Pharmacological blockade of protease-Activated Receptor 2 improves airway remodeling and lung inflammation in experimental allergic asthma

Abstract Protease-activated receptors (PARs) are metabotropic G-protein-coupled receptors that are activated via proteolytic cleavage of a specific sequence of amino acids in their N-terminal region. PAR2 has been implicated in mediating allergic airway inflammation. This study aims to study the effect of PAR2 antagonist ENMD1068in lung inflammation and airway remodeling in experimental asthma. Allergic lung inflammation was induced in sensitized BALB/c mice through intranasal instillations of ovalbumin (OVA), and mice were pretreated with ENMD1068 1 hour before each OVA challenge. Bronchoalveolar lavage fluid (BALF) was collected, and the lungs were removed at different time intervals after OVA challenge to analyze inflammation, airway remodeling and airway hyperresponsiveness. Ovalbumin promoted leukocyte infiltration into BALF in a PAR2-dependent manner. ENMD1068 impaired eosinophil peroxidase (EPO) and myeloperoxidase (MPO) activity in the lung parenchyma into BALF and reduced the loss of dynamic pulmonary compliance, lung resistance in response to methacholine, mucus production, collagen deposition and chemokine (C-C motif) ligand 5 expression compared to those in OVA-challenged mice. We propose that proteases released after an allergen challenge may be crucial to the development of allergic asthma in mice, and PAR2 blockade may be useful as a new pharmacological approach for the treatment of airway allergic diseases.

The effects of different body positions on pulmonary function in healthy adults / Os efeitos de diferentes posições corporais na função pulmonar em adultos saudáveis

Abstract Introduction: Pulmonary function testing, or spirometry, is a validated, globally recognized test that contributes to the diagnosis, staging, and longitudinal follow-up of lung diseases. The exam is most often performed in a sitting position in clinical practice; hence, there are no predicted values for its performance in other positions, such as in different decubitus. Objective: The present study aimed to evaluate the effects of position on pulmonary function test results in healthy adults. Methods: Forty-two healthy adults of both sexes, divided into male (MG) and female groups (FG), were provided respiratory questionnaires. Subsequently, the pulmonary function test was conducted to evaluate the ventilatory parameters of forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and FEV1/FVC ratio in the sitting (S), dorsal decubitus (DD), right lateral decubitus (RLD), and left lateral decubitus (LLD) positions. A comparison of the parametric data was performed via one-way analysis of variance followed by Tukey post-hoc tests. Correlations between the S position variables along with the other positions were evaluated using the Pearson test. Results: The mean and standard error for the FVC values of the MG at positions DD (4.3 ± 0.7/L), RLD (4.1 ± 0.6/L) and LLD (4.1 ± 0.6/L) were lower when compared to S (5.05 ± 0.6 L). There was a strong positive correlation between the values of FVC, FEV1, and FEV1/FVC in the S position compared to other positions analyzed in both groups. Conclusion: Body positioning altered the parameters of the pulmonary function test in healthy adults.

Resumo Introdução: A prova de função pulmonar, ou espirometria, é um teste validado e reconhecido mundialmente que contribui para o diagnóstico, estadiamento e acompanhamento longitudinal das doenças pulmonares. O exame é mais frequentemente realizado na posição sentada na prática clínica; portanto, não há valores previstos para seu desempenho em outras posições, como em decúbitos diferentes. Objetivo: O presente estudo teve como objetivo avaliar os efeitos da posição nos resultados dos testes de função pulmonar em adultos saudáveis. Métodos: Quarenta e dois adultos saudáveis de ambos os sexos, divididos nos grupos masculino (GM) e feminino (GF), receberam questionários respiratórios. Posteriormente, realizou-se o teste de função pulmonar para avaliar os parâmetros ventilatórios de capacidade vital forçada (CVF), volume expiratório forçado no primeiro segundo (VEF1) e relação VEF1/CVF nas posições sentada (S), decúbito dorsal (DD), decúbito lateral direito (DLD) e decúbito lateral esquerdo (DLE). A comparação dos dados paramétricos foi realizada por meio de análise de variância unidirecional seguida do pós-teste de Tukey. As correlações entre as variáveis da posição S com as demais posições foram avaliadas por meio do teste de Pearson. Resultados: A média e o erro padrão dos valores de CVF do MG nas posições DD (4,3 ± 0,7/L), DLD (4,1 ± 0,6/L) e DLE (4,1 ± 0,6/L) foram menores quando comparados com S (5,05 ± 0,6 L). Houve forte correlação positiva entre os valores de CVF, VEF1 e VEF1/CVF na posição S em relação às demais posições analisadas em ambos os grupos. Conclusão: O posicionamento corporal alterou os parâmetros do teste de função pulmonar em adultos saudáveis.