RESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation, which results in the progressive development of dyspnea and exercise limitation. OBJECTIVE AND METHODS: To compare the effect of tiotropium with placebo on forced vital capacity (FVC) in patients with moderate-to-severe COPD and lung hyperinflation, using exercise endurance, dyspnea and health-related quality of life (HRQoL) as secondary endpoints. One hundred patients were randomized to receive either tiotropium 18 mug once daily or placebo for 12 weeks. RESULTS: Trough (predose) FVC was significantly improved with tiotropium compared to placebo on day 42 (0.27 +/- 0.08 liters) and 84 (0.20 +/- 0.08 liters; p < 0.05 for both). Trough inspiratory capacity (IC) was also significantly improved with tiotropium compared to placebo on day 42 (0.16 +/- 0.07 liters) and 84 (0.15 +/- 0.07 liters; p < 0.05 for both). Tiotropium increased the mean distance walked during the shuttle walking test by 33 +/- 12 (day 42) and 36 +/- 14 m (day 84) compared to placebo (p < 0.05 for both). On day 84, 59% of the patients in the tiotropium group and 35% of the patients in the placebo group had significant and clinically meaningful improvements in the St. George's Respiratory Questionnaire total score (p < 0.05). Numerical decreases in the focal score in the Transition Dyspnea Index in patients receiving tiotropium versus placebo suggest that tiotropium also improved dyspnea during activities of daily living. CONCLUSION: Tiotropium 18 mug once daily reduced hyperinflation with consequent improvements in walking distance and HRQoL in patients with COPD and lung hyperinflation.
Asunto(s)
Broncodilatadores/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Derivados de Escopolamina/uso terapéutico , Adulto , Anciano , Método Doble Ciego , Femenino , Volumen Espiratorio Forzado , Francia , Humanos , Masculino , Persona de Mediana Edad , Selección de Paciente , Placebos , Pletismografía , Bromuro de TiotropioRESUMEN
Several studies have demonstrated that nasal challenges can induce reflex responses in the respiratory system. Some authors have described bronchoconstriction and modification of the pattern of breathing following nasal challenges by irritants and cold air. We propose to determine the effect of nasal stimulation with cold dry air on airway mucosal blood flow (Qaw) in the proximal tracheal bronchial tree of healthy humans. Nine healthy subjects participated in the study. Baseline measurement Qaw, nasal airway resistance (NAR) and airway caliber by specific airways conductance (SGaw) were followed by nasal challenge with cold dry air. Qaw, NAR and Sgaw were determined after the challenge. In those subjects in which a significant decline in Qaw was recorded the protocol was repeated after pretreatment with nasal anesthesia using topical lidocaine. Cold dry air challenge produced a significant decrease in mean Qaw for the nine subjects and this response was abolished by pretreatment with nasal anesthesia using topical lidocaine. There was no significant change in Sgaw and NAR after the challenge and topical lidocaine anesthesia. Our data indicates that nasal stimulation with cold dry air leads to a reduction in Qaw and that this effect may be mediated by a nasal reflex.
Asunto(s)
Aire , Mucosa Nasal/irrigación sanguínea , Adulto , Anestésicos Locales/farmacología , Frío , Femenino , Humanos , Lidocaína/farmacología , Masculino , Persona de Mediana Edad , Mucosa Nasal/efectos de los fármacos , Flujo Sanguíneo Regional/efectos de los fármacos , Flujo Sanguíneo Regional/fisiologíaRESUMEN
We determined the effect of breathing cold dry air (-39 degrees C, 0.1% relative humidity, RH) and warm humid air (43 degrees C, 100% RH) on airway mucosal blood flow (Qaw) in normal human subjects (n = 8, age 25-53 years) at rest. Qaw was measured with a dimethylether uptake technique which reflects blood flow in the mucosa of large airways corresponding to a 50 ml anatomical dead-space segment extending distally from the trachea. Mean Qaw was 10.1 +/- 1.9 ml min-1 (mean +/- S.D.) during room air breathing (25 degrees C, 70% RH) and decreased to 4.7 +/- 2.1 ml min-1 during cold dry air breathing (p < 0.05). Within 20 min of resuming room air breathing, mean Qaw had returned to baseline. Breathing warm humid air had no significant effect on mean Qaw (8.2 +/- 1.4 ml min-1). These results indicate that quiet breathing of frigid air causes vasoconstriction in central airways.
