RESUMO
Lung physiology research advanced significantly over the last 100 years. Respiratory mechanics applied to animal models of lung disease extended the knowledge of the workings of respiratory system. In human research, a better understanding of respiratory mechanics has contributed to development of mechanical ventilators. In this review, we explore the use of respiratory mechanics in basic science to investigate asthma and chronic obstructive pulmonary disease (COPD). We also discuss the use of lung mechanics in clinical care and its role on the development of modern mechanical ventilators. Additionally, we analyse some bench-developed technologies that are not in widespread use in the present but can become part of the clinical arsenal in the future. Finally, we explore some of the difficult questions that intensive care doctors still face when managing respiratory failure. Bringing back these questions to bench can help to solve them. Interaction between basic and translational science and human subject investigation can be very rewarding, as in the conceptualization of "Lung Protective Ventilation" principles. We expect this interaction to expand further generating new treatments and managing strategies for patients with respiratory disease.
RESUMO
Signal disruptions in small animals during the realization of the Forced Oscillation Technique are a well-known cause of data loss as it leads to non-reliable estimations of the respiratory impedance. In this work, we assessed the effects of removing the disrupted epoch when a 3-seconds input signal composed of one and a half 2-seconds full cycle is used.We tested our hypothesis in 25 SAMR1 mice under different levels of bronchoconstriction due to methacholine administration by iv bolus injections in different doses (15 animals) and by iv continuous infusion in different infusion rates (10 animals). Signal disruptions were computationally simulated as sharp drops in the pressure signal within a short timescale, and signal processing was performed using own developed algorithms.We found that the model goodness of fit worsens when averaging techniques to estimate the input respiratory impedance are not used. However, no statistically significant differences were observed in the comparison between Constant Phase Model parameters of the full 3-s signal and the 2-s non disrupted epoch in all doses or infusion rates for both methacholine delivery strategies.The proposed technique presents reliable outcomes that can reduce animal use in Forced Oscillation Technique realization.
Assuntos
Broncoconstrição , Mecânica Respiratória , Resistência das Vias Respiratórias , Animais , Cloreto de Metacolina/farmacologia , Camundongos , Testes de Função Respiratória/métodosRESUMO
Aim: This study aimed to analyze the Constant Phase Model (CPM) Coefficient of Determination (COD) and an index of harmonic distortion ([Formula: see text]) behavior in intravenous methacholine dose response curve. We studied the COD and [Formula: see text] behavior of Control and Lung Inflammation (OVA) groups of mice and we proposed an alternative for moments when the CPM should not be applied. Methods: 9-week female BALB/c mice were studied, 8 of the control group (23.11 ± 1.27 g) and 11 of the lung inflammation group (OVA) (21.45 ± 2.16 g). The COD values were obtained during the respiratory mechanics assessment via Forced Oscillation Technique (FOT) and the [Formula: see text] was estimated a posteriori. Both control and OVA groups were submitted to 4 doses of Methacholine (MCh) protocol. Results: A strong correlation between COD and [Formula: see text] was present at the last two doses (0.3 mg/kg: r = -0.75, p = 0.0013 and 1 mg/kg: r = -0.91; p < 0.0001) in the OVA group. Differences were found in doses of 0.3 mg/kg between control and OVA for the maximum values of Rn (Newtonian Resistance) and G (tissue viscous); and between groups at PBS and doses of 0.03, 0.1 and 0.3 mg/kg for H (Elastance). A similar behavior was observed for the analysis of Area Under the Curve with the exclusion of the 3 first measurements of each dose. However, in this scenario, the comparison with the maximum value presented a higher discriminatory capacity of the parameters associated with the parenchyma. Conclusions: During severe bronchoconstriction there is a strong negative correlation between model goodness of fit and nonlinearities levels, reinforcing that COD is a robust acceptance criterion, whether still simple and easily obtained from the ventilator. We also pointed out the area under the CPM parameters dose response curve is a useful and can be used as a complementary analysis to peak comparison following bolus injections of methacholine.
Assuntos
Cloreto de Metacolina/administração & dosagem , Cloreto de Metacolina/farmacologia , Mecânica Respiratória/efeitos dos fármacos , Resistência das Vias Respiratórias/efeitos dos fármacos , Animais , Broncoconstrição/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Pulmão/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/farmacologia , Pneumonia/tratamento farmacológico , Testes de Função Respiratória/métodosRESUMO
BACKGROUND AND OBJECTIVE: Integer and fractional-order models have emerged as powerful methods for obtaining information regarding the anatomical or pathophysiological changes that occur during respiratory diseases. However, the precise interpretation of the model parameters in light of the lung structural changes is not known. This study analyzed the associations of the integer and fractional-order models with structural changes obtained using multidetector computed tomography densitometry (MDCT) and pulmonary function analysis. METHODS: Integer and fractional-order models were adjusted to data obtained using the forced oscillation technique (FOT). The results obtained in controls (nâ¯=â¯20) were compared with those obtained in patients with silicosis (nâ¯=â¯32), who were submitted to spirometry, body plethysmograph, FOT, diffusing capacity of the lungs for carbon monoxide (DLCO), and MDCT. The diagnostic accuracy was also investigated using ROC analysis. RESULTS: The observed changes in the integer and fractional-order models were consistent with the pathophysiology of silicosis. The integer-order model showed association only between inertance and the non-aerated compartment (R = -0.69). This parameter also presented the highest associations with spirometry (Râ¯=â¯0.81), plethysmography (-0.61) and pulmonary diffusion (Râ¯=â¯0.53). Considering the fractional-order model, the increase in the poorly aerated and non-aerated regions presented direct correlations with the fractional inertance (Râ¯=â¯0.48), respiratory damping (Râ¯=â¯0.37) and hysteresivity (Râ¯=â¯0.54) and inverse associations with its fractional exponent (R = -0.62) and elastance (-0.35). Significant associations were also observed with spirometry (Râ¯=â¯0.63), plethysmography (0.37) and pulmonary diffusion (Râ¯=â¯0.51). Receiver operator characteristic analysis showed a higher accuracy in the FrOr model (0.908) than the eRIC model (0.789). CONCLUSIONS: Our study has shown clear associations of the integer and fractional-order parameters with anatomical changes obtained via MDCT and pulmonary function measurements. These findings help to elucidate the physiological interpretation of the integer and fractional-order parameters and provide evidence that these parameters are reflective of the abnormal changes in silicosis. We also observed that the fractional-order model showed smaller curve-fitting errors, which resulted in a higher diagnostic accuracy than that of the eRIC model. Taken together, these results provide strong motivation for further studies exploring the clinical and scientific use of these models in respiratory medicine.