The hybrid protein BTH2 suppresses allergic airway inflammation in a murine model of HDM-specific immunotherapy.

BACKGROUND: Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment approach to change disease-causing allergens. Hypoallergenic derivatives show promise as potential therapeutics, amongst which BTH2 was designed to induce tolerance against Blomia tropicalis allergy. Our aim was to investigate the hypoallergenicity and immunoregulatory activity of BTH2 in vitro and its therapeutic potential in a mouse model of AIT. METHODS: Recombinant Blo t 5 and Blo t 21 allergens and their hybrid derivatives (BTH1 and BTH2) were expressed and purified. IgE binding capacity was tested by ELISA using sera from Brazilian, Colombian, and Ecuadorian subjects. Secretion of cytokines in supernatants from human cell cultures was measured following stimulation with the four recombinants and controls. The capacity of BTH2 to ameliorate allergic airway inflammation induced by B. tropicalis extract was evaluated in a murine model of AIT. RESULTS: rBlo t 5 and rBlo t 21 were identified as major allergens in Latin American patients, and BTH2 had the lowest IgE binding. In vitro stimulation of human cells induced greater levels of IL-10 and IFN-γ and reduced the secretion of Th2 cytokines. BTH2 ameliorated allergic airway inflammation in B. tropicalis-challenged A/J mice, as evidenced by the histopathological and humoral biomarkers: decreased Th2 cytokines and cellular infiltration (especially eosinophils), lower activity of eosinophil peroxidase, an increase in IgG blocking antibodies and strong reduction of mucus production by goblet cells. CONCLUSIONS: Our study shows that BTH2 represents a promising candidate for the treatment of B. tropicalis allergy with hypoallergenic, immune regulatory and therapeutic properties. Further pre-clinical studies are required in murine models of chronic asthma to further address the efficacy and safety of BTH2 as a vaccine against B. tropicalis-induced allergy.

Association between periodontitis and severe asthma in adults: A case-control study.

OBJECTIVE: To evaluate the association between periodontitis and severe asthma, with participants in treatment for severe asthma, controlled by therapy. METHODS: A case-control investigation was performed to compare 130 adults with severe asthma with 130 without asthma. Individuals with periodontitis were those with ≥4 teeth with ≥1 site with probing depth ≥4 mm, clinical attachment level ≥3 mm, and bleeding upon probing at the same site. Severe asthma diagnosis was based on Global Initiative for Asthma criteria. RESULTS: Association between exposure to periodontitis and severe asthma was found: ORcrude  = 2.98 (95% CI: 1.74-5.11). When confounders were considered, the association between exposure to periodontitis and severe asthma was maintained: ORadjusted  = 3.01-3.25. Individuals with periodontitis had about a threefold increased risk of severe asthma than those without periodontitis. Frequency of periodontitis in participants with severe asthma was greater than that of those without asthma (46.6% vs 22.3%, p ≤ .05). CONCLUSIONS: Association between periodontitis and severe asthma was observed. Further investigation is required to determine the direction of this relationship. It may be causal, but it may also be a consequence of the immunopathological process that characterizes asthma, or else, consequence of the medication used for treatment.

Increased risk of allergic rhinitis among children delivered by cesarean section: a cross-sectional study nested in a birth cohort.

BACKGROUND: Few studies have evaluated the association between delivery by cesarean section (CS) and asthma, allergic rhinitis and chronic rhinitis and whether this association is different in children with and without a family history of asthma. This study aims to investigate whether children born by CS have a higher chance to develop asthma, allergic rhinitis and chronic rhinitis and to evaluate the influence of parental history of asthma on these associations. METHODS: This is a cross-sectional study of 672 children nested in a birth cohort evaluated at 6-years of age. Asthma and chronic/allergic rhinitis were identified by means of the mother's responses to the ISAAC questionnaire. The association between CS, asthma, chronic rhinitis and allergic rhinitis was evaluated by multivariable logistic regression. The evidence of effect modification of parental history of asthma on the association CS and outcomes was examined by introducing interactions terms in the logistic regression models adjusting for confounders. RESULTS: Asthma was not associated with birth by CS irrespective of parental history of asthma (odds ratio (OR) 1.03; 95 % CI 0.61-1.74). Chronic rhinitis and allergic rhinitis were both significantly associated with birth by CS but only in the subgroup of children with by parental history of asthma (OR 1.56; 95 % CI 1.04-2.34) and (OR 1.60; 95 % CI 1.01-2.55) respectively, after adjustment for confounders. The parental history of asthma was a effect modifier in the association between CS, chronic rhinitis and allergic rhinitis (p for effect modification = 0.10 and 0.02, respectively). CONCLUSION: CS increases the risk of chronic rhinitis and allergic rhinitis in children at 6 years of age with parental history of asthma. Health professionals must be alerted with regard to the increased risk of allergic rhinitis and made aware this is another reason to avoid unnecessary CS.

