Albuterol delivery by metered-dose inhaler in a mechanically ventilated pediatric lung model.

OBJECTIVES: To assess albuterol delivery by metered-dose inhaler in a mechanically ventilated pediatric lung model and to determine the influence of the following variables on albuterol delivery: endotracheal tube diameter; type of spacer; humidification; and pulmonary mechanics. DESIGN: Prospective, in vitro, laboratory study. SETTING: Research laboratory. INTERVENTIONS: A model, consisting of a volume-cycled ventilator, pediatric breathing circuit, 4.0- or 6.0-mm endotracheal tube, and lung simulator, was assembled. Ventilator settings were: tidal volume 250 mL; FIO2 0.5; inspiration/expiration ratio 1:3; respiratory rate 25 breaths/min; positive end-expiratory pressure 3 cm H2O; temperature 35 degrees C; and a decelerating flow pattern, using dry and humidified air. Lung simulator compliance and resistance values were consistent with those values reported for healthy childeren (20 mL/cm H2O and 40 cm H20/L/sec) and children with pulmonary disease (10 mL/cm H2O and 60 cm H2O/L/sec). Pulmonary mechanics were verified with a pulmonary function diagnostic system. Ten metered-dose inhaler canisters were used to administer 2000 micrograms of albuterol, using either a collapsible or a rigid spacer. A circuit filter placed immediately proximal to the test lung collected drug exiting the endotracheal tube. The filter was rinsed with water and albuterol concentrations were determined by high-performance liquid chromatography. Each variable was tested in triplicate. MEASUREMENTS AND MAIN RESULTS: Albuterol delivery was significantly (p < or = .05) greater for the 6.0-mm endotracheal tube, rigid spacer, dry air, and pulmonary disease mechanics by multifactor analysis of variance. Drug delivery in humidified air with pulmonary disease mechanics using the rigid chamber was 2.5 =/- 0.27% and 6.3 =/- 0.99% for the 4.0- and 6.0-mm endotracheal tubes, respectively. CONCLUSIONS: These in vitro results suggest that pulmonary disease mechanics and a 6.0-mm endotracheal tube improve albuterol delivery. Future clinical investigations in intubated pediatric patients with pulmonary disease are needed to address the clinical significance of these results.

Adjuvant therapy of node-negative breast cancer.

OBJECTIVE: To present the controversies regarding adjuvant cytotoxic chemotherapy or hormonal therapy in patients with node-negative breast cancer, and to evaluate the use of prognostic factors in identifying patients with node-negative breast cancer who will benefit from adjuvant therapy. DATA SOURCE: A MEDLINE search was performed to identify pertinent primary literature and review articles. Articles also were identified through Current Contents, textbooks, and bibliographies of selected articles. DATA EXTRACTION: The most recent clinical trials that evaluated cytotoxic chemotherapy or hormonal therapy in patients with node-negative breast cancer were chosen. Recent review articles and clinical trials that analyzed prognostic factors also were evaluated. DATA SYNTHESIS: The treatment of patients with node-negative breast cancer remains controversial. Approximately 60-80% of patients with this diagnosis will be alive 10 years after initial treatment without adjuvant therapy. The use of chemotherapy or hormonal therapy in node-negative disease increased after the 1988 National Cancer Institute Clinical Alert. Since that time, the research in node-negative breast cancer has focused on identifying prognostic factors and evaluating new treatment regimens. It is hoped that prognostic factors will help direct treatment decisions by identifying subgroups of patients who may benefit from adjuvant therapy. Prognostic factors currently being evaluated include tumor size, hormonal receptors, ploidy status, S-phase fraction, and cathepsin D. CONCLUSIONS: Many patients with node-negative breast cancer will be cured by local therapy alone. Even so, up to 58% of node-negative patients may develop recurrent disease. Reduction of breast cancer recurrence in patients with node-negative breast cancer has been documented as a result of adjuvant chemotherapy or tamoxifen. Of utmost priority is the identification of patients with node-negative breast cancer at highest risk for recurrence so that they may receive appropriate adjuvant therapy with curative intent, while sparing patients at lower risk for recurrence the toxic effects and financial burden incurred by unnecessary adjuvant treatment.