Global Initiative for Asthma (GINA) Strategy Report provides clinicians with an annually updated evidence-based strategy for asthma management and prevention, which can be adapted for local circumstances (e.g., medication availability). This article summarizes key recommendations from GINA 2021, and the evidence underpinning recent changes. GINA recommends that asthma in adults and adolescents should not be treated solely with short-acting β 2 -agonist (SABA), because of the risks of SABA-only treatment and SABA overuse, and evidence for benefit of inhaled corticosteroids (ICS). Large trials show that as-needed combination ICS-formoterol reduces severe exacerbations by ⩾60% in mild asthma compared with SABA alone, with similar exacerbation, symptom, lung function, and inflammatory outcomes as daily ICS plus as-needed SABA. Key changes in GINA 2021 include division of the treatment figure for adults and adolescents into two tracks. Track 1 (preferred) has low-dose ICS-formoterol as the reliever at all steps: as needed only in Steps 1-2 (mild asthma), and with daily maintenance ICS-formoterol (maintenance-and-reliever therapy, "MART") in Steps 3-5. Track 2 (alternative) has as-needed SABA across all steps, plus regular ICS (Step 2) or ICS-long-acting β 2 -agonist (Steps 3-5). For adults with moderate-to-severe asthma, GINA makes additional recommendations in Step 5 for add-on long-acting muscarinic antagonists and azithromycin, with add-on biologic therapies for severe asthma. For children 6-11 years, new treatment options are added at Steps 3-4. Across all age groups and levels of severity, regular personalized assessment, treatment of modifiable risk factors, self-management education, skills training, appropriate medication adjustment, and review remain essential to optimize asthma outcomes.

Objective: To evaluate the exercise capacity of children and adolescents with severe therapy resistant asthma (STRA) aiming to identify its main determinants., Methods: Cross-sectional study including individuals aged 6-18 years with a diagnosis of STRA. Clinical (age and gender), anthropometric (weight, height and body mass index) and disease control data were collected. Lung function (spirometry), cardiopulmonary exercise testing (CPET) and exercise-induced bronchoconstriction (EIB) test were performed., Results: Twenty-four patients aged 11.5 ± 2.6 years were included. The mean forced expiratory volume in one second (FEV 1 ) was 91.3 ± 9.2%. EIB occurred in 54.2% of patients. In CPET, the peak oxygen uptake ( V O 2peak ) was 34.1 ± 7.8 mL kg -1  min -1 . A significant correlation between ventilatory reserve and FEV 1 ( r  = 0.57; p  = 0.003) was found. Similarly, there was a significant correlation between CPET and percent of FEV 1 fall in the EIB test for both V E / V O 2 ( r  = 0.47; p  = 0.02) and V E / V CO 2 ( r  = 0.46; p  = 0.02). Patients with FEV 1 <80% had lower ventilatory reserve ( p  = 0.009). In addition, resting heart rate correlated with V O 2peak (r=-0.40; p  = 0.04), V E / V O 2 ( r  = 0.46; p  = 0.02) and V E / V CO 2 ( r  = 0.48; p  = 0.01)., Conclusions: Exercise capacity is impaired in approximately 30% of children and adolescents with STRA. The results indicate that different aspects of aerobic fitness are influenced by distinct determinants, including lung function and EIB.

