Cardiopulmonary exercise testing (CPET) in pulmonary emphysema.

In patients affected by chronic obstructive pulmonary disease (COPD), cardiopulmonary response to exercise was never related to the severity of emphysema (E) measured by high resolution computed tomography (HRCT). Sixteen patients (age=65±8 yrs; FEV(1)=54±18%pred; RV=160±28%pred) with moderate to severe E (quantified by lung HRCT as % voxels <-910 HU) were exercised on a cycle-ergometer to exhaustion. Oxygen uptake (V˙(O2)), carbon dioxide output (V˙(CO2)), ventilation (V˙(E)), tidal volume (V(T)), and end-tidal P(CO2) (PET(CO2)) derived variables were measured breath-by-breath. The % of E correlated with: (1) the ratio V(Tpeak) (r=0.74; p=0.001); (2) the V˙(E)/V˙(CO2) slope (r=-0.77; p=0.0004); (3) PET(CO2) values at peak exercise (r=0.80; p=0.0001). Also, the %E was strongly predicted by the following exercise equation: %E(EST) = 58.1 + 11.9 × ΔV˙(E)/V˙(CO2) (r=0.94; p<0.0001). A V(Tpeak)/FEV1 ratio>1 is typically observed in severe E patients; furthermore, the V˙(E)/V˙(CO2) slope and the PET(CO2peak) values decrease and increase respectively as more as the emphysema is severe.

Effect of heliox on heart rate kinetics and dynamic hyperinflation during high-intensity exercise in COPD.

Respiratory mechanical abnormalities in patients with chronic obstructive pulmonary disease (COPD) may impair cardiodynamic responses and slow down heart rate (HR) kinetics compared with normal resulting in reduced convective oxygen delivery during exercise. We reasoned that heliox breathing (79% helium-21% oxygen) and the attendant reduction of operating lung volumes should accelerate HR kinetics in the transition from rest to high-intensity exercise. Eleven male ambulatory patients with clinically stable COPD undertook constant work-rate cycle testing at 80% of each individuals' maximum work capacity while breathing room air (RA) or heliox (HX), randomly. Mean response time (MRT) for HR and dynamic end-expiratory lung volume (EELV) were measured. Resting EELV was not affected by HX breathing, while exercise EELV decreased significantly by 0.23 L at isotime during HX breathing compared with RA. During HX breathing, MRT for HR significantly accelerated (p = 0.002) by an average of 20 s (i.e., 17%). Speeded MRT for HR correlated with indices of reduced lung hyperinflation, such as EELV at isotime (r = 0.88, p = 0.03), and with improved exercise endurance time (r = -0.64, p = 0.03). The results confirm that HX-induced reduction of dynamic lung hyperinflation is associated with consistent improvement in indices of cardio-circulatory function such as HR kinetics in the rest-to-exercise transition in COPD patients.

Analyses of T cell phenotype and function reveal an altered T cell homeostasis in systemic sclerosis. Correlations with disease severity and phenotypes.

We investigated in systemic sclerosis (SSc) patients the T cell homeostasis and its relationship with the clinical course of the disease. Distribution of peripheral T cell subsets, thymic output, lymphocyte proliferation and apoptosis were analyzed by flow cytometry or ELISA. Age inappropriate levels of naive CD4(+) T cells and thymic output were observed. Proliferation of CD4(+) T cells, lymphocyte apoptosis and CD4(+) regulatory T (Treg) cell frequency were significantly higher than those observed in controls and significantly correlated with clinical phenotypes and clinical progression parameters i.e., diffusing capacity of the lung for carbon monoxide (DLCO) and disease activity. These data indicate that the evaluation of the T cell homeostasis can represent a valuable prognostic tool for SSc patients and it is useful to distinguish between limited and diffuse phenotypes. A therapeutic intervention targeted at reversing T cell homeostasis abnormalities would therefore potentially be helpful in counteracting disease progression.

Effect of heliox on lung dynamic hyperinflation, dyspnea, and exercise endurance capacity in COPD patients.

We tested the hypothesis that heliox breathing, by reducing lung dynamic hyperinflation (DH) and dyspnea (Dys) sensation, may significantly improve exercise endurance capacity in patients with chronic obstructive pulmonary disease [n = 12, forced expiratory volume in 1 s = 1.15 (SD 0.32) liters]. Each subject underwent two cycle ergometer high-intensity constant work rate exercises to exhaustion, one on room air and one on heliox (79% He-21% O2). Minute ventilation (VE), carbon dioxide output, heart rate, inspiratory capacity (IC), Dys, and arterial partial pressure of CO2 were measured. Exercise endurance time increased significantly with heliox [9.0 (SD 4.5) vs. 4.2 (SD 2.0) min; P < 0.001]. This was associated with a significant reduction in lung DH at isotime (Iso), as reflected by the increase in IC [1.97 (SD 0.40) vs. 1.77 (SD 0.41) liters; P < 0.001] and a decrease in Dys [6 (SD 1) vs. 8 (SD 1) score; P < 0.001]. Heliox induced a state of relative hyperventilation, as reflected by the increase in VE [38.3 (SD 7.7) vs. 35.5 (SD 8.8) l/min; P < 0.01] and VE/carbon dioxide output [36.3 (SD 6.0) vs. 33.9 (SD 5.6); P < 0.01] at peak exercise and by the reduction in arterial partial pressure of CO2 at Iso [44 (SD 6) vs. 48 (SD 6) Torr; P < 0.05] and at peak exercise [46 (SD 6) vs. 48 (SD 6) Torr; P < 0.05]. The reduction in Dys at Iso correlated significantly (R = -0.75; P < 0.01) with the increase in IC induced by heliox. The increment induced by heliox in exercise endurance time correlated significantly with resting increment in resting forced expiratory in 1 s (R = 0.88; P < 0.01), increase in IC at Iso (R = 0.70; P < 0.02), and reduction in Dys at Iso (R = -0.71; P < 0.01). In chronic obstructive pulmonary disease, heliox breathing improves high-intensity exercise endurance capacity by increasing maximal ventilatory capacity and by reducing lung DH and Dys.