Predictive genetic panel for adult asthma using machine learning methods.

Background: Asthma is a chronic inflammatory disease of the airways that is heterogeneous and multifactorial, making its accurate characterization a complex process. Therefore, identifying the genetic variations associated with asthma and discovering the molecular interactions between the omics that confer risk of developing this disease will help us to unravel the biological pathways involved in its pathogenesis. Objective: We sought to develop a predictive genetic panel for asthma using machine learning methods. Methods: We tested 3 variable selection methods: Boruta's algorithm, the top 200 genome-wide association study markers according to their respective P values, and an elastic net regression. Ten different algorithms were chosen for the classification tests. A predictive panel was built on the basis of joint scores between the classification algorithms. Results: Two variable selection methods, Boruta and genome-wide association studies, were statistically similar in terms of the average accuracies generated, whereas elastic net had the worst overall performance. The predictive genetic panel was completed with 155 single-nucleotide variants, with 91.18% accuracy, 92.75% sensitivity, and 89.55% specificity using the support vector machine algorithm. The markers used range from known single-nucleotide variants to those not previously described in the literature. Our study shows potential in creating genetic prediction panels with tailored penalties per marker, aiding in the identification of optimal machine learning methods for intricate results. Conclusions: This method is able to classify asthma and nonasthma effectively, proving its potential utility in clinical prediction and diagnosis.

Blomia tropicalis Blo t 5 and Blo t 21 recombinant allergens might confer higher specificity to serodiagnostic assays than whole mite extract.

BACKGROUND: Blomia tropicalis is a dust mite and an important source of allergens in tropical regions. Up to now, the assays to diagnose atopy to this mite use whole body extract as antigens. However, anti-B. tropicalis IgE antibodies cross-react with Ascaris lumbricoides antigens, hindering the diagnosis of allergy to this mite. In this study, B. tropicalis recombinant allergens were evaluated with the purpose of developing an immunodiagnostic assay for allergy to this mite with greater specificity than those commercially available. METHODS: Two B. tropicalis allergens (Blo t 5 and Blo t 21) were cloned into a plasmidial expression vector, expressed in Escherichia coli and purified by affinity chromatography. Sixty-three sera containing anti-B. tropicalis extract (BtE) IgE antibodies were used to investigate IgE reactivity to the recombinant Blot 5 and 21 allergens. Inhibition assays with 20 sera pre-adsorbed with A. lumbricoides extract were performed using rBlo t 5, rBlo t 21, and BtE as antigens. All the assays were carried using indirect ELISA. RESULTS: Eighty-two point nine percent and 80.0% of the sera with anti-BtE antibodies from 35 children reacted with rBlo t 5 and rBlo t 21, respectively, whereas 92.8% and 89.3% of the 28 sera with anti-BtE antibodies from adult asthma patients reacted with the same allergens, and 96.4% of these sera reacted with a mixture of rBlo t 5 and rBlo t 21. In an inhibition ELISA, the absorption of sera by A. lumbricoides extract affected less the reaction with rBlo t 5 and rBlo t 21 than with BtE. CONCLUSIONS: The rBlo t 5 and rBlo t 21 allergens contain important epitopes recognized by IgE antibodies of individuals allergic to B. tropicalis antigens. Moreover, the assays using the recombinant allergens had lower IgE cross-reactivity with A. lumbricoides antigens, a fact which would confers higher specificity to serodiagnostic assays than the crude mite extract. However, additional recombinant allergens should be evaluated in order to reach the same sensitivity of the commercially available assays based on mite extract.

