Scholarship 23/10331-6 - Fisioterapia respiratória, Exercícios cardio-respiratórios - BV FAPESP
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Measuring physiological dead space during exercise with breath-by-breath volumetric capnography in dyspneic patients with mild COPD

Grant number: 23/10331-6
Support Opportunities:Scholarships abroad - Research Internship - Doctorate (Direct)
Start date until: September 14, 2024
End date until: May 03, 2025
Field of knowledge:Health Sciences - Physiotherapy and Occupational Therapy
Principal Investigator:Audrey Borghi Silva
Grantee:Guilherme Dionir Back
Supervisor: José Alberto Neder Serafini
Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
Institution abroad: Queen's University, Canada  
Associated to the scholarship:20/15726-0 - Evaluation of pulmonary and endothelial function, autonomic cardiac control and its relation to the exercise capacity in surviving patients of COVID-19: a segment study, BP.DD

Abstract

Mild chronic obstructive pulmonary disease (COPD) is a highly prevalent condition that affects millions of Canadians with a history of smoking. A considerable fraction of these patients reports disproportionately exertional dyspnea compared to their "preserved" forced expiratory volume in one second (FEV1). Extensive evidence generated by our research group in the past decade (summarized here) supports the notion that certain specific abnormalities, whose severity is not adequately captured by FEV1, may be mechanically linked to excessive ventilation (VE) of non-perfused (alveolar dead space or under-perfused areas ("VD effect") of the lungs. These increased areas of "wasted" VE ultimately signal regions of high alveolar ventilation (VA)/capillary perfusion (Qc) ratio, i.e., increased physiological dead space. It is important to note that decreased pulmonary perfusion in patients with mild COPD may not be a mere consequence of capillary destruction, i.e., early/incipient emphysema. Potentially reversible causes of impaired pulmonary blood flow include capillary compression by irregular gas trapping areas induced by small airway disease and, more importantly, endothelial dysfunction associated with decreased sensitivity to endogenous vasodilators. In fact, a low pulmonary diffusing capacity for carbon monoxide (DLCO), indicating inefficient gas exchange due to poor microvascular pulmonary blood flow, was the main correlate of high carbon dioxide production VE (VCO2) in our investigations. Therefore, the objective will be to compare physiological dead space breath-by-breath (VDphys) by volumetric capnography with alveolar ventilation (VA)/capillary perfusion (Qc) measurements by phase-resolved functional pulmonary magnetic resonance imaging (PREFUL-MRI) at rest and during mild to moderate exercise in dyspneic patients with mild COPD presenting with or without excess ventilation, i.e., elevated VE-VCO2. Quantifying the burden of elevated VDphys and VA/Qc in emphysematous and non-emphysematous lung areas at rest and during mild-moderate exercise in dyspneic patients with mild COPD. Methods: Twenty stage GOLD I ("mild") COPD patients (forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio < 0.7 and FEV1 e 80% predicted) will be enrolled. Patients will be evenly divided based on the presence or absence of clinically relevant excess effort ventilation, as established in our previous studies (VE-VCO2nadir e 34).Cardiopulmonary exercise testing (CPET): Standard sensory (0-10 Borg scores of dyspnea and leg discomfort), metabolic, ventilatory, gas exchange (including volumetric capnography), and cardiovascular variables will be obtained during a rapid incremental CPET on a magnetically braked cycle ergometer. VE/VCO2nadir will be defined as the lowest observed value during the incremental phase. After 30 minutes of rest, patients will undergo a two-stage CPET (3 minutes of rest, 4 minutes of exercise each stage, 3 minutes of passive recovery) on an ergometer, magnetically neutral, capable of increasing metabolic demands for light (~0.5±0.1 L/min VO2) and moderate (0.75±0.1 L/min VO2) exercise. Breath-by-breath volumetric capnography: This method utilizes the expired concentration of CO2 (FECO2) as a function of volume for each breath to calculate various compartments of dead space (VD) and relate it to tidal volume (VT), producing the VD/VT, i.e., physiological dead space (VDphys) or the fraction of breath that does not participate in gas exchange. (AU)

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