Intranasal deferoxamine affects memory loss, oxidation, and the insulin pathway in the streptozotocin rat model of Alzheimer's disease.

Accumulation of metal and the accompanying increase in oxidative stress and inflammation plays an important role in neurodegenerative disease. Deferoxamine (DFO) is a metal chelator found to be beneficial in several animal models of neurodegenerative disease and insult including Alzheimer's disease, Parkinson's disease, stroke, and subarachnoid hemorrhage. In this study, we determine whether intranasally (IN) administered DFO is beneficial in the intracerebroventricular streptozotocin (ICV STZ) rat model of sporadic Alzheimer's disease, which is different from previous models in that it exhibits dysregulation of insulin metabolism as well as oxidative stress and inflammation. Surgical induction of the model included ICV injections of either STZ or citrate buffer (sham in rats), which were treated IN with either saline or DFO (n=10-15/group). Treatment started either before or after injection of STZ to induce the model, and continued throughout the study. IN treatment continued three times per week for three weeks before behavior tests started followed by eventual euthanasia with tissue collection. Spatial memory tests with the Morris water maze showed that STZ rats treated with IN DFO both before and after model induction had significantly shorter escape latencies. Pre-treatment with IN DFO also significantly decreased footslips on the tapered balance beam test. Brain tissue analyses showed DFO treatment decreased oxidation as measured by oxyblot and increased insulin receptor expression. These results further support the potential of IN DFO for use as a treatment for Alzheimer's disease, and show benefit in a non-amyloid/tau rodent model.

Increased blood-oxygen binding affinity in Tibetan and Han Chinese residents at 4200 m.

High-altitude natives are challenged by hypoxia, and a potential compensatory mechanism could be reduced blood oxygen-binding affinity (P50), as seen in several high-altitude mammalian species. In 21 Qinghai Tibetan and nine Han Chinese men, all resident at 4200 m, standard P50 was calculated from measurements of arterial PO2 and forehead oximeter oxygen saturation, which was validated in a separate examination of 13 healthy subjects residing at sea level. In both Tibetans and Han Chinese, standard P50 was 24.5 ± 1.4 and 24.5 ± 2.0 mmHg, respectively, and was lower than in the sea-level subjects (26.2 ± 0.6 mmHg, P < 0.01). There was no relationship between P50 and haemoglobin concentration (the latter ranging from 15.2 to 22.9 g dl(-1) in Tibetans). During peak exercise, P50 was not associated with alveolar-arterial PO2 difference or peak O2 uptake per kilogram. There appears to be no apparent benefit of a lower P50 in this adult high-altitude Tibetan population.

Intranasally-administered deferoxamine mitigates toxicity of 6-OHDA in a rat model of Parkinson׳s disease.

Deferoxamine (DFO) has shown therapeutic promise for the treatment of Parkinson׳s disease (PD) as it has reduced both behavioral and biochemical deficits when injected into the brain of rodent models of PD. Intranasally administered DFO targets the brain directly but non-invasively and has been effective in animal models of stroke and Alzheimer׳s disease. In this study we sought to determine whether intranasal (IN) DFO could be neuroprotective for PD in a rat model. PD was induced with a unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle, while sham surgery rats received saline injections. Rats were pre-treated three times with either IN DFO or saline (starting 4 days before 6-OHDA), and post-treated twice/wk for one month before behavioral tests. In the apomorphine-induced rotational test, IN DFO significantly decreased the number of contralateral turns after injection of apomorphine HCl (p<0.05). Also, IN DFO significantly decreased limb asymmetry in the rearing tube as measured with contralateral limb touches (p<0.05). The IN DFO treatment yielded a trend towards decreased contralateral foot-slips on the tapered balance beam, though the difference was not significant. Finally, IN DFO-treated rats had increased preservation of tyrosine hydroxylase immunoreactive neurons in the substantia nigra (p<0.05). These results confirm that DFO is beneficial in a 6-OHDA model and demonstrate improvement in motor deficits and dopaminergic neuronal survival with non-invasive intranasal delivery, making this an attractive potential treatment for PD.

Removal of sedimentation decreases relative deposition of coarse particles in the lung periphery.