The effect of single and multiple infections on atopy and wheezing in children.

BACKGROUND: The current epidemic of asthma and atopy has been explained by alterations in immune responses related to reduction in childhood infections. However, the findings of epidemiologic studies investigating the association between infection with atopy and asthma have been inconsistent. OBJECTIVE: We sought to investigate the effect of single or multiple infections (pathogen burden) on atopy and wheeze in urban children from Latin America. METHODS: Specific IgE against aeroallergens (sIgE) and skin prick test (SPT) reactivity for the most common local allergens were measured in 1128 children aged 4 to 11 years. Data on wheezing and potential confounders were collected by questionnaire. Infections by 8 pathogens were assessed by using serology and stool examination. Associations of wheeze and atopic outcomes with single and multiple infections were analyzed by means of logistic regression. RESULTS: Negative results for Toxoplasma gondii were associated with a higher prevalence of sIgE (≥0.70 kU/L), whereas negative results for Ascaris lumbricoides, T gondii, herpes simplex virus, and EBV were associated with a higher prevalence of SPT reactivity. Children with 3 or fewer infection markers had a higher prevalence of sIgE and SPT reactivity compared with those with 4 or more infection markers. However, isolated infections or pathogen burden were not associated with the prevalence of atopic or nonatopic wheeze. CONCLUSION: The findings provide support for the idea that the hygiene hypothesis is operating in an urban Latin American context, but its expression is thus far restricted to the atopic status of patients and not the perceived asthma symptoms.

Exposure to intimate partner violence and lack of asthma control in adults: a cross-sectional study.

BACKGROUND: Asthma is a chronic airway disease that affects 339 million people worldwide. It is a heterogeneous disease with different risks, including in family environments, where intimate partner violence occurs. OBJECTIVE: This study aimed to investigate the possible association between psychosocial factors and asthma control in adults exposed to intimate partner violence. DESIGN AND SETTING: This cross-sectional study was conducted at a Brazilian public higher education institution in Salvador, Bahia, Brazil. METHODS: The study population consisted of adults clinically diagnosed with severe asthma and those with mild/moderate asthma identified at an asthma referral outpatient clinic. The sample comprised 492 participants who underwent clinical evaluation and completed questionnaires to assess asthma control, depression, stress, and resilience. The Conflict Tactics Scale, which measures tactics for managing marital conflicts, was used to estimate the level of intimate partner violence. RESULTS: Of the 492 participants, 76.2% were women and 91% self-referenced color black/brown, 37.8% reported low family income, 87.4% reported low education level, 71.7% reported high stress, 32.5% reported low resilience, 18.5% reported moderate or severe depression, 83.3% reported resolute negotiation, 49.4% reported major psychological aggression, 19.6% reported major physical aggression, 15.5% reported major injury, and 7.3% reported major sexual coercion. Regression analysis revealed that sex was an effect modifier. CONCLUSION: Women in situations of social vulnerability, with low income and poor education, with depression, severe asthma, and those who used aggression to resolve marital conflicts had a profile associated with a lack of asthma control.

Correlation between peak nasal inspiratory flow and peak expiratory flow in children and adolescents.

BACKGROUND: PEAK nasal inspiratory flow (PNIF) has been proposed as a simple method to evaluate nasal patency. Asthma and allergic rhinitis are commonly associated, and lower airway assessment can provide information concerning an objective interpretation of nasal function. AIMS: TO determine whether the PNIF is correlated with peak expiratory flow (PEF) in children and adolescents. METHODS AND RESULTS: Cross-sectional study carried out in healthy students randomly chosen in 14 public schools of the city of Belo Horizonte. PNIF and PEF were assessed for each subject as the following characteristics: gender, height, weight and age. We created a linear regression model to explain the PNIF, in which we included all the variables with a p value ≤ 0.25 in a univariate analysis, and to calculate the relationship between the maximum PNIF and maximum PEF by the Spearman correlation coefficient. In total, 297 healthy subjects, aged between six and eighteen years were evaluated. A positive and significant correlation between PNIF and PEF was found. CONCLUSIONS: PEF is predictive of PNIF. However, these measures evaluate two distinct segments of the airways and should be both obtained for a more precise assessment of airflow limitation.

