An antibacterial, multifunctional nanogel for efficient treatment of neutrophilic asthma.

Asthma is a chronic and heterogeneous disease affecting the lungs and respiratory tract. In particular, the neutrophil subtype of asthma was described as persistent, more severe, and corticosteroid-resistant. Growing evidence suggested that nontypeable Haemophilus influenzae (NTHi) infection contributes to the development of neutrophilic asthma, exacerbating clinical symptoms and increasing the associated medical burden. In this work, arginine-grafted chitosan (CS-Arg) was ionically cross-linked with tris(2-carboxyethyl) phosphine (TCEP), and a highly-efficient antimicrobial agent, poly-ε-L-Lysine (ε-PLL), was incorporated to prepare ε-PLL/CS-Arg/TCEP (ECAT) composite nanogels. The results showed that ECAT nanogels exhibited highly effective inhibition against the proliferation of NTHi, Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). In addition, ECAT nanogels could effectively inhibit the formation of mucins aggregates in vitro, suggesting that the nanogel might have the potential to destroy mucin in respiratory disease. Furthermore, in the ovalbumin (OVA)/NTHi-induced Balb/c mice model of neutrophilic asthma, the number of neutrophils in the alveolar lavage fluid and the percentage of inflammatory cells in the blood were effectively reduced by exposure to tower nebulized administration of ECAT nanogels, and reversing airway hyperresponsiveness (AHR) and reducing inflammation in neutrophilic asthma mice. In conclusion, the construction of ECAT nanogels was a feasible anti-infective and anti-inflammatory therapeutic strategy, which demonstrated strong potential in the clinical treatment of neutrophilic asthma.

Impact of obesity in asthma: Possible future therapies.

Obesity is one of the factors associated with the severity of asthma. Obesity is associated with aggravation of the pathophysiology of asthma, including exacerbations, airway inflammation, decreased pulmonary function, and airway hyperresponsiveness. The present review addresses the characteristics of asthma with obesity, focusing especially on the heterogeneity caused by the degree of type 2 inflammation, sex differences, the onset of asthma, and race differences. To understand the severity mechanisms in asthma and obesity, such as corticosteroid resistance, fatty acids, gut microbiome, and cytokines, several basic research studies are evaluated. Finally, possible future therapies, including weight reduction, microbiome-targeted therapies, and other molecular targeted therapies are addressed. We believe that the present review will contribute to better understanding of the severity mechanisms and the establishment of novel treatments for severe asthma patients with obesity.

Severe pediatric asthma therapy: Dupilumab.

Severe asthma is a rare disease affecting <5% of children with asthma. This group of patients account for about 50% of the costs of healthcare for children with asthma. Nowadays, several biological agents are available for pediatric severe asthma. One of these is dupilumab, a monoclonal antibody against the Interleukin (IL)-4 receptor α-subunit that acts as an antagonist against both IL-4 and IL-13. Dupilumab binds the subunit of the IL-4 receptor, at the level of the subunit shared by the IL-13 receptor, blocking the inflammatory cascade of these two cytokines and the progression of the Th2-inflammatory pathway. The efficacy and safety of dupilumab have been investigated in recently published randomized controlled trials including pediatric patients with asthma. Currently, its use in asthma is approved in adults, adolescents, and children with severe asthma with type 2 inflammation, that are not controlled in spite of high-dose inhaled corticosteroids plus another maintenance drug. Studies are warranted for the evaluation of long-term treatment with dupilumab, including steroid sparing effect and discontinuation of treatment. Further research should also be planned in order to investigate dupilumab potential ability to interfere with the natural history of atopy since early childhood.

Efficacy of a loading dose of IV salbutamol in children with severe acute asthma admitted to a PICU: a randomized controlled trial.