Lung deposition of >0.5-µm particles is strongly influenced by gravitational sedimentation, with deposition being reduced in microgravity (µG) compared with normal gravity (1G). Gravity not only affects total deposition, but may also alter regional deposition. Using gamma scintigraphy, we measured the distribution of regional deposition and retention of radiolabeled particles ((99m)Tc-labeled sulfur colloid, 5-µm diameter) in five healthy volunteers. Particles were inhaled in a controlled fashion (0.5 l/s, 15 breaths/min) during multiple periods of µG aboard the National Aeronautics and Space Administration Microgravity Research Aircraft and in 1G. In both cases, deposition scans were obtained immediately postinhalation and at 1 h 30 min, 4 h, and 22 h postinhalation. Regional deposition was characterized by the central-to-peripheral ratio and by the skew of the distribution of deposited particles on scans acquired directly postinhalation. Relative distribution of deposition between the airways and the alveolar region was derived from data acquired at the various time points. Compared with inhalation in 1G, subjects show an increase in central-to-peripheral ratio (P = 0.043), skew (P = 0.043), and tracheobronchial deposition (P < 0.001) when particles were inhaled in µG. The absence of gravity caused fewer particles to deposit in the lung periphery than in the central region where deposition occurred mainly in the airways in µG. Furthermore, the increased skew observed in µG likely illustrates the presence of localized areas of deposition, i.e., "hot spots", resulting from inertial impaction. In conclusion, gravity has a significant effect on deposition patterns of coarse particles, with most of deposition occurring in the alveolar region in 1G but in the large airways in µG.

Intranasal deferoxamine improves performance in radial arm water maze, stabilizes HIF-1α, and phosphorylates GSK3ß in P301L tau transgenic mice.

Deferoxamine (DFO), a metal chelator, has been previously reported to slow the loss of spatial memory in a mouse model of amyloid accumulation when delivered intranasally (IN). In this study, we determined whether IN DFO also has beneficial effects in the P301L mouse, which accumulates hyperphosphorylated tau. Mice were intranasally treated three times per week with either 10% DFO (2.4 mg) or saline for 5 months, and a battery of behavioral tests were conducted before tissue collection and biochemical analyses of brain tissue with Western blot and ELISA. Wild-type (WT) mice statistically outperformed transgenic (TG) saline mice in the radial arm water maze, while performance of TG-DFO mice was not different than WT mice, suggesting improved performance in the radial arm water maze. Other behavioral changes were not evident. Beneficial changes in brain biochemistry were evident in DFO-treated mice for several proteins. The TG mice had significantly less pGSK3ß and HIF-1α, with more interleukin-1ß and total protein oxidation than wild-type controls, and for each protein, DFO treatment significantly reduced these differences. There was not a significant decrease in phosphorylated tau in brain tissue of DFO-treated mice at the sites we measured. These data suggest that IN DFO is a potential treatment not only for Alzheimer's disease, but also for other neurodegenerative diseases and psychiatric disorders in which GSK3ß and HIF-1α play a prominent role.

Production and fate of the sea lamprey migratory pheromone.

Biochemical studies demonstrate that three steroids postulated to function as the sea lamprey migratory pheromone are released in sufficient quantities, and possess adequate stability and binding characteristics, to function as a multi-component pheromone in natural river waters. Mass spectrometric (MS) analyses of the holding water of recently fed larval lamprey demonstrated that each of these compounds is released at rates of 5-25 ng larva(-1) h(-1), adequate to produce picomolar (biologically relevant) concentrations in river waters. Petromyzonamine disulfate (PSDS) was released at about twice the rate of the other two components, petromyzonamine disulfate (PADS) and petromyzonol sulfate (PS). Unfed larvae also released all three steroids but only at about two-thirds the rate of fed larvae and in a different ratio. However, a behavioral test of fed and unfed larval holding waters suggested this change in pheromone ratio does not diminish pheromonal signal function in the winter when larvae are not feeding. A study of steroid degradation found that PADS and PSDS had half-lives of about 3 days, similar to values previously described for PS and sufficiently slow for the entire pheromone to persist in river mouths. Finally, both MS and electro-olfactogram recording found that contrary to previous suggestions, natural levels of natural organic matter found in streams do not bind to these steroids in ways that diminish their natural biological potency. In conclusion, it appears highly likely that a mixture of PADS, PSDS and PS is present at biologically relevant concentrations and ratios in many Great Lakes streams where it functions as a pheromonal attractant.

