Periostin as an important biomarker of inflammatory phenotype T2 in Brazilian asthma patients.

OBJECTIVE: The aim of this study was to assess the laboratory performance of periostin associated with a panel of biomarkers to identify the inflammatory phenotype of Brazilian asthma patients. METHODS: We evaluated 103 Brazilian individuals, including 37 asthmatics and 66 nonasthmatic controls. Both groups underwent analyses for serum periostin, eosinophil levels in the peripheral blood, the fraction of exhaled nitric oxide (FeNO), total serum IgE, urinary leukotriene E4, and serum cytokines. RESULTS: Higher levels of periostin (p = 0.005), blood eosinophils (p = 0.012), FeNO (p = 0.001), total IgE (p < 0.001), and IL-6 (p ≤ 0.001) were found in the asthmatic patients than the controls. Biomarker analyses by the ROC curve showed an AUC greater than 65%. Periostin (OR: 12,550; 95% CI: 2,498-63,063) and IL-6 (OR: 7,249; 95% CI: 1,737-30,262) revealed to be suitable asthma inflammation biomarkers. Blood eosinophils, FeNO, total IgE, IL-6, TNF, and IFN-g showed correlations with clinical severity characteristics in asthmatic patients. Periostin showed higher values in T2 asthma (p = 0.006) and TNF in non-T2 asthma (p = 0.029). CONCLUSION: The panel of biomarkers proposed for the identification of the inflammatory phenotype of asthmatic patients demonstrated good performance. Periostin proved to be an important biomarker for the identification of T2 asthma.

Periostin as an important biomarker of inflammatory phenotype T2 in Brazilian asthma patients / Periostina como um importante biomarcador do fenótipo inflamatório T2 em pacientes brasileiros com asma

ABSTRACT Objective: The aim of this study was to assess the laboratory performance of periostin associated with a panel of biomarkers to identify the inflammatory phenotype of Brazilian asthma patients. Methods: We evaluated 103 Brazilian individuals, including 37 asthmatics and 66 nonasthmatic controls. Both groups underwent analyses for serum periostin, eosinophil levels in the peripheral blood, the fraction of exhaled nitric oxide (FeNO), total serum IgE, urinary leukotriene E4, and serum cytokines. Results: Higher levels of periostin (p = 0.005), blood eosinophils (p = 0.012), FeNO (p = 0.001), total IgE (p < 0.001), and IL-6 (p ≤ 0.001) were found in the asthmatic patients than the controls. Biomarker analyses by the ROC curve showed an AUC greater than 65%. Periostin (OR: 12,550; 95% CI: 2,498-63,063) and IL-6 (OR: 7,249; 95% CI: 1,737-30,262) revealed to be suitable asthma inflammation biomarkers. Blood eosinophils, FeNO, total IgE, IL-6, TNF, and IFN-g showed correlations with clinical severity characteristics in asthmatic patients. Periostin showed higher values in T2 asthma (p = 0.006) and TNF in non-T2 asthma (p = 0.029). Conclusion: The panel of biomarkers proposed for the identification of the inflammatory phenotype of asthmatic patients demonstrated good performance. Periostin proved to be an important biomarker for the identification of T2 asthma.

RESUMO Objetivo: O objetivo deste estudo foi de avaliar o desempenho laboratorial da periostina associada a um painel de biomarcadores para identificar o fenótipo inflamatório de pacientes brasileiros com asma. Métodos: Foram avaliados 103 indivíduos brasileiros, incluindo 37 asmáticos e 66 controles não asmáticos. Ambos os grupos foram submetidos a análises de periostina sérica, níveis de eosinófilos no sangue periférico, a fração exalada de óxido nítrico (FeNO), IgE sérica total, leucotrieno E4 urinário e citocinas séricas. Resultados: Maiores níveis de periostina (p = 0,005), eosinófilos periféricos (p = 0,012), FeNO (p = 0,001), IgE total (p < 0,001) e IL-6 (p ≤ 0,001) foram encontrados nos pacientes asmáticos do que nos controles. As análises de biomarcadores pela curva ROC mostraram uma AUC superior a 65%. A periostina (OR: 12.550; IC 95%: 2.498-63.063) e a IL-6 (OR: 7.249; IC 95%: 1.737-30.262) se mostraram biomarcadores adequados da inflamação da asma. Eosinófilos periféricos, FeNO, IgE total, IL-6, TNF e IFN-g apresentaram correlação com características clínicas de gravidade em pacientes asmáticos. A periostina teve valores mais elevados na asma T2 (p = 0,006) e o TNF na asma não T2 (p = 0,029). Conclusão: O painel de biomarcadores proposto para a identificação do fenótipo inflamatório de pacientes asmáticos demonstrou bom desempenho. A periostina provou ser um importante biomarcador para a identificação da asma T2.

