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Biomedical subjects

G C Smaldone

Publications and source records attributed to G C Smaldone.

11 recordsLinked to original sources
PubMed1992

Nebulizer function during mechanical ventilation.

In the setting of mechanical ventilation, recent studies have cast doubt on the ability of nebulizer systems to deliver adequate amounts of medication. We therefore studied ventilator-related and nebulizer-related factors that could potentially affect the amount of aerosol inhaled by an intubated subject. Utilizing two separate protocols, we used a bench model of a ventilator circuit, radiolabeled (technetium pertechnetate, 99mTc) saline droplets and a filter technique to measure the percentage of radioaerosol delivered. First, we compared four commercially available jet nebulizers and found that there were significant differences in rate of aerosol production between systems, ranging from 3 to 37%. Delivered aerosol was measured at different ventilator settings, and it was found that the duty cycle can potentially influence output by sevenfold. Some nebulizers were also sensitive to changes in the initial volume of solution placed in the nebulizer. The inclusion of a humidification device significantly reduced output by a mean of 41 +/- 3.5%, but it did not affect particle distribution. Endotracheal tube diameter was not an important variable. Then, with the effects of the above variables established, a separate series of experiments was performed to test whether the use of different radiolabeling compounds can confound the measurement of inhaled drugs. Two nebulizers (AeroTech II and Twin Jet) and pentamidine as the test drug were studied with fixed ventilator settings, treatment time, endotracheal tube size, and volume fill. No humidification was used. The nebulizer solution was labeled with 99mTc, which was bound to either human serum albumin (HSA) or sulfur colloid (SC).(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1992

Mucociliary clearance in adult asthma.

Severe impairment of mucociliary clearance (MC) in hospitalized asthmatics has recently been demonstrated in peripheral and central airways. MC was also shown to improve with clinical recovery and hospital discharge (2). In the present study, we measure MC in chronic, stable asthma in subjects with a wide range of obstruction to see if MC was related to the severity of chronic disease. We separated the subjects into those with severe obstruction with expiratory flow limitation during tidal breathing (FL subjects) and those without tidal flow limitation (NFL subjects) to see if the presence of chronic flow limitation was associated with regional MC abnormalities. Seventeen asthmatic patients were studied. Mucociliary clearance was assessed using inhaled radioaerosol and serial measurements of the retention of radioactivity over 2 h. By controlling breathing pattern, the initial pattern of deposition in the lungs was matched, with all subjects having a predominance of particles in the central airways. This pattern was normalized for regional lung volume using a xenon equilibrium scan and expressed as a specific central to peripheral (sC/P) ratio. The percentage retention of deposited radioactivity at 120 min ranged from 19 to 83% (mean, 52%). FL subjects had a mean retention at 120 min of 66% (range, 55 to 83%). The NFL subjects had a mean retention at 120 min of 33% (range, 19 to 51%). Throughout the 2-h study period, retention by the FL group was significantly greater than that of the NFL group with separation of 95% confidence intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Deposition of aerosolized pentamidine and failure of pneumocystis prophylaxis.

OBJECTIVE: To determine if outcome of Pneumocystis carinii prophylaxis is related to total lung dose of aerosolized pentamidine. SETTING: AIDS treatment centers at a VA and University Hospital. PATIENTS: Fifty-eight HIV-infected patients receiving P carinii prophylaxis with aerosolized pentamidine using a nebulizer (CIS-US AeroTech II) were followed up over a 90-week period. Treatment consisted of 60 to 90 mg every two weeks. MEASUREMENTS: In all patients, deposition of pentamidine aerosol was measured using a radioaerosol filter technique. Factors thought to be important in deposition, nebulizer output and breathing pattern were also measured. Six months later, repeated deposition studies were performed in 20 patients. Pentamidine dose to the lung was related to occurrence of P carinii pneumonia and correlated with nebulizer function and breathing parameters. Outcome was assessed in terms of pentamidine deposition and patient characteristics, including demographic, immunologic, physiologic, and medical variables. RESULTS: Ten patients (17.2 percent) had development of P carinii pneumonia. However, pentamidine deposited in the failures (8.18 +/- 4.74 mg) was no different than deposition in protected patients (6.39 +/- 3.07 mg, p = NS). Most of the variability in deposition was accounted for by variability in nebulizer output (r = 0.919, p less than 0.001). Deposition did not significantly correlate with any of the measured breathing parameters. Serial deposition measurements were not significantly different by paired analysis. The incidence of P carinii pneumonia did not correlate with any measured patient characteristic. CONCLUSIONS: Failure of aerosolized pentamidine prophylaxis is not related to total lung dose of pentamidine. Other factors such as inadequate microscopic deposition between alveoli, pentamidine clearance, or drug resistance may be important. In HIV-infected patients, interpatient variability in aerosol deposition can be reduced by reducing variability in nebulizer output rather than control of breathing pattern.

Aerosols↗
PubMed1992

Exposure of health care workers to aerosolized pentamidine.

