Long-term use of Viozan (sibenadet HCl) in patients with chronic obstructive pulmonary disease: results of a 1-year study.

Viozan (sibenadet HCl, AR-C68397AA) is a novel dual D2 dopamine receptor, beta2-adrenoceptor agonist that has been investigated for efficacy in alleviating the symptoms of chronic obstructive pulmonary disease (COPD). The slowly progressive nature of this disease means that patients will require ongoing therapeutic management for many years, or even decades. With such long-term treatment, the safety profile of new agents will be of paramount importance. As part of the large-scale assessment of sibenadet, a 12-month safety study has been conducted. Following completion of a 2-week baseline period, 435 adults with stable, symptomatic, smoking-related COPD were randomized to receive either 500 microg sibenadet or placebo delivered via pressurized metered dose inhaler (pMDI), three times daily for 52 weeks. Sibenadet therapy was generally well tolerated, with the only notable differences seen in the incidence of tremor and taste of treatment (16.9% vs. 4.1% and 14.5% vs. 4.1% in the sibenadet and placebo groups respectively). There were a total of 79 patients with serious adverse events (SAEs), 43 (14.8%) in the sibenadet pMDI group and 36 (24.8%) in the placebo group. No clinically significant abnormal laboratory values or overall differences between treatment groups were noted. Similarly, there were no clinically significant differences between the two treatment groups for cardiac variables, or in vital signs. The secondary variables showed no notable differences with respect to lung function, exacerbations or health-related quality of life. Due to the effective beta2-agonist properties, patients in the sibenadet group did, however, report reduced rescue medication usage at all timepoints. While the results of this study show that, overall, sibenadet therapy was well tolerated, the lack of sustained benefit reported in large-scale clinical efficacy studies means that sibenadet development will not be continued.

Expression of functional beta 2-adrenergic receptors in a rat airway epithelial cell line (SPOC1) and cell density-dependent induction by glucocorticoids.

The beta 2-adrenergic receptor (beta 2AR) signal transduction system regulates many key functions of airway epithelium. In this study, we have pharmacologically characterized the beta 2AR and determined the impact of glucocorticoids on beta 2AR gene transcription in SPOC1 cells, a continuous cell line derived from the tracheal epithelium of rats. [125I]Cyanoiodopindolol assays demonstrated that binding to SPOC1 cell membranes was saturable (Bmax = 62.6 +/- 6 fmol/mg protein) and of high affinity (Kd = 6.3 +/- 0.8 pM). From competition experiments, the rank order of potency of agonists (isoproterenol > epinephrine >> norepinephrine) and the high affinity (Ki = 0.37 +/- 0.05 nM) of the beta 2-selective antagonist ICI 118,551 suggested the predominance of the beta 2AR subtype. Two isoforms of the alpha subunit of Gs (45 and 52 kDa) were identified by Western blot analysis. Isoproterenol-stimulated cyclic AMP levels increased in a dose-dependent manner, confirming that SPOC1 cell beta 2ARs are functionally coupled to adenylyl cyclase. The effect of glucocorticoids on beta 2AR expression was assessed in radioligand and transient transfection assays. Dexamethasone treatment of SPOC1 cells increased both beta 2AR protein and beta 2AR-luciferase fusion gene expression 1.6- to 3.1-fold, with the greatest increase demonstrated in cells cultured at low density compared to cells grown at high density.

Identification of a glucocorticoid response element in the rat beta2-adrenergic receptor gene.

Regulation of beta2-adrenergic receptor (beta2AR) levels by glucocorticoids is a physiologically important mechanism for altering beta2AR responsiveness. Glucocorticoids increase beta2AR density by increasing the rate of beta2AR gene transcription, but the cis-elements involved have not been well characterized. We now show that one of six potential glucocorticoid response elements (GREs) in the 5'-flanking region of the rat beta2AR gene is necessary for glucocorticoid-dependent stimulation of receptor gene expression. Using a nested set of deletion fragments of the rat beta2AR gene 5'-flanking region fused to a luciferase reporter gene, glucocorticoid-dependent induction of reporter gene expression in HepG2 cells was localized to a region between positions -643 and -152, relative to the transcription initiation site. In electrophoretic mobility shift assays, a double-stranded oligonucleotide incorporating a near-consensus GRE from this region (positions -379 to -365) formed complexes with the human recombinant glucocorticoid receptor, as well as with nuclear protein from dexamethasone-treated HepG2 cells. Mutation of a single base within this GRE sequence greatly diminished interaction of the mutated oligonucleotide with the human recombinant glucocorticoid receptor. The functional activity of the GRE was characterized using a luciferase reporter construct driven by a minimal thymidine kinase promoter. In HepG2 cells transfected with constructs containing the GRE, dexamethasone increased reporter gene expression approximately 3-fold, whereas a dexamethasone effect was not observed with constructs lacking the GRE. Taken together, these findings show that a GRE located at positions -379 to -365 in the 5'-flanking region of the rat beta2AR gene mediates glucocorticoid stimulation of beta2AR gene transcription.