A statewide initiative to improve the care of hospitalized pneumonia patients: The Connecticut Pneumonia Pathway Project.

PURPOSE: A statewide quality improvement initiative was conducted in Connecticut to improve process-of-care performance and to decrease length of stay for patients hospitalized with community-acquired pneumonia. SETTING AND METHODS: Data were collected on 1,242 elderly (> or =65 years) pneumonia patients hospitalized at 31 of 32 acute care hospitals between January 16, 1995, and March 15, 1996, and on 1,146 patients hospitalized between January 1, 1997, and June 30, 1997. Interventions included feedback of performance data (Qualidigm, the Connecticut Peer Review Organization), dissemination of an evidence-based pneumonia critical pathway (Connecticut Thoracic Society), and sharing of pathway implementation experiences (hospitals). Process and outcome measures included early antibiotic administration, blood culture collection, oxygenation assessment, length of stay, 30-day mortality, and 30-day readmission rates. Analyses were adjusted for severity of illness and hospital-specific practice patterns. RESULTS: After the statewide initiative, improvements were noted in antibiotic administration within 8 hours of hospital arrival (improvement from 83.4% to 88.8%, relative risk [RR] = 1.21; 95% confidence interval [CI]: 1.10 to 1.32), oxygenation assessment within 24 hours of hospital arrival (93.6% to 95.4%; RR = 1.23, 95% CI: 1.11 to 1.38), and length of stay (7 days to 5 days, P <0.001). There were no significant changes in blood culture collection within 24 hours of hospital arrival, blood culture collection before antibiotic administration, 30-day mortality, or 30-day readmission rates. CONCLUSIONS: Statewide improvements were demonstrated in the care of hospitalized pneumonia patients concurrent with a multifaceted quality improvement intervention. Further research is needed to separate the effects of the quality improvement interventions from secular trends.

Characterization of clinical tolerance to inhaled zinc oxide in naive subjects and sheet metal workers.

Clinical tolerance to the acute effects of zinc oxide inhalation develops in workers during periods of repeated exposure. The aims of this study were to determine whether clinical tolerance is accompanied by a reduction in the acute pulmonary inflammatory and cytokine responses to zinc oxide exposure and whether tolerance can be demonstrated in sheet metal workers who chronically inhale low levels of zinc oxide. Naive (never-exposed) subjects inhaled 5 mg/m3 zinc oxide on 1 or 3 days and underwent bronchoalveolar lavage 20 hours after the final exposure. Sheet metal workers inhaled zinc oxide on 1 day and control furnace gas on another day. Among naive subjects in whom tolerance was induced, bronchoalveolar lavage fluid percent neutrophils and interleukin-6 (IL-6) levels were significantly decreased compared with subjects who underwent only a single exposure. Sheet metal workers were much less symptomatic, but they still experienced a significant increase in plasma IL-6. The results indicate that clinical tolerance to zinc oxide is accompanied by reduced pulmonary inflammation and that chronically exposed sheet metal workers are not clinically affected by exposure to zinc oxide fume at the Occupational Safety and Health Administration Permissible Exposure Limit. The increase in IL-6 levels observed in the clinically responsive, and to a lesser extent, tolerant, states following zinc oxide inhalation is consistent with the dual role of IL-6 as a pyrogen and anti-inflammatory agent.

Associations between initial antimicrobial therapy and medical outcomes for hospitalized elderly patients with pneumonia.

BACKGROUND: Although medical practice guidelines exist, there have been no large-scale studies assessing the relationship between initial antimicrobial therapy and medical outcomes for patients hospitalized with pneumonia. OBJECTIVE: To determine the associations between initial antimicrobial therapy and 30-day mortality for these patients. METHODS: Hospital records for 12945 Medicare inpatients (> or = 65 years of age) with pneumonia were reviewed. Associations between initial antimicrobial regimens and 30-day mortality were assessed with Cox proportional hazards models, adjusting for baseline differences in patient characteristics, illness severity, and processes of care. Comparisons were made with patients treated with a non-pseudomonal third-generation cephalosporin alone (the reference group). RESULTS: Initial treatment with a second-generation cephalosporin plus macrolide (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52-0.96), a non-pseudomonal third-generation cephalosporin plus macrolide (HR, 0.74; 95% CI, 0.60-0.92), or a fluoroquinolone alone (HR, 0.64; 95% CI, 0.43-0.94) was independently associated with lower 30-day mortality. Adjusted mortality among patients initially treated with these 3 regimens became significantly lower than that in the reference group beginning 2, 3, and 7 days, respectively, after hospital admission. Use of a beta-lactam/beta-lactamase inhibitor plus macrolide (HR, 1.77; 95% CI, 1.28-2.46) and an aminoglycoside plus another agent (HR, 1.21; 95% CI, 1.02-1.43) were associated with an increased 30-day mortality. CONCLUSIONS: In this study of primarily community-dwelling elderly patients hospitalized with pneumonia, 3 initial empiric antimicrobial regimens were independently associated with a lower 30-day mortality. The more widespread use of these antimicrobial regimens is likely to improve the medical outcomes for elderly patients with pneumonia.