Competing Interests: Conflict of interest: L.B. Bacharier reports receiving royalties for textbooks from Elsevier; consulting fees from GlaxoSmithKline, Teva, AstraZeneca, Sanofi, Regeneron, Vectura, Circassia, Kinaset, Merck and Boehringer Ingelheim; honoraria for lectures from GlaxoSmithKline, Genentech/Novartis, Teva Honoraria, AstraZeneca, Sanofi/Regeneron and WebMD/Medscape; participation on a data safety monitoring board or advisory board for DBV Technologies, AstraZeneca and Vertex (CF Foundation); leadership or fiduciary roles in other board, society, committee or advocacy group, paid or unpaid for AAAAI Board of Directors (unpaid) and ABAI Board of Directors, in the past 36 months. E.D. Bateman reports receiving advisory board, consultant and speaker fees from AstraZeneca, Sanofi Genzyme, Regeneron, Novartis and ALK; speaker fees from Boehringer Ingelheim, Menarini and Orion; and advisory board and speaker fees from Chiesi, since the initial planning of this work; E.D. Bateman reports receiving consulting fees from AstraZeneca, Sanofi Genzyme, Regeneron, Novartis and ALK; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca, Menarini, Orion, Novartis, Regeneron, Sanofi Genzyme, Chiesi and ALK; support for attending meetings and/or travel from Novartis (to attend European Respiratory Society Congress 2021); participation on a data safety monitoring board or advisory board from AstraZeneca, ALK, Sanofi Genzyme, Regeneron, Novartis and Chiesi; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid for Global Initiative for Asthma (Member of Board and Science Committee, unpaid), in the past 36 months. L-P. Boulet reports grants paid to institution for multicentre or investigator-generated clinical studies from Amgen, AstraZeneca, GlaxoSmithKline, Merck, Novartis and Sanofi-Regeneron; royalties from UpToDate; consultancy fees from AstraZeneca, Novartis, GlaxoSmithKline, Merck and Sanofi-Regeneron; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca, Covis, GlaxoSmithKline, Novartis, Merck and Sanofi; and is Chair of the Global Initiative for Asthma (GINA) Board of Directors, President of the Global Asthma Organisation (Interasma), member of the Canadian Thoracic Society Respiratory Guidelines Committee, and Laval University Chair on Knowledge Transfer, Prevention and Education in Respiratory and Cardiovascular Health. C.E. Brightling reports receiving grants or contracts from GSK, AZ, Novartis, Chiesi, BI, Mologic, 4DPharma, Gossamer, Merck and Roche/Genentech (all paid to institution); consulting fees from AZ, Novartis, Chiesi, BI, Mologic, TEVA, 4DPharma, Gossamer, Regeneron, Sanofi and Roche/Genentech (all paid to institution), in the past 36 months. G.G. Brusselle reports receiving payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Sanofi and Teva; participation on a data safety monitoring board or advisory board for AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, MSD, Novartis, Sanofi and Teva, in the past 36 months. R. Buhl reports grants from Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Roche; lecture honoraria from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Novartis, Roche, Sanofi, Teva; participation on advisory board from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Roche, Sanofi, Teva; outside the submitted work; and has acted as a Member of the Scientific Committee of the Global Initiative for Asthma (GINA). A.A. Cruz reports lecture honoraria from Abdi Ibrahim, AstraZeneca, Boehringer Ingelheim, Chiesi, Glennmark, GSK, Mylan, Novartis and Sanofi; travel support from AstraZeneca, Boehringer Ingelheim and Chiesi, outside the submitted work. L. Duijts reports grants from European Union's Horizon 2020 research and innovation programme (LIFECYCLE, grant agreement number 733206, 2016; EUCAN-Connect grant agreement number 824989; ATHLETE, grant agreement number 874583), outside the submitted work. J.M. FitzGerald reports grants from AstraZeneca, GSK, TEVA, Sanofi, CIHR and NIH; consulting fees and lecture honoraria from AstraZeneca, GSK, TEVA and Sanofi; outside the submitted work. L.J. Fleming reports consulting fees from GSK, Sanofi, Respiri UK and AstraZeneca; lecture honoraria from Novartis and Teva, outside the submitted work. H. Inoue reports grants to institution from Boehringer Ingelheim, GlaxoSmithKline, Kyorin, MerckSharp&Dohme and Ono; personal consulting fees from Boehringer Ingelheim; lecture honoraria from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Kyorin, MerckSharp&Dohme, Novartis and Sanofi; has participated on an advisory board for AstraZeneca, GlaxoSmithKline, Novartis and Sanofi; board leadership with Japanese Respiratory Society (Board of Directors and Chairman of Education Committee) and Japanese Society of Allergology (Former Chairman of Education Committee), outside the submitted work. F.W. Ko reports support for travel from Novartis, Boehringer Ingelheim and GSK, outside the submitted work. J.A. Krishnan reports grants from Regeneron Pharmaceuticals, Sergey Brin Family Foundation, Patient Centered Outcomes Research Institute, COPD Foundation and American Lung Association; consulting fees from GlaxoSmithKline for COVID-19 mAb; board leadership at COPD Foundation and Respiratory Health Association, outside the submitted work. M.L. Levy reports grants from Consorzio Futuro in Ricerca and AstraZeneca; royalties from Class Publishing and Taylor & Francis; consulting fees from Respiri, Ltd, TEVA and NSHI Ltd; lecture honoraria from TEVA, Novartis, Chiesi and Orion; payment for expert testimony from HM Coroner Walthamstow, London, and HM Coroner, Waltham Forrest, London; travel support from Orion Pharmaceuticals, Menarini Pharmaceuticals, Napp Pharmaceuticals and TEVA; participation on advisory board at Chiesi, Novartis, GSK and Sandoz; and board leadership at GINA (Board of Directors), outside the submitted work. K. Mortimer has participated as member of advisory boards for AstraZeneca, outside the submitted work. P.M. Pitrez reports consulting fees and lecture honoraria from AstraZeneca, Boehringer Ingelheim, GSK, Sanofi and Novartis; travel support from GSK and Boehringer Ingelheim; and held an unpaid position as President of the Brazilian Severe Asthma Group, outside the submitted work. H.K. Reddel reports grants from AstraZeneca, GlaxoSmithKline and Novartis; consulting fees from Novartis; lecture payments from AstraZeneca, GlaxoSmithKline, Teva, Boehringer Ingelheim, Sanofi and Chiesi; participation on advisory boards for AstraZeneca, GlaxoSmithKline, Novartis, Chiesi and Sanofi; acted as Chair of Scientific Committee and Member of Board of Directors for Global Initiative for Asthma, and acted as Member of Australian Asthma Guidelines Committee for National Asthma Council, outside the submitted work. A. Sheikh reports grants from HDRUK BREATHE Hub, and Asthma UK Centre for Applied Research; and participated in the AstraZeneca Unmet Asthma Need Working Group; outside the submitted work. A.A. Yorgancioglu reports grants from MSD, AstraZeneca, Sanofi and Novartis; consulting fees from AstraZeneca, GSK, Novartis, Sanofi, Chiesi and Deva; lecture honoraria from AstraZeneca, Abdi İbrahim, GSK, Novartis, Sandoz, Chiesi and Vem İlaç; advisory board participation from GSK and AstraZeneca; outside the submitted work. All other authors have nothing to disclose.

