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Synergistic interaction of ozone and respirable aerosols on rat lungs. IV. Protection by quenchers of reactive oxygen species.

In previous studies we have shown interactions between ozone and acidic respirable aerosols as evaluated by sensitive biochemical and quantitative morphological endpoints. In the present paper we have attempted to test the hypothesis that active oxygen species might play a role in lung damage caused by ozone +/- sulfuric acid aerosol. Rats were administered various scavengers of active oxygen species via the intraperitoneal (i.p.) route before and during exposure to 0.12, 0.20, or 0.64 ppm of ozone +/- 0.04, 0.1, 0.2, 0.5, or 1.0 mg/m3 of sulfuric acid aerosol. Vitamin E, a lipid-soluble free radical scavenger, beta-carotene (the precursor of vitamin A), a singlet oxygen scavenger, and dimethylthiourea, a hydrogen peroxide scavenger, were tested. Dimethylthiourea at doses of 50-500 mg/kg per day was able to protect rats from the effects of ozone, suggesting a role for hydrogen peroxide in ozone-induced lung damage in vivo. Neither vitamin E nor beta-carotene at 100 mg/kg doses had any protective activity in our experiments, despite documentation of increased lung content of the scavengers in animals receiving these agents. These results suