N T Bateman

Pulmonary deposition of nebulised pentamidine isethionate: effect of nebuliser type, dose, and volume of fill.

An estimate of the absolute pulmonary deposition of nebulised pentamidine isethionate was obtained in nine patients with AIDS. Two nebuliser systems were compared, System 22 Mizer (Medic-Aid) and Respirgard II (Marquest), with 50 and 150 mg doses of pentamidine in a 3 ml solution driven by an air flow of 6 l/min with the patient in the sitting position. The 50 mg pentamidine dose was repeated with a 6 ml fill with both devices. The nebuliser cloud was labelled with technetium-99m human serum albumin (Ventocol) and lung deposition was measured with a gamma camera. Of the two nebulisers studied, System 22 Mizer delivered more drug to the lungs as a whole and to each individual lung region, including the peripheral and upper zones. For the 50 mg dose the mean (SEM) total pulmonary deposition with the 3 and the 6 ml fill respectively was 2.63 (0.34) and 3.71 (0.41) mg for the System 22 Mizer and 1.37 (0.26) and 1.45 (0.18) mg for the Respirgard II. For the 150 mg dose the System 22 Mizer delivered 7.16 (1.02) mg and the Respirgard II 4.34 (0.57) mg. Increasing the volume of fill from 3 to 6 ml increased pulmonary deposition with System 22 Mizer, and this was related to an increase in nebuliser output. Neither pulmonary deposition nor nebuliser output was increased by using a 6 ml solution in the Respirgard II. Increasing the volume of fill prolonged the time required for nebulisation with both nebulisers. The System 22 Mizer produced more nonpulmonary (gastric and oropharyngeal) deposition of drug, more frequent local adverse effects (cough, burning in the throat, and a metallic taste), and small reductions in lung function, particularly with the 150 mg pentamidine dose. Thus nebuliser type, volume of fill, and nebuliser dose affect the pulmonary deposition of pentamidine. A 300 mg dose of pentamidine via a Respirgard II is generally recommended as providing effective prophylaxis; our results suggest that similar pulmonary deposition can be produced with System 22 Mizer and 150 mg pentamidine. A clinical trial would be needed to show whether this regimen provides similar prophylactic benefit.

The place of lung 99mTc DTPA aerosol transfer in the investigation of lung infections in HIV positive patients

Pneumocystis carinii pneumonia (PCP) is the most common cause of pneumonia in HIV antibody positive patients, but other pneumonias remain important, i.e. streptococcal and mycobacterial infections. A definitive diagnosis relies on obtaining samples from the lung either noninvasively (induced sputum), or invasively (bronchoalveolar lavage, transbronchial or open lung biopsy). We have used the noninvasive technique of nebulized 99mTc DTPA transfer, to assess patients with PCP (n = 30) and other lung infections (n = 20) to see whether this test will distinguish between the various infections. The presence of a biphasic, rapid transfer curve indicates severe extensive alveolar damage and is seen in PCP or legionella pneumonia. The mean transfer time (T50 +/- SEM) for patients with PCP (whether smokers or nonsmokers) was 2.1 +/- 0.2 min, and for two of the patients with legionella 3.2 min. In PCP effective treatment causes the transfer to slow (mean T50 22.7 +/- 3.3 min, n = 24) and become monoexponential. Other causes of these changes in transfer are discussed. The other pneumonias (streptococcal, mycobacterial, and staphylococcal) did not result in biphasic curves or very rapid times, their T50 values are indistinguishable from cigarette smokers. In this patient group the DTPA transfer is a useful noninvasive investigation with a very rapid, biphasic curve indicating a high probability of PCP.

Alveolar permeability in HIV antibody positive patients with Pneumocystis carinii pneumonia.

Pulmonary permeability was assessed using the technique of 99mTc (technetium-99m) diethylene triamene pentacetic acid (DTPA) aerosol transfer in 10 patients who had antibodies to human immunodeficiency virus (HIV) and were non-smokers and in 20 HIV antibody positive smokers. Five patients had Pneumocystis carinii pneumonia (PCP) proved by transbronchial lung biopsy; four were non-smokers and one a smoker. Two findings emerged: patients with PCP had greater epithelial permeability than non-smokers and smokers; and the permeability curves were monophasic in smokers and non-smokers, but biphasic in patients with PCP. The biphasic curve observed is indicative of diffuse alveolar damage and might be useful to predict PCP in patients with antibodies to HIV who have normal chest radiographs. As the study was of only five patients with PCP, however, further studies are necessary to confirm this observation.

Ventilation-perfusion lung scans for pulmonary emboli

Reports were made on combined ventilation-perfusion lung scans by three observers on three occasions and by another observer once. Reproducibility for each observer varied between 80 and 88%. There was complete agreement about the areas of scans reported as abnormal. Agreement between observers on whether or not the abnormality represented a pulmonary embolus averaged 77%. There was 86% agreement with the final clinical diagnosis. Our results show that reporting of ventilation perfusion lung scans by eye is reproducible. They support the claims that, under routine clinical conditions, the technique is 91% to 95% accurate for pulmonary emboli.

Disposition of intravenous 123iodopentamidine in man

This study compared the disposition of the radiopharmaceutical [123I]iodopentamidine with that of pentamidine after intravenous infusion by measuring plasma concentrations of each using scintilation counting and high-performance liquid chromatography (HPLC), respectively. There was rapid hepatic uptake and biliary excretion of the 123I label. Distribution kinetics of the 123I label were similar to those of pentamidine, but its elimination half-life (41 +/- 27 h) was longer than that of pentamidine measured by HPLC (11 +/- 8 h). [123I]iodopentamidine distribution reflects that of pentamidine, but elimination of the radiopharmaceutical appears slower.