Advances in the understanding that severe asthma is a complex and heterogeneous disease and in the knowledge of the pathophysiology of asthma, with the identification of different phenotypes and endotypes, have allowed new approaches for the diagnosis and characterization of the disease and have resulted in relevant changes in pharmacological management. In this context, the definition of severe asthma has been established, being differentiated from difficult-to-control asthma. These recommendations address this topic and review advances in phenotyping, use of biomarkers, and new treatments for severe asthma. Emphasis is given to topics regarding personalized management of the patient and selection of biologicals, as well as the importance of evaluating the response to treatment. These recommendations apply to adults and children with severe asthma and are targeted at physicians involved in asthma treatment. A panel of 17 Brazilian pulmonologists was invited to review recent evidence on the diagnosis and management of severe asthma, adapting it to the Brazilian reality. Each of the experts was responsible for reviewing a topic or question relevant to the topic. In a second phase, four experts discussed and structured the texts produced, and, in the last phase, all experts reviewed and approved the present manuscript and its recommendations.

Objective: The aim of this study was to evaluate the association between possible functional interleukin-10 (IL-10) polymorphisms, IL-10 expression and regulatory T cells (Tregs) frequency, and/or asthma severity in a sample of children and adolescents., Methods: This is a nested case-control genetic association study. The study sample consisted of children and adolescents aged 8-14 from public schools. Four polymorphisms of the IL-10 gene (rs1518111, rs3024490, rs3024496, rs3024491) were genotyped in asthmatic subjects and controls using real-time PCR. Tregs cells and IL-10 were analyzed in peripheral blood mononuclear cells by flow cytometry. The severity of asthma was defined according to the Global Initiative for Asthma (GINA) guideline., Results: One hundred twenty-three asthmatic subjects and fifty-eight controls participated in the study. The single nucleotide polymorphism (SNP) rs3024491 (T allele) showed association with asthma severity, presenting a higher frequency in patients in the moderate asthma group. The T allele of variant rs3024491 also showed an association with reduced IL-10 levels (p=0.01) and with increased Tregs frequency (p=0.01). The other variants did not present consistent associations., Conclusions: Our results suggest that moderate asthma is associated with a higher frequency of the T allele in the SNP rs3024491. In addition, the variant rs3024491 (TT) was associated with a reduction in IL-10 production and an increased percentage of Tregs cells, suggesting possible mechanisms that influence asthma severity., (Copyright © 2020 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

We conducted a cross-sectional study to assess how the top 3 highest circulation newspapers from 25 countries are comparing and presenting COVID-19 epidemiological data to their readers. Of 75 newspapers evaluated, 51(68%) presented at their websites at least one comparison of cases and/or deaths between regions of their country and/or between countries. Quality assessment of the comparisons showed that only a minority of newspapers adjusted the data for population size in case comparisons between regions (37.2%) and between countries (25.6%), and the same was true for death comparisons between regions (27.3%) and between countries (27%). Of those making comparisons, only 13.7% explained the difference in the interpretation of cases and deaths. Of 17 that presented a logarithmic curve, only 29.4% explained its meaning. Although the press plays a key role in conveying correct medical information to the general public, we identified inconsistencies in the reporting of COVID-19 epidemiological data., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: The aim of the study was to evaluate the diagnostic performance of the item concerning physical activity of the Global Initiative for Asthma (GINA) asthma control questionnaire for detection of exercise-induced bronchoconstriction (EIB) in children and adolescents., Material and Methods: We divided participants (aged 6-18 years) with a diagnosis of asthma into two groups according to the GINA severity classification: mild/moderate asthma (MMA) and severe therapy-resistant asthma (STRA). We collected anthropometric, clinical and functional data (spirometry) and performed an EIB test. We used item 4 of the GINA questionnaire regarding exercise-induced symptoms to assess the diagnostic power of this instrument., Results: We included 40 patients (17 with MMA and 23 with STRA) with a mean age of 11.3 years and a mean FEV 1 z-score of -0.33, of who 13 (32.5%) were classified as having uncontrolled asthma. Of the patients with uncontrolled asthma, 7 (53.8%) exhibited a decrease in the FEV 1 after the EIB test. We found a higher frequency of EIB in participants with FEV 1 z-score values of less than -1.0 compared to those with a z-score of -1.0 or greater (P = .05). There were no significant differences in the frequency of EIB based on disease severity and control. We also found no association of item 4 (GINA) with EIB. The area under the ROC curve demonstrated that the discriminative power of the GINA questionnaire for the detection of EIB is inadequate (P = .41), with sensitivity of 42.1% and specificity of 57.1%., Conclusions: The item concerning physical activity in the GINA questionnaire has insufficient diagnostic power to detect EIB in children and adolescents with asthma., (Copyright © 2021 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Lower exercise tolerance is an important component of asthma and the possible effects of non-invasive ventilation on exercise capacity in individuals with severe therapy-resistant asthma (STRA) are unknown. This study aimed to evaluate the immediate effect of continuous positive airway pressure (CPAP) on exercise tolerance in children with STRA., Methods: We performed a controlled, randomized, crossover clinical trial including subjects aged 6 to 18 years old diagnosed with STRA. Clinical, anthropometric and lung function data were collected. The participants in the intervention group (IG) used CPAP (PEEP 10cmH 2 O and FiO 2 0.21) for a period of 40 min. Subjects in the control group (CG) used CPAP with minimum PEEP at 1 cmH 2 0 also for 40 min. Afterwards, subjects from both groups underwent cardiopulmonary exercise testing (CPET). After a 15-day washout period, on a subsequent visit, subjects participated in the opposite group to the initial one., Results: Thirteen subjects with a mean age of 12.30 ± 1.7 years were included. The variables of peak expiratory flow (PEF) and forced expiratory volume in the first second (FEV 1 ) before using CPAP and after performing CPET did not show significant differences. Regarding CPET results, there was no significant difference (P = 0.59) between groups at peak exercise for oxygen consumption-VO 2 (CG: 33.4 ± 6.3 and IG: 34.5 ± 5.9, mL kg -1  min -1 ). However, the IG (12.4 ± 2.1) presented a total test time (min) significantly (P = 0.01) longer than the CG (11.5 ± 1.3)., Conclusion: The results suggest that the use of CPAP before physical exercise increases exercise duration in children and adolescents with STRA.

Background: Respiratory syncytial virus (RSV) and influenza are prevalent seasonal community viruses. Although not completely understood, SARS-CoV-2 may have the same means of transmission. Preventive social measures aimed at preventing SARS-CoV-2 spread could impact transmission of other respiratory viruses as well. The aim of this study is to report the detection of RSV and influenza during the period of social distancing due to COVID-19 pandemic in a heavily affected community., Methods: Prospective study with pediatric and adult populations seeking care for COVID-19-like symptoms during the fall and winter of 2020 at two hospitals in Southern Brazil. RT-PCR tests for SARS-CoV-2, influenza A (Flu A), influenza B (Flu B) and respiratory syncytial virus (RSV) was performed for all participants., Results: 1435 suspected COVID-19 participants (1137 adults, and 298 children). were included between May and August. Median age was 37.7 years (IQR = 29.6-47.7), and 4.92 years (IQR = 1.96-9.53), for the adult and child cohorts, respectively. SARS-CoV-2 was positive in 469 (32.7%) while influenza and RSV were not detected at all., Conclusions: Measures to reduce SARS-CoV-2 transmission likely exerted a huge impact in the spread of alternate respiratory pathogens. These findings contribute to the knowledge about the dynamics of virus spread. Further, it may be considered for guiding therapeutic choices for these other viruses., Competing Interests: Competing interests: The authors completed the ICMJE Unified Competing Interest form (available upon request from the corresponding author), and declare no conflicts of interest., (Copyright © 2021 by the Journal of Global Health. All rights reserved.)

Introduction: The long-term effects caused by COVID-19 are unknown. The present study aims to assess factors associated with health-related quality of life and long-term outcomes among survivors of hospitalization for COVID-19 in Brazil., Methods: This is a multicenter prospective cohort study nested in five randomized clinical trials designed to assess the effects of specific COVID-19 treatments in over 50 centers in Brazil. Adult survivors of hospitalization due to proven or suspected SARS-CoV-2 infection will be followed-up for a period of 1 year by means of structured telephone interviews. The primary outcome is the 1-year utility score of health-related quality of life assessed by the EuroQol-5D3L. Secondary outcomes include all-cause mortality, major cardiovascular events, rehospitalizations, return to work or study, physical functional status assessed by the Lawton-Brody Instrumental Activities of Daily Living, dyspnea assessed by the modified Medical Research Council dyspnea scale, need for long-term ventilatory support, symptoms of anxiety and depression assessed by the Hospital Anxiety and Depression Scale, symptoms of posttraumatic stress disorder assessed by the Impact of Event Scale-Revised, and self-rated health assessed by the EuroQol-5D3L Visual Analog Scale. Generalized estimated equations will be performed to test the association between five sets of variables (1- demographic characteristics, 2- premorbid state of health, 3- characteristics of acute illness, 4- specific COVID-19 treatments received, and 5- time-updated postdischarge variables) and outcomes., Ethics and Dissemination: The study protocol was approved by the Research Ethics Committee of all participant institutions. The results will be disseminated through conferences and peer-reviewed journals.

Currently, Brazil lacks a national asthma management program and is burdened with nearly 200,000 hospitalizations due to the disease per year and approximately 5 deaths per day. The purpose of this article was to analyze the current issues surrounding severe asthma in Brazil, as the status of diagnosis and treatment is largely unknown, and to provide feasible recommendations to elicit imminent action. A panel of Brazilian medical experts in the field of severe asthma was provided with a series of relevant questions to address prior to a multi-day conference. Within this conference, each narrative was discussed and edited by the entire group. Through numerous rounds of discussion consensus was achieved. In order to overcome barriers to adequate asthma treatment, this panel recommends specific initiatives that can be implemented in the short-term to decrease the burden of severe asthma in Brazil. With increasing healthcare costs and limited resources globally, there is an opportunity to implement these recommendations in other countries in order to achieve adequate asthma care. Severe asthma is a heterogeneous and complex disease with various phenotypes that requires strict attention for diagnosis and management. Although this disease affects only a small proportion of the population with asthma, it poses a great burden to healthcare systems. Thus, barriers to diagnosis, treatment, and management should be overcome as quickly and efficiently as possible.