Sensitivity of aerosol bolus behavior to methacholine-induced bronchoconstriction.

STUDY OBJECTIVES: Airway narrowing causes alterations in the shape of an exhaled aerosol bolus that can serve as indexes of airway changes during bronchoprovocation. We compared the sensitivities of aerosol bolus behavior and specific airway conductance (SGaw) during bronchoprovocation in normal subjects. DESIGN AND PARTICIPANTS: Fifteen normal, nonsmoking subjects were studied. Doubling methacholine (MCh) concentrations were delivered during tidal breathing. After each dose, SGaw was determined followed by inhalation of narrow pulses of 1-microm particles introduced into 1-L breaths. Inhaled and exhaled particle concentrations were measured with light scattering photometry. Using plots of concentration vs volume, the exhaled bolus was compared with the inhaled bolus for measurements of volumetric change in mode location (modal shift), particle deposition, and dispersion. To determine baseline intrasubject variability, sham studies using buffer solution were performed on five subjects. RESULTS: MCh caused a proximal modal shift, and increased dispersion and deposition of the exhaled bolus. At most doses, a greater percentage of subjects showed significant change (p<0.05) from baseline for modal shift and deposition than for SGaw. Aerosol bolus behavior displayed less intrasubject variability than did SGaw during sham studies. CONCLUSION: Aerosol bolus behavior is at least as sensitive as SGaw in detecting MCh-induced airway constriction in normal subjects and exhibits less intrasubject variability.

Pharmacokinetics of (R,S)-Albuterol after aerosol inhalation in healthy adult volunteers.

The pharmacokinetics of inhaled (R,S)-albuterol following pulmonary absorption were studied in healthy human subjects. Ten subjects (5 females and 5 males) inhaled two puffs (180 microg) of albuterol via a metered-dose inhaler and spacer device. All subjects were nonsmoking and had normal pulmonary function. Charcoal slurries were ingested to block gastrointestinal absorption of drug. Venous samples were obtained from each subject at thirteen time points from 0 through 12 h post dose. (R,S)-Albuterol concentration in plasma was measured using a gas chromatography-mass spectrometry (GC-MS) assay. The plasma concentration-time profiles conformed to a two-compartment extravascular model with first-order absorption kinetics. The drug levels reached maximum in 12.6 +/- 2.2 (SD) minutes, which is in contrast with previous reports that maximum plasma concentrations occur within 2 to 4 h. The mean peak plasma level was 1469 +/- 410 pg/mL. The mean half-life of distribution was 17.9 +/- 8.2 min. The mean half-life of elimination was 4.4 +/- 1.5 h. Female subjects achieved peak concentration more rapidly than male subjects (10.4 vs 14.8 min, p = 0.01) and had a higher mean peak concentration (1778 vs 1159 pg/mL, p = 0.04).

Structural and functional analysis of the 5'-flanking region of the rat beta 2-adrenergic receptor gene.

We have analyzed 3.4 kb of DNA from the 5'-flanking region of the rat beta 2-adrenergic receptor gene and assessed its promoter activity in A549 cells, a human lung adenocarcinoma cell line. A single transcription start site was identified approx. 223 bp upstream of the ATG start codon. A549 cells were transfected with luciferase reporter plasmids containing segments of the rat beta 2-adrenergic receptor 5'-flanking region. Our results suggest that both positive and negative cis-acting regulatory sequences are present in the 5'-flanking region of the rat beta 2-adrenergic receptor gene.

Regulation of the beta 2-adrenergic receptor and its mRNA in the rat lung by dexamethasone.