In patients, urinary levels of pentamidine have been shown to reflect pulmonary deposition of aerosolized drug. Using urinary levels and air filter samples, we assessed factors responsible for health care worker (HCW) exposure. We measured serial urine samples in HCWs who administered aerosol pentamidine over an 11-month period and compared them with serial urine levels measured over 30 days in a normal volunteer in whose lungs a known amount of pentamidine (3.39 mg) had been deposited. Ambient exposure to pentamidine was determined by continuous high volume air sampling in the treatment room during routine therapy. In addition, the amount of pentamidine released by six HIV-positive subjects, performing tidal breathing with a Respirgard II nebulizer in an airtight booth, was measured by extracting air from the booth through a filter. The effect of adding noseclips, of coughing (with nebulizer shut down), and of removing the nebulizer from the patient's mouth without turning it off, were determined. Pentamidine in the urine of the normal volunteer reached a peak concentration of 9.5 ng/mg creatinine/ml and was detectable for 30 days following the exposure. In HCWs, pentamidine was detected intermittently in four of five individuals with levels as high as 18.2 ng/mg creatinine/ml. Samples of ambient treatment room air indicated small daily releases of pentamidine (0.013 +/- 0.02 mg per patient treated), but simultaneous urine levels in HCWs were negative. The data from the airtight booth revealed that removing the nebulizer from a patient's mouth without turning it off caused a 360-fold increased in pentamidine release compared to tidal breathing. Coughing resulted in a 6.9 (range 0.9-14.2)-fold increase in release, while the addition of noseclips had no significant effect. The pattern of intermittently positive urine tests and the low levels of ambient pentamidine detected in the air of the treatment room suggest that HCWs are being exposed to episodic but high concentrations of pentamidine. High level exposure is most likely to occur during treatment interruptions which are usually precipitated by coughing episodes. Because of the intermittent pattern of exposure and slow clearance of pentamidine, urine assay is useful for detecting high intermittent exposure. Random air sampling is a sensitive indicator of low level exposures but may not detect episodic high level releases.

Aerosols↗
PubMed1991

Factors determining pulmonary deposition of aerosolized pentamidine in patients with human immunodeficiency virus infection.

Although aerosolized pentamidine (AP) has recently been approved for prophylaxis and is undergoing clinical trials for treatment of pneumocystis, pneumonia (PCP), factors important in the deposition of AP have not been described. Using radioaerosol techniques, deposition was measured in 22 patients receiving AP for prophylaxis or treatment of PCP. In all patients total and regional deposition of pentamidine, breathing pattern, pulmonary function (PFT), regional ventilation, and type of nebulizer were analyzed. Bronchoalveolar lavage (BAL) was performed 24 h after inhalation to assess the relationship between pentamidine levels in BAL fluid and measured aerosol deposition. The nebulizers tested were the Marquest Respirgard II and the Cadema AeroTech II, both previously characterized in our laboratory. The aerosol particles consist of water droplets containing dissolved pentamidine and technetium 99m bound to albumin. Analysis of particles sampled during inhalation via cascade impaction confirmed a close relationship between radioactivity in the droplets and the concentration of pentamidine as measured by HPLC (r = 0.971, p less than 0.0001; n = 18). Deposition was measured by capturing inhaled and exhaled particles on absolute filters and measuring radioactivity. This technique allows the determination of the deposition fraction (DF, the fraction of the amount inhaled that is deposited), which provides information on factors strictly related to the patient. To confirm the filter measurements, pentamidine deposition was also measured by gamma camera. The camera measurement was possible because each patient's thoracic attenuation of radioactivity was determined by a quantitative perfusion scan (mg pentamidine deposited via both techniques, r = 0.949, p less than 0.0001; n = 26). Regional lung volume and ventilation were determined by xenon 133 equilibrium scan and washout. Pentamidine deposition varied markedly between patients, but BAL levels of pentamidine significantly correlated with measured deposition (r = 0.819, p less than 0.01; n = 9). DF averaged 0.621 +/- 0.027 (SEM) and did not correlate with any measured lung parameter, including breathing pattern and PFT. Regional deposition did not correlate with regional ventilation. The major factor influencing pentamidine deposition was aerosol delivery (mg deposited versus mg inhaled; r = 0.963, p less than 0.0001; n = 26). The nebulizer was an important determinant of aerosol delivery, with the AeroTech delivering between 2.5 and 5 times more drug than the Respirgard. These observations are important in assessing treatment failure and cost of therapy.

Aerosols↗
PubMed1991

Changes in mucociliary clearance during acute exacerbations of asthma.