Objective: To compare quantitative CT parameters between children with severe asthma and healthy subjects, correlating to their clinical features., Methods: We retrospectively analyzed CT data from 19 school-aged children (5-17 years) with severe asthma and 19 control school-aged children with pectus excavatum. The following CT parameters were evaluated: total lung volume (TLV), mean lung density (MLD), CT air trapping index (AT%) (attenuation ≤856 HU), airway wall thickness (AWT), and percentage of airway wall thickness (AWT%). Multi-detector computed tomography (MDCT) data were correlated to the following clinical parameters: forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), forced expiratory flow at 25-75% (FEF 25-75%), FEV1/FVC ratio, sputum and bronchoalveolar lavage analysis, serum IgE levels, and previous hospitalizations due to asthma., Results: Asthma patients presented higher mean values of AT% (23.8 ± 6.7% vs. controls, 9.7 ± 3.2%), AWT (1.46 ± 0.22 mm vs. controls, 0.47 ± -735 ± 28 HU vs. controls, -666 ± 19 HU). Mean AT% was 29.0 ± 4.7% in subjects with previous hospitalization against 19.2 ± 5.0% in those with no prior hospitalization (p < 0.001). AT% presented very strong negative correlations with FVC (r = -0.933, p < 0.001) and FEV1 (r = -0.841, p < 0.001) and a moderate correlation with FEF 25-75% (r = -0.608, p = 0.007). AT% correlation with FEV1/FVC ratio and serum IgE was weak (r = -0.184, p = 0.452, and r = -0.363, p = 0.202) CONCLUSION: Children with severe asthma present differences in quantitative chest CT scans compared to healthy controls with strong correlations with pulmonary function tests and previous hospitalizations due to asthma., (Copyright © 2020 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

This study aimed to evaluate the effects of early-life exposure to different extracts of Angiostrongylus cantonensis (A. cantonensis) on airway inflammation in an allergic asthma model. The total soluble extract (TE) and the soluble extracts of the digestive (AcD), reproductive (AcR), and cuticle (AcC) systems of A. cantonensis were used for immunisation before ovalbumin (OVA)-sensitisation/challenge in an OVA-induced allergic asthma model. The initial hypothesis of the study was that some soluble extract of the systems (AcD, AcR, or AcC) could be more potent to the modulation of inflammation than the TE. Our data, however, shows that immunisation with the TE is more promising because it decreased the high influx of inflammatory cells on airways and promoted an increase of interferon-γ (IFN-ɣ) and interleukin-10 (IL-10) levels. Besides this, the immunisation with the TE also led to a reduction of goblet cells and mucus overproduction in the lung tissue of asthmatic mice. We believe that the extracts have a distinct capacity to modulate the immune system, due to the TE possessing a greater variability of molecules, which together leads to control of airway inflammation. In conclusion, this is the first study to reveal that the TE of A. cantonensis adult worms has a greater potential for developing a novel therapeutic for allergic asthma.

Objective: This study aims to describe the clinical characteristics and predictors of mechanical ventilation of adult inpatients with COVID-19 in a single center., Methods: A retrospective cohort study was performed and included adult inpatients hospitalized from March 17th to May 3rd, 2020, who were diagnosed with SARS-CoV-2 infection. Clinical and demographic characteristics were extracted from electronic medical records., Results: Overall, 88 consecutive patients were included in this study. The median age of the patients was 63 years (IQR 49 - 71); 59 (67%) were male, 65 (86%) had a college degree and 67 (76%) had at least one comorbidity. Twenty-nine (33%) patients were admitted to the intensive care unit, 18 (20%) patients needed mechanical ventilation, and 9 (10.2%) died during hospitalization. The median length of stay in the intensive care unit and the median duration of mechanical ventilation was 23 and 29.5 days, respectively. An age ≥ 65 years was an independent risk factor for mechanical ventilation (OR 8.4 95%CI 1.3 - 55.6 p = 0.02)., Conclusion: Our findings describe the first wave of Brazilian patients hospitalized for COVID-19. Age was the strongest predictor of respiratory insufficiency and the need for mechanical ventilation in our population.

During chronic inflammatory disease, such asthma, leukocytes can invade the central nervous system (CNS) and together with CNS-resident cells, generate excessive reactive oxygen species (ROS) production as well as disbalance in the antioxidant system, causing oxidative stress, which contributes a large part to neuroinflammation. In this sense, the aim of this study is to investigate the effects of treatment with neostigmine, known for the ability to control lung inflammation, on oxidative stress in the cerebral cortex of asthmatic mice. Female BALB/cJ mice were submitted to asthma model induced by ovalbumin (OVA). Control group received only Dulbecco's phosphate-buffered saline (DPBS). To evaluate neostigmine effects, mice received 80 μg/kg of neostigmine intraperitoneally 30 min after each OVA challenge. Our results revealed for the first time that treatment with neostigmine (an acetylcholinesterase inhibitor that no crosses the BBB) was able to revert ROS production and change anti-oxidant enzyme catalase in the cerebral cortex in asthmatic mice. These results support the communication between the peripheral immune system and the CNS and suggest that acetylcholinesterase inhibitors, such as neostigmine, should be further studied as possible therapeutic strategies for neuroprotection in asthma.