Factors inhibiting use of the pneumococcal polysaccharide vaccine: a survey of Connecticut physicians.

BACKGROUND: The pneumococcal polysaccharide vaccine (PPV) is effective in preventing invasive pneumococcal disease, but remains underutilized. Prior surveys of physicians revealed concern regarding the safety and efficacy of the vaccine, but there has been little information published in the last 10 years that sheds light on why the vaccine remains underutilized. Although there is currently emphasis on providing PPV to hospitalized patients, there is even less known about what factors prevent PPV use in the hospital setting and chronic care setting. We performed a survey of physicians in Connecticut to determine what factors prevent utilization of the vaccine in three patient care settings. METHODS: A survey of internists and family practitioners in Connecticut that ascertained their frequency of utilization of PPV and what factors inhibited utilization of PPV. RESULTS: Three hundred ninety-seven responses are included in the analysis. Forgetting to administer the vaccine (59% of respondents) and patient refusal (55% of respondents) were the factors most frequently noted as being important in preventing vaccination in the outpatient setting. In the inpatient and chronic care settings, difficulty in determining the patient's vaccine status was also noted. Concerns regarding the efficacy or safety of the vaccine did not seem to be important. The factor that correlated most closely with the respondents' reported frequency of vaccine use was forgetting to vaccinate. CONCLUSIONS: Physicians, although accepting the efficacy of PPV, are inhibited from its more frequent use by several factors.

Quality of care, process, and outcomes in elderly patients with pneumonia.

CONTEXT: Pneumonia is a frequent cause of hospitalization and death among elderly patients, but the relationships between processes of care for pneumonia and outcomes are uncertain, making quality improvement a challenge. OBJECTIVES: To assess quality of care for Medicare patients hospitalized with pneumonia and to determine whether process of care performance is associated with lower 30-day mortality. DESIGN: Multicenter retrospective cohort study with medical record review. SETTING: A total of 3555 acute care hospitals throughout the United States. PATIENTS: A total of 14069 patients at least 65 years old hospitalized with pneumonia. MAIN OUTCOME MEASURES: Four processes of care: time from hospital arrival to initial antibiotic administration; blood culture collection before initial hospital antibiotics; blood culture collection within 24 hours of hospital arrival; and oxygenation assessment within 24 hours of hospital arrival. Associations between processes of care and 30-day mortality were determined with logistic regression analysis. RESULTS: National estimates of process-of-care performance were antibiotic administration within 8 hours of hospital arrival, 75.5% (95% confidence interval [CI], 73.1-77.9); blood cultures before antibiotics, 57.3% (95% CI, 54.5-60.1); initial blood culture collection, 68.7% (95% CI, 66.2-71.2); and initial oxygenation assessment, 89.3% (95% CI, 87.5-90.9). Lower 30-day mortality was associated with antibiotic administration within 8 hours of hospital arrival (odds ratio [OR], 0.85; 95% CI, 0.75-0.96) and blood culture collection within 24 hours of arrival (OR, 0.90; 95% CI, 0.81-1.00). State and territory performance estimates varied from 49.0% to 89.7% for antibiotics given within 8 hours and from 45.6% to 82.6% for blood cultures drawn within 24 hours. CONCLUSIONS: Administering antibiotics within 8 hours of hospital arrival and collecting blood cultures within 24 hours were associated with improved survival. The fact that states varied widely in the performance of these measures suggests that opportunities exist to improve hospital care of elderly patients with pneumonia.

Metal fume fever: characterization of clinical and plasma IL-6 responses in controlled human exposures to zinc oxide fume at and below the threshold limit value.