Previous studies have suggested that mucociliary clearance (MC) is impaired in asthmatic subjects. If so, impaired clearance may be an important factor in acute exacerbation. We proposed that if MC plays a significant role in acute illness, MC should be impaired during the exacerbation but improve after recovery. To test this hypothesis, five asthmatic patients with attacks requiring hospitalization underwent measurement of MC using radiolabeled aerosol and a gamma camera. They were studied on the second or third day after admission with repeat measurements after discharge. Spirometry was performed before all studies. After an equilibrium xenon scan (133Xe), which defined lung borders and measured regional volume, radiolabeled saline particles containing technetium-labeled (99mTC) sulfur colloid were deposited and used to label airway mucus. Deposition patterns were matched by regulating particle distribution and breathing pattern. MC was then measured as percentage retention of radioactivity at 10-min intervals for 2 h. When hospitalized, 96.0 +/- 2.06% (SEM) of the initial radioactivity was retained in the lung after 2 h, indicating little clearance of mucus from the lung. In fact, no significant changes were detected when activity at 120 min was compared with measurements at 10 min (99.2 +/- 0.22%, NS). After discharge clearance was markedly enhanced. That is, retention of lung activity was significantly lower at all time intervals from 10 min onward, with only 70.9 +/- 3.86% retained at 120 min (p = 0.008). During an asthmatic attack warranting hospital admission, MC is significantly impaired, with marked improvement following recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1991

Urine pentamidine as an indicator of lung pentamidine in patients receiving aerosol therapy.

To determine if urine pentamidine was reflective of lung pentamidine, we compared levels of the drug in bronchoalveolar lavage fluid and simultaneously obtained urine. Thirty-one patients who were receiving aerosolized pentamidine either as treatment or as prophylaxis underwent BAL and submitted urine samples for pentamidine analysis. Pentamidine was analyzed in both phases of BAL fluid (supernatant and cell pellet) and in urine using high performance liquid chromatography. Urine results were normalized for creatinine. Patients were categorized as prophylaxis failures (active Pneumocystis carinii pneumonia on prophylaxis), electives (free from PCP on prophylaxis), treatment (daily AP in treatment doses for active PCP, or miscellaneous (single dose of AP). Levels in BAL fluid and urine varied widely over several orders of magnitude. However, for all patients, we found a highly significant relationship between BAL supernatant and urine (r = 0.97, p less than 0.0001). No statistical differences were found when comparing levels of pentamidine between failures and electives; however, the number of failures was small. We conclude that urine pentamidine is related to lung pentamidine and can be used as a clinical indicator in patients receiving aerosolized therapy.

Administration, Inhalation↗
PubMed1976

Delineation of flow-limiting segment and predicted airway resistance by movable catheter.

Using intrabronchial lateral pressure catheters, we determined the precise location and movement of the flow-limiting segment (FLS) in excised dog and human lungs; under maximal flow conditions, profiles of resistance and transmural pressure from the "mouth" to segmental bronchi were also obtained. In the same lungs, using the interrupter technique, IVFP curves were constructed; with these curves and lung compliance, the relationship between Vmax and Pel was studied using the analysis of Pride et al. The FLS consisted of well-demarcated short lengths (2-3 cm) of the trachea at large lung volumes which moved to lobar or semental bronchi at small volumes (10-20% TLC). These relationships, coupled with observations of the movement of the equal pressure point (EPP), support the idea that in the excised lung the location of the FLS is determined by both the location of the EPP and the compliance of the downstream airway wall; thus FLS MAY NOT FOLLOW UPSTREAM MOVEMENTS OF EPP until EPP reaches a more compliant segment of the bronchial tree (lobar and proximal segmental bronchi). Upstream resistance (Rs) and transmural pressure of collapse (Ptm') calculated indirectly from the slope and intercept of the Vmax vs. Pel relationship accurately predicted values of resistance and transmural pressure measured directly in the same lungs at a point just upstream to FLS.

Airway Resistance↗
PubMedDate not supplied

Relationship between tracheobronchial particle clearance rates and sites of initial deposition in man.

Mucociliary clearance was compared in three groups of normal subjects; each group inhaled a different type of aerosol (sebecate, iron oxide, and aqueous) labelled with 99Tc, to determine the relationship between deposition pattern and the subsequent total lung clearance. Standardization for deposition was accomplished by measuring a central to peripheral ratio (C/P) of deposited radioactivity in the thorax. Lung particle retention at 30, 60, 90, 120 min, and 24 h was measured, and compared at each time period to the C/P ratio. A linear relationship between the retention of aerosol at each time period and the C/P ratio was seen among all aerosols, e.g., aerosol with high C/P ratios had less retention of aerosol at a given time period than aerosols with more diffuse deposition patterns and lower C/P ratios. Furthermore, the relationship was similar to that of the more traditional measurement of regional deposition, the 24-h percentage retention. Lung particle retention was compared among aerosols, using analysis of covariance to standardize for C/P ratio. The intersubject variability was similar among all three aerosol groups. Thus, mucociliary clearance can be standardized in healthy subjects by using an initial deposition index, the C/P ratio, with similar accuracy to the 24-h percentage retention, as an index of aerosol deposition. The use of the C/P ratio, however, has distinct advantages over the 24-h retention, in that studies can be conveniently shortened, used with short lived isotopes, and be adapted to techniques investigating lung permeability instead of tracheobronchial clearance. An unexpected finding was the more rapid clearance of sebecate particles, compared with iron oxide or aqueous particles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