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1.
J Physiol ; 599(5): 1665-1683, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33428233

RESUMEN

KEY POINTS: Patients with mild chronic obstructive pulmonary disease (COPD) have an elevated ventilatory equivalent to CO2 production ( V̇E / V̇CO2 ) during exercise, secondary to increased dead space ventilation. The reason for the increased dead space is unclear, although pulmonary microvascular dysfunction and the corresponding capillary hypoperfusion is a potential mechanism. Despite emerging evidence that mild COPD is associated with pulmonary microvascular dysfunction, limited research has focused on experimentally modulating the pulmonary microvasculature during exercise in mild COPD. The present study sought to examine the effect of inhaled nitric oxide (iNO), a selective pulmonary vasodilator, on V̇E / V̇CO2 , dyspnoea and exercise capacity in patients with mild COPD. Experimental iNO increased peak oxygen uptake in mild COPD, secondary to reduced V̇E / V̇CO2 and dyspnoea. This is the first study to demonstrate that experimental manipulation of the pulmonary circulation alone, can positively impact dyspnoea and exercise capacity in mild COPD. ABSTRACT: Patients with mild chronic obstructive pulmonary disease (COPD) have an exaggerated ventilatory response to exercise, contributing to dyspnoea and exercise intolerance. Previous research in mild COPD has demonstrated an elevated ventilatory equivalent to CO2 production ( V̇E / V̇CO2 ) during exercise, secondary to increased dead space ventilation. The reason for the increased dead space is unclear, although pulmonary microvascular dysfunction and the corresponding capillary hypoperfusion is a potential mechanism. The present study tested the hypothesis that inhaled nitric oxide (iNO), a selective pulmonary vasodilator, would lower V̇E / V̇CO2 and dyspnoea, and improve exercise capacity in patients with mild COPD. In this multigroup randomized-control cross-over study, 15 patients with mild COPD (FEV1  =  89 ± 11% predicted) and 15 healthy controls completed symptom-limited cardiopulmonary exercise tests while breathing normoxic gas or 40 ppm iNO. Compared with placebo, iNO significantly increased peak oxygen uptake (1.80 ± 0.14 vs. 1.53 ± 0.10 L·min-1 , P < 0.001) in COPD, whereas no effect was observed in controls. At an equivalent work rate of 60 W, iNO reduced V̇E / V̇CO2 by 3.8 ± 4.2 units (P = 0.002) and dyspnoea by 1.1 ± 1.2 Borg units (P < 0.001) in COPD, whereas no effect was observed in controls. Operating lung volumes and oxygen saturation were unaffected by iNO in both groups. iNO increased peak oxygen uptake in COPD, secondary to reduced V̇E / V̇CO2 and dyspnoea. These data suggest that mild COPD patients demonstrate pulmonary microvascular dysfunction that contributes to increased V̇E / V̇CO2 , dyspnoea and exercise intolerance. This is the first study to demonstrate that experimental manipulation of the pulmonary circulation alone, can positively impact dyspnoea and exercise capacity in mild COPD.


Asunto(s)
Óxido Nítrico , Enfermedad Pulmonar Obstructiva Crónica , Estudios Cruzados , Disnea , Prueba de Esfuerzo , Tolerancia al Ejercicio , Humanos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico
2.
Clin Auton Res ; 31(3): 443-451, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33560461

RESUMEN

PURPOSE: Obstructive sleep apnea (OSA) is a common disorder (~ 4%) that augments sympathetic nerve activity (SNA) and elevates blood pressure. The relationship between sympathetic vasomotor outflow and vascular responsiveness, termed sympathetic neurovascular transduction (sNVT), has been sparsely characterized in patients with OSA. Therefore, we sought to quantify spontaneous sympathetic bursts and related changes in diastolic pressure. METHODS: Twelve participants with variable severities of OSA were recruited. We collected muscle sympathetic nerve activity (MSNA) (microneurography) and beat-by-beat diastolic pressure (finger photoplethysmography) during normoxia (FiO2 = 0.21) and hyperoxia (FiO2 = 1.0) to decrease MSNA burst frequency. MSNA burst sequences (i.e. singlets, doublets, triplets and quadruplets) were identified and coupled to changes in diastolic pressure over 15 cardiac cycles as an index of sNVT. sNVT slope for each individual was calculated from the slope of the relationship between peak responses in outcome plotted against normalized burst amplitude. RESULTS: sNVT slope was unchanged during hyperoxia compared to normoxia (normoxia 0.0024 ± 0.0011 Δ mmHg total activity [a.u.]-1 vs. hyperoxia 0.0029 ± 0.00098 Δ mmHg total activity [a.u.]-1; p = 0.14). sNVT slope was inversely associated with burst frequency during hyperoxia (r = -0.58; p = 0.04), but not normoxia (r = -0.11; p = 0.71). sNVT slope was inversely associated with the apnea-hypopnea index (AHI) (r = -0.62; p = 0.030), but not after age was considered. CONCLUSIONS: We have demonstrated that the prevailing MSNA frequency is unmatched to the level of sNVT, and this can be altered by acute hyperoxia.