Depression, suicidal motivation and suicidal ideation among individuals with asthma: a cross-sectional study.

BACKGROUND: Asthma is a chronic disease associated with risk of depression and suicidal events. The present study estimated the frequency of depression, suicidal motivation (SM) and suicidal ideation (SI) and identified clinical and psychosocial factors associated with these outcomes among individuals with asthma. METHODS: Cross-sectional study of a non-probabilistic sample of 1,358 adults with asthma and controls without asthma. Asthma severity and asthma control were assessed by a physician according to WHO (2009) and GINA (2012) criteria. Depression, SM and SI were screened by Beck Depression Inventory (BDI). Psychosocial factors were evaluated by a Community Violence Questionnaire, a Social Support Scale, a Stress Perceived Scale and a Resilience Scale. Chi-Square Test, and logistic regression models were performed to evaluate association between variables and outcomes. RESULTS: Among all participants, 222 (16.30%) had depression, 331 (24.40%) SM and 73 (5.40%) SI. There were 138 (12.10%) individuals with mild depression and SM, and 14 (1.20%) with mild depression and SI. After adjustment, severe asthma (SA) increased the chance of depression by 53.00% whereas mild to moderate asthma (MMA) increased by eleven-fold the likelihood of SI. Perception of low social support increased the chance of depression (OR 3.59; 95% CI, 2.44-5.28) and low resilience by (OR 2.96; 95% CI, 2.00-4.38); distress increased the odds of SM by 37.00%, and low affective support perception raised the likelihood of SI by (OR 6.82; 95% CI, 1.94-2.90). CONCLUSIONS: Asthma, whether mild to moderate or severe, increased the chance of depression and SI. It is noteworthy that individuals with mild depression and MMA are at greater risk for SM and SI. Among the psychosocial variables, perception of low social support and low resilience were the variables associated with depression; distress impacted on SM, and the perception of low affective support raised the chance of SI.

Hospital admission rate in children and adolescents with mild persistent asthma.

INTRODUCTION: The health and financial burden of mild-persistent asthma has been poorly investigated. OBJECTIVE: Our aim was to compare the rate of hospital admissions that have occurred during the preceding year between children and adolescents with current mild-persistent (MP) and moderate-severe (MS) asthma. METHODS: We screened children and adolescents with asthma at eight outpatient clinics. The inclusion criteria were asthma diagnosis, age from 6 to 18 years and follow-up with a physician during the preceding 6 months. Subjects answered standardized questionnaires and underwent spirometry. RESULTS: We enrolled 220 MP and 102 MS asthmatic subjects. The proportion of subjects with HA during the preceding year was similar between MP and MS asthma groups (7% vs. 7%; p = .89). Symptoms score and the financial values spent by the family in the care of asthma were lower in MP asthma as compared with MS asthma group (asthma control questionnaire score 0.7 [0.3-1.0) vs. 2.0 [1.1-2.5]; p < .01) (asthma expenses in USD 13 [2-43] vs. 28 [10-83]; p < .01). The frequency of subjects using inhaled corticosteroids maintenance therapy was lower in the MP asthma group as compared with the MS asthma group (54% vs. 100%; p < .01). CONCLUSION: We conclude that the frequency of hospital admissions that have occurred during the preceding year was similar between subjects with current MP and MS asthma. Symptoms score and the financial values spent by the family in the care of asthma were lower in the MP asthma group.

2021 Brazilian Thoracic Association recommendations for the management of severe asthma.

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.

Asthma cases in childhood attributed to atopy in tropical area in Brazil.

OBJECTIVE: This study aimed to explore the association between asthma and atopy in a cohort of children living in a large urban center in Brazil. Atopy was defined by the presence of allergen-specific IgE in serum or by a positive skin prick test. METHODS: In a sample of 1 445 Brazilian children, the association between the prevalence of asthma, skin prick test positivity, and allergen-specific IgE in serum was investigated. RESULTS: The prevalence of asthma was 22.6%. The presence of serum allergen-specific IgE was frequent in asthmatics and nonasthmatics, and the prevalence of asthma increased only with levels of allergen-specific IgE > 3.5 kilounits/L. The proportion of asthma attributable to atopy was estimated to be 24.5% when atopy was defined by the presence of allergen-specific IgE. With a given level of specific IgE, no association between skin test reactivity and asthma was observed. Skin prick tests were less sensitive than specific IgE for detection of atopy. CONCLUSIONS: Most asthma cases in an urban underprivileged setting in Brazil were not attributable to atopy. This observation has important implications for understanding the risk factors for the asthma epidemic in Latin America.