Asunto(s)
Aire , Humedad , Fenómenos Fisiológicos Respiratorios , Sistema Respiratorio/irrigación sanguínea , Temperatura , Adulto , Resistencia de las Vías Respiratorias/fisiología , Velocidad del Flujo Sanguíneo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Membrana Mucosa/irrigación sanguínea , Membrana Mucosa/fisiologíaRESUMEN
PURPOSE: To test the hypothesis that a physiological compensatory mechanism maintains respiratory gas exchange during normovolaemic haemodilution. METHODS: Pulmonary gas exchange capacity was evaluated in seven healthy subjects by measuring the lung diffusion of carbon monoxide (DLCO). During the measurement, various breath-holding times, inspiratory volumes, and sitting or supine positions, were randomly selected in an attempt to alter pulmonary capillary perfusion. KCO was calculated as the percentage of theoretical values of the ratio of DLCO by alveolar volume and normalized by sex, age, and height. Normovolaemic haemodilution (NH) was performed by bleeding an average blood volume of 1 L with simultaneous Dextran 60 replacement to obtain an haematocrit below 35%. RESULTS: After NH, haemoblogin concentration [Hb] decreased from 14.94 +/- 0.96 to 12.5 +/- 0.98 g.dl-1 (P < 0.001). KCO decreased (P < 0.02) but remained closely correlated to [Hb] at every lung volume (P < 0.02). Breathholding time and body position had no effect. CONCLUSION: Moderate NH impairs pulmonary gas exchange capacity in awake, resting healthy subjects. There is no evidence of any compensatory mechanism since the KCO vs [Hb] relationship is unchanged.
Asunto(s)
Hemodilución , Intercambio Gaseoso Pulmonar , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
In order to assess whether different doses and/or plasma levels of almitrine bismesylate (ABM) could induce preferential effects on ventilation or on lung perfusion, we performed a single-blind placebo-controlled study of ABM treatment with different dosages (0.75, 1.5 and 2.25 mg.kg-1 single oral dose) in 26 patients suffering from chronic obstructive pulmonary disease (COPD). All measurements were performed according to the same time table. At control and at three 1.5-hour intervals, we measured alveolar-arterial (A-a) differences, alveolar dead space, total ventilation and ABM plasma levels. The effect on ventilation was estimated using changes in ventilatory parameters and (A-a)O2 differences. The effect on perfusion was indirectly estimated by analysis of arterial-end-tidal (a-ET)CO2 difference and alveolar dead space. The response to treatment was significant for the 1.5- and the 2.25-mg.kg-1 ABM groups, but not for the 0.75 mg.kg-1 ABM and the placebo group. A ventilatory response was often present in both 1.5- and 2.25-mg.kg-1 ABM groups, but a nonventilatory effect was present only at the highest dose according to the Severinghaus and Stupfel concept. Only the parameters reflecting an effect of the distribution of perfusion (a-ET)CO2 difference and alveolar dead space were significantly correlated with ABM plasma levels. The results suggest that a dose-dependent effect of ABM on lung perfusion may explain the controversial data in the literature about the mode of action of ABM.
Asunto(s)
Almitrina/uso terapéutico , Enfermedades Pulmonares Obstructivas/tratamiento farmacológico , Administración Oral , Anciano , Almitrina/administración & dosificación , Almitrina/sangre , Relación Dosis-Respuesta a Droga , Humanos , Masculino , Intercambio Gaseoso Pulmonar/efectos de los fármacos , Distribución AleatoriaRESUMEN
The respiratory function of pregnant women is changed for more than one reason. There is a mechanical effect due to the increase in the uterine volume and the elevation of the diaphragm. However, there are only modest functional consequences, because the pulmonary volumes are only little changed, with the exception of a reduction in the functional residual capacity. Bronchial permeability is unaltered due to the balancing of constrictors (mechanical, hypocapnia) and dilators (hormonal influences). As regards pulmonary haemodynamics, the hypovolaemia of the pregnant woman has no repercussions on pulmonary vascular pressure. Gas exchange and alveolar-capillary diffusion are normal or even improved as a consequence of chronic hyperventilation. The latter is the most important functional change, sometimes expressed as a sensation of dyspnoea. The origin of this hyperventilation relates to the diminution of the threshold of sensibility in the respiratory centres to CO2 due to the effect of raised progesterone levels.
Asunto(s)
Pulmón/fisiología , Embarazo/fisiología , Respiración , Femenino , Humanos , Oxígeno/fisiología , Progesterona/fisiología , Circulación Pulmonar , Capacidad de Difusión Pulmonar , Intercambio Gaseoso Pulmonar , Centro Respiratorio/fisiologíaRESUMEN
We compared the frequency of airway obstruction in 27 patients with pulmonary sarcoidosis using both spirography (FEV1, FEF25-75) and plethysmography (Gus50). FEF25-75 was abnormal in 5 patients and Gus in 8 patients; however, only 3 of them showed abnormal values of both parameters. In the 2 patients with only a spirographic obstruction we observed an increase in static lung compliance. In 5 patients without spirographic obstruction we observed an increase of the elastic recoil of the lung, which probably balanced the decrease of Gus, leading to normal flow. In conclusion, airway obstruction is not frequent in sarcoidosis and can be masked in fibrosing forms, if spirographic measurements only are used.