Results from animal and preliminary human exposure studies have called into question whether the 5 mg/m3 8-hour time-weighted average threshold limit value (TLV) for zinc oxide fume is sufficient to protect workers against metal fume fever. The objectives of this study were to determine the clinical effects of exposures to low concentrations of zinc oxide and to ascertain whether these exposures elevated circulating levels of specific cytokines, which could account for the symptoms of the metal fume fever syndrome. Thirteen resting naive subjects inhaled, on separate days, air and 2.5 and 5 mg/m3 of furnace-generated zinc oxide fume for 2 hours. Subjects recorded symptoms and temperature and had blood drawn before and after each exposure. The mean (+/- SE) maximum rise in oral temperature at 6 to 12 hours after exposure was 1.4 +/- 0.3 degrees F after 5 mg/m3, compared with 0.6 +/- 0.5 degrees F after air exposure (P < 0.05). Mean temperature was also elevated after exposure to 2.5 mg/m3 zinc oxide (1.2 +/- 0.3 degrees F). In a parallel fashion, plasma levels of interleukin 6 (IL-6), a pyrogen, were significantly elevated after exposure to 5 mg/m3 zinc oxide. Mean IL-6 values (pg/mL) at pre-exposure and at 3 and 6 hours post-exposure were 1.9 (+/- 0.6), 2.8 (+/- 0.7), and 2.9 (+/- 0.6), respectively, on the air day and 1.6 (+/- 0.6), 4.4 (+/- 1.2), and 6.4 (+/- 1.1) on the 5 mg/m3 zinc oxide day. Zinc oxide exposure did not significantly affect plasma levels of tumor necrosis factor. Total symptom scores peaked 9 hours after the 5 mg/m3 zinc oxide exposure. Myalgias, cough, and fatigue were the predominant symptoms reported. Inhalation of zinc oxide for 2 hours at the current TLV of 5 mg/m3 produces fever and symptoms along with elevation in plasma IL-6 levels.

Summertime haze air pollution and children with asthma.

In order to investigate associations between summertime haze air pollution and asthma at an individual level, 52, 58, and 56 children (ages 7 to 13) attending a summer "asthma camp" were followed during the last week of June in 1991, 1992, and 1993, respectively. Most of the subjects had moderate to severe asthma. Daily records were kept of the environmental conditions, as well as of subject medication use, lung function, and medical symptoms. Air pollution was found to be significantly and consistently correlated with acute asthma exacerbations, chest symptoms, and lung function decrements. The pollutant most consistently associated with adverse health consequences was ozone (O3), although associations with sulfates and hydrogen ion suggest a possible role by fine particles as well. Effects were found to be roughly monotonic as a function of O3 concentration. Regression of morning (8:00 A.M.) to afternoon (5:00 P.M.) peak flow change on O3 indicated pulmonary function reductions similar to those previously reported for more active children without asthma. Moreover, analyses also indicated an increased risk of an asthma exacerbation and of experiencing chest symptoms of approximately 40% on the highest pollution day, relative to the mean. Based on these relative risk estimates, a rise in the 1-h daily maximal O3 from 84 ppb to 160 ppb was associated in this group with an increase from 20 to 28 (+/- 2) in the expected number of unscheduled medications administered/day, and from 29 to 41 (+/- 3) in the expected total number of chest symptoms/day. Thus, air pollution can be a major contributor to the respiratory problems experienced by children with asthma during the summer months.

Recombinant human DNase in management of lobar atelectasis due to retained secretions.

Recombinant human deoxyribonuclease (rhDNase) is an agent which reduces the viscoelasticity of purulent sputum. Two cases are reported in which rhDNase was utilised for the management of lobar atelectasis due to retained purulent secretions.

Sodium depletion prevents albuminuria in hypertensive rats.

The effect of short term (8 weeks) sodium (Na+) depletion and its repletion on glomerular synthesis of heparan sulfate and urinary excretions of albumin, total protein, heparan sulfate, Na+ and potassium (K+) was studied in spontaneous hypertensive rats (SHR) and their control normotensive Wistar-Kyoto rats (WKY). Na+ depletion in SHRs significantly increased the synthesis of glomerular heparan sulfate and decreased urinary excretions of albumin, Na+ and heparan sulfate when compared with the Na+ repleted group. In WKY rats, Na+ depletion did not cause any of the above changes. These data suggest that Na+ depletion prevents the urinary loss of protein through preservation of glomerular heparan sulfate only in SHRs.