Clinical features and associated factors with severe asthma in Salvador, Brazil. / Características clínicas e fatores associados à asma grave em Salvador, Brasil.

Objective To describe the clinical features and to identify factors associated with significant severe asthma in samples of patients followed in a reference center in Salvador. Methods A cross-sectional study of 473 adults, regularly followed in the "Asthma Control Program" in Bahia (Programa de Controle da Asma e da Rinite Alérgica na Bahia (ProAR)), reassessed systematically between 2013 and 2015. The patients were admitted for meeting previous criteria of severe asthma and were reclassified according to the most current definition proposed by a joint document of the "European Respiratory Society/American Thoracic Society" (ERS/ATS) (ERS/ATS 2014). Results Only 88/473 (18%) were reclassified as having severe asthma by ERS/ATS criteria (SA-ERS/ATS). Among these patients, 87% were women, 48% obese, with a median Body Mass Index (BMI) of 29 kg·m2 (IQ 26-34), furthermore, 99% had symptoms of chronic rhinitis and 83% had symptoms of Gastroesophageal Reflux Disease (GERD). None of the 88 patients claimed to be current smokers. The most frequently corticosteroids were beclomethasone dipropionate (BDP) (88%) and budesonide (BUD) (69%). The majority of the evaluations reported adequate adherence (77%), however, the minority (0,6%) detected serious errors in inhalation techniques. The median Forced Expiratory Volume (FEV1) associated with post-bronchodilator test (post-BD) was 67% predicted (IQ 55-80). The median number of eosinophils in the peripheral blood was lower in patients with SA-ERS/ATS (258 cells/mm3 (IQ 116-321) than in the other patients studied [258 cells/mm3 (IQ 154-403)]. Gastroesophageal reflux symptoms were associated with a higher severity [OR = 2.2 95% CI (1.2-4.2)]. Conclusion In this group of patients, symptoms of GERD were associated with SA-ERS/ATS and eosinophil count > 260 cells/mm3 were associated 42% with less chance SA-ERS/ATS.

Oral health-related quality of life in individuals with severe asthma.

OBJECTIVE: To evaluate oral health-related quality of life (OHRQoL) among individuals with severe asthma, comparing it with that observed among individuals with mild-to-moderate asthma and individuals without asthma. METHODS: We conducted a cross-sectional study of 125 individuals: 40 with severe asthma; 35 with mild-to-moderate asthma; and 50 without asthma. We calculated the decayed, missing, and filled teeth (DMFT) index, as well as the Periodontal Screening and Recording index, and determined the stimulated salivary flow rate. We applied three structured questionnaires: the 14-item Oral Health Impact Profile (OHIP-14); the Medical Outcomes Study 36-Item Short-Form Health Survey, version 2 (SF-36v2); and the Work Ability Index (WAI). RESULTS: Periodontitis and reduced salivary flow were both more common in the severe asthma group than in the mild-to-moderate asthma and no-asthma groups. In addition, the WAI scores were lower in the severe asthma group than in the mild-to-moderate asthma and no-asthma groups, as were the scores for all SF-36v2 domains. The individuals with severe asthma also scored lower for the OHIP-14 domains than did those without asthma. Although the mean DMFT index did not differ significantly among the groups, the mean number of missing teeth was highest in the severe asthma group. Strong correlations between the SF-36v2 Component Summaries and poorer OHRQoL were only observed in the severe asthma group. CONCLUSIONS: Severe asthma appears to be associated with poorer oral health, poorer OHRQoL, a lower WAI, and lower scores for SF-36v2 domains.

Exposure to secondhand smoke among patients with asthma: a cross-sectional study.

