Bronchial edema alters (99m)Tc-DTPA clearance from the airway surface in sheep.

Airway wall edema, prominent in inflammatory airways disease, may alter barrier properties at the airway air-liquid interface such that normal absorption of soluble substances into the airway circulation is altered. We studied the effects of bradykinin-induced airway wall edema on the clearance of the soluble tracer technetium-99m-labeled diethylenetriamine pentaacetic acid ((99m)Tc-DTPA) from subcarinal airways in sheep (n = 8). (99m)Tc-DTPA (6-10 microl) was delivered by a microspray nozzle inserted through a bronchoscope to a fourth-generation bronchus both before and 1 h after bradykinin (20 ml; 10(-6) M) had been infused through a cannulated and perfused bronchial artery. Airway retention (by scintigraphy) and blood levels of radiolabel were monitored for 30 min after the local deposition of (99m)Tc-DTPA. During control conditions, 85-90% of the tracer cleared from the deposition site within 30 min. The maximum blood level during that time was 17% of the total delivered tracer. However, 1 h after bradykinin infusion, there was significant retention of the marker at the deposition site with clearance within 30 min reduced to 63-70% and decreased blood levels of radiolabel (8%; both P < 0.05). These results demonstrate that moderate airway wall edema alters blood uptake and removal of soluble substances delivered to the subcarinal airways. We suggest that the interplay between vascular and mucociliary clearance routes will impact the resident time for clearance of soluble air toxins and/or therapeutic agents from the epithelial surface.

The role of the bronchial vasculature in soluble particle clearance.

Although a role for the airway circulation in the clearance of inhaled particles is generally assumed, there is little information to confirm its importance. We studied the effects of decreased bronchial blood flow on the uptake of the soluble tracer technetium=99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) from subcarinal airways in sheep (n = 7). The bronchial artery was cannulated and perfused with autologous blood at a control flow (0.6 mL/min/kg) or when the perfusion pump was stopped (no flow). (99m)Tc-DTPA (6-10 microL) was delivered by a microspray nozzle inserted through a bronchoscope to a fourth-generation bronchus both during control blood flow conditions and no-flow conditions. Airway retention (by scintigraphy) and blood uptake were monitored for 30 min after the local deposition of (99m(Tc-DTPA. During control flow conditions, 30 min after the delivery of the radiolabel, 21% of the tracer remained at the deposition site. Of the total delivered tracer, maximum blood uptake was 18% (n) = 3). When bronchial perfusion was stopped, airway retention 30 min after deposition increased to 43%, and maximum blood uptake decreased to 7% of the total delivered tracer. Although mucociliary clearance was not directly measured, radiolabel tracer was observed to move progressively from the deposition site up to larger airways and contributed to the overall removal of tracer from the site of deposition during both flow conditions. However, these results demonstrate that decreased bronchial perfusion increases airway retention by limiting vascular uptake of the soluble tracer. These results emphasize the importance of normal perfusion of the airway vasculature for uptake of therapeutic agents delivered specifically to the conducting airways.

Airflow and device effects on aerosol delivery for large animals.

Aerosol delivery of medications has recently gained acceptance in large animal veterinary medicine. However, delivery of therapeutic aerosols currently relies on equipment modified from human use and delivery of medical aerosols may be adversely affected by the equipment design. In this study, we demonstrate the effect of typical large animal inspiratory flow rates on aerosol delivery characteristics. A benchtop system was assembled to simulate aerosol delivery to large animals. Phasic airflow was generated using a large animal anesthesia machine set to deliver 6 bpm (7 L/breath) at 100, 150 and 180 L/min mean inspiratory airflow. Aerosol from a DeVilbis ultrasonic nebulizer was delivered to a simulated facemask using standard 22 mm tubing and fittings. Total mass, delivery efficiency and mass median aerosol diameter (MMAD) was measured with and without an inspiratory one-way valve on the facemask. Delivered aerosol mass ranged from 0.26 to 0.08 g/min and delivery efficiency ranged from 30 to 6%. Both parameters were significantly reduced by both increasing flow rates and the presence of a one-way valve between the nebulizer and the facemask. Average MMAD was 0.7 microm and was not affected by any experimental variable. These results demonstrate that current aerosol equipment used on large animals has a substantial adverse effect on aerosol delivery. Elimination of one-way valves between the aerosol source and the patient is expected to improve delivery of the aerosol in these patients.

