Effects of lung deflation induced by tiotropium/olodaterol on the cardiocirculatory responses to exertion in COPD.

BACKGROUND: Hyperinflation has been associated with negative cardiocirculatory consequences in patients with chronic obstructive pulmonary disease (COPD). These abnormalities are likely to worsen when the demands for O2 increase, e.g., under the stress of exercise. Thus, pharmacologically-induced lung deflation may improve cardiopulmonary interactions and exertional cardiac output leading to higher limb muscle blood flow and oxygenation in hyperinflated patients with COPD. METHODS: 20 patients (residual volume = 201.6 ±â€¯63.6% predicted) performed endurance cardiopulmonary exercise tests (75% peak) 1 h after placebo or tiotropium/olodaterol 5/5 µg via the Respimat® inhaler (Boehringer Ingelheim, Ingelheim am Rhein, Germany). Cardiac output was assessed by signal-morphology impedance cardiography. Near-infrared spectroscopy determined quadriceps blood flow (indocyanine green dye) and intra-muscular oxygenation. RESULTS: Tiotropium/olodaterol was associated with marked lung deflation (p < 0.01): residual volume decreased by at least 0.4 L in 14/20 patients (70%). The downward shift in the resting static lung volumes was associated with less exertional inspiratory constraints and dyspnoea thereby increasing exercise endurance by ~50%. Contrary to our premises, however, neither central and peripheral hemodynamics nor muscle oxygenation improved after active intervention compared to placebo. These results were consistent with those found in a subgroup of patients showing the largest decrements in residual volume (p < 0.05). CONCLUSIONS: The beneficial effects of tiotropium/olodaterol on resting and operating lung volumes are not translated into enhanced cardiocirculatory responses to exertion in hyperinflated patients with COPD. Improvement in exercise tolerance after dual bronchodilation is unlikely to be mechanistically linked to higher muscle blood flow and/or O2 delivery.

Low-density areas on high-resolution computed tomograms in chronic pediatric asthma.

OBJECTIVE: In children with chronic persistent asthma, we evaluated whether the presence of increased residual volume (RV) after anti-inflammatory treatment correlates with the detection of low-density areas on high-resolution computed tomography (HRCT), similar to those in emphysema. METHODS: Children with a confirmed diagnosis of asthma (n = 32) were enrolled in a prospective study. All patients had reduction of airflow in the peripheral airways, increased RV, and increased serum eosinophil cationic protein (ECP) values indicating airway inflammation. All the children were treated with salmeterol (50 microg twice daily) and fluticasone (250 microg twice daily) for a 3-month period. RESULTS: At the end of treatment, peripheral eosinophil counts, serum ECP, forced expiratory volume in 1 second (FEV(1)), mean forced expiratory flow during the middle half of forced vital capacity (FEF(25-75)), RV, and total lung capacity values improved in all the patients. HRCT was normal in 22 children (68.8%); in the remaining 10 subjects, low-density areas were found despite normalization of FEV(1), FEF(25-75), and significant reduction in ECP. A significant correlation was found between persistence of RV values >150% predicted and the presence of low-density areas on HRCT (r = 0.84, P <.0001). CONCLUSIONS: Structural changes similar to emphysema are also present in asthmatic children. Our findings suggest that the persistence of increased RV may be used to identify subjects with low-density areas on HRCT.