OBJECTIVE: To estimate the frequency of secondhand smoke exposure among patients with asthma. METHODS: A cross-sectional study of asthma patients and non-asthmatic controls using questionnaires to identify secondhand smoke exposure at home, school, work, and public places. RESULTS: We studied 544 severe asthma patients, 452 mild/moderate asthma patients, and 454 non-asthmatic patients. Among severe patients, the mean age was 51.9 years, 444 (81.6%) were female, 74 (13.6%) were living with a smoker, 383 (71.9%) reported exposure in public spaces and, of the 242 (44.5%) who worked/ studied, 46 (19.1%) reported occupational exposure. Among those with mild/moderate asthma, the mean age was 36.8 years, 351 (77.7%) were female, 50 (11.1%) reported living with a smoker, 381 (84.9%) reported exposure in public settings and, of the 330 (73.0%) who worked/ studied, 58 (17.7%) reported occupational exposure. An association between secondhand smoke exposure and disease control was found among patients with mild/moderate asthma. Among those interviewed, 71% of severe asthma patients and 63% of mild/moderate asthma patients avoided certain places due to fear of secondhand smoke exposure. CONCLUSION: Secondhand smoke exposure is a situation frequently reported by a significant proportion of asthma patients. Individuals with asthma are exposed to this agent, which can hamper disease control, exacerbate symptoms and pose unacceptable limitations to their right to come and go in public settings.

Asthma mortality in children and adolescents of Brazil over a 20-year period.

OBJECTIVE: To evaluate the number of asthma deaths and the temporal trend of the asthma-specific mortality rate in children and adolescents up to 19 years of age in Brazil. METHODS: This is an ecological time-series study of asthma deaths reported in Brazil, in the population up to 19 years of age, between 1996 and 2015. The specific asthma mortality rate and its temporal trend were analyzed. RESULTS: There were 5014 deaths during the 20 years evaluated, with the majority, 68.1%, being recorded in children under 5 years of age. The specific asthma mortality rate ranged from 0.57/100,000 in 1997 to 0.21/100,000 in 2014, with a significant reduction of 59.8%. Regarding the place of death, 79.4% occurred in a hospital setting. In this sample, the adolescents had a 1.5-fold higher chance of death out-of-hospital than children up to nine years of age. There was no significant difference in the temporal trend between the genders and no significant decrease in out-of-hospital deaths. CONCLUSIONS: This study found a temporal trend for a reduction in asthma deaths over 20 years in children and adolescents in Brazil. Mortality rates varied across the geographic regions of the country and were higher in the Northeast. The prevalence of deaths under 5 years of age may be associated with the greater vulnerability of this age group in low-income countries. In adolescence, deaths outside the hospital environment are noteworthy. Asthma deaths are rare but unacceptable events, considering the treatable nature of the disease and the presence of avoidable factors in most of fatal outcomes.

Genetic polymorphisms in vitamin D pathway influence 25(OH)D levels and are associated with atopy and asthma.

BACKGROUND: Vitamin D deficiency or insufficiency, has been associated with atopy and lack of asthma control. Our objective was to investigate associations between variants in genes of vitamin D pathway with serum levels of 25-hydroxyvitamin D (25(OH)D), atopy, asthma and asthma severity in teenagers from Northeast Brazil. METHODS: This is a cross sectional study nested in a cohort population of asthma. 25(OH)D was quantified from 968 of 11-17 years old individuals by ELISA. Asthma diagnosis was obtained by using the ISAAC Phase III questionnaire. Specific IgE was determined by ImmunoCAP; genotyping was performed using the 2.5 HumanOmni Biochip from Illumina. Statistical analyses were performed in PLINK 1.07 and SPSS 22.1. RESULTS: After quality control, 104 Single Nucleotides Variants (SNVs) in vitamin D pathway genes, typed in 792 individuals, were included in the analysis. The allele A of rs10875694 on VDR was positively associated with atopy (OR = 1.35; 95% CI 1.01-1.81). The allele C of rs9279 on VDR, was negatively associated with asthma risk (OR = 0.66; 95% CI 0.45-0.97), vitamin D insufficiency (OR = 0.78; 95% CI 0.70-0.96) and higher VDR expression. Two variants in VDR were associated with asthma severity, the allele A of rs2189480 (OR = 0.34; 95% CI 0.13-0.89) and the allele G of rs4328262 (OR = 3.18; 95% CI 1.09-9.28). The combination of variants in CYP2R1 and CYP24A1 (GAC, to rs10500804, rs12794714 and rs3886163, respectively) was negatively associated with vitamin D production (ß = - 1.24; 95% CI - 2.42 to - 0.06). CONCLUSIONS: Genetic variants in the vitamin D pathway affect vitamin D serum levels and, thus, atopy and asthma.