Interdependence of bronchial circulation and clearance of 99mTc-DTPA from the airway surface.

The extent to which the systemic vasculature is involved in soluble-particle uptake in the conducting airways has not been studied extensively. In anesthetized, ventilated sheep, 6-10 microl of technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) was delivered through a microspray nozzle to a fourth-generation airway. Perfusion of the cannulated bronchial artery was varied between control flow (0.6 ml x min(-1) x kg(-1)), high flow (1.8 ml x min(-1) x kg(-1)) or no flow (the infusion pump was stopped). Airway retention of the radioactive tracer was monitored using gamma camera imaging, and venous blood was sampled. During control perfusion, tracer retention at the site of deposition at 30 min averaged 20 +/- 6% (n = 7). With no flow, retention was significantly elevated to 32 +/- 8% (P = 0.03). In another group of sheep (n = 5) with a control retention of 13 +/- 4%, high flow resulted in an increase in tracer (25 +/- 4%; P = 0.04). Maximum blood uptake of tracer was calculated by estimating circulating blood volume and averaged 16% of total activity during control flow. Only during high-flow conditions was 99mTc-DTPA in the blood decreased (10%; P = 0.04). Most of the tracer was cleared by mucociliary clearance as visualized by imaging. This component was substantially decreased during no flow. The results demonstrate that both decreased and increased airway perfusion limit removal of soluble tracer applied to the conducting airways.

Methodology for the measurement of mucociliary function in the mouse by scintigraphy.

The objective of the study was to develop a scintigraphic method for measurement of airway mucociliary clearance in small laboratory rodents such as the mouse. Previous investigations have characterized the secretory cell types present in the mouse airway, but analysis of the mucus transport system has been limited to in vitro examination of tissue explants or invasive in vivo measures of a single airway, the trachea. Three methods were used to deposit insoluble, radioisotopic colloidal particles: oropharyngeal aspiration, intratracheal instillation, and nose-only aerosol inhalation. The initial distribution of particles within the lower respiratory tract was visualized by gamma-camera, and clearance of particles was followed intermittently over 6 h and at the conclusion, 24 h postdelivery. Subsets of mice underwent lavage for evidence of tissue inflammation, and others were restudied for reproducibility of the methods. The aspiration and instillation methods of delivery led to greater distributions of deposited activity within the lungs, i.e., approximately 60--80% of the total respiratory tract radioactivity, whereas the nose-only aerosol technique attained a distribution of 32% to the lungs. However, the aerosol technique maximized the fraction of particles that cleared the airway over a 24-h period, i.e, deposited onto airway epithelial surfaces and cleared by mucociliary function such that lung retention at 24 h averaged 57% for delivery by aerosol inhalation and > or =80% for the aspiration or intratracheal instillation techniques. Particle delivery methods did not cause lung inflammation/injury with use of inflammatory cells and chemoattractant cytokines as criteria. Scintigraphy can discern particle deposition and clearance from the lower respiratory tract in the mouse, is noninvasive and reproducible, and includes the capability for restudy and lung lavage when time course or chronic treatments are being considered.

Bronchial reactivity of healthy subjects: 18-20 h postexposure to ozone.

Exposure of humans to ambient levels of ozone (O(3)) causes inflammatory changes within lung tissues. These changes have been reported for the "initial" (1- to 3-h) and "late" (18- to 20-h) postexposure periods. We hypothesized that at the late period, when protein and cellular markers of inflammation at the airway surface remain abnormal and the integrity of the epithelial barrier is compromised, bronchial reactivity would be increased. To test this, we measured airway responsiveness to cumulative doses of methacholine (MCh) aerosol in healthy subjects 19+/-1 h after a single exposure to O(3) (130 min at ambient levels between 120 and 240 parts/billion and alternate periods of rest and moderate exercise) or filtered air. Exposures were conducted at two temperatures: mild (22 degrees C) and moderate (30 degrees C). At the late period, bronchial reactivity to MCh increased, i.e., interpolated dose of MCh leading to a 50% fall in specific airway conductance (PC(50)) was less after O(3) than after filtered air. PC(50) for O(3) at 22 degrees C was 27 mg/ml (20% less than the PC(50) after filtered air), and for O(3) at 30 degrees C it was 19 mg/ml (70% less than the PC(50) after filtered air). The forced expiratory volume in 1 s (FEV(1)) at the late time point after O(3) was slightly but significantly reduced (2.3%) from the preexposure level. There was no relationship found between the functional changes observed early after exposure to O(3) and subsequent changes in bronchial reactivity or FEV(1) at the late time point. These results suggest that bronchial reactivity is significantly altered approximately 1 day after O(3); this injury may contribute to the respiratory morbidity that is observed 1-2 days after an episode of ambient air pollution.