Glucocorticoids increase beta 2-adrenergic responsiveness and receptor density in the lung, but the underlying mechanisms have not been clearly elucidated. To determine whether changes in beta 2-adrenergic receptor gene expression are involved in vivo, we measured beta 2-adrenergic receptor mRNA levels and beta 2-adrenergic receptor density in lungs from Sprague-Dawley rats treated with a daily injection of dexamethasone (1 mg/kg subcutaneously) for 1, 3, or 7 days. Animals were sacrificed either 2 or 24 h after receiving the last injection. beta 2-Adrenergic receptor mRNA levels were significantly (p < .05) elevated compared to saline-treated controls in the lungs of animals sacrificed 2 h after dexamethasone injection for 1 day (174 +/- 12%), 3 days (236 +/- 18%), and 7 days (220 +/- 11%). Receptor mRNA levels measured 24 h after dexamethasone injection did not differ significantly from the control group. Induction of beta 2-adrenergic receptor mRNA by dexamethasone was transient, since no significant cumulative or sustained increase in receptor mRNA levels was observed during the study period. Treatment with dexamethasone increased beta 2-adrenergic receptor density as expected, but no significant increase in receptor density was detected until 24 h after the third daily injection of dexamethasone, when levels reached 2045 +/- 150 fmol/mg protein compared to 1292 +/- 34 fmol/mg protein in the control group. Receptor density then remained at this elevated level through 7 days of treatment. These results show that dexamethasone up-regulates both the beta 2-adrenergic receptor and its mRNA in vivo in the lung. The induction of beta 2-adrenergic receptor mRNA levels indicates that glucocorticoids may regulate receptor density in the lung through modulation of gene expression. However, the difference between the time course of induction for the beta 2-adrenergic receptor and its mRNA suggests that additional translational or post-translational mechanisms may also be involved.

Detection of small airway dysfunction in asymptomatic smokers using aerosol bolus behavior.

Tests using inhaled particles assess ventilatory nonuniformities and may be sensitive to early changes in the small airways of cigarette smokers. We measured aerosol bolus behavior in 20 asymptomatic smokers and 20 age- and sex-matched nonsmokers for comparison with pulmonary function parameters including the single-breath nitrogen test. Narrow boluses containing 1-micron particles were introduced into 1-I breaths and inhaled to varying lung depths. We examined changes in bolus shape between inhalation and exhalation using plots of aerosol concentration versus respired volume for measurement of bolus dispersion, volumetric change in mean location (mean shift), and quantitative particle deposition. We found exhaled bolus dispersion to be significantly increased in smokers compared with nonsmokers. Volumetric mean shift was significantly different in smokers at shallow lung depths, with the center of bolus mass occurring later in exhalation. FEV1/FVC in smokers was significantly inversely correlated with dispersion at deeper lung depths and with mean shift at all lung depths. Smokers with abnormal spirometry (n = 4) or an abnormal single-breath nitrogen test (n = 7) had significantly increased dispersion compared with smokers with normal pulmonary function tests. We conclude that aerosol bolus dispersion is a useful tool for examination of small airway function in asymptomatic smokers.

Nicotine absorption after pulmonary instillation.

Levels of nicotine in plasma were determined by gas chromatography in eight mongrel dogs after instillation of 0.5 mg of nicotine in 100 microL of normal saline at three levels of the tracheobronchial tree: the trachea, a subsegmental bronchus of the right middle lobe, and a subpleural location of the right middle lobe ("distal"). An equivalent dose was given intravenously (iv). Peak of nicotine concentrations in plasma were significantly lower after instillation at the trachea (11.5 +/- 4.4 ng/mL) and the subsegmental bronchus (18.2 +/- 5.0 ng/mL) than after an iv dose (30.3 +/- 10.7 ng/mL); p < 0.05 for each comparison. In addition, the peak concentration after instillation at the trachea was significantly lower than that after instillation at the distal site (22.1 +/- 6.2 ng/mL, p < 0.05). Time to peak concentration was significantly longer after tracheal instillation (5.3 +/- 3.0 min) than after subsegmental instillation (2.0 +/- 0.0 min) or iv infusion (2.0 +/- 0.0 min); p < 0.05 for each comparison. Total drug absorbed, half-life, and clearance were equivalent from all four sites. This study demonstrated that quantitative absorption of nicotine from the described lung sites is equivalent to that after an iv dose, with slower absorption and lower peak concentrations from the tracheal site.