Asunto(s)
Apnea Obstructiva del Sueño , Sistema Nervioso Simpático , Presión Sanguínea , Humanos , Músculo Esquelético , Músculos
3.
J Physiol ; 596(15): 3233-3244, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29528117

RESUMEN

KEY POINTS: The reason(s) for the increased central arterial stiffness in chronic obstructive pulmonary disease (COPD) are not well understood. In this study, we inhibited the carotid chemoreceptor with both low-dose dopamine and hyperoxia, and observed a decrease in central arterial stiffness and muscle sympathetic nervous activity in COPD patients, while no change was observed in age- and risk-matched controls. Carotid chemoreceptor inhibition increased vascular conductance, secondary to reduced arterial blood pressure in COPD patients. Findings from the current study suggest that elevated carotid chemoreceptor activity may contribute to the increased arterial stiffness typically observed in COPD patients. ABSTRACT: Chronic obstructive pulmonary disease (COPD) patients have increased central arterial stiffness and muscle sympathetic nervous activity (MSNA), both of which contribute to cardiovascular (CV) dysfunction and increased CV risk. Previous work suggests that COPD patients have elevated carotid chemoreceptor (CC) activity/sensitivity, which may contribute to the elevated MSNA and arterial stiffness. Accordingly, the effect of CC inhibition on central arterial stiffness, MSNA and CV function at rest in COPD patients was examined in a randomized placebo-controlled study. Thirteen mild-moderate COPD patients (forced expired volume in 1 s (FEV1 ) predicted ± SD: 83 ± 18%) and 13 age- and risk-matched controls completed resting CV function measurements with either i.v. saline or i.v. dopamine (2 µg kg-1  min-1 ) while breathing normoxic or hyperoxic air (100% O2 ). On a separate day, a subset of COPD patients and controls completed MSNA measurements while breathing normoxic or hyperoxic air. Arterial stiffness was determined by pulse-wave velocity (PWV) and MSNA was measured by microneurography. Brachial blood flow was determined using Doppler ultrasound, cardiac output was estimated by impedance cardiography, and vascular conductance was calculated as flow/mean arterial pressure (MAP). CC inhibition with dopamine decreased central and peripheral PWV, and MAP (P < 0.05) while increasing vascular conductance in COPD. No change in CV function was observed with dopamine in controls. CC inhibition with hyperoxia decreased peripheral PWV and MSNA (P < 0.05) in COPD, while no change was observed in controls. CC inhibition decreased PWV and MSNA, and improved vascular conductance in COPD, suggesting that tonic CC activity is elevated at rest and contributes to the elevated arterial stiffness in COPD.


Asunto(s)
Cuerpo Carotídeo/fisiología , Oxígeno/farmacología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Rigidez Vascular/fisiología , Anciano , Dopamina/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Método Simple Ciego
4.
J Behav Med ; 37(3): 480-90, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23494667

RESUMEN

Techniques to increase physical activity among pulmonary rehabilitation patients outside of the rehabilitation context are warranted. Implementation intentions are a strategy used to initiate goal-directed behaviour, and have been found to be useful in other populations. This study compared the long-term effects of exercise and social implementation intentions interventions on objectively measured physical activity in 40 pulmonary rehabilitation patients randomly assigned to condition. Repeated measures ANOVAs found that those in the exercise implementation intentions group took more steps (p = .007) at the end of pulmonary rehabilitation than those in the social implementation intentions group. Improvements attained by the exercise group during the intervention were not maintained 6-months following rehabilitation. Implementation intentions targeting physical activity appear to have positive short term effects on physical activity, although the long term effects are less consistent. This may be due in part to methods used to assess physical activity behaviour.