Regional clearance of solute from peripheral airway epithelia: recovery after sublobar exposure to ozone.

The influence of local exposure to ozone (O3) on respiratory epithelial permeability of sublobar lung segments was studied by using aerosolized 99mTc-diethylenetriamine pentaacetic acid (DTPA; mol wt, 492). Two bronchoscopes were inserted through an endotracheal tube in anesthetized, mechanically ventilated, mixed breed dogs and were wedged into sublobar bronchi located in the right and left lower lobes, respectively. Segments were ventilated via the bronchoscope with 5% CO2 in air delivered at 200 ml/min, and an aerosol of 99mTc-DTPA was generated and delivered through the scope and into the sublobar segment over a 30-s period. Clearance of 99mTc-DTPA was measured simultaneously from right and left lower lung segments at baseline and 1, 7, and 14 days after a 6-h sublobar exposure to filtered air or 400 parts per billion O3. O3 treatment significantly decreased the clearance halftime (t50) of 99mTc-DTPA by 50% from the baseline mean of 32.3 to 16.0 min at 1 day postexposure. After 7 days of recovery, t50 was still reduced by 28. 8%; however, by 14 days postexposure, clearance of 99mTc-DTPA had recovered, and the t50 had a mean value of 30.0 min. 99mTc-DTPA clearance was not altered by exposure to filtered air, and t50 values were comparable to baseline at 1, 7, and 14 days postexposure. These results reveal that a single local exposure to O3 increases transepithelial clearance, but only for epithelia directly exposed to O3, and that 7-14 days of recovery are required before permeability to small-molecular-weight solutes returns to normal.

Retention of soluble 99mTc-DTPA in the human lung: 24-h postdeposition.

Clearance of low-molecular-weight solutes, e.g., radiolabeled chelate diethylenetriaminepentaacetate (DTPA), across epithelial surfaces of distal airways and the lung parenchyma is a broadly used technique to assess epithelial integrity. It has been generally assumed that clearance of solute follows a simple first-order process and that DTPA clearance through the respiratory epithelium and into blood and lymphatic channels is complete within a few hours. Using gamma-camera imaging and a radiolabeled aerosol of 99mTc-labeled DTPA, we observed in eight healthy subjects lung retention of radioisotope approximately 24 h postdeposition of the 99mTc-DTPA. Residual lung retention at the 24-h end point averaged 6.0 +/- 1.8 (SD)% of the amount of radioisotope initially deposited in the lung. This suggests that for normal healthy subjects a small amount of the 99mTc radioisotope, either in a dissociated or chelated form, is nonpermeable or slowly cleared from respiratory tisssues.

Importance of airway blood flow on particle clearance from the lung.

The role of the airway circulation in supporting mucociliary function has been essentially unstudied. We evaluated the airway clearance of inert, insoluble particles in anesthetized ventilated sheep (n = 8), in which bronchial perfusion was controlled, to determine whether airway mucosal blood flow is essential for maintaining surface transport of particles through airways. The bronchial branch of the bronchoesophageal artery was cannulated and perfused with autologous blood at control flow (0.6 ml.min-1.kg-1) or perfusion was stopped. With the sheep in a supine position and after a steady-state 133Xe ventilation scan for designation of lung zones of interest, an inert 99mTc-labeled sulfur colloid aerosol (2.1-microns diameter) was deposited in the lung. The clearance kinetics of the radiolabeled particles were determined from the activity-time data obtained for right and left lung zones. At 60 min postdeposition of aerosol, average airway particle retention for control bronchial blood flow conditions was 57 +/- 7 (SE)% for the right and 53 +/- 8% for the left lung zones. Clearance of particles was significantly impaired when bronchial blood flow was stopped, e.g., right and left lung zones averaged 77 +/- 6 and 76 +/- 7% at 60 min, respectively (P < 0.05). These data demonstrate a significant influence of the bronchial circulation on mucociliary transport of insoluble particles. Potential mechanisms that may account for these results include the importance of the bronchial circulation for nutrient flow, maintenance of airway wall temperature and humidity, and release of mediators and sequelae associated with tissue ischemia.