The effects of gamma-hydroxybutyrate on the sleep of narcolepsy patients: a double-blind study.

The effects of gamma-hydroxybutyrate (GHB: 25 mg/kg h.s. and 3 h later) vs. placebo on objectively evaluated nighttime sleep and daytime sleepiness in narcolepsy were evaluated in a double-blind, counterbalanced crossover design. Twenty narcolepsy patients were given an overnight polysomnogram (PSG), followed by a daytime multiple sleep latency test (MSLT) at baseline and on the 1st and 29th days of GHB and placebo treatment. The overnight PSGs indicated that the narcolepsy patients had the following significant results during GHB versus placebo treatment: decreased stage 1 (p = 0.012), increased stage 3 (p = 0.008), increased delta (stage 3 and 4 combined) sleep (p = 0.049), fewer stage shifts (p = 0.002), and fewer awakenings (p = 0.006). Minutes of wakefulness were significantly increased only for the last 2 h of the 8 h sleep period on GHB versus placebo (p = 0.019), which is beyond the time of GHB's direct influence. The MSLTs indicated that the narcolepsy patients had a marginally increased sleep latency mean during GHB versus placebo treatment (p = 0.074) and significantly increased total stage 0 (wakefulness) on day 29 of GHB versus day 29 of placebo treatment (p = 0.038). Female narcolepsy patients had significantly fewer naps with REM sleep (REM naps) on day 29 of GHB vs. day 29 of placebo treatment (p = 0.020). The therapeutic effect of GHB in narcolepsy patients, i.e., decreases cataplexy, appears to be due to its improving nocturnal sleep quality, since its half-life is only 1.5 to 2 h. It is conjectured that GHB, an endogenous neurochemical, may be a sleep neurotransmitter or neuromodulator, since GHB rapidly induces sleep, and increases sleep continuity and delta sleep without suppressing REM sleep in both normals and narcolepsy patients.

Family consent to orders not resuscitate. Reconsidering hospital policy.

Hospital policies typically require that cardiopulmonary resuscitation be attempted unless a do-not-resuscitate order has been written, and they further require that family permission for the order be obtained. This sometimes forces physicians to perform procedures that are useless or that add to the patient's suffering without corresponding benefit. Policies should be changed to allow physicians to write a do-not-resuscitate order over family objections when (1) the patient lacks decision-making capacity, (2) the burdens of treatment clearly outweigh the benefits, (3) the surrogate does not give an appropriate reason in terms of patient values, preferences, or best interests, and (4) the physician has made serious efforts to communicate with the family and to mediate the disagreement. Furthermore, when resuscitation would clearly provide no medical benefit to the patient, policy should not require that it be discussed with either the patient or the family.

KIE: The authors call for reform of hospital policies that now require family permission before a do-not-resuscitate (DNR) order may be written for patients who are not competent to give consent themselves. Hackler and Hiller report two cases where the lives and suffering of dying patients were prolonged when family members insisted upon cardiopulmonary resuscitation (CPR) despite hopeless prognoses. They argue that the authority of family members to make treatment decisions is limited when neither patients' preferences nor best interests are served. They propose that hospital policies concerning resuscitation be changed so that: 1) the option of futile resuscitation need not be offered to patients or family members, and 2) family agreement to CPR need not be obtained in every case where the procedure is not clearly futile.

Respiratory tract deposition of ultrafine particles in subjects with obstructive or restrictive lung disease.

To evaluate the effects of lung disease on deposition of inhaled ultrafine particles (less than 0.1 micron diameter), we measured total respiratory tract deposition of nonhygroscopic particles of 0.02 to 0.24 micron in five subjects with obstructive lung disease and three subjects with restrictive lung disease and compared it with that in ten normal subjects. Deposition was measured as concentration difference of five size fractions in inhaled and exhaled air using an electrical aerosol analyzer. The data showed that deposition of these ultrafine particles was increased in subjects with obstructive lung disease when compared with normal subjects, while it was unchanged in subjects with restrictive lung disease. The increase in deposition in the subjects with obstructive lung disease was significant for particle sizes 0.04 to 0.24 micron. Possible mechanisms for increased deposition in airway obstruction include increased transit time of particles, abnormal expiratory collapse of airways due to flow limitation, and flow perturbations resulting from decreased airway caliber.

Plasma nicotine levels after inhalation of aerosolized nicotine.

