Comparison of powder and aerosol formulations of salmeterol in the treatment of asthma.

BACKGROUND: The efficacy and safety of the aerosol metered-dose inhaler (MDI) formulation of salmeterol for asthma symptoms have been established. Recently, salmeterol has been introduced as a micronized powder formulation administered via a breath-activated multidose powder inhaler (Diskus). OBJECTIVE: A multicenter, randomized, double-blind, double-dummy, parallel-group, placebo-controlled study involving 498 adolescents and adults with mild-to-moderate asthma was conducted to compare the efficacy and safety of salmeterol powder 50 microg twice daily via Diskus, salmeterol aerosol 42 microg twice daily via MDI, and placebo. METHODS: Patients were randomized to one of the three treatment groups for 12 weeks. Efficacy was assessed by serial measurements of forced expiratory volume in one second (FEV1) over 12 hours, daily peak expiratory flow (PEF), self-rated asthma symptom scores, nighttime awakenings, and supplemental albuterol use. Safety of each treatment was evaluated by monitoring vital signs, electrocardiograms, Holter monitoring, and occurrence of adverse events. RESULTS: As compared with placebo, both salmeterol powder and aerosol produced significant improvement in FEV1 and PEF and decreased nighttime awakenings and supplemental albuterol use. There were no significant differences in the efficacy of the two salmeterol formulations. The magnitude of improvement in pulmonary function was undiminished over the 12-week study. Both formulations of salmeterol were well tolerated, with safety profiles not significantly different from placebo. CONCLUSION: Results of this study indicate that salmeterol, administered either as a powder 50 microg twice daily via Diskus or as an aerosol 42 microg twice daily via MDI, produces clinically significant and comparable improvement in pulmonary function and is well tolerated in patients with mild-to-moderate persistent asthma.

Scurvy resembling cutaneous vasculitis.

Various conditions can imitate cutaneous vasculitis. Scurvy is a less appreciated cause of rash that can resemble vasculitis. Three patients were referred to our rheumatology service for "vasculitis," who subsequently were found to have scurvy. Findings included a purpuric skin rash, myalgias, and malaise. The patients had low vitamin C levels and findings on skin biopsy specimens indicative of scurvy. The three patients were on idiosyncratic diets deficient in vitamin C, and the two patients who allowed us to administer vitamin C therapy improved clinically. We emphasize the importance of a careful dietary history. Early recognition of scurvy is important because it can be treated specifically, and toxic treatment of vasculitis can be avoided.

"AS-SCORE": a multi-attribute clinical index of illness severity.

As techniques to assess the quality of care have proliferated, appropriate concern has arisen about study methods employed by researchers. In particular, studies that focus on a single variable, such as mortality, length of stay (LOS), or complication rate, have sometimes been justly criticized because they have failed to account for differences in the case mixes of providers and the differing severity of illnesses among patients treated. The issue has become even more controversial as third-party payers have attempted to tie reimbursement mechanisms to a single variable, often median or average LOS or average charges for given diagnoses. In the February 1980 issue of the Quality Review Bulletin, the authors of this article discussed a method to investigate variations from areawide average LOS (see "Length of Stay Variations: A Focused Review," pagae 6). The authors concluded that actual differences exist among plhysician practice patterns for the treatment of the same conditions. Although not discussed in that article, the authors devised a method of analysis that incorporated case mix and severity of illness variables to determine whether the correlations they reported were valid. In this article, the authors explain the theory and application of the illness severity index they devised. The index may be of special interest to researchers concerned about whether they are comparing "apples with oranges" or truly discovering differences among providers' practice patterns.--The Editors.

Rib cage deformation during static inspiratory efforts.

Patterns of rib cage (RC) deformation were studied in six normal subjects during moderate static inspiratory efforts such that esophageal pressure (Pes) as an index of transthoracic pressure fell to between -30 and -60 cmH2O during each maneuver. At lung volumes below 50% inspiratory capacity (IC), static inspiratory efforts deformed RC to a more elliptical shape; RC lateral diameter became smaller and RC lateral diameter became larger. However, at high lung volumes (greater than 50% IC) the opposite change in RC dimensions occurred despite similar changes in Pes, i.e., the RC became more circular. These differences in RC deformation did not appear to be a possive consequence of increased lung volume because the RC could be voluntarily deformed to a more circular shape at low lung volume when a) subjects performed static inspiratory efforts mainly with their intercostal and accessory muscles rather than their diaphragm as judged by a smaller change in transdiaphragmatic pressure for the same Pes; or b) subjects statically contracted their diaphragm with it held in a relatively flattened configuration as assessed by a large abdominal AP dimension. We suggest that deformation of the RC during static inspiratory efforts is not as predictable as has previously been suggested but depends on the pattern of contraction and configuration of the respiratory muscles.

Bilateral diaphragmatic paralysis with hypercapnic respiratory failure. A physiologic assessment.

Bilateral diaphragmatic paralysis was suspected in a patient presenting with hypercapnic respiratory failure who exhibited paradoxic (i.e., inward) abdominal movement on inspiration during tidal breathing in the supine posture; no paradoxic abdominal motion was observed at the bedside with the patient upright. Transdiaphragmatic pressure measurements established the diagnosis of diaphragmatic paralysis, although 20 cm H2O pressure developed across the diaphragm during the latter part of a forced expiration, presumably due to the development of passive tension in the diaphragm as it was stretched near residual volume. Analysis of the relative motion of the rib cage and abdomen during breathing by the use of magnetometers confirmed the presence of abdominal paradox throughout the breathing cycle when the patient was supine, and established that paradoxic motion of the abdomen also occurred when the patient was in the erect posture but only in the latter half of inspiration. Our findings confirm that the use of transdiaphragmatic pressure measurements and magnetometry will help to quantify diaphragmatic function, that passive tension develops in the paralyzed diaphragm near residual volume and should not be confused with active contraction, and that paradoxic motion of the abdomen may be masked from the clinician when the patient is erect.

Hyperosmolar nature of diabetic coma.

Stupor in patients with nonketotic hyperglycemia has been ascribed to hyperosmolarity, but the cause of depressed consciousness in patients with ketoacidosis has been puzzling. In this study, blood pH, serum glucose and sodium concentrations, and serum osmolality were measured in eighty-five consecutive episodes of diabetic ketoacidosis and forty-seven of nonketotic hyperglycemia. In the acidotic patients, as in those with nonketotic hyperglycemia, stupor closely paralleled hyperosmolarity and not the severity of acidemia. Indeed, the mean elevations of serum osmolarity were almost the same in the ketotic and in the nonketotic patients who were deeply obtunded. It seems likely that depression of consciousness in patients with severely uncontrolled diabetes mellitus, if not due to a nonmetabolic disorder, such as acute stroke, is attributable to hyperosmolarity, whether or not ketoacidosis is present.