RATIONALE: It has been proposed that forced expiratory flow between 25 and 75 percent ) might be considered to be a more sensitive early marker of obstruction in small airways than forced expiratory volume in 1 second (FEV 1 ).Thus, we proposed that the presence and degree of positive responses to bronchial methacholine testing were related to the difference (DFF) and the ratio (RFF) between FEV 1 and FEF 25-75 in asthmatic children.METHODS: Subjects were 583 symptomatic children, including 323 children with BHR and 259 controls.Pulmonary function tests, methacholine challenge tests and skin prick tests were performed, and total eosinophil count, total serum IgE, serum eosinophil cationic protein were measured in all subjects.From a concentration-response curve, the methacholine concentration required to produce a decrease of 20% from post-saline FEV 1 was calculated (PC 20 ).RESULTS: The median DFF and RFF values decreased in controls compared to subjects with bronchial hyperresponsiveness, and this trend was found in groups ranked by its severity.PC 20 had a strong negative correlation with DFF and RFF.Cutoff values of 0.5 for DFF and 1.042 for RFF were identified, and sensitivity and specificity were calculated.CONCLUSION: This study revealed that DFF and RFF might be predictive of bronchial hyperresponsiveness in the context of normal FEV 1 in children.

RATIONALE: The purpose of this study was to assess the diurnal variability of eNO in patients with asthma. METHODS: 31 asthmatic patients (19 adults, 12 pediatrics) across severity were recruited for a single-site, double-blinded study to obtain daily measurements of eNO for 30 days utilizing a novel biosensor-based technology. Patients measured eNO in the morning and in the evening, completed a daily diary and provided FEV1 measurements at weekly clinic visits. Patients were grouped according to their level of control. The unstable group was defined as having at least one "event" during the course of the study, defined by an increase in inhaled corticosteroid use or the institution of prednisone, ≥ a 15% decrease in FEV1, ≥ 2 night awakenings in 3 out of 7 days or > 4 puffs of albuterol on at least 3 of 7 days. RESULTS: 21 patients were characterized as stable and 10 were characterized as unstable. The average diurnal change (AM minus PM eNO) in the stable group was 2.3 ± 7.4 ppb (p=0.17) and in the unstable group prior to an event was 5.3 ± 9.2 ppb (p=0.10). The average diurnal change between groups was not significantly different (p=0.38). CONCLUSIONS: Differences between morning and evening eNO measured on the same day were not clinically relevant. Therefore, it is not necessary to measure eNO at a particular time of day. Additionally, diurnal variability of eNO was not an indicator or a predictor of pending instability of asthma.

RATIONALE: The purpose of this study was to assess the value of frequent eNO measurements in patients with asthma. METHODS: 31 asthmatic patients (19 adults, 12 pediatrics) were recruited for a single-site, double-blinded study utilizing a novel biosensor-based technology. Patients had varying severity of asthma and were grouped according to their level of control. The study involved obtaining daily measurements of eNO for 30 days in the morning and the evening, daily symptom diaries, and FEV1 measurements at weekly clinic visits. The unstable group was defined as having at least one “event” during the course of the study, defined by an increase in inhaled corticosteroid use or the institution of prednisone, ≥15% decrease in FEV1, ≥2 night awakenings in 3 out of 7 days or >4 puffs of albuterol on at least 3 of 7 days. RESULTS: Of the 31 patients, 21 were characterized as stable and 10 were characterized as unstable. Diurnal variability was not statistically different between groups (p=0.10). Mean morning eNO prior to an event in the unstable group was significantly higher than the mean morning eNO in the stable group (54 ± 38 vs. 29 ± 19 ppb, p=0.049). Using the previous morning's eNO measurement as the predictor variable for an instability event, the area under the receiver operating characteristic curve for all subjects was 0.72 (95% CI: 0.64-0.81) indicating the predictive value of eNO for an acute asthmatic event. CONCLUSION: Frequent eNO measurements may have predictive power for impending instability of asthma.

In 17 patients with moderate to severe asthma, we compared acute bronchodilator effects of the following drugs or drug combinations using a double-blind crossover design: terbutaline, 5; aminophyline 400; terbutaline, 5, plus aminophyline, 400; terbutaline, 2.5; aminophylline, 200; terbutaline, 2.5, plus aminophyline, 200 mg; and placebo. The higher doses of terbutaline and aminophylline alone produced comparable bronchodilation and similarly frequent adverse side effects; low doses of each drug also had comparable effects. The high-dose combination produced significantly (P less than 0.05) greater bronchodilatation than either drug alone. The low dose combination had bronchodilator effects comparable to those produced by the higher dose of either drug alone. These findings suggest therapeutic advantages in combining high doses of theophylline and an oral beta adrenergic agonist (terbutaline) in asthma not well controlled on high doses of either drug alone and in combining these drugs in lower doses in patients experiencing intolerable side effects from a high dose of either drug.

Abnormal pulmonary perfusion pathways found at autopsy in patients with hepatic cirrhosis have been suggested as a major cause of hypoxemia in cirrhosis. However, these abnormal vascular channels have been difficult to document during life. In the present study, the pathophysiology of hypoxemia (arterial oxygen tension [PaO2] 48.5 to 68 mm Hg) in three patients with hepatic cirrhosis was investigated utilizing conventional cardiopulmonary tests and a special radionuclide technic for the detection of shunting through small dilated pulmonary vessels. Pulmonary function tests revealed normal spirometry and lung volumes; normal closing volume and single-breath nitrogen washout; abnormal diffusing capacity (41 to 68 per cent of predicted); increased venous admixture on 100 per cent oxygen (O2) (8.1 to 29 per cent); and a decrease in PaO2 after change from the supine to the sitting position and after exercise. Cardiac catheterization revealed normal pulmonary arterial pressures at rest and during exercise, increased cardiac outputs and no intracardiac shunts. Chest roentgenograms and pulmonary angiograms were within normal limits. Utilizing a quantitative radionuclide technic, 10 per cent, 46 per cent and 70.5 per cent of intravenously injected technetium 99m-macroaggregated albumin (99mTc-MAA) particles traversed the pulmonary vasculature and lodged in endorgan systemic capillary beds in the three patients with cirrhosis compared with ⩽6 per cent in eight control subjects.