Smokers were given 5 mg of aerosolized nicotine over a 5-min period on 3 separate days to determine if this mode of nicotine delivery could produce nicotine levels similar to those reported from cigarette smoking. Our subjects' mean nicotine level increased from a pretrial level of 12 +/- 2 ng/ml to a peak of 32 +/- 7 ng/ml at 2.5 min after completion of the inhalation. Cough was the most prominent side effect and seemed to be related to irritant effects of the aerosol. Seven of the 16 subjects dropped out of the study because of unpleasant side effects. Side effects did not seem to correlate with nicotine blood levels. We conclude that aerosolized nicotine can produce plasma nicotine levels analogous to cigarette smoking. Cough was a limiting side effect and was presumably due to an irritant effect of the aerosol on the upper airway.

Efficacy of gamma-hydroxybutyrate versus placebo in treating narcolepsy-cataplexy: double-blind subjective measures.

The efficacy of gamma-hydroxybutyrate (GHB) versus placebo for treating narcolepsy was evaluated in 20 patients with narcolepsy, 10 men and 10 women, using a double-blind counterbalanced crossover design. Each patient completed a daily sleep-wake log and questionnaire during a 14-day baseline, a 29-day placebo period, a 29-day GHB period (50 mg GHB/kg/night given 25 mg/kg h.s. and 25 mg/kg 3 hr later), and a 6-day washout period after each treatment. Cataplexy frequency was significantly lower during GHB treatment than during placebo treatment (p = 0.022). Compared to baseline values, the number of cataplexy attacks per day declined by 52% and 69% during GHB treatment weeks 1 and 4, respectively. The number of subjective arousals from sleep was less with GHB than with placebo (p = 0.035), and the number of sleep attacks was not significantly different during GHB versus placebo treatment. GHB did not have a significant effect on subjective estimates of sleep onset latency, total sleep time, Stanford Sleepiness Scale ratings at morning wake-up, methylphenidate usage, or the number of naps per day. The results indicate that GHB is efficacious for reducing the frequency of cataplexy attacks and subjective nocturnal arousals in patients with narcolepsy within the first 4 weeks of treatment.

Particle size distribution of mainstream tobacco and marijuana smoke. Analysis using the electrical aerosol analyzer.

Accurate measurement of cigarette smoke particle size distribution is important for estimation of lung deposition. Most prior investigators have reported a mass median diameter (MMD) in the size range of 0.3 to 0.5 micron, with a small geometric standard deviation (GSD), indicating few ultrafine (less than 0.1 micron) particles. A few studies, however, have suggested the presence of ultrafine particles by reporting a smaller count median diameter (CMD). Part of this disparity may be due tot he inefficiency to previous sizing methods in measuring ultrafine size range, to evaluate size distribution of smoke from standard research cigarettes, commercial filter cigarettes, and from marijuana cigarettes with different delta 9-tetrahydrocannabinol contents. Four 35-cm3, 2-s puffs were generated at 60-s intervals, rapidly diluted, and passed through a charge neutralizer and into a 240-L chamber. Size distribution for six cigarettes of each type was measured, CMD and GSD were determined from a computer-generated log probability plot, and MMD was calculated. The size distribution parameters obtained were similar for all cigarettes tested, with an average CMD of 0.1 micron, a MMD of 0.38 micron, and a GSD of 2.0. The MMD found using the EAA is similar to that previously reported, but the CMD is distinctly smaller and the GSD larger, indicating the presence of many more ultrafine particles. These results may explain the disparity of CMD values found in existing data. Ultrafine particles are of toxicologic importance because their respiratory tract deposition is significantly higher than for particles 0.3 to 0.5 micron and because their large surface area facilitates adsorption and delivery of potentially toxic gases to the lung.

Effect of three alcohol doses on breathing during sleep in 30-49 year old nonobese snorers and nonsnorers.

