Dose-ranging study of a new steroid for asthma: mometasone furoate dry powder inhaler.

A new formulation of mometasone furoate (MF) for administration by dry powder inhaler (DPI) was evaluated for the treatment of asthma. A 12-week, double-blind, placebo-controlled dose-ranging study compared the efficacy and safety of three doses of MF DPI (100, 200 and 400 mcg b.i.d) with beclomethasone dipropionate (BDP) 168 mcg b.i.d. administered by metered dose inhaler in 365 adult or adolescent patients being treated with inhaled glucocorticoids. The mean change from baseline to endpoint (last treatment visit) for forced expiratory volume in 1 sec (FEV1) was the primary efficacy variable. Secondary efficacy variables included other objective measures of pulmonary function [forced vital capacity (FVC), forced expiratory flow 25-75% (FEV25-75%.) and peak expiratory flow rate (PEFR)] as well as subjective measures of therapeutic response (patients' daily evaluation of asthma symptoms and physicians' evaluation). At endpoint, all four active treatments were significantly more effective than placebo (P < 0.01) in improving FEV1 (MF DPI 5 to 7%, BDP 3%, placebo -6.6%) and all other measures of pulmonary function (FVC: MF DPI 4 to 5%, BDP 2%, placebo -4.7%; FEF25-75%: MF DPI 6 to 18%, BDP 7.5%, placebo -9.5%; PEFR (AM): MF DPI 5 to 10%, BDP 5.7%, placebo -7%). A consistent trend was observed for better improvement in patients treated with MF DPI 200 mcg b.i.d. than with MF DPI 100 mcg b.i.d., with no apparent additional benefit of MF DPI 400 mcg b.i.d. Results for the MF DPI 100 mcg b.i.d. and BDP 168 mcg b.i.d. treatment groups were similar. Patients' and physicians' subjective evaluations of symptoms found similar improvement in the MF DPI 200 and 400 mcg b.i.d. treatment groups, which were slightly better than that in the MF DPI 100 mcg b.i.d. group. Symptoms tended to worsen in the placebo group. MF DPI was well tolerated at all dose levels and the most frequently reported treatment-related adverse effects were headache, pharyngitis and oral candidiasis. No evidence of HPA-axis suppression was detected in any treatment group. In summary, all doses of MF DPI were well tolerated and significantly improved lung function and MF DPI 400 mcg (200 mcg b.i.d.) was the optimal dose in this study of patients with moderate persistent asthma.

Utility of thallium-201 scintigraphy in detecting right ventricular dysfunction in pulmonary embolism.

Acute right ventricular dysfunction has been established both as a diagnostic and prognostic indicator in pulmonary embolism. This report illustrates the utility of thallium-201 scintigraphy as an adjunctive noninvasive test in the diagnosis of pulmonary embolism by demonstrating increases in regional right ventricular perfusion and its subsequent resolution with treatment presumably as a result of decreased pressure work.

Acute respiratory failure in pregnancy. An analysis of 19 cases.

We studied 19 peripartum patients with acute respiratory failure associated with pregnancy. Although it is an uncommon event, noncardiogenic pulmonary edema is the most common cause of respiratory failure in the peripartum period. This acute lung injury syndrome was observed to be associated with a variety of complications of pregnancy including premature labor, the use of tocolytics, infection, hypertension, leukoagglutinin reactions, aspiration, abruptio placentae, and amniotic fluid embolism. From 1989 through 1992 there were 10,852 deliveries and 19 patients with noncardiogenic pulmonary edema at our institution. Analyzing these cases has led us to favor the hypothesis that the respiratory failure associated with the various complications of pregnancy primarily represents the fatal and nonfatal cases of amniotic fluid embolism that Steiner and Lushbaugh initially believed undoubtedly to exist. Moreover, we suggest, as have others, that the nonspecific symptom complex of inflammation, coagulopathy, and cardiopulmonary failure represents the release of soluble mediators into the maternal circulation. It is not clear what the predominant mediator is, but we have focused on platelet activating factor. It is also not established whether the mediator(s) is of amniotic fluid origin or a result of maternal anaphylactoid-type of response to a fetal or amnioplacental antigen. In conclusion, monitoring maternal oxygenation either directly or indirectly by oximetry should be considered routinely in the peripartum period, especially in complicated pregnancies, to detect at an early stage "asymptomatic" or preclinical cases of noncardiogenic pulmonary edema, in hopes of then modifying management to prevent their progression.

Thallium-201 scintigraphy in the evaluation of graft dysfunction in lung transplantation. Newark Beth Israel Medical Center Lung Transplant Group.

The object of this study was to evaluate graft dysfunction utilizing thallium-201 scintigraphy in patients who had undergone lung transplantation. We studied 11 patients who had undergone single-lung transplantation and had 44 evaluations for suspected graft dysfunction. All evaluations included a lung thallium-201 scan and chest radiography. In addition, 42 transbronchial biopsies, 19 gallium-67 scans and 28 pulmonary function tests were obtained. Rejection was defined by histopathology and/or the response to an empirical pulse of methylprednisolone, while cultures of protected specimen brushes and blood with a positive chest radiograph were used to define infection. The sensitivity of thallium scintigraphy for diagnosing rejection and/or infection (94%) was higher than that for transbronchial biopsy (86%), gallium scintigraphy (47%), chest radiography (67%), or spirometry testing (30%). Specificity was 100% for thallium scintigraphy and transbronchial biopsy, as compared to chest radiography and spirometry, which were 75 and 80% respectively. This study indicated that thallium-201 scintigraphy is useful for screening lung transplant recipients for episodes of acute rejection and/or infection. A positive scan is confirmation of graft parenchymal dysfunction and may then be followed by empirical treatment or bronchoscopy with transbronchial biopsy and culture to differentiate rejection and infection.

Right ventricular dysfunction in obstructive sleep apnoea: reversal with nasal continuous positive airway pressure.

The incidence and pathogenesis of right ventricular dysfunction in obstructive sleep apnoea (OSA) remains controversial. Using nuclear ventriculography, the prevalence of right ventricular dysfunction (RVD) was therefore determined in obese patients with OSA, as well as their clinical characteristics, arterial blood gas values, spirometry and sleep parameters. The reversibility of RVD was evaluated after long-term use of nasal continuous positive airway pressure (nCPAP). We studied 112 obese patients with OSA by nuclear ventriculography, 35 with RVD (Group 1), 77 without RVD (Group 2), and 14 patients without OSA as controls (Group 3). Repeat nuclear ventriculography was performed in seven patients who used nCPAP nightly for 6-24 months. The mean right ventricular ejection fractions (RVEF) were 31%, 47% and 44% in Groups 1, 2 and 3, respectively. Group 1 also had a lower left ventricular ejection fraction (LVEF) of 55 vs 63% in Group 2. The OSA groups did not differ in mean spirometric or arterial blood gas values. Group 1 had a lower mean nocturnal arterial oxygen saturation (Sa,O2) of 82 vs 87% in Group 2, and a longer apnoea duration of 22.3 vs 19.2 s. All but two patients in Group 1 had either awake alveolar hypoventilation or an apnoea + hypopnoea index > 40 disordered breathing events.h-1. Repeat nuclear ventriculography after nCPAP revealed an increase in RVEF from 30 to 39%. In conclusion, right ventricular dysfunction is common in obstructive sleep apnoea, but it is reversible with nasal continuous positive airway pressure treatment and appears to be related to nocturnal oxygen desaturation.

Exercise and resting pulmonary function in sarcoidosis.

Patients with sarcoidosis frequently complain of exercise intolerance but reports of the value of static tests of pulmonary function in predicting disability have been contradictory. We studied 32 patients with sarcoidosis and dyspnea, correlating x-ray stages, spirometry and lung volume measurements with graded exercise testing. Patients demonstrated a reduction in maximum workload (Wmax) when compared to an age matched group of 7 normal subjects (p < 0.05). While ventilation (VEmax) at Wmax was lower in patients, when adjusted for workload (V/E/watt) there was relative hyperventilation (p < 0.05). Exercise induced arterial desaturation (PaO2 decrease) was significantly related to resting DLCO% predicted (r = 0.74, p < 0.05). When patients were separated into subgroups of > < DLCO 55% predicted, the lower diffusing capacity group had a lower Wmax and greater fall in exercise PaO2. Chest radiograph staging and the vital capacity proved to be poor predictors of exercise capacity though maximum impairment was associated with advanced x-ray changes and greater decreases in vital capacity. In conclusion, the magnitude of functional impairment may vary widely from apparent histopathologic involvement as reflected by chest x-ray and lung volumes. Actual exercise testing is necessary to accurately characterize and quantitate the impairment in patients with sarcoidosis complaining of dyspnea.