Objective: To evaluate the health-related quality of life (HRQoL) of children/adolescents with asthma and that of their caregivers, comparing the two., Methods: This was a systematic review and meta-analysis based on the criteria of Preferred Reporting Items for Systematic Reviews and Meta-Analyses, with a strategy of searching five health-related databases (MEDLINE/PubMed, EMBASE, ScienceDirect, SciELO, and LILACS). We included studies that evaluated the HRQoL of children/adolescents with asthma and that of their caregivers with the Pediatric Asthma Quality of Life Questionnaire and the Pediatric Asthma Caregiver's Quality of Life Questionnaire, respectively, using the total scores and the scores on the domains activity limitation, symptoms (children/adolescents only), and emotional function., Results: We identified 291 articles, and we evaluated 133 of those. A total of 33 articles, collectively including 4,101 subjects, were included in the meta-analysis. An analysis stratified by study design showed no differences between the HRQoL of the caregivers and that of the children/adolescents in the activity limitation domain and in the total score. However, the mean emotional function domain scores were significantly higher (better) among children/adolescents with asthma than among their caregivers in longitudinal studies-Δ = 0.82 (0.21-1.44)-and randomized clinical trials-Δ = 0.52 (0.29-0.79)-although not in cross-sectional studies-Δ = -0.20 (-0.03 to 0.43)., Conclusions: The total HRQoL scores proved to be similar between children/adolescents with asthma and their caregivers. However, the two groups differed in their perception of their emotional function, the caregivers scoring significantly lower than the children/adolescents in that domain.

Objective: To generate reference values for spirometry in Brazilian children 3-12 years of age and to compare those values with the values employed in the equations currently in use in Brazil., Methods: This study involved healthy children, 3-12 years of age, recruited from 14 centers (primary data) and spirometry results from children with the same characteristics in six databases (secondary data). Reference equations by quantile regressions were generated after log transformation of the spirometric and anthropometric data. Skin color was classified as self-reported by the participants. To determine the suitability of the results obtained, they were compared with those predicted by the equations currently in use in Brazil., Results: We included 1,990 individuals from a total of 21 primary and secondary data sources. Of those, 1,059 (53%) were female. Equations for FEV1, FVC, the FEV1/FVC ratio, FEF between 25% and 75% of the FVC (FEF25-75%) and the FEF25-75%/FVC ratio were generated for white-, black-, and brown-skinned children. The logarithms for height and age, together with skin color, were the best predictors of FEV1 and FVC. The reference values obtained were significantly higher than those employed in the equations currently in use in Brazil, for predicted values, as well as for the lower limit of normality, particularly in children with self-reported black or brown skin., Conclusions: New spirometric equations were generated for Brazilian children 3-12 years of age, in the three skin-color categories defined. The equations currently in use in Brazil seem to underestimate the lung function of Brazilian children 3-12 years of age and should be replaced by the equations proposed in this study.

Objective: A significant proportion of the infants developed recurrent wheezing after an acute bronchiolitis (AB) event. Recent studies have demonstrated protection for recurrent wheeze and lower respiratory morbidity in infants treated with azithromycin during an acute respiratory wheezing. The aim of the present study was to test the hypothesis that administration of azithromycin during an AB event reduces subsequent wheezing and hospital re-admissions., Methods: This is a secondary analysis of a randomized, double-blinded, placebo-controlled trial, including unpublished data of wheezing and hospitalizations during the initial 6 months following admission for acute viral bronchiolitis. The study was performed in a tertiary University hospital. Infants (<12 months of age) hospitalized with AB were randomized to receive either azithromycin or placebo, administered orally, for 7 days. Families were contacted by telephone at 3 and 6 months after the initial acute event and answered to a standardized questionnaire in order to identify recurrent wheezing and hospital readmissions., Results: One hundred and four patients were included (Azithromycin group, n= 50; placebo group, n=54). Considering the total of patients contacted 3 months after hospitalization (n=70), the recurrence rate of wheezing in the azithromycin group was significantly lower than in the placebo group (RR = 0.48; CI = 0.24-0.98; p = 0.038)., Conclusion: Azithromycin significantly reduces the risk of subsequent wheezing between 0 and 3 months after hospital admission due to acute bronchiolitis irrespective of the presence of respiratory syncytial virus.

The pharmacological management of asthma has changed considerably in recent decades, as it has come to be understood that it is a complex, heterogeneous disease with different phenotypes and endotypes. It is now clear that the goal of asthma treatment should be to achieve and maintain control of the disease, as well as to minimize the risks (of exacerbations, disease instability, accelerated loss of lung function, and adverse treatment effects). That requires an approach that is personalized in terms of the pharmacological treatment, patient education, written action plan, training in correct inhaler use, and review of the inhaler technique at each office visit. A panel of 22 pulmonologists was invited to perform a critical review of recent evidence of pharmacological treatment of asthma and to prepare this set of recommendations, a treatment guide tailored to use in Brazil. The topics or questions related to the most significant changes in concepts, and consequently in the management of asthma in clinical practice, were chosen by a panel of experts. To formulate these recommendations, we asked each expert to perform a critical review of a topic or to respond to a question, on the basis of evidence in the literature. In a second phase, three experts discussed and structured all texts submitted by the others. That was followed by a third phase, in which all of the experts reviewed and discussed each recommendation. These recommendations, which are intended for physicians involved in the treatment of asthma, apply to asthma patients of all ages.