To test the effect of alcohol ingestion and snoring on sleep-disordered breathing (SDB), the sleep and respiration of 31 nonobese healthy males ages 30-49 (15 snorers, 16 nonsnorers) were studied overnight after alcohol ingestion. Subjects received placebo, 0.32, 0.65, and 0.81 g alcohol/kg body weight prior to their evening bedtime, with each dose given on one of four nonconsecutive nights in a repeated-measures counterbalanced design. On each night, respiration was assessed by recording respiratory effort from intercostal surface electromyography (EMG), ventilation from oral and nasal thermistors, and arterial oxygen saturation (SaO2) from an ear oximeter (BIOX III). Snorers had significantly: (a) more total SDB, (b) more obstructive sleep apnea (OSA), and (c) lower minimum SaO2 than nonsnorers after the placebo and each alcohol dose. Snorers had more hypoxic events than nonsnorers after each alcohol dose but not after placebo. Increasing alcohol dose caused a statistically significant (p = 0.0004) decrease in minimum SaO2 in snorers only, but this decrease was small and probably not clinically important. Alcohol did not cause significant increases in SDB and hypoxic events, and did not have different effects on SDB and hypoxic events for snorers versus nonsnorers. Because this experiment included only nonobese 30-49-year-old males, these results do not imply that alcohol has no significant effects on obese subjects or those older than 50.

Sleep apnea in epistaxis patients treated with nasal packs.

The presence of anterior and posterior nasal packs in patients with epistaxis is known to be associated with cardiorespiratory problems and sometimes death, although the mechanism has not been well understood. To determine the incidence and severity of obstructive sleep apnea in patients with epistaxis treated with both anterior and posterior nasal packs, we obtained polysomnograms on twelve patients while the packs were in place. Ten of these patients demonstrated obstructive sleep apnea. The apnea index (apneas/hour sleep) ranged from 1 to 83, with a mean of 29; the hypopnea index (hypopneas/hour sleep) ranged from 9 to 33, with a mean of 20; and the lowest oxygen saturation (SaO2) ranged from 17% to 91%, with a mean of 77%. Ten patients returned for another polysomnogram after removal of the packs. These baseline studies showed improvement in the apnea index and in the lowest SaO2 in all patients, although four patients still demonstrated at least mild obstructive sleep apnea. This study demonstrates that nasal packs used for the treatment of epistaxis may induce obstructive sleep apnea or markedly exacerbate underlying obstructive sleep apnea and, therefore, contribute to the sudden deaths that have been reported in epistaxis patients.

Management of tetanus.

Two cases of tetanus are presented, and the diagnosis, clinical features, and management of tetanus are reviewed. The first patient, an 86-year-old woman, had marked muscle rigidity but was able to breathe spontaneously. A dark eschar with purulent drainage was noted on her left foot, but Clostridium tetani was not isolated. She was placed in a semidark room and was treated with penicillin G; tetanus immune globulin (TIG) 5000 units i.m.; tetanus toxoid 0.5 mL i.m.; diazepam, chlorpromazine, and morphine for sedation, muscle relaxation, and analgesia; ranitidine for stress ulcer prophylaxis; heparin for prevention of deep-vein thrombosis; and peripheral-vein nutrition. Her condition improved gradually, and she was discharged to a rehabilitation institute after 32 days. The second patient, a 46-year-old woman, experienced progressive descending paralysis and required ventilatory support. She had a periodontal abscess, but cultures of the drainage were negative. She was placed in a semidark room and treated with erythromycin, TIG, tetanus toxoid, diazepam, pancuronium bromide, morphine, ranitidine, and heparin. Autonomic instability occurred during the second and third weeks, but cardiac output was maintained without treatment. The patient was extubated after five weeks, and was transferred out of the intensive-care in the following week. The diagnosis of tetanus is based primarily on characteristic findings of muscle rigidity and reflex spasms; cultures for C. tetani are of limited value. A history of trauma or injury is common. Pulmonary infections and cardiovascular instability are the most common complications. Therapy consists of ventilatory support; control of neuromuscular symptoms with benzodiazepines, narcotics, and neuromuscular blockers; antibiotic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Deposition of sidestream cigarette smoke in the human respiratory tract. II. Deposition of ultrafine smoke particles.

Sidestream cigarette smoke was generated into an inhalation chamber from which five normal male volunteers inhaled the smoke. Size distribution of the smoke aerosol was: count median diameter, 0.11 micron, mass median diameter 0.43 micron. Deposition fraction measured as concentration difference for each size fraction between inhaled and exhaled aerosol for each size interval was: 0.075 micron, 0.24 +/- 0.04; 0.13 micron, 0.15 +/- 0.04; 0.24 micron, 0.10 +/- 0.04; and 0.42 micron, 0.07 +/- 0.02. The declining deposition fraction as size approaches 0.5 micron is consistent with previous theoretical and experimental data.