Cardiopulmonary resuscitation in intensive care unit and non-intensive care unit patients. Immediate and long-term survival.

OBJECTIVE: To determine the effect of location within the hospital and preexisting electrocardiographic rhythm on the outcome of cardiopulmonary resuscitation, the cardiopulmonary resuscitation records for a 3-year period, including 668 hospitalized patients, were retrospectively reviewed. RESULTS: Resuscitation was successful in only 12 patients in the intensive care unit (3.3%) and 43 patients not in the intensive care unit (14.0%), 20 of whom were on a telemetry unit. Patients who survived to discharge had similar 1-year survival rates regardless of initial hospital location, although intensive care unit patients had the best 3-year survival rate, and there were no survivors at 3-years in the group that received cardiopulmonary resuscitation in the nonmonitored hospital bed. Survival was best with an initial cardiac rhythm of ventricular tachycardia or fibrillation, but all non-ventricular tachyarrhythmias were associated with survival. Age was not an apparent factor, while survival to hospital discharge favored whites over blacks. CONCLUSIONS: Futile resuscitative efforts are routinely performed in part because physicians and patients are unaware of outcome results and factors that influence survival. A wider recognition of the limitations of cardiopulmonary resuscitation should lead to advanced directives that reflect this awareness, with substantially more patients choosing not to have cardiopulmonary resuscitation.

Superior vena cava syndrome: current concepts of management.

Superior vena cava syndrome usually results from extraluminal compression by tumor or intraluminal thrombosis due to an indwelling catheter. Percutaneous interventional techniques and thrombolysis allow for immediate relief of symptoms with low recurrence rates.

Comparison of thallium-201 and gallium-67 citrate scintigraphy in the diagnosis of pulmonary disease.

Gallium is presently used in the diagnosis of inflammatory, granulomatous, and neoplastic lung disease despite its many logistical problems. In contrast, thallium-201 scintigraphy, which was initially developed for myocardial imaging, offers the principal advantage of immediate imaging and diagnosis although it had not been investigated previously for use in pulmonary disease. In this study, thallium and gallium were prospectively compared with each other for the diagnosis of a variety of lung diseases. The overall concordance rate was 75%. Thallium was found to be significantly more sensitive than gallium for the entire group studied (N = 51, p < 0.006). In a subset of patients in whom a firm diagnosis was established, thallium was also found to be more sensitive, 86% vs 64%. The greater sensitivity of thallium-201 and its several inherent advantages suggest that thallium-201 should replace gallium-67 citrate as the radioisotope of choice for nuclear imaging of the chest.

Environmental lung disease in New Jersey.

The lungs are peculiarly susceptible to insults that are experienced indoors and outdoors, infectious and noninfectious. Diagnosis is made through history and awareness of the increasing prevalence and number of causes of environmental lung disease.

Current concepts in chronobiology and medicine.

Circadian rhythms must be considered as potential causes of medical problems if they are disrupted. These problems can be treated, with drugs, light, and chronotherapeutic techniques. Utilizing chronobiologic principles, some patients may be able to cope and overcome desynchronization.

Cardiopulmonary effects of environmental tobacco smoke.

Passive smoking causes pulmonary and cardiovascular disease in children and adults. Environmental exposure to tobacco smoke in the home and in the workplace puts nonsmokers at risk and creates significant health and economic consequences.

Asthmatic extrathoracic upper airway obstruction: laryngeal dyskinesis.

Laryngeal dyskinesis is a functional asthma-like disorder refractory to bronchodilator regimens. Patients treated with electroencephalographic neurofeedback training demonstrate clinical improvement with reversal of their variable extrathoracic upper airway obstruction.