2020 Brazilian Thoracic Association recommendations for the management of asthma.

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.

Severe asthma: Comparison of different classifications of severity and control.

BACKGROUND: Criteria of asthma severity and control lack standardization. OBJECTIVE: to compare classifications of asthma severity and control, applied to patients from a severe asthma clinic. METHODS: Cross-sectional study of 473 patients followed up for ≥6 months, reclassified using three criteria: 1) the World Health Organization (WHO) 2010, 2) the American Thoracic Society (ATS) 2000, and 3) the European Respiratory Society (ERS)/ATS 2014. In order to evaluate disease control, the 2012 and 2014 Global Initiative for Asthma (GINA) classifications were compared. RESULTS: According to the definition of WHO 2010, 429 had Difficult-to-treat severe asthma and only 12 presented Treatment-resistant severe asthma. 114 patients had Refractory asthma by ATS 2000 and 88 had Severe asthma by ERS/ATS 2014. Considering the definitions of WHO 2010, only 9 out of 12 with Treatment-resistant and 64 out of 429 with Difficult-to-treat severe asthma met the criteria of ATS 2000 and ERS/ATS 2014. As for GINA classification of control, 208 (44%) of the 473 subjects were classified as having asthma controlled by the 2014 criteria, whereas only 45 (10%) patients had controlled asthma by the GINA 2012 criteria. The Kappa statistic indicates the highest agreement of the severity classification occurred between the criteria of ATS 2000 and ERS/ATS 2014 (0.64). CONCLUSION: Good agreement was found between Refractory asthma ATS 2000 and Severe asthma ERS/ATS 2014 classifications. However, poor agreement was observed between the severity rating proposed by the WHO and other classifications. The GINA control classifications of 2012 and 2014 also agreed poorly.

Aproximando a Atenção Especializada da Atenção Primária à Saúde: em busca do cuidado integral ao paciente com asma no Brasil / Aligning Specialized Care with Primary Health Care: in search of comprehensive care for asthma patients in Brazil

A ocorrência de doenças alérgicas e asma ainda cresce em muitos países. Dados mostram que aproximadamente um quarto dos habitantes de países industrializados apresenta algum tipo de alergia, e nos países em desenvolvimento estas doenças podem alcançar proporções ainda maiores da população. No Brasil, embora não exista até o momento uma agenda política nacional de atenção à saúde dos pacientes com alergias e asma, iniciativas individuais em diferentes regiões têm beneficiado milhares de pacientes ao longo das últimas décadas. Estes programas têm como principais objetivos qualificar o cuidado em saúde, melhorar a qualidade de vida (especialmente dos pacientes com asma e rinite alérgica) e reduzir os indicadores de morbimortalidade relacionados às doenças. Com essa finalidade, os programas vêm se ocupando de diversas ações de educação em saúde, capacitação profissional, busca ativa para garantir diagnóstico e tratamento oportuno, e proporcionar acesso a medicamentos de forma gratuita e continuada. Entretanto, a falta de um caráter institucional que garanta o acesso universal a ações cientificamente fundamentadas, impede a equidade e a continuidade do cuidado, além de dificultar a atenção integral em asma e em outras doenças alérgicas.

Allergic diseases and asthma are on the rise in many countries. Data show that approximately 25% of the inhabitants of industrialized countries have some type of allergy, reaching even greater proportions in developing countries. Although a national health care agenda for patients with allergies and asthma has not yet been developed in Brazil, individual initiatives in different regions have benefited thousands of patients in recent decades. The main objectives of these programs are to improve health care, quality of life (especially for patients with asthma and allergic rhinitis), and reduce disease-related morbidity and mortality indicators. To this end, these programs have been engaged in health education actions, professional training, performing active searches to ensure timely diagnosis and treatment, and providing free and continuous access to medication. However, the due to the non-institutional character of these programs, universal access, evidence-based actions, and continuity of care are not guaranteed, and it is difficult to provide comprehensive care for asthma and other allergic diseases.