Nirmal B. Charan

Impaired Bronchodilator Response to Albuterol in Healthy Elderly Men and Women

BACKGROUND Lymphocytes of normal elderly subjects and young asthmatics display dysfunctional beta-adrenoceptors. If beta-adrenoceptor dysfunction were found in senescent airways, it might help explain the pathogenesis of late onset asthma. METHODS The bronchodilatory effects of albuterol after methacholine-provoked bronchoconstriction were compared in 17 healthy young (age 20 to 36 years) and 17 healthy elderly (age 60 to 76 years) volunteer subjects. Albuterol was inhaled via dosimeter (initially 7.8 micrograms, doubling every 7.5 min) with forced expiratory flow at 50% vital capacity (FEF50) measured prior to each dose. Albuterol sensitivity was expressed as the cumulative logarithm of the area under the FEF50 recovery curve (AUC); a greater AUC meant lower sensitivity. On another study day, spontaneous recovery from methacholine was assessed similarly. RESULTS There was no intergroup difference in spontaneous recovery. Despite lower methacholine doses provoking similar (35%) FEF50 falls in elderly subjects, albuterol AUC was greater in elderly subjects (6,552%.min.microgram) than young subjects (3,922%.min microgram; p = 0.03). Multiple regression showed that AUC and age were related (p = 0.02). CONCLUSION Airway beta 2-adrenoceptor responsiveness is diminished in old age, suggesting that airway beta-adrenoceptor dysfunction may be implicated in late-onset asthma.

Controlled trial of inhaled fluticasone propionate in moderate to severe COPD

Inhaled corticosteroids are often used in the treatment of stable chronic obstructive pulmonary disease (COPD), however, studies of these agents have had mixed results. Previous trials have often excluded subjects with bronchodilator response, have failed to evaluate effect on gas exchange, and have usually looked at only post- rather than prebronchodilator forced expiratory volume (FEV). Our objective was to better assess the efficacy of topical corticosteroids in the treatment of COPD. We used a prospective, randomized, double-blinded, placebo-controlled, crossover study at the Outpatient Department, Department of Veterans Affairs Medical Center. Thirty-six COPD patients with a mean (± SD) FEV1 of 1.10 ± 0.43 L, with or without significant bronchodilator response participated in the study. Subjects received a 3-month course of inhaled fluticasone propionate (220 mg/puff) or identical-appearing placebo by metered-dose inhaler at 2 puffs twice daily, followed by crossover to the alternative inhaler for an additional 3 months. Fluticasone treatment resulted in a higher prebronchodilator FEV1 (1.17 ± 0.08 L [mean ± SEM] versus 1.07 ± 0.08 L, p = 0.001), a higher PaO2 (66.6 ± 1.4 mmHg versus 63.6 ± 1 .6 mmHg, p = 0.002), and a better dyspnea score on the chronic respiratory questionnaire (3.70 ± 0.18 versus 3.47 ± 0.19, p = 0.03). A trend towards fewer exacerbations with fluticasone did not quite meet statistical significance (p = 0.11). Inhaled fluticasone over 3 months improved prebronchodilator airflow obstruction and oxygenation while decreasing dyspnea in moderate to severe COPD. Postbronchodilator FEV1 was not significantly changed.

Effect of increased coronary venous pressure on left ventricular function in sheep.

We studied the effect of increased coronary venous pressure (Pcv) on left ventricular (LV) function in nine anesthetized open-chested sheep. Pcv was increased by inflating a balloon in the coronary sinus. LV function was estimated by measuring maximum rate of change in LV pressure (dP/dt max) and LV end-diastolic pressure (LVEDP). Left anterior descending (LAD) coronary artery blood flow was measured with an electromagnetic flow probe. A control group (n=6) was studied similarly except that Pcv was not elevated. After completion of the experiment, LV wet/dry weight ratios were measured to estimate LV myocardial water content. The balloon inflation increased Pcv from 8.6+/-1.1 to 23.8+/-1.7 mmHg (mean+/-SEM), which decreased dP/dt max from 1611+/-236 at baseline to 1041+/-210 after 120 min of increased Pcv (P < 0.05). The dP/dt max in the control group did not change significantly. Heart rate, LAD flow, LVEDP, and aortic pressures were similar in two groups but the LV water content was significantly higher (P < 0.05) in the experimental group (76.2+/-1.0 vs. 79.1+/-0.5%). These data suggest that acute increases in Pcv result in LV dysfunction and that coronary vascular congestion and myocardial edema may, at least in part, be responsible for this finding.

A Catastrophic Presentation of Adult Croup

Figure 1. (A) Chest radiograph upon arrival to the emergency department. (B) A magnified view of airway section of chest radiograph to demonstrate “steeple sign” (a tapering of subglottic airway) indicating airway narrowing as marked by arrow. Figure 2. Computed tomography neck without contrast at the level of the arytenoid cartilages after intubation showing complete obliteration around the endotracheal tube (arrow) of airway at the level of glottis, and below (seen in other images).

Bronchovascular Responses to Intravenous Contrast Media for Helical CT Pulmonary Angiography

CT angiography is now commonly used for the diagnosis of pulmonary embolism, but the contrast media used for imaging produces various hemodynamic changes. In this study, we investigated the bronchovascular and hemodynamic responses to intravenous iopromide, a non-ionic contrast agent used for pulmonary CT angiograms, in anesthetized, mechanically ventilated sheep (n = 6). Bronchial blood flow and cardiac output were measured with ultrasonic flow probes. Systemic and pulmonary arterial pressures were continuously monitored. Injections of 0.9% NaCl (120 ml over 30 s) or iopromide (300 mg/ml, 120 ml over 30 s) were given in random order in a peripheral vein with an angiogram infuser and hemodynamic changes were determined. After these parameters returned to baseline, the left pulmonary artery (LPA) was occluded with a snare and the animals were allowed to stabilize. Injections of NaCl and iopromide were repeated in random order as before. There were no significant hemodynamic effects with infusion of NaCl. With intact pulmonary vasculature, NaCl and iopromide did not cause significant changes in arterial blood gases, however, cardiac output (QT, L/min), mean systemic and pulmonary arterial pressures (PSA and PPA, Torr) increased and bronchovascular resistance (BVR, Torr × min/ml), decreased. Following LPA ligation, pH and PO2 significantly decreased over baseline, whereas PCO2 increased. After LPA ligation, iopromide produced a greater decrease in BVR as compared with preligation intact pulmonary vasculature. In conclusion, iopromide caused rapid hemodynamic changes and decreased BVR, likely secondary to osmolar stress. Bronchovascular effects were more pronounced after pulmonary arterial occlusion.

Regulation of Lung Water: Role of the Bronchial Circulation

The main function of the lung is to allow transfer of oxygen and carbon dioxide molecules across the alveolar-capillary membrane. In order to achieve this task most efficiently, the lung must free itself of excess liquid, proteins, and other debris. Under normal conditions, there is continuous leakage of water from the alveolar capillaries into the interstitial space, which is eventually reabsorbed and restored to the circulation.