The optimal dose regimen for intravenous (IV) treatment in children with severe acute asthma (SAA) is still a matter of debate. We assessed the efficacy of adding a salbutamol loading dose to continuous infusion with salbutamol in children admitted to a pediatric intensive care unit (PICU) with SAA. This multicentre, placebo-controlled randomized trial in the PICUs of four tertiary care children's hospitals included children (2-18 years) with SAA admitted between 2017 and 2019. Children were randomized to receive either a loading dose IV salbutamol (15 mcg/kg, max. 750 mcg) or normal saline while on continuous salbutamol infusion. The primary outcome was the asthma score (Qureshi) 1 h after the intervention. Analysis of covariance models was used to evaluate sensitivity to change in asthma scores. Serum concentrations of salbutamol were obtained. Fifty-eight children were included (29 in the intervention group). Median baseline asthma score was 12 (IQR 10-13) in the intervention group and 11 (9-12) in the control group (p = 0.032). The asthma score 1 h after the intervention did not differ significantly between the groups (p = 0.508, ß-coefficient = 0.283). The median increase in salbutamol plasma levels 10 min after the intervention was 13 µg/L (IQR 5-24) in the intervention group and 4 µg/L (IQR 0-7) in the control group (p = 0.001). Side effects were comparable between both groups. CONCLUSION: We found no clinical benefit of adding a loading dose IV salbutamol to continuous infusion of salbutamol, in children admitted to the PICU with SAA. Clinically significant side effects from the loading dose were not encountered. WHAT IS KNOWN: • Pediatric asthma guidelines struggle with an evidence-based approach for the treatment of SAA beyond the initial steps of oxygen suppletion, repetitive administration of inhaled ß2-agonists, and systemic steroids. • During an SAA episode, effective delivery of inhaled drugs is unpredictable due to severe airway obstruction. WHAT IS NEW: • This study found no beneficial effect of an additional loading dose IV salbutamol in children admitted to the PICU. • This study found no clinically significant side effects from the loading dose.

School-supervised Asthma Therapy is Associated with Improved Long-Term Asthma Outcomes for Underrepresented Minority Children.

Asthma morbidity disproportionately impacts children from low-income and racial/ethnic minority communities. School-supervised asthma therapy improves asthma outcomes for up to 15 months for underrepresented minority children, but little is known about whether these benefits are sustained over time. We examined the frequency of emergency department (ED) visits and hospital admissions for 83 children enrolled in Asthma Link, a school nurse-supervised asthma therapy program serving predominantly underrepresented minority children. We compared outcomes between the year preceding enrollment and years one-four post-enrollment. Compared with the year prior to enrollment, asthma-related ED visits decreased by 67.9% at one year, 59.5% at two years, 70.2% at three years, and 50% at four years post-enrollment (all p-values< 0.005). There were also significant declines in mean numbers of total ED visits, asthma-related hospital admissions, and total hospital admissions. Our results indicate that school nurse-supervised asthma therapy could potentially mitigate racial/ethnic and socioeconomic inequities in childhood asthma.

Impact of Therapeutics on Unified Immunity During Allergic Asthma and Respiratory Infections.

Asthma is a common chronic respiratory disease that affects millions of people worldwide. Patients with allergic asthma, the most prevalent asthma endotype, are widely considered to possess a defective immune response against some respiratory infectious agents, including viruses, bacteria and fungi. Furthermore, respiratory pathogens are associated with asthma development and exacerbations. However, growing data suggest that the immune milieu in allergic asthma may be beneficial during certain respiratory infections. Immunomodulatory asthma treatments, although beneficial, should then be carefully prescribed to avoid misuse and overuse as they can also alter the host microbiome. In this review, we summarize and discuss recent evidence of the correlations between allergic asthma and the most significant respiratory infectious agents that have a role in asthma pathogenesis. We also discuss the implications of current asthma therapeutics beyond symptom prevention.

Quality improvement project to increase screening and referral for biologic therapy for patients with uncontrolled asthma.

BACKGROUND: Asthma is a treatable chronic disease of airway inflammation with varying levels of control and severity. Biological therapy is an effective evidence-based treatment for patients with allergic and eosinophilic phenotypes of asthma who are classified as poorly controlled moderate to severe asthma. Yet, evidence-based treatments are infrequently used to support effective care of poorly controlled moderate and severe asthma. This quality improvement (QI) project aimed to increase the number of patients with uncontrolled moderate to severe asthma at an outpatient asthma center who are screened and referred for biologic therapy when appropriate. METHODS: A guideline-based biologic screening protocol was implemented using plan-do-study-act (PDSA) methodology allowing for a systematic approach for implementation, monitoring and making adjustments. A pre- and post-independent groups comparative design was utilized to evaluate screening and referral data. RESULTS: Screening improved significantly from pre- (n = 30, 23.8%) to post-implementation (n = 17, 70.8%), p < 0.001; phi = .372. Referrals to biologics also improved from 42.4% (n = 28) to 93.3% (n = 14), p < 0.001; phi = .396. Providers reported increased knowledge, confidence, and satisfaction with the asthma screening protocol at post-implementation. CONCLUSIONS: The implementation of an asthma screening protocol for asthma patients in an ambulatory center is an effective way of increasing screening for eligibility for biologic therapy. Adhering to the standard of care based on evidence-based guidelines increased access to biologic therapy with a higher percentage of patients being referred for therapy.