Intravenous lidocaine and oral mexiletine block reflex bronchoconstriction in asthmatic subjects.

Stimulation of the airways of asthmatic individuals causes severe bronchoconstriction, which is in part neurally mediated via the vagus nerve. Local anesthetics are commonly administered to prevent this reflex-induced bronchoconstriction. Therefore, in a double-blind, placebo-controlled prospective study, we tested the effectiveness of oral mexiletine and intravenous lidocaine at blocking histamine-induced reflex bronchoconstriction. Fifteen subjects with mild asthma were selected (for whom the provocative concentration of histamine aerosol causing a 20% decrease in FEV1 (PC20) was less than 18 mg/ml). Subsequently, the subjects were pretreated with oral mexiletine, intravenous lidocaine, or placebo, and the histamine challenges were repeated. The baseline PC20 for histamine was 8.8 +/- 1.8 mg/ml. Mexiletine and lidocaine at therapeutic serum concentrations blocked reflex bronchoconstriction. Oral mexiletine increased the PC20 to 21.1 +/- 5.0 mg/ml (serum concentration: 0.7 +/- 0.05 microg/ml). Likewise, intravenous lidocaine increased the PC20 to 24.5 +/- 4.9 mg/ml (serum concentration: 2.6 +/- 0.15 microg/ml). Oral mexiletine and intravenous lidocaine block reflex-induced bronchoconstriction. Furthermore, mexiletine may have additional airway benefits when selected for the treatment of dysrhythmias or chronic pain in patients with coexisting lung diseases.

Regional clearance of solute from the respiratory epithelia: 18-20 h postexposure to ozone.

Exposure of humans to ambient levels of ozone causes inflammatory changes within lung tissues. These changes have been reported for the "initial" (1- to 3-h) and "late" (18- to 20-h) postexposure periods. We hypothesized that at the late period when protein and cellular markers of inflammation in bronchoalveolar lavage remain abnormal, permeability of respiratory epithelia would be altered. To test this, we measured by gamma-camera imagery the clearance kinetics in healthy subjects (n = 9) of 99mTc-labeled solute [diethylenetriaminepentaacetic acid (DTPA)] that was deposited by aerosol onto epithelial surfaces 19 +/- 1 h after a single exposure to ozone (O3; 130 min at ambient levels between 150 and 350 parts per billion and alternate periods of rest and moderate exercise) or filtered air. At the late period, the lung clearance of 99mTc-DTPA over a 120-min period was significantly increased, i.e., 0.732%/min for O3 exposures compared with 0.661%/min for filtered-air exposures (P < 0.05). Regional analysis demonstrated that 99mTc-DTPA clearance from the periphery (excluding the lung hilum) and lung apexes were significantly increased by O3 but changes in clearance for the base of the lung were not significant. The forced expiratory volume in 1 s at the late time after O3 was slightly but significantly reduced (-2.1%) from preexposure levels. There was no relationship between the functional changes observed acutely after exposure to O3 and subsequent changes in 99mTc-DTPA clearance or forced expiratory volume in 1 s observed at the late period. These results suggest that epithelial permeability of the lung is altered 18-20 h post-O3; this injury is regional, and the lung base appears to have a different time course of response or is in an adapted state with respect to O3 exposure.

Bloodborne markers in humans during multiday exposure to ozone.