Asunto(s)
Terapia Conductista/métodos , Ejercicio Físico/psicología , Enfermedades Pulmonares/rehabilitación , Actividad Motora/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Terapia por Ejercicio/psicología , Femenino , Humanos , Intención , Masculino , Persona de Mediana Edad , Educación del Paciente como Asunto/métodos , Resultado del Tratamiento
5.
COPD ; 9(5): 538-45, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23030585

RESUMEN

Although participation in pulmonary rehabilitation (PR) improves the health outcomes in patients with Chronic Obstructive Pulmonary Disease (COPD), there are insufficient resources to provide PR to all patients with COPD. Thus, predicting which patients are at risk for drop-out and non-response to rehabilitation is necessary in order to optimize limited resources. This study examined which patient characteristics are predictive of PR drop-out and non-response. 814 patients with COPD took part in standard out-patient PR for 8 weeks. Demographic and standard clinical data were collected before the rehabilitation program had started. Data was analyzed retrospectively to determine if baseline patient characteristics could predict drop-out and non-response to rehabilitation. Drop-out was defined as participation in less than 50% of the rehabilitation sessions. Non-response was defined as improvement less than 4% on the St. George's Respiratory Questionnaire (SGRQ). A discriminant function analysis identified age, smoking history, and health status as predictors of patient drop-out, p < .0001, with younger, current smokers and patients with lower health status being at risk for drop-out. No variables measured significantly predicted who those at risk would be for non-response to rehabilitation, p > .05. Pulmonary function data did not predict drop-out or non-response to PR. These findings indicate that perceived impairment (i.e., health status) is more likely to influence completion of rehabilitation than actual pulmonary impairment and that demographic and standard clinical data do not adequately predict patient drop-out and non-response to rehabilitation.


Asunto(s)
Pacientes Desistentes del Tratamiento/estadística & datos numéricos , Enfermedad Pulmonar Obstructiva Crónica/rehabilitación , Insuficiencia del Tratamiento , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Femenino , Predicción , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Cooperación del Paciente/estadística & datos numéricos , Estudios Retrospectivos , Factores de Riesgo , Fumar/epidemiología , Resultado del Tratamiento
6.
Chest ; 160(2): e209-e215, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34366047

RESUMEN

CASE PRESENTATION: A 34-year-old previously healthy man of Korean descent (height, 174 cm; weight, 47.4 kg) demonstrated dyspnea with cough and chest tightness. The patient had no relevant occupational exposures and no history of illicit drug or tobacco use. His medical history was notable for chronic sinus tachycardia of undetermined cause, hypertension, gout, glaucoma of the right eye, and a remote history of an intracranial malignancy 24 years prior treated with unspecified chemotherapy, craniotomy, and ventriculoperitoneal shunt placement. His active medications included diltiazem, candesartan, and colchicine as needed.


Asunto(s)
Fibrosis Pulmonar Idiopática/diagnóstico , Enfermedades Pleurales/diagnóstico , Adulto , Diagnóstico Diferencial , Diagnóstico por Imagen , Disnea , Humanos , Masculino , Neumotórax
7.
J Appl Physiol (1985) ; 127(5): 1278-1287, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31295067