Objective: To compare the frequency of respiratory tract infections in children treated with OM-85 BV and placebo during the 3-month therapy period, and observation for a further 3 months after treatment., Methods: A randomized, double-blind, placebo-controlled trial was conducted with 54 children (6 months to 5 years old) with no past history of recurrent respiratory infections attending daycare center. Family members were instructed to administer one capsule per day for 10 consecutive days, for 3 months of OM-85 BV or placebo. Telephone interviews were conducted every 30 days., Results: There was no significant difference in the number of respiratory infections between the groups. The mean number of respiratory tract infection in the OM-85 BV Group in the first 3 months was 0.92±0.87, and in the Placebo Group was 0.74±1.02, and at 6 months it was 1.62±1.47 and 1.03±1.34, respectively., Conclusion: OM-85 BV was not effective in the primary prevention of respiratory tract infections. Although most authors recommend the use of this immunostimulant in children with a history of recurrent respiratory infections, more studies are needed to define its usefulness in the primary prevention of respiratory infections in healthy children exposed to few risk factors.

Asthma is characterized by the influx of inflammatory cells, especially of eosinophils as well as reactive oxygen species (ROS) production, driven by the release of the T helper 2 (Th2)-cell-associated cytokines. The cholinergic anti-inflammatory pathway (CAP) inhibit cytokines production and controls inflammation. Thus, we investigated the effects of pharmacological activation of CAP by neostigmine on oxidative stress and airway inflammation in an allergic asthma model. After the OVA challenge, mice were treated with neostigmine. We showed that CAP activation by neostigmine reduced the levels of pro-inflammatory cytokines (IL-4, IL-5, IL-13, IL-1β, and TNF-α), which resulted in a decrease of eosinophils influx. Furthermore, neostigmine also conferred airway protection against oxidative stress, attenuating ROS production through the increase of antioxidant defense, evidenced by the catalase (CAT) activity. We propose, for the first time, that pharmacological activation of the CAP can lead to new possibilities in the therapeutic management of allergic asthma., (© 2019 Wiley Periodicals, Inc.)

Introduction: Pertussis is an important public health problem worldwide, especially in infants. An increase in the incidence in many countries occurred after 2010, including Brazil. In 2013, dTpa vaccine was introduced in the Brazil national immunization schedule of pregnant women. The objective of this study was to evaluate the national trends in the incidence of pertussis in Brazil in children under 1 year old, and the impact of the introduction of dTpa vaccine during pregnancy., Methods: The incidence of hospitalizations and non-hospitalized confirmed cases of pertussis in neonates (< 1 month age) and young infants (1 month-< 1 year age) were analyzed, comparing the incidence in pre maternal vaccination (2011-2013) with the post-vaccination (2015-2017). We used non-respiratory hospitalizations as comparison, during the same period. A database of the Brazilian Ministry of Health (DATASUS) was used to analyze cases from 2007 to 2017 and the subsets of 2011-2013 and 2015-2017, after Pertussis resurgence. The vaccination data was accessed through the link of the Information System of the National Immunization Program (pni.datasus.gov.br)., Results: Between 2007 and 2017, 17,818 children under one year of age were hospitalized due to pertussis in Brazil. In the pre maternal vaccination period 2011-2013, the mean annual incidence of non-hospitalized confirmed cases of pertussis in children under 1 month was 722.2 / 100,000 and in the period of 2015-2017 the average was 377.3 / 100,000, representing a decrease of 47.7% [IRR 0.52 (0.46-0.59)]. At those periods of time, the average incidence per year for children of one month-< 1 year aged was 64.9 / 100,000 (2011-2013) and 29.3 / 100,000 (2015-2017) [IRR 0.45 (CI 0.29-0.69)]., Conclusion: Vaccination of pregnant woman coincides with the reduction in the number of cases of pertussis in children under 1 month of age from 2015. Immunization of pregnant woman seems to have an important impact on the prevention of the disease in young infants who have not yet received their own pertussis vaccine., Competing Interests: The authors have declared that no competing interests exist.

Objective: To evaluate the impact of pediatric asthma on patients of a specialized outpatient clinic in Southern Brazil., Methods: The study included children aged 8 to 17 years old with asthma diagnosis (mild, moderate and severe) under treatment at the asthma clinic of Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Brazil. Measurements of spirometry, quality of life, disease control and atopy tests were applied., Results: A total of 66 children were included in the study and divided into groups, according to the severity of the disease: mild, moderate or severe asthma. The results showed similarities in both the treatment and the impact of asthma between groups, except for adherence to treatment: the group with mild asthma showed least adherence to treatment, and the group with severe asthma, greater adherence (p=0.011). As to school absenteeism, the group with severe asthma showed higher frequency (p=0.012), with over 10 days per year (p=0.043). Spirometry showed lower volume/capacity for the group with moderate asthma, followed by the groups with severe and mild asthma. All groups had a high prevalence of allergic asthma, with mites as the main allergens. For quality of life (QOL), and health-related quality of life (HRQOL) levels, there were no differences between groups. In addition, the values were close to the acceptable levels for the total score and for each one of the six domains. The same occurred for the HRQOL-asthma module., Conclusions: QOL and HRQOL present acceptable levels regardless of the severity of the disease.