Intermittent exposure of the human lung to ambient levels of ozone (O3) was assayed in systemic fluids by using serum alpha-tocopherol (ST) as a gauge of oxidative stress and the blastogenic activity of peripheral blood monocytes as an index of immune function. Healthy men (n = 10) were evaluated over 3 consecutive days (130 min/day) of chamber exposure to O3 and filtered air (FA); subjects alternated between rest and light treadmill exercise during exposures. For O3, the level was varied at 20-min intervals, i.e., 250, 350, 450, 450, 350, and 250 parts/billion, and concluded with 10 min at 250 parts/billion. ST was quantitated by high-performance liquid chromatography techniques, and T-lymphocyte blastogenesis was measured in cell cultures of peripheral blood monocytes by comparing [3H]thymidine incorporation in mitogen-stimulated (concanavalin A) and nonstimulated cells. After the third day of O3 at 20 h postexposure, ST levels were reduced significantly compared with the FA control subjects (down 14%; -0.96 mumol/l). Mitogen-activated T lymphocytes exhibited a 61% increase in blastogenic activity after 3 days of O3 exposure, significant compared with the proliferative activity of activated T lymphocytes collected after FA or before O3. Acute airway function was impaired by O3, e.g., on day 1, the forced vital capacity and forced expiratory volume in 1 s were decreased 8% (-0.92 liter) and 14% (-0.86 l/s), respectively, from preexposure values, and full recovery was delayed beyond 24 h. Effects of O3 exposure on cellular and biochemical markers increased in magnitude after each exposure and did not parallel the apparent adaptability of bronchial sensitivity to O3.

Breath isoprene: temporal changes in respiratory output after exposure to ozone.

Isoprene is a major hydrocarbon found in human breath. This study was conducted to evaluate whether respiratory isoprene output could serve as a monitor for ozone exposure. Healthy young adult subjects (n = 10) underwent chamber exposure on separate days to filtered air and to a variable concentration of ozone. Exposures had durations of 130 min that included alternate periods of rest and light treadmill exercise; breath was sampled pre- and postexposure. For six subjects, breath was resampled 19 +/- 1 h postexposure. Breath samples were concentrated cryogenically and analyzed by capillary gas chromatography. Isoprene output immediately postexposure was significantly reduced by ozone or filtered air (17 and 19%, respectively). These results suggest that exercise alone reduces isoprene levels in breath without an additive ozone effect. However, in the six subjects restudied 19 +/- 1 h postexposure to ozone, breath isoprene concentrations were now increased above the preexposure output by 99% (P < 0.01) and exceeded the 51% increase in output of isoprene at this time point after filtered-air exposure (P < 0.01). Therefore, breath isoprene is proposed as a noninvasive marker of a physiological response to oxidant-induced injury to epithelial membranes and fluid linings of the lower respiratory tract by ozone.

Evidence for ozone-induced small-airway dysfunction: lack of menstrual-cycle and gender effects.

Recently, we analyzed FEF25-75 isovolumetrically to assess the acute effects of ozone (O3) on small-airway function: the reduction in isovolumetric (isoV) FEF25-75 at end exposure progressed during the next 25 min even as FVC was recovering. To evaluate this effect over a longer period, we measured isovolumetric FEFs, helium-oxygen (He-O2) volume of isoflow (VisoV), the multiple breath nitrogen washout (MBNW) curve, FRC, and RV in 24 subjects 24 h after a 130-min exposure to filtered air (FA) and O3 (0.35 ppm). Men and women were studied to test for gender-based differences in response, after first determining that menstrual-cycle phase did not itself influence response. Isovolumetric FEF25-75, Vmax50, and Vmax75 were reduced about equally at 25 min after O3 exposure (p < or = 0.02) and showed no recovery at 24 h. FVC and FEV1, although still depressed after 24 h (p < 0.05), showed substantial recovery (p < 0.01). FRC, RV, and VisoV showed no effect of O3 exposure. No gender differences in O3 responsiveness were found. In summary, O3-induced reductions in isovolumetric flow rates, suggestive of small-airway dysfunction, may persist for 24 h following acute exposure to O3, a time-course consistent with inflammation.

Breath ethane generation during clinical total body irradiation as a marker of oxygen-free-radical-mediated lipid peroxidation: a case study.

Total body irradiation (TBI) is used therapeutically for treatment of leukemias and other malignancies of the hemopoietic system. Ionizing radiation produces oxygen free radicals that contribute to cytotoxicity. Breath collected from one patient undergoing therapeutic TBI showed measurable changes in levels of ethane during treatment. Breath ethane is a marker of lipid peroxidation of n-3 fatty acids. The TBI treatment involved 4 days of irradiation. The largest changes in breath ethane occurred on Day 2. The increased levels of breath ethane on Day 2 were correlated to clinical manifestations of toxicity. The correlation of the onset of gastrointestinal side effects with higher levels of breath ethane suggests that breath ethane may be a clinically useful measure of the toxicity of various TBI fractionation treatment protocols currently in use at different medical centers. The levels of breath ethane on the other days of treatment were lower, suggesting that the oxidative-antioxidative balance of the patient may be important in protection against free radical mediated injury. These results for a single patient suggest that breath ethane may be a promising approach to elucidate the role of antioxidants in clinical TBI and should be extended for verification to a larger volunteer patient population.