RESUMEN

Recent work demonstrates that carotid chemoreceptor (CC) activity/sensitivity is elevated in patients with chronic obstructive pulmonary disease (COPD) compared with healthy controls, and this elevated chemoreception appears to contribute to increased cardiovascular risk. Exercise training has been shown to normalize CC activity/sensitivity in other populations, and therefore, the purpose of this study was to determine whether pulmonary rehabilitation (PR) can reduce CC activity/sensitivity in COPD. Forty-five COPD patients [mean FEV1 (forced expiratory volume in 1 s) = 56.6% predicted] completed PR, while 15 COPD patients (mean FEV1 = 74.6% predicted) served as non-PR controls. CC activity was determined by the reduction in ventilation while breathing transient hyperoxia ([Formula: see text] = 1.0); CC sensitivity was evaluated by the increase in ventilation relative to the drop in arterial saturation while breathing hypoxia. Dyspnea, six-minute walk and autonomic function data were also obtained. PR improved 6-minute walk distance (P < 0.001) and dyspnea (P = 0.04); however, there was no effect on CC activity (P = 0.60), sensitivity (P = 0.69), or autonomic function (P > 0.05 for all). Subgroup analyses indicated that PR reduced CC activity in those with elevated baseline CC activity, independent of changes in autonomic function. No change in dyspnea (P = 0.24), CC activity (P = 0.19), sensitivity (P = 0.80), or autonomic function (P > 0.05 for all) was observed in the control group. Despite improvements in exercise tolerance and dyspnea, PR appears to be generally ineffective at reducing CC sensitivity in stable COPD patients; while PR reduced CC activity in those with elevated basal CC activity, the physiological significance of this is unclear. Further investigations aimed at improving CC function in COPD are needed.NEW & NOTEWORTHY While work in other chronic diseases has shown that exercise training may help normalize carotid chemoreceptor (CC) activity/sensitivity, the current study found that exercise training through pulmonary rehabilitation did not consistently reduce CC activity/sensitivity in patients with chronic obstructive pulmonary disease (COPD). These results suggest that other interventions are needed to normalize CC activity/sensitivity in COPD.


Asunto(s)
Cuerpo Carotídeo/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/rehabilitación , Anciano , Estudios de Casos y Controles , Disnea/fisiopatología , Humanos , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología
8.
Respir Med ; 160: 105815, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31739245

RESUMEN

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have an exaggerated ventilatory response to exercise, contributing to exertional dyspnea and exercise intolerance. We recently demonstrated enhanced activity and sensitivity of the carotid chemoreceptor (CC) in COPD which may alter ventilatory and cardiovascular regulation and negatively affect exercise tolerance. We sought to determine whether CC inhibition improves ventilatory and cardiovascular regulation, dyspnea and exercise tolerance in COPD. METHODS: Twelve mild-moderate COPD patients (FEV1 83 ±â€¯15 %predicted) and twelve age- and sex-matched healthy controls completed two time-to-symptom limitation (TLIM) constant load exercise tests at 75% peak power output with either intravenous saline or low-dose dopamine (2 µg·kg-1·min-1, order randomized) to inhibit the CC. Ventilatory responses were evaluated using expired gas data and dyspnea was evaluated using a modified Borg scale. Inspiratory capacity maneuvers were performed to determine operating lung volumes. Cardiac output was estimated using impedance cardiography and vascular conductance was calculated as cardiac output/mean arterial pressure (MAP). RESULTS: At a standardized exercise time of 4-min and at TLIM; ventilation, operating volumes and dyspnea were unaffected by dopamine in COPD patients and controls. In COPD, dopamine decreased MAP and increased vascular conductance at all time points. In controls, dopamine increased vascular conductance at TLIM, while MAP was unaffected. CONCLUSION: There was no change in time to exhaustion in either group with dopamine. These data suggest that the CC plays a role in cardiovascular regulation during exercise in COPD; however, ventilation, dyspnea and exercise tolerance were unaffected by CC inhibition in COPD patients.


Asunto(s)
Dopamina/administración & dosificación , Tolerancia al Ejercicio , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Estudios Cruzados , Humanos , Enfermedad Pulmonar Obstructiva Crónica/metabolismo
9.
Respir Med ; 145: 57-65, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30509717

RESUMEN

BACKGROUND: Previous work suggests that mild chronic obstructive pulmonary disease (COPD) patients have greater lung dysfunction than previously appreciated from spirometry alone. There is evidence of pulmonary microvascular dysfunction in mild COPD, which may reduce diffusing capacity (DLCO) and increase ventilatory inefficiency during exercise. The purpose of this study was to determine if DLCO, pulmonary capillary blood volume (Vc), and membrane diffusing capacity (Dm) are diminished during exercise in mild COPD, and whether this is related to ventilatory inefficiency and dyspnea. METHODS: Seventeen mild COPD patients (FEV1/FVC: 64 ±â€¯4%, FEV1 = 94 ±â€¯11%pred) and 17 age- and sex-matched controls were recruited. Ten moderate COPD patients were also tested for comparison (FEV1 = 66 ±â€¯7%pred). DLCO, Vc, and Dm were determined using the multiple-fraction of inspired oxygen (FIO2) DLCO method at baseline and during steady-state cycle exercise at 40W, 50%, and 80% of V˙O2peak. Using expired gas data, ventilatory inefficiency was assessed by V˙E/V˙CO2. RESULTS: Compared to controls, mild COPD had lower DLCO at baseline and during exercise secondary to diminished Vc (P < 0.05). No difference in Dm was observed between controls and mild COPD at rest or during exercise. Patients with high V˙E/V˙CO2 (i.e. ≥34) had lower Vc and greater dyspnea ratings compared to control at 40W. Moderate COPD patients were unable to increase Vc with increasing exercise intensity, suggesting further pulmonary vascular impairment with increased obstruction severity. CONCLUSION: Despite relatively minor airflow obstruction, mild COPD patients exhibit a diminished DLCO and capillary blood volume response to exercise, which appears to contribute to ventilatory inefficiency and greater dyspnea.


