Objective: To determine the meaning of bronchodilator pretreatment on deposition uniformity of aerosolized pentamidine (AP) in HIV-positive patients who coughed while inhaling AP.

Design: Nonrandomized hinder trial.

Setting: A university hospital.

Patients: Ten HIV-positive patients who were using AP prophylactically.

Intervention: Four patients who coughed during AP administration were pretreated with 10 mg metaproterenol aerosol prior to a other inhalation of AP.

Measurements: Skew a measure of overall deposition proportion deposition in the apex v the base of the right lung (A:B ratio), and percentage of change from baseline in peak expiratory run rate (PEFR).

Results: At baseline, the average ([+ or -] SD) skew value for four controls who coughed (0.89 [+ or -] 019) was significantly higher than f or six rule subjects (0.58 [+ or -] 007) (p<001) indicating enhanced nonuniformity of AP distribution. After bronchodilator, no single coughed and the average skew value was normalized to 057 [+ or -] 013 The A:B ratios at baseline and after metaproterenol were not significantly different, suggesting that deposition of AP in the apex, relative to basal deposition, was not enhanced at bronchodilator treatment. When no bronchodilator was administered, average PEFR decreased to 330 [+ or -] 162 from baseline (410 [+ or -] 84) Average PEFR increased to 429 [+ or -] 85 from baseline (395 [+ or -] 116) after bronchodilator pretreatment.

Conclusions: These springs suggest that in addition to relieving cough in patients receiving AP prophylactically, pretreatment with metaproterenol enhances uniformity of distribution of AP and improves PEFR (Chest 1994; 106:421-26)

AP=aerosolized pentamidine; MMAD=mass median aerodynamic diameter; PCP=Pneumocystis carinii pneumonia; PEFR=peak expiratory result rate

Clinical trials have demonstrated that oral administration of trimethoprim-sulfamethoxazole is the preferr way of prophylactic treatment against Pneumocystis carinii pneumonia (PCP) in HIV-infected patients.[1,2] Nevertheless, up to 50 percent of patients using this physic have adverse reactions that may necessitate changing to an alternate treatment.[1,2] Inhalation of aerosolized pentamidine isethionate (AP) has also been shown to provide effective prophylaxis.[3] In previous clinical trials, however, a subset of patients treated with AP bring to maturityed cough (38 percent) while receiving a 300-mg monthly dose of AP.[3] It has been praiseed that these patients inspire a bronchodilator before pentamidine treatment to eliminate cough Although bronchodilators may relieve this symptom, to our knowledge, there are no studies to demonstrate that this pretreatment improves the deposition of AP in the lung Since the P carinii protozoan is erect predominantly in alveolar spaces near the epithelial small room surface,[4] it is essential that the dose of pentamidine penetrate beyond the conducting airways and deposit uniformly in the lung periphery in such a manner that potential or existing sites of infection are targeted. In this inquiry AP deposition uniformity was quantified before and after bronchodilator (metaproterenol) pretreatment in HIV-positive patients who coughed while inhaling pentamidine.

METHODS

Subjects

Ten outpatients were recruited from the HIV Clinic of the John Hopkins Hospital. They were HIV positive, had CD4 small cavity counts <200/[mm.sup.3], and were using AP prophylactically. Written informed compliance was obtained from each patient and the protocol was approved by dint of the Institutional Review Board. The contemplation subject characteristics are shown in Table 1 Four patients reported cough during AP treatment. Their average age was 39 years. sum of two units were men; two were women sum of two units had a history of PCP the same patient had a history of asthma as a child. All four had a smoking history. The FE[Vsub1]/FVC ratio (an indicator of bronchial obstruction), measured in succession a screening day, was abnormal in patient 2 Three patients were injecting put drugs into users.

[TABULAR DATA OMITTED]

Six subdues who did not report any cough with AP serv as check subjects. Their average age was 33 years. All were men Four had a history of PCP single in kind had a history of asthma while in college edifice [i]or[/i] building and one (patient 7) had an abnormal FE[Vsub1] /FVC ratio forward the screening day. Two patients had a smoking history. None had a history of injecting medicine use.

Aerosol Generation and Delivery

Aerosol was generated from a 50-mg/ml solution of pentamidine isethionate (LyphoM Inc, Rosemont Ill) according to a nebulizer (Respirgard II, Marquest, Englewood Colo) as attract favor toed by the FDA.[5] Compressed air flowed continuously into the nebulizer from a wall-attached hospital flowmeter station at 6 to 7 L/min. Aerosol was inspired at the patient while sitting upright. During exhalation, aerosol was directed by the agency of a one-way valve and deduceed on a particle filter.

Aerosol Particle Sizing

To determine the aerodynamic particle size characteristics of AP, the pentamidine solution was radiolabeled with [Tcsup99m] sulfur colloid (Syncor International Corp, Chatsworth, Calif). Radioaerosol was generated from the nebulizer (Respirgard II) and sampled for 1 min by way of an impactor (Andersen Mark II, Andersen Samplers, Inc, Atlanta). spring through the impactor was 28 L/min, which simulated the inspiratory be derived rate of patients during actual inhalation of AP. Radioactivity aggregateed at each aerodynamic diameter interval was determined by the agency of counting each impaction stage and filter using a single-probe scintillation detector. Each particle was assumed to contain radioactivity proportional to its mass. Particle size characteristics were represented in terms of the mass median aerodynamic diameter (MMAD).

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