Assuntos
Imunidade Inata/efeitos dos fármacos , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/imunologia , Ozônio/farmacologia , Administração por Inalação , Adulto , Animais , Feminino , Voluntários Saudáveis , Humanos , Imunidade Inata/genética , Imunidade Inata/fisiologia , Técnicas In Vitro , Receptores de Lipopolissacarídeos/genética , Lipopolissacarídeos/farmacologia , Macrófagos Alveolares/metabolismo , Masculino , Camundongos , Ozônio/administração & dosagem , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Receptor 4 Toll-Like/genética , Adulto JovemRESUMO
Although xenon is classically taught to be a "perfusion-limited" gas, (129)Xe in its hyperpolarized (HP) form, when detected by magnetic resonance (MR), can probe diffusion limitation. Inhaled HP (129)Xe diffuses across the pulmonary blood-gas barrier, and, depending on its tissue environment, shifts its resonant frequency relative to the gas-phase reference (0 ppm) by 198 ppm in tissue/plasma barrier and 217 ppm in red blood cells (RBCs). In this work, we hypothesized that in patients with idiopathic pulmonary fibrosis (IPF), the ratio of (129)Xe spectroscopic signal in the RBCs vs. barrier would diminish as diffusion-limitation delayed replenishment of (129)Xe magnetization in RBCs. To test this hypothesis, (129)Xe spectra were acquired in 6 IPF subjects as well as 11 healthy volunteers to establish a normal range. The RBC:barrier ratio was 0.55 ± 0.13 in healthy volunteers but was 3.3-fold lower in IPF subjects (0.16 ± 0.03, P = 0.0002). This was caused by a 52% reduction in the RBC signal (P = 0.02) and a 58% increase in the barrier signal (P = 0.01). Furthermore, the RBC:barrier ratio strongly correlated with lung diffusing capacity for carbon monoxide (DLCO) (r = 0.89, P < 0.0001). It exhibited a moderate interscan variability (8.25%), and in healthy volunteers it decreased with greater lung inflation (r = -0.78, P = 0.005). This spectroscopic technique provides a noninvasive, global probe of diffusion limitation and gas-transfer impairment and forms the basis for developing 3D MR imaging of gas exchange.
Assuntos
Fibrose Pulmonar/patologia , Isótopos de Xenônio , Adulto , Idoso , Idoso de 80 Anos ou mais , Monóxido de Carbono/metabolismo , Eritrócitos/metabolismo , Feminino , Voluntários Saudáveis , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Perfusão , Capacidade de Difusão Pulmonar , Fibrose Pulmonar/fisiopatologia , Reprodutibilidade dos Testes , Testes de Função Respiratória , Adulto JovemRESUMO
Effect of laboratory exposure to O3 (220 ppb) and filtered air (FA) on respiratory physiology were evaluated at two time points (acute and 1 day postexposure) in healthy cohort (n = 138, 18-35 yr, 40% women) comprised mainly of Caucasian (60%) and African American (33.3%) subjects. Randomized exposures had a crossover design and durations of 2.25 h that included rest and treadmill walking. Airway responsiveness (AHR) to methacholine (Mch) and permeability of respiratory epithelium (EI) to hydrophilic radiomarker ((99m)Tc-DTPA, MW = 492), were measured at 1-day postexposure. O3 significantly affected FEV1 and FVC indices acutely with mean decrements from pre-exposure values on the order of 7.7 to 8.8% and 1.8 to 2.3% at 1-day post. Acute FEV1 and FVC decreases were most robust in African American male subjects. At 1-day post, O3 induced significant changes in AHR (slope of Mch dose response curve) and EI (Tc(99m)-DTPA clearance half-time). Based on conventional thresholds of response and dichotomous classification of subjects as responders and nonresponders, sensitivity to O3 was shown to be nonuniform. Acute decrements ≥ 15% in FEV1, a doubling of Mch slope, or ≥ 15% increase in EI developed in 20.3%, 23.1%, and 25.9%, respectively, of subjects evaluated. Results demonstrate a diffuse sensitivity to O3 and physiological responses, either acutely (decreases in FEV1) or 1 day post (development of AHR or change in EI) occur differentially in healthy young adults. Random overlap among subjects classified as responsive for respective FEV1, AHR, and EI endpoints suggests these are separate and independent phenotypes of O3 exposure.