Asunto(s)
Volumen Sanguíneo/fisiología , Capilares , Ejercicio Físico/fisiología , Pulmón/irrigación sanguínea , Pulmón/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad
10.
PLoS One ; 11(6): e0158341, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27355356

RESUMEN

UNLABELLED: COPD is associated with elevated cardiovascular risk and a potentiated ventilatory response to exercise. Enhanced carotid chemoreceptor (CC) activity/sensitivity is present in other clinical conditions, has been shown to contribute to sympathetic vasoconstrictor outflow, and is predictive of mortality. CC activity/sensitivity, and the resulting functional significance, has not been well examined in COPD. We hypothesized that CC activity/sensitivity would be elevated in COPD, and related to increased pulse wave velocity (a marker of CV risk) and the ventilatory response to exercise. METHODS: 30 COPD patients and 10 healthy age-matched controls were examined. Participants performed baseline cardiopulmonary exercise and pulmonary function testing. CC activity was later evaluated by the drop in ventilation with breathing 100% O2, and CC sensitivity was then assessed by the ventilatory response to hypoxia (ΔVE/ΔSpO2). Peripheral arterial stiffness was subsequently evaluated by measurement of pulse wave velocity (PWV) using applanation tonometry while the subjects were breathing room air, and then following chemoreceptor inhibition by breathing 100% O2 for 2 minutes. RESULTS: CC activity, CC sensitivity, PWV and the ventilatory response to exercise were all increased in COPD relative to controls. CC sensitivity was related to PWV; however, neither CC activity nor CC sensitivity was related to the ventilatory response to exercise in COPD. CC inhibition by breathing 100% O2 normalized PWV in COPD, while no effect was observed in controls. CONCLUSION: CC activity and sensitivity are elevated in COPD, and appear related to cardiovascular risk; however, CC activity/sensitivity does not contribute to the potentiated ventilatory response to exercise.


Asunto(s)
Enfermedades Cardiovasculares/complicaciones , Ejercicio Físico , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Pruebas de Función Respiratoria , Anciano , Enfermedades Cardiovasculares/fisiopatología , Sistema Cardiovascular/fisiopatología , Estudios de Casos y Controles , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxígeno , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Análisis de la Onda del Pulso , Respiración , Riesgo , Rigidez Vascular/fisiología
11.
Respir Physiol Neurobiol ; 189(1): 188-94, 2013 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-23933008

RESUMEN

Arterial stiffness is predictive of cardiovascular events and is elevated in chronic obstructive pulmonary disease (COPD). As physical inactivity and exercise intolerance are associated with elevated arterial stiffness in health, we hypothesized that lower physical activity would be related to increased arterial stiffness in COPD; and that active COPD patients would have reduced arterial stiffness compared to sedentary counterparts. Arterial stiffness was evaluated using pulse wave velocity (PWV) in 33 COPD patients (FEV1=65% predicted) and 10 controls. FEV(1%pred), peak oxygen consumption (VO(2peak)), and physical activity data were obtained. The inactive COPD group had higher PWV than controls (9.6 vs. 8.3 ms(-1), p<0.05); while there was no difference in PWV between the active COPD group and controls. Within the COPD patients, VO(2peak) (r=-0.44, p=0.01) and physical activity (r=-0.38, p=0.03) were the best predictors of PWV. Physical inactivity and exercise intolerance appear to be related to arterial stiffness in COPD, and may contribute to increased cardiovascular disease risk in COPD.


Asunto(s)
Actividad Motora , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Rigidez Vascular/fisiología , Anciano , Prueba de Esfuerzo , Humanos , Masculino , Pruebas de Función Respiratoria
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