The West Philadelphia asthma care implementation study (NHLBI# U01HL138687).

Asthma is the most common chronic condition among children, with low-income families living in urban areas experiencing significantly higher rates. Evidence based interventions for asthma are routinely implemented in either the home, school, or primary care setting. However, even when caregivers of poor children are engaged in asthma interventions in one setting, they often have to navigate challenges in another setting, such as an under-resourced home, non-supportive school, or disengaged health care provider. The West Philadelphia Asthma Care Implementation Plan aims to compare the effectiveness of a primary care-based intervention, school-based intervention, and combined primary care and school intervention to usual care for improving asthma control in school-age children to explore if the synergistic effect of Community Health Worker (CHW) support in the home, school, and health care environments will result in improved asthma control. Children ages 5-13 with uncontrolled asthma from four West Philadelphia recruitment sites will be eligible for enrollment. The families of school age children interested in participating will be randomized to receive a primary care CHW or usual care. Those identified as attending a participating school will have a CHW-led school intervention or usual care in school. If proven effective, this care coordination program will assist caregivers in assessing resources, improving self-management skills, and ultimately reducing asthma-related ED visits and hospitalizations as well as provide additional information for healthcare systems and policy makers to inform their decisions about how and where to focus additional resources and investments in childhood asthma care to improve health outcomes.

Nontuberculous Mycobacteria Prevalence in Aerosol and Spiders' Webs in Karst Caves: Low Risk for Speleotherapy.

A total of 152 aerosol and spider web samples were collected: 96 spider's webs in karst areas in 4 European countries (Czech Republic, France, Italy, and Slovakia), specifically from the surface environment (n = 44), photic zones of caves (n = 26), and inside (aphotic zones) of caves (n = 26), 56 Particulate Matter (PM) samples from the Sloupsko-Sosuvsky Cave System (speleotherapy facility; n = 21) and from aerosol collected from the nearby city of Brno (n = 35) in the Czech Republic. Nontuberculous mycobacteria (NTM) were isolated from 13 (13.5%) spider's webs: 5 isolates of saprophytic NTM (Mycobacterium gordonae, M. kumamotonense, M. terrae, and M. terrae complex) and 6 isolates of potentially pathogenic NTM (M. avium ssp. hominissuis, M. fortuitum, M. intracellulare, M. peregrinum and M. triplex). NTM were not isolated from PM collected from cave with the speleotherapy facility although mycobacterial DNA was detected in 8 (14.3%) samples. Temperature (8.2 °C, range 8.0-8.4 °C) and relative humidity (94.7%, range 93.6-96.6%) of air in this cave were relatively constant. The average PM2.5 and PM10 mass concentration was 5.49 µg m-3 and 11.1 µg m-3. Analysed anions (i.e., F-, Cl-, NO2-, SO42-, PO43- and NO3-) originating largely from the burning of wood and coal for residential heating in nearby villages in the surrounding area. The air in the caves with speleotherapy facilities should be monitored with respect to NTM, PM and anions to ensure a safe environment.

Patient and Physician Perspectives on Asthma and Its Therapy in Romania: Results of a Multicenter Survey.

Background and Objectives: Patient's behaviours, attitudes and beliefs related to asthma and its treatment were shown to influence the adherence to therapy and the level of asthma control. This survey aimed to assess the level of asthma control and patient-reported behaviours, attitudes and expectations related to their disease in Romanian patients. Materials and Methods: This cross-sectional quantitative survey was performed in February-March 2019 and enrolled 70 specialist physicians experienced in asthma management and 433 asthma patients under their care. Results: Of the 433 patients enrolled, 19.4% had mild asthma, 60.5% moderate asthma and 20.1% severe asthma. For the previous 12 months, asthma symptoms, exacerbations and emergency room visits were common in the sample analysed, with significantly higher figures in severe asthma patients (p < 0.001). The most important treatment goal for asthma patients was participation in all activities of daily living, while for physicians this was preventing asthma exacerbations. The valuation of the treatment goals was different between patients with severe asthma and those with mild and moderate forms. Based on the patients' responses, 3 attitude clusters were identified: empowered savvy (36.5% of the patients), pessimistic non-compliers (43.2%), and anxious strugglers (20.3%). "Empowered savvy" had the lowest frequency of severe asthma, the highest adherence to maintenance therapy and the highest level of confidence in the effectiveness of asthma medication. The opposite of this attitude cluster is the "anxious strugglers", containing more patients with severe asthma, a higher score for worries about asthma therapy and better self-reported knowledge of their treatment, contrasting with a proportion of 25% taking maintenance therapy only when having breathing difficulties. Conclusion: Asthma control in Romania remains poor, with frequent exacerbations and hospitalizations. The differences in treatment goals found between patients and physicians and between different asthma severity groups suggest the need for more patient-centred approaches.