Alteration of pulmonary macrophage intracellular pH regulation by sulfuric acid aerosol exposures.

In vivo exposure to sulfuric acid aerosols produces profound effects on pulmonary macrophage (PM phi) phagocytic function and cytokine release and perturbs intracellular pH (pHi) homeostasis. Because pHi influences a multitude of cellular processes, we sought to investigate the mechanism by which acid aerosol exposure affects its regulation. Guinea pigs underwent a single or 5 repeated 3-hr exposures to sulfuric acid aerosol (969 and 974 micrograms/m3 for single and repeated exposures, respectively). PM phi harvested immediately after exposure were incubated in HCO3-free media and their pHi recovery from an intracellular acid load was examined. The overall pHi recovery was depressed after single and multiple exposures to sulfuric acid aerosol. delta pHi (the difference between initial pHi and the one measured at 150 sec) decreased by 15.6 and 23.3% (p < 0.05) for single and repeated exposures, respectively. Initial dpHi/dt (maximum pHi recovery rate) after cytoplasmic acidification diminished by 20.3 and 32.2%, which were not statistically significant (p = 0.08 for repeated exposure). To determine whether the activity of the H(+)-ATPase pump the Na(+)-H+ exchanger was specifically altered by the acid exposures, PM phi were first incubated in Na+ and HCO3-free media with NBD-Cl (7-chloro-4-nitrobenz-2-oxa-1,3-diazol, blocking H(+)-ATPase and leaving only the Na(+)-H+ exchanger in effect) and then challenged with 30 mM NaCl. The pHi recovery of PM phi after Na challenge was significantly reduced in acid aerosol exposed guinea pigs (p < 0.05) compared to controls (for delta pHi, 18.2% lower in single exposure and 22.7% in multiple exposure groups; for initial dpHi/dt, 26.9% lower in single exposure and 22.4% in multiple exposure groups). In contrast, the H(+)-ATPase pump was inconsistently affected as indicated by delta pHi and initial dpHi/dt measured in the presence of MIA (amiloride-5-N-methylisobutyl, inhibiting the Na(+)-H+ exchanger and leaving only the H(+)-ATPase pump in effect). These results suggest that in vivo exposure to sulfuric acid aerosols induces alterations in pHi regulation in guinea pig PM phi attributable to changes in Na(+)-H+ exchanger activity.

Metal fume fever.

Metal fume fever is an acute self-limited illness induced most commonly by inhalation of zinc oxide fumes. The affected individual characteristically experiences the rapid onset of intense shaking chills, fever, and body aches a few hours after exposure, and symptoms dissipate spontaneously. While the occurrence of metal fume fever appears to be widespread and the current TLV/PEL of 5 mg/m3 and STEL of 10 mg/m3 may not be fully protective, no chronic health sequelae have been documented to date. Nonetheless, as any worker who has experienced a full-blown case will likely testify, metal fume fever remains one of the more noxious short-term illnesses contracted in the workplace, and its prevention deserves serious attention.

A novel system for the in vitro exposure of pulmonary cells to acid sulfate aerosols.

While ambient acid aerosols are considered a potential respiratory health hazard, the mechanism by which they induce responses in the lungs is not known. Attempts to ascertain these mechanisms using inhalation exposures are complicated by a number of technical difficulties, chief among which are neutralization of inhaled acids by endogenous ammonia and variations in deposition with inhaled particle size. To control for these variables, a novel in vitro exposure system allowing experimental evaluation of factors which influence biologic responses to acid sulfate particles was developed. The system consists of two subunits, a generation/delivery component and a cell exposure component. Sulfuric acid aerosols are generated by nebulizing dilute acid solutions. Particles larger than a specified size of interest (based upon the specific exposure conditions desired) are removed, and particles at the desired size and mass concentration are uniformly delivered onto a target cell monolayer. The system is capable of delivering acid particles larger than 0.7 micron (mass median diameter), yet at constant particle mass concentrations. This paper describes the design of the exposure system and its performance characteristics and presents initial results of some biological responses obtained using it. In conjunction with inhalation studies, this exposure system may provide additional insights into mechanisms by which acid aerosols adversely affect the respiratory tract and into the physical characteristics of acid particles which modulate toxicity.