Exposure to ozone alters regional function and particle dosimetry in the human lung.

Effects of experimental exposure to O3 (0.33 ppm) or filtered air on regional lung function were assessed in nine healthy male subjects. Immediately after 2-h chamber exposures, regional ventilation and particle dosimetry were measured by gamma camera imaging. The vertical distributions of a radiolabeled gas (133Xe) and aerosol (3.5-microns-diam insoluble 99mTc-tagged Fe2O3 particles) were quantitated for upper, middle, and lower lung regions; distribution data were corrected for regional differences in lung volume and tissue attenuation. Indexes of mechanical function, inspiratory capacity, and mid-maximal expiratory flow rates were significantly reduced after O3, but functional residual capacity remained unchanged. Exposure to O3 significantly enhanced the fraction of respired aerosol retained by the lung and altered the distribution pattern of deposited aerosol by increasing particle deposition to the middle lung region (P < 0.05). Aerosol penetration indexes, i.e., ratio of particle deposition in central lung regions to that in peripheral lung regions, and particle retention 24 h postinhalation (an index of aerosol deposition within alveoli and slowly clearing bronchioles) indicated that particle filtration efficiency had increased for tracheobronchial and parenchymal lung regions. For seven of the nine subjects, regional ventilation after O3 was reduced by 14% to the lung base and enhanced by 8 and 6% to the upper and middle lung regions, respectively; these changes were significant (P < 0.02) compared with ventilation after filtered air.(ABSTRACT TRUNCATED AT 250 WORDS)

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. Patients with COPD and chronic flow limitation were compared with non-flow-limited normal volunteers. Deposition was normalized for regional lung volume and expressed as the specific central to peripheral (sC/P) ratio. In COPD subjects, clearance from the whole lung and central airways was significantly different from that of normal subjects after 20 min of observation. In the peripheral airways, there were no significant differences between COPD and normal subjects. An alternative analysis of regional MC indicated patients retained particles in central airways while normal subjects, with intact MC, emptied central airways. Thus, COPD subjects with tidal expiratory flow limitation have impaired MC in their central airways.

Aerosolized lidocaine reduces dose of topical anesthetic for bronchoscopy.

Conventional aerosol techniques were used to determine if inhalation of lidocaine can supplement topical anesthesia applied during bronchoscopy. Aerosols of either saline or lidocaine (50 mg at either 2 or 4% concentrations) were generated by jet nebulizer and administered with or without intermittent positive-pressure breathing. Patients (n = 38) after aerosol inhalation were administered 2% lidocaine (atomized and instilled) for suppression of the gag reflex, control of cough, and airway anesthesia. For five of the patients, prior to bronchoscopy, additional studies with radioaerosols and scintillation scans were accomplished with the same aerosol methodology to demonstrate lung distribution of deposited aerosol. For five patients who received 2% lidocaine aerosol prior to bronchoscopy, the subsequent topical dose of anesthetic required for the procedure was 186 +/- 34 (SEM) mg lidocaine. Nine patients in a control group received saline aerosol and required significantly more anesthetic, i.e., 308 +/- 26 mg; procedures were completed on average within 50 min. The largest difference was in the amount delivered to the upper airway (naris, pharynx, epiglottis, and larynx), i.e., 144 +/- 26 mg for saline control versus 48 +/- 16 mg for lidocaine aerosol protocol. Airways distal to the cords required less anesthesia also, on average, 77 mg for the saline control versus 46 mg for the lidocaine aerosol protocol (p < 0.05). Topical anesthetic dosage data were replicated in 12 additional patients studied by a different bronchoscopist. No additional benefit was afforded by premedication with 4% lidocaine aerosol rather than the 2% aerosol (n = 12). We conclude that aerosol modalities can supplement topical anesthesia during bronchoscopy, primarily by reducing the dose required to anesthetize the upper airway.