Cost comparison of dupilumab and omalizumab for the treatment of severe allergic asthma patients from the Brazilian private healthcare system perspective / Comparação dos custos de dupilumabe e omalizumabe para o tratamento de pacientes com asma alérgica grave na perspectiva do sistema de saúde privado brasileiro

Objective: To compare the costs of dupilumab and omalizumab for treating severe allergic asthma patients from the perspective of the Brazilian private healthcare system. Methods: Using clinical and demographic inputs from the literature, we simulated a cohort of 5,000 severe allergic asthma patients and estimated the treatment cost with omalizumab. Results: In the simulated cohort, 81.3% were female, the mean body weight was 75.1 kg (SD 13.1), and the mean serum IgE was 532 IU/mL (SD 688). All patients were eligible for treatment with dupilumab, but 830 (16.6%) were ineligible for treatment with omalizumab due to serum IgE level and/or body weight combinations, according to the product label. Over four weeks, the mean dose of omalizumab was 537 mg (SD 285). The annual mean per-patient cost for treatment with omalizumab was BRL 110,783.89 (SD 58,385.81), ranging from BRL 31,797.49 to BRL 246,643.15. The treatment cost with dupilumab is BRL 111,724.21 for the first year and BRL 107,599.91 for subsequent years. Conclusions: We observed slightly lower mean treatment costs with dupilumab than with omalizumab. However, while the treatment cost with dupilumab is fixed and predictable, the treatment cost with omalizumab is highly variable, depending on patients' characteristics. Health managers should consider these findings for reimbursement and clinical protocol development decisions.

Objetivo: Comparar os custos de dupilumabe e omalizumabe para o tratamento de pacientes com asma alérgica grave na perspectiva do sistema de saúde privado brasileiro. Métodos: Utilizando parâmetros clínicos e demográficos a partir de dados da literatura, simulamos uma coorte com 5.000 pacientes com asma alérgica grave e estimamos o custo de tratamento com o omalizumabe. Resultados: Na coorte simulada, 81,3% eram do sexo feminino, com peso médio de 75,1 kg (DP 13,1) e IgE sérica de 532 IU/mL (DP 688). Todos os pacientes eram elegíveis para o tratamento com dupilumabe, porém 830 (16,6%) não eram elegíveis para o tratamento com omalizumabe devido a combinações específicas de IgE sérica e/ou peso corporal, de acordo com a bula do produto. Para o período de 4 semanas, a dose média de omalizumabe foi de 537 mg (DP 285). O custo médio anual por paciente do tratamento com omalizumabe foi de R$ 110.783,89 (DP 58.385,81), variando de R$ 31.797,49 a R$ 246.643,15. O custo do tratamento com dupilumabe é de R$ 111.724,21 no primeiro ano e R$ 107.599,91 nos anos seguintes. Conclusões: Foi observado que o custo médio do tratamento com dupilumabe é ligeiramente menor que o custo com omalizumabe. Todavia, enquanto o custo do tratamento com dupilumabe é fixo e previsível, o custo do tratamento com omalizumabe é altamente variável, dependendo de características dos pacientes. Esses achados devem ser considerados pelos gestores de saúde para decisões sobre reembolso e desenvolvimento de protocolos clínicos.

The pathology of small airways disease in COPD: historical aspects and future directions.

Small airways disease (SAD) is a cardinal feature of chronic obstructive pulmonary disease (COPD) first recognized in the nineteenth century. The diverse histopathological features associated with SAD underpin the heterogeneous nature of COPD. Our understanding of the key molecular mechanisms which drive the pathological changes are not complete. In this article we will provide a historical overview of key histopathological studies which have helped shape our understanding of SAD and discuss the hallmark features of airway remodelling, mucous plugging and inflammation. We focus on the relationship between SAD and emphysema, SAD in the early stages of COPD, and the mechanisms which cause SAD progression, including bacterial colonization and exacerbations. We discuss the need to specifically target SAD to attenuate the progression of COPD.

Airway vascular endothelial function in healthy smokers without systemic endothelial dysfunction.

BACKGROUND: Cigarette smoking can lead to systemic endothelial dysfunction. Since the airway circulation is exposed to a high concentration of cigarette smoke constituents, we reasoned that airway vascular endothelial dysfunction could be present in healthy smokers without systemic endothelial dysfunction. OBJECTIVES: The purpose of this study was to compare airway and systemic endothelial function and measure markers of systemic inflammation in lung-healthy current smokers. Since endothelial dysfunction in smokers has been related to systemic inflammation, we also investigated its response to an inhaled glucocorticosteroid (ICS). METHODS: Fifteen healthy, current smokers and 17 healthy, lifetime nonsmokers were enrolled. Smokers were randomly assigned to 3-week treatments with inhaled fluticasone propionate or placebo in a crossover design. Vascular endothelial function was assessed in the airway by the airway blood-flow response to inhaled albuterol (ΔQaw) and in the extrapulmonary circulation by brachial arterial flow-mediated vasodilation (FMD). Venous blood was collected for C-reactive protein and IL-6. RESULTS: Baseline parameters did not differ between groups except for ΔQaw, which was greater in nonsmokers (45% ± 12%) than smokers (1% ± 12%) (P = .001). In the smokers, ICS treatment increased Qaw to 41% ± 7% (P < .001), but had no effect on FMD or inflammatory markers. There was an inverse relationship between baseline and ICS-induced changes in ΔQaw. CONCLUSIONS: Healthy smokers with no signs of systemic inflammation or endothelial dysfunction display impaired airway vascular endothelial function, possibly preceding systemic endothelial dysfunction. Airway endothelial function was restored with an ICS, and the response was directly related to the severity of endothelial dysfunction.