The Changes in Expression of NaV1.7 and NaV1.8 and the Effects of the Inhalation of Their Blockers in Healthy and Ovalbumin-Sensitized Guinea Pig Airways.

BACKGROUND: The presented study evaluated the suppositional changes in the airway expression of Nav1.8 and Nav1.7 and their role in the airway defense mechanisms in healthy animals and in an experimental asthma model. METHODS: The effects of the blockers inhalation on the reactivity of guinea pig airways, number of citric-acid-induced coughs and ciliary beating frequency (CBF) were tested in vivo. Chronic inflammation simulating asthma was induced by repetitive exposure to ovalbumin. The expression of Nav1.7 and Nav1.8 was examined by ELISA. RESULTS: The Nav 1.8 blocker showed complex antitussive and bronchodilatory effects and significantly regulated the CBF in healthy and sensitized animals. The Nav1.7 blockers significantly inhibited coughing and participated in CBF control in the ovalbumin-sensitized animals. The increased expression of the respective ion channels in the sensitized animals corresponded to changes in CBF regulation. The therapeutic potency of the Nav1.8 blocker was evidenced in combinations with classic bronchodilators. CONCLUSION: The allergic-inflammation-upregulated expression of Nav1.7 and Nav1.8 and corresponding effects of blocker inhalation on airway defense mechanisms, along with the Nav1.8 blocker's compatibility with classic antiasthmatic drugs, bring novel possibilities for the treatment of various respiratory diseases. However, the influence of the Nav1.8 blocker on CBF requires further investigation.

Identifying patients at risk of poor asthma outcomes associated with making inhaler technique errors.

OBJECTIVES: Correct inhaler technique is essential to optimal clinical outcomes in asthma patients. The study aim was to use real-life data from the iHARP database to determine patient factors associated with the performance of inhaler technique errors associated with poor asthma outcomes (as identified in the Critikal study) in patients with asthma prescribed the Turbuhaler (TH), Metered Dose Inhaler (MDI), and Accuhaler (AH) device. METHODS: This was a retrospective cross-sectional study using the iHARP database, a multinational initiative including questionnaires and technique review. Identification of inhaler technique errors specifically associated with poor asthma outcomes was performed by reference to the Critikal study. Multivariable logistic regression was used to identify demographic and clinical factors associated with ≥ 1 of these errors. RESULTS: Factors significantly associated with ≥ 1 inhaler technique error and worsening asthma outcomes for the TH cohort include female gender, very poor to average self-assessment of inhaler technique; for the MDI cohort, female gender, secondary education, and current smoking status; and, in the AH cohort, lack of inhaler technique review by a trained healthcare professional in the previous twelve months and very poor to average self-assessment of inhaler technique. CONCLUSIONS: Numerous specific patient demographic and clinical factors associated with the performance of these errors have been identified, differing according to device. Inhaler technique error associated with poor asthma outcomes is further widespread across devices. Knowledge of these factors and the frequency of their occurence may assist in optimizing device selection and training.

Outcomes from a pilot patient-centered hospital-to-home transition program for children hospitalized with asthma.

OBJECTIVE: To evaluate a multi-component hospital-to-home (H2H) transition program for children hospitalized with an asthma exacerbation. METHODS: A pilot prospective randomized clinical trial of guideline-based asthma care with and without a patient-centered multi-component H2H program among children enrolled in K-8th grade on Medicaid hospitalized for an asthma exacerbation. H2H program includes 5 components: medications in-hand at discharge, school-based asthma therapy (SBAT) for controller medications, referral for home trigger assessments, communication with the primary care provider (PCP), and patient navigator support. Primary outcomes included feasibility and acceptability. Secondary outcomes included healthcare utilization, asthma morbidity, and caregiver quality of life. RESULTS: A total of 32 children were enrolled and randomized. Feasibility outcomes in the intervention group included: medications in-hand at discharge (100%); SBAT for controller medication initiated (100%); home visit referrals made (100%) and home visits completed within 4 weeks of discharge (44%); PCP communication (100%); patient navigator communication at 3 days (81.3%) and 14 days (46.7%). Acceptability outcomes in the intervention group included: 87.5% of families continued SBAT, and 87.5% of families reported it was extremely helpful to have the home visit referral. Adjusting for baseline differences in age, asthma severity and control, there was no significant difference in healthcare utilization outcomes. CONCLUSION: These pilot data suggest that comprehensive care coordination initiated during the inpatient stay is feasible and acceptable. A larger trial is justified to determine if the intervention may reduce healthcare utilization for urban, minority children with asthma.

