Equivalence of continuous flow nebulizer and metered-dose inhaler with reservoir bag for treatment of acute airflow obstruction.

Traditionally, patients with acute airflow obstruction are treated with bronchodilator aerosols delivered by continuous flow nebulizers. While bronchodilator administration with the metered dose inhaler (MDI) and reservoir or spacer attachment is as effective as administration with the nebulizer in most settings, the former has not been widely accepted for treatment of acute airway obstruction in the emergency room. We compared the efficacy of the continuous flow nebulizer to that of the MDI with InspirEase (reservoir spacer) in 75 patients (45 men and 30 women), ages 18-73 (chi 44 years) who presented to the emergency room with acute asthma and COPD. Subjects in each group (22 COPD and 53 asthma) were randomly assigned to treatment with three puffs of metaproterenol (0.65 mg/puff) via the MDI with InspirEase plus nebulizer with placebo, or placebo MDI with InspirEase plus nebulizer with 15 mg metaproterenol in double blind fashion. Either treatment was given three times at 30 min intervals. The FEV1 and dyspnea scores according to the Borg scale were measured at baseline, 30 min after the first treatment, and 30 min after the third. There was no significant outcome difference between the two treatments in either diagnostic group. There also was no significant outcome difference for patients with baseline FEV1 less than 0.9L. Serum theophylline levels, the need for concomitant therapy with corticosteroids, or additional emergency room therapy after the study, hospitalizations and treatment side effects did not differ between treatment groups. We conclude that there is no demonstrable advantage of a continuous flow nebulizer over an MDI with InspirEase for the treatment of acute airflow obstruction.

Occupational exposure to aerosolized pentamidine.

Occupational exposure to aerosolized pentamidine has raised questions regarding transmission of tuberculosis and the effect of the drug itself. To estimate the exposure of a health care worker, we measured the ambient concentration of aerosolized pentamidine in field conditions in 36 m3 unventilated treatment room. The amount of pentamidine averaged in three different environmental air samples over a four-hour period was 4.5 +/- 3.6 x 10(-5) mg/m3. This amount is very small compared to the doses received by the patients in whom long-term adverse effects are few. The greater risk to health care workers is probably transmission of tuberculosis from undiagnosed cases, especially in populations with an increased incidence of tuberculosis. Tuberculosis control measures such as improved ventilation and masks should also decrease exposure to ambient air pentamidine until toxicity studies determine long-term adverse effects, if any, of aerosolized pentamidine.

Aerosolized pentamidine as second line therapy in patients with AIDS and Pneumocystis carinii pneumonia.

The use of aerosolized pentamidine was investigated in ten patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia (PCP) who had previous or concurrent severe adverse reactions or contraindications to trimethoprim-sulfamethoxazole or parenteral pentamidine. A dose of 600 mg pentamidine in 6 ml sterile water, aerosolized in a small-particle producing jet nebulizer was administered for 25 minutes once daily for an average of 10.5 days to these ten patients. All patients improved their arterial O2 saturation and showed clinical and roentgenographic improvement within six to 21 days of aerosol pentamidine therapy. No adverse systemic reactions occurred. The results of this small open trial indicate that aerosolized pentamidine is effective and can be given safely to AIDS patients with PCP who have had adverse reactions to trimethoprim-sulfamethoxazole or parenteral pentamidine.

Aerosols for systemic delivery of macromolecules.

During the past 50 years, aerosol therapy with small molecules has become the mainstay for managing lung diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. During the past decade, a new therapeutic paradigm has evolved-the delivery of macromolecules into the systemic circulation through the lung. Systemic pulmonary therapy with proteins and peptides resulted from major developments in dry powder drug formulations and aerosol delivery technology. These new technologies will enable the treatment of systemic disease, such as diabetes mellitus, noninvasively by means of the deep lung. Within a decade, it is likely that many medications will be administered in this way.

Aerosolised pentamidine as sole therapy for Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome.

15 patients with first episodes of Pneumocystis carinii pneumonia and the acquired immunodeficiency syndrome were treated with only aerosolised pentamidine, which they inhaled for 20 minutes every day for 21 days. 13 of the 15 responded to therapy. Mean PaO2 (mm Hg) and vital capacity (% predicted) were 67.9 and 50.8 before therapy and 80.1 and 67.9 after therapy in patients successfully treated. No systemic side-effects occurred and serum pentamidine concentrations were low in all patients. The only local adverse reaction was cough in 12 patients. Aerosolised pentamidine may be an effective non-toxic treatment for P carinii pneumonia.

Selective delivery of pentamidine to the lung by aerosol.

In 8 patients with diffuse infiltrates on chest radiograph undergoing fiberoptic bronchoscopy for suspected Pneumocystis carinii pneumonia, bronchoalveolar lavage sediment and supernatant concentrations of pentamidine were compared 18 to 24 h after administration of 4 mg/kg intravenous (n = 3) and aerosolized (n = 5) pentamidine isethionate. Aerosol was inhaled for 35 to 40 min with 300 mg of pentamidine isethionate in a jet nebulizer, baffled to decrease the particle size to 1.42 micron +/- 1.88 (mass median aerodynamic diameter +/- geometric standard deviation). Bronchoalveolar pentamidine concentrations were: In sediment, 9.34 +/- 1.74 postintravenous versus 705 +/- 242 ng/ml postaerosol (mean +/- SEM, p less than 0.05); supernatant, 2.64 +/- 0.73 postintravenous versus 23.2 +/- 7.75 ng/ml postaerosol (mean +/- SEM, p less than 0.05). Serum pentamidine levels were low or undetectable after aerosolization. Aerosol administration delivers significantly higher concentrations of pentamidine to the air spaces than does intravenous delivery in patients with diffuse alveolar infiltrates.