Studies have shown autophagy participation in the immunopathology of inflammatory diseases. However, autophagy role in asthma and in eosinophil extracellular traps (EETs) release is poorly understood. Here, we attempted to investigate the autophagy involvement in EETs release and in lung inflammation in an experimental asthma model. Mice were sensitized with ovalbumin (OVA), followed by OVA challenge. Before the challenge with OVA, mice were treated with an autophagy inhibitor, 3-methyladenine (3-MA). We showed that 3-MA treatment decreases the number of eosinophils, eosinophil peroxidase (EPO) activity, goblet cells hyperplasia, proinflammatory cytokines, and nuclear factor kappa B (NFκB) p65 immunocontent in the lung. Moreover, 3-MA was able to improve oxidative stress, mitochondrial energy metabolism, and Na + , K + -ATPase activity. We demonstrated that treatment with autophagy inhibitor 3-MA reduced EETs formation in the airway. On the basis of our results, 3-MA treatment can be an interesting alternative for reducing lung inflammation, oxidative stress, mitochondrial damage, and EETs formation in asthma., (© 2019 Wiley Periodicals, Inc.)

Objective: To investigate the effect of levels of physical activity on asthma control in children., Methods: A cross-sectional study, including public school students aged 8 to 12 years, of both sexes, with asthma, from a capital and a medium-sized cities in Southern Brazil. At home, the students answered the questionnaire on levels of physical activity and disease control., Results: A total of 482 schoolchildren with asthma participated in the study, with mean age of 10.9±2.2 years, and 253 (52%) were girls. Regarding disease control, 50% had controlled asthma, and 67% were considered sedentary. Schoolchildren with controlled asthma were more active than those with uncontrolled asthma (p=0.032). Active schoolchildren were more likely to have asthma controlled (OR=1.5; 95%CI: 1.04-2.25)., Conclusion: The results demonstrated an association between physical activity levels and asthma control. More active schoolchildren were more likely to have asthma controlled.

Background: Respiratory viral infections are the leading cause of asthma exacerbations. Eosinophil activation results in the formation of eosinophil extracellular traps (EETs), which release web-like structures of DNA and proteins that bind, disarm and extracellularly kill pathogens., Objective: We investigated whether the respiratory syncytial virus (RSV) in vitro could induce EETs in bronchoalveolar lavage fluid eosinophils in a murine model of asthma., Methods: BALB/cJ mice (6-8 weeks old) were sensitized with 2 subcutaneous injections of ovalbumin (20 μg) on days 0 and 7, followed by three intranasal challenges with ovalbumin (100 μg) on days 14, 15, and 16 of the protocol. The control group received Dulbecco's phosphate-buffered saline. Bronchoalveolar lavage fluid eosinophils of ovalbumin group or control group were stimulated with RSV (10 3 PFU/mL) in vitro for 3 hours. After that, culture supernatant was collected to perform the analyses proposed in this study., Results: We verified an increase in extracellular DNA concentration in bronchoalveolar lavage fluid eosinophils from ovalbumin group stimulated with RSV (10 3 PFU/mL) in vitro , which was confirmed by confocal microscopy. We demonstrated that most cells are negative for annexin V and propidium iodide in all groups evaluated. Also, RSV in vitro decreased interferon-ɣ in culture supernatant when compared to the ovalbumin group., Conclusion: In this study, we demonstrated for the first time that RSV in vitro induces EETs formation in eosinophils from asthmatic mice., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2019. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.)

Introduction: Several tests may be used to assess exercise intolerance in severe therapy-resistant asthma (STRA), including the gold standard cardiopulmonary exercise test (CPET) and the modified shuttle test (MST)., Objective: To correlate the distance achieved in the MST with peak oxygen uptake (VO 2 peak) and to compare the maximal heart rate (HRmax) obtained in both tests in children and adolescents with STRA., Methods: This is a cross-sectional study, with 19 children and adolescents with STRA. Demographic, anthropometric, clinical data, and spirometric values were collected. CPET and the MST were performed in two consecutive visits. HRmax, pulse oxygen saturation, and dyspnea were compared between tests. The distance achieved in the MST was correlated with VO 2 peak., Results: Nineteen patients with a mean age of 11.5 ± 2.5 years were included. The mean HRmax (bpm) achieved was 180.8 ± 12.10 for the MST and 187.6 ± 9.35 for CPET, whereas the mean HRmax as a percentage of predicted (HRmax%) was 90.7 ± 6.5 for the MST and 93.8 ± 4.5 for CPET. A difference of only 6 bpm was found for HRmax ( p = 0.10) and of 3% for HRmax% ( p = 0.06) between tests. A strong correlation was found between the MST ( r = 0.79; p = 0.001) and VO 2 peak measured through CPET. However, there were no correlations between the MST and both body mass index ( r = -0.14; p = 0.564) and forced expiratory volume in the first second - FEV 1 ( r = -0.02; p = 0.917)., Conclusion: The results demonstrate that the MST distance strongly correlates with VO 2 peak, measured through CPET, and the main physiological variable responses were similar between both tests. Our results provide additional data for the use of the MST to assess exercise capacity in children and adolescents with STRA., (Copyright © 2019 Schiwe, Heinzmann-Filho, Schindel, Gheller, Campos, Pitrez and Donadio.)