Does 99Tcm human serum albumin alter the characteristics of nebulized pentamidine isethionate

Nebulized pentamidine has been used as therapy for Pneumocystis carinii pneumonia. The lung dose delivered using different nebulizer systems and doses of pentamidine from 50-600 mg is unknown. To measure this a marker which does not alter the characteristics of the nebulized pentamidine solution must be found. We have assessed the aerosol characteristics of four jet nebulizers (System 22, System 22 Mizer, Optimist, Respigard II) and one ultrasonic device (Pulmosonic) using two concentrations of pentamidine isethionate (50 mg and 300 mg) in 3 ml of solution. The jet nebulizers were operated at a flow rate of 6 l min-1, a rate suitable for home use. These measurements were repeated with 99Tcm labelled human serum albumin (HSA) added to the solutions. A linear relationship between 99Tcm-HSA activity and pentamidine concentration was demonstrated by using a nine stage cascade impactor. The Respigard II and Optimist produced the best results in terms of particle size (96% less than 5 microns), but the addition of the tracer to the latter led to a smaller particle size range and a reduction in the amount of aerosol present at the mouthpiece. The Mizer system had 52% of particles less than 5 microns, the Pulmosonic 46%. The Respigard II had a total output of 8.7 mg for the 50 mg concentration and 30.9 mg for the 300 mg concentration. The System 22 produced corresponding outputs of 18.0 mg and 67.1 mg with 54% of the aerosol particles less than 5 microns.(ABSTRACT TRUNCATED AT 250 WORDS)

Disposition of nebulized pentamidine measured using the direct radiolabel 123I-iodopentamidine

The pulmonary deposition of nebulized pentamidine (300 mg, Respirgard II nebulizer) was measured in seven human immunodeficiency virus (HIV)-positive men using a new radiopharmaceutical, 123I-iodopentamidine. Mean total pulmonary deposition was 15.3 mg or 5.1% of the initial nebulizer dose. Further studies in two of the patients showed that at 24 h, 87% of deposited 123I was retained in the lungs. Small amounts of activity (expressed as a percentage of the initial nebulizer activity) were also detected over the thyroid (0.4%), bladder (1%) and gut (0.7%). The ratio of 123I activity to pentamidine concentration was similar in the nebulizer solution and urine. These results suggest that 123I-pentamidine may be sufficiently stable in vivo to be used to study the biodistribution of inhaled and parenteral pentamidine in humans.

Pulmonary Permeability in Hematologic Malignancies Effects of the Disease and Cytotoxic Agents

Pulmonary permeability was assessed using the technique of DTPA aerosol transfer in untreated patients with chronic lymphocytic leukemia (CLL) and in patients with a variety of hematologic malignancies that had all been treated with alkylating agents. Two findings emerged: (1) In the untreated CLL patients, the permeability of the upper and middle lung regions was reduced. This may be due to diffuse infiltration by the CLL; and (2) Treatment with cytotoxic agents increased epithelial permeability in both middle and lower lung regions. Further prospective studies are required to determine the cause of the long T50 values in untreated CLL and to confirm that the DTPA transfer test is a sensitive indicator of the damage which eventually leads to pulmonary fibrosis.

Tine testing in HIV positive patients.

BACKGROUND--The incidence of tuberculosis is increased in HIV positive patients. Purified protein derivative (PPD, tuberculin) testing has not been performed routinely on patients infected with HIV in the UK and its usefulness in diagnosing tuberculosis in these patients is unclear. METHODS--198 HIV positive patients were Tine tested and a CD4+ lymphocyte count and chest radiograph were performed. Of the 179 male patients 164 were homosexual or bisexual, 11 were injecting drug users (IDUs), and four were both homosexual and IDUs. Of 19 women 14 were heterosexual and five were IDUs. Patients assessed their own skin reactions at 72 hours, recording the grade on a card which was returned by post. Patients with a grade 0 reaction were requested to have a second test one month later. RESULTS--Details were available on 168 of the 198 patients. Grade 0 reactions occurred in 89 of the 168 patients, requiring a second Tine test, and 73 completed Tine 2 results were received. Of 57 patients with CD4+ lymphocyte counts below 200/mm3, low grade PPD reactivity was seen in 18 on Tine 1 and nine on Tine 2. No history of BCG immunisation of tuberculosis was found in 33 Tine positive patients. Two patients treated for tuberculosis in the previous six months were PPD positive with CD4+ counts of 60/mm3 and 4/mm3 respectively. CONCLUSIONS--PPD reactivity may be maintained despite a CD4+ count of 100/mm3 or less when there is a history of tuberculosis or BCG immunisation.

Mycobacterium avium complex infection presenting as acute hepatitis in an AIDS patient: clinical and ethical problems encountered.

A patient with Acquired Immunodeficiency Syndrome (AIDS) presented with acute hepatitis and a cough productive of sputum containing auramine positive mycobacteria. Clinical management was complicated by the fact that the patient shared accommodation with an HIV-positive relative and her 14-month-old son whose HIV status was unknown. Moreover, each was unaware of the others HIV status and the patient refused to disclose details of his illness to his relative. Though initia~ly treated as a case of open pulmonary tuberCUlOSIS, subsequent investigations revealed the mycobacterium to be Mycobacterium avium complex (MAC). The lack of a rapid method for differentiating between MAC and Mycobacterium tuberculosis (MTB) complicated management greatly. We believe that the acute hepatitis was an unusual presentation of disease caused by disseminated MAC.