Regional impairment of mucociliary clearance in chronic obstructive pulmonary disease.

Asthmatic subjects with tidal expiratory flow limitation have mucociliary clearance (MC) impairment in central airways. Because tidal flow limitation develops in COPD, it is possible that regional MC in these patients also may be affected. We tested this hypothesis by measuring MC in the presence or absence of flow limitations.

Changing patterns of aerosol deposition during methacholine bronchoprovocation.

During bronchoprovocation testing with methacholine, induced changes in airway geometry are known to affect sites of drug deposition. However, it is not known if changes in these sites determine measured responsiveness. We assessed the importance of sites of deposition as determinants of reactivity by comparing particle behavior in two subject groups with and without hyperresponsiveness.

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.

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.

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.

Drug delivery via aerosol systems: concept of "aerosol inhaled".

The mass of aerosol inhaled is primarily a function of the patient's breathing pattern and the aerosol delivery system. Once inhaled, deposition is governed by factors related to the properties of the aerosol and the individual characteristics of the patient (e.g.

Technetium 99m radiolabeling of aerosolized drug particles from metered dose inhalers.

To assess mechanisms of bronchodilation and effectiveness of metered dose inhalers, it may be useful to determine sites of drug deposition in the lung. To establish suitable test aerosols, two brands of metered dose inhalers containing bronchodilator (Brethaire, Proventil) were radiolabeled with technetium ( 99mTc) and tested to determine if the distribution of radioisotope in the aerosol was representative of the distribution of agonist activity. Cascade impaction was used to determine the particle size distribution of the radioisotope and drug aerosols by assaying each state of the cascade using scintillation and HPLC techniques.

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.

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.

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.

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.

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.

Use of aerosols to estimate mean air-space size in chronic obstructive pulmonary disease.

Using in vivo measures of aerosol recovery (RC) as a function of breath-hold time (t) (Gebhart et al. J. Appl.

Quantitative deposition of aerosolized gentamicin in cystic fibrosis.

In cystic fibrosis (CF), the clinical effectiveness of aerosolized antibiotics is controversial. Previous investigators have not considered the type of nebulizer, droplet size, and dose to the lung in assessing the results of aerosol therapy. The present study tests the importance of these factors by standardizing an aerosol system for delivery of antibiotics and other agents to patients with CF.

Human variation in the peripheral air-space deposition of inhaled particles.

Intersubject variability in both peripheral air-space dimensions and breathing pattern [tidal volume (VT) and respiratory frequency (f)] may play a role in determining intersubject variation in the fractional deposition of inhaled particles that primarily deposit in the lung periphery (i.e., distal to conducting airways).

Effect of exercise on deposition and subsequent retention of inhaled particles.

To investigate the effect of exercise and its associated increase in ventilation on the deposition and subsequent retention of inhaled particles, we measured the fractional and regional lung deposition of a radioactively tagged (99mTc) monodisperse aerosol (2.6 microns mass median aerodynamic diam) in normal human subjects at rest and while exercising on a bicycle ergometer. Breath-by-breath deposition fraction (DF) was measured throughout the aerosol exposures by Tyndallometry.

Quantitative assays of pharmacologic aerosols used in studying asthma.

To more nearly accurately quantitate the dose of pharmacologic agents delivered to human and animal airways via aerosols, we have developed a monodisperse aerosol containing either methacholine or histamine that permits a light scattering device (tyndallometry) to measure accurately the quantity of inspired and expired particles. These aerosols (described in previous studies) are simultaneously tagged with a radioactive label (technetium 99m) to permit the use of external gamma camera imaging. Present work focuses on the development of assay techniques to measure the quantity of methacholine delivered in these aerosols.

Flow limitation, cough, and patterns of aerosol deposition in humans.

We studied deposition of radioactive monodisperse 1.5-micron aerosol in humans following inhalation during quiet breathing. Two groups were studied: normal, defined by tidal loops below the maximum expiratory flow-volume (MEFV) envelope [forced expiratory volume at 1 s at percent of forced vital capacity (FEV1%) 62-78]; and flow-limited, with tidal loops superimposed on MEFV relationship (FEV1% 21-57) and flow-limiting segments (FLS) known to exist in central airways.

Enhancement of particle deposition by flow-limiting segments in humans.

Severe chronic obstructive pulmonary disease is associated with central deposition of inhaled aerosols. This pattern may be due to functional narrowing of the large airways during expiration at flow-limiting segments (FLS). Using a gamma camera and 2.

Location of flow-limiting segments via airway catheters near residual volume in humans.

Previous studies have demonstrated sites of flow limitation in the central airways of dogs and humans. At low lung volumes, however, during a forced expiration, it is not clear whether flow-limiting segments (FLS) move into the lung periphery. Using intrabronchial lateral pressure catheters, we located FLS in human subjects at all lung volumes between functional residual capacity (FRC) and residual volume (RV).

Evaluation of quantitative aerosol techniques for use in bronchoprovocation studies.

To investigate airway physiology by use of inhaled aerosols, it is frequently necessary to measure the actual amount of material deposited on the airway wall as well as the site of particle deposition. To satisfy these needs, radiolabeled aerosols and gamma camera techniques have been used to measure regional deposition of inhaled particles. To make quantitative measurements of the amount deposited, previous investigators have used a "phantom" technique to indirectly calibrate the gamma camera for the attenuation of gamma rays through the lungs and chest wall.

Voluntary induced alterations in regional ventilation in normal humans.

We tested the hypothesis that voluntary changes of thoraco-abdominal shape can influence regional ventilation via altering regional pleural pressure swings (Ppl). Regional ventilation was measured simultaneously with regional Ppl during tidal volume breathing maneuvers in five normal subjects while they were performing one of three thoracoabdominal patterns of breathing: normal, preferential intercostal (IC), or preferential diaphragmatic (DIA). In every subject, the lower lung region's 133Xe washout rate was faster than the upper region's, regardless of the pattern of thoracoabdominal breathing adopted.

Role of alveolar recruitment in lung inflation: influence on pressure-volume hysteresis.

The behavior of terminal lung units (alveoli) with changes in lung volume is controversial. For example, different investigators using similar techniques have suggested that alveoli expand homogeneously or, conversely, get smaller with increases in lung volume. We studied this problem by filling excised dog lobes with monodisperse aerosol and observing deposition at zero airflow.