Obesity-associated asthma in childhood.

Obesity and bronchial asthma are very common diseases in children and adolescents, associated with a considerable burden of disease, reduced quality of life and comorbidities. Obesity is a significant risk factor for bronchial asthma. On the one hand, obesity leads to changes in the mechanics and function of the lungs and chest. On the other hand, obesity-associated inflammatory processes with increased production of leptin and cytokines may trigger bronchial inflammation with the appearance of asthmatic symptoms. The diseases are also linked by genetic factors. Physical activity and weight reduction have a significant benefit. Pharmacotherapy must be based on the pattern of inflammation. This article summarizes the current state of the literature on the association of asthma and obesity and presents current and possible future treatment options.

Pharmacotherapeutic strategies for critical asthma syndrome: a look at the state of the art.

INTRODUCTION: 'Critical Asthma Syndrome' (CAS) is an umbrella term proposed to include several forms of asthma, responsible for acute and life-threatening exacerbations. CAS requires urgent and adequate supportive and pharmacological treatments to prevent serious outcomes. AREAS COVERED: The purpose of this review is to discuss current knowledge on the pharmacotherapeutic strategies for treatment of CAS. EXPERT OPINION: Airflow limitation, airway wall edema, and mucus plugs are the pathophysiological targets of pharmacological therapies. Strategies to achieve these goals are based on the use of various classes of drugs. Inhaled beta2-agonists are the mainstay of the initial therapy of CAS. Inhaled anticholinergic agents may be considered in the treatment of CAS in addition to beta 2 agonists. Systemic corticosteroids should be administered as soon as possible in order to counteract airway inflammation and restore normal airway sensitivity. The effectiveness of pharmacological therapies in CAS is linked not only to the timely use of drugsbut also to the dosage and route of administration. Early recognition and aggressive treatment are essential for the management of CAS; however, prevention is the best cure. Although significant progress has been made, further efforts are needed to implement an optimal exacerbation prevention strategy.

Airway epithelial-targeted nanoparticles for asthma therapy.

Asthma is a common chronic inflammatory disease associated with intermittent airflow obstruction caused by airway inflammation, mucus overproduction, and bronchial hyperresponsiveness. Despite current treatment and management options, a large number of patients with asthma still have poorly controlled disease and are susceptible to acute exacerbations, usually caused by a respiratory virus infection. As a result, there remains a need for novel therapies to achieve better control and prevent/treat exacerbations. Nanoparticles (NPs), including extracellular vesicles (EV) and their synthetic counterparts, have been developed for drug delivery in respiratory diseases. In the case of asthma, where airway epithelium dysfunction, including dysregulated differentiation of epithelial cells, impaired barrier, and immune response, is a driver of disease, targeting airway epithelial cells with NPs may offer opportunities to repair or reverse these dysfunctions with therapeutic interventions. EVs possess multiple advantages for airway epithelial targeting, such as their natural intrinsic cell-targeting properties and low immunogenicity. Synthetic NPs can be coated with muco-inert polymers to overcome biological barriers such as mucus and the phagocytic response of immune cells. Targeting ligands could be also added to enhance targeting specificity to epithelial cells. The review presents current understanding and advances in NP-mediated drug delivery to airway epithelium for asthma therapy. Future perspectives in this therapeutic strategy will also be discussed, including the development of novel formulations and physiologically relevant preclinical models.

Androgens are effective bronchodilators with anti-inflammatory properties: A potential alternative for asthma therapy.

Changes in plasma androgen levels in asthmatic men may be linked to asthma severity, seemingly acting through nongenomic and genomic effects. Nongenomic effects include rapid relaxation of carbachol or antigenic challenge pre-contracted guinea pig airway smooth muscle (ASM) in vitro: testosterone (TES) blocks l-type voltage dependent Ca2+ channels, stored operated Ca2+ channels, inositol 1,4,5-trisphosphate receptors and promotes prostaglandin E2 biosynthesis. In ASM at rest, TES lowers basal intracellular Ca2+ concentration and tension, maintaining a proper airway patency keeping steady smooth muscle tension and basal intracellular Ca2+ concentration at rest. Moreover, the bronchospasm in sensitized guinea-pigs was ablated by dehydroepiandrosterone (DHEA), a precursor of steroids, TES and its metabolites 5α- and 5ß-dihydrotestosterone (DHT). On the other hand, genomic effects related to androgens' anti-inflammatory properties in asthma have been recently studied. Briefly, TES negatively regulates type 2 immune response sustained by CD4+ Th2 and group 2 innate lymphoid cells, diminishing allergic airway inflammation in males. Also, novel findings establish that TES decreases interleukin (IL)-17A protein expression produced by CD4+ Th17 cells and therefore neutrophilic airway inflammation. Clearly, DHEA, TES or its 5ß-reduced metabolite that possesses minimal androgenic effect, might have potential therapeutic capacities in the treatment of severe asthma via mechanisms distinct from corticosteroid treatment.

Colony-stimulating factor 1 and its receptor are new potential therapeutic targets for allergic asthma.

BACKGROUND: A new approach targeting aeroallergen sensing in the early events of mucosal immunity could have greater benefit. The CSF1-CSF1R pathway has a critical role in trafficking allergens to regional lymph nodes through activating dendritic cells. Intervention in this pathway could prevent allergen sensitization and subsequent Th2 allergic inflammation. OBJECTIVE: To examine the therapeutic effectiveness of CSF1 and CSF1R inhibition for blocking the dendritic cell function of sensing aeroallergens. METHODS: We adopted a model of chronic asthma induced by a panel of three naturally occurring allergens and novel delivery system of CSF1R inhibitor encapsulated nanoprobe. RESULTS: Selective depletion of CSF1 in airway epithelial cells abolished the production of allergen-reactive IgE, resulting in prevention of new asthma development as well as reversal of established allergic lung inflammation. CDPL-GW nanoprobe containing GW2580, a selective CSF1R inhibitor, showed favorable pharmacokinetics for inhalational treatment and intranasal insufflation delivery of CDPL-GW nanoprobe ameliorated asthma pathologies including allergen-specific serum IgE production, allergic lung and airway inflammation and airway hyper-responsiveness (AHR) with minimal pulmonary adverse reaction. CONCLUSION: The inhibition of the CSF1-CSF1R signaling pathway effectively suppresses sensitization to aeroallergens and consequent allergic lung inflammation in a murine model of chronic asthma. CSF1R inhibition is a promising new target for the treatment of allergic asthma.

2020 Brazilian Thoracic Association recommendations for the management of asthma / Recomendações para o manejo da asma da Sociedade Brasileira de Pneumologia e Tisiologia - 2020

ABSTRACT 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.

RESUMO O manejo farmacológico da asma mudou consideravelmente nas últimas décadas, com base no entendimento de que a asma é uma doença heterogênea e complexa, com diferentes fenótipos e endótipos. Agora está claro que o objetivo do tratamento da asma deve ser alcançar e manter o controle da doença e evitar riscos futuros (exacerbações, instabilidade da doença, perda acelerada da função pulmonar e efeitos adversos do tratamento). Isso implica em uma abordagem personalizada, incluindo tratamento farmacológico, educação do paciente, plano de ação por escrito, treinamento para uso do dispositivo inalatório e revisão da técnica inalatória a cada visita ao consultório. Um painel de 22 pneumologistas brasileiros foi convidado a revisar criticamente evidências recentes de tratamento farmacológico da asma e a preparar esta recomendação, um guia de tratamento adaptado à nossa realidade. A escolha dos tópicos ou questões relacionadas às mudanças mais significativas nos conceitos e, consequentemente, no manejo da asma na prática clínica foi realizada por um painel de especialistas. Foi solicitado a cada especialista que revisasse criticamente um tópico ou respondesse a uma pergunta, com base em evidências, para estas recomendações. Numa segunda fase, três especialistas discutiram e estruturaram todos os textos submetidos pelos demais e, na última fase, todos revisaram e discutiram cada recomendação. As presentes recomendações se aplicam a adultos e crianças com asma e destinam-se a médicos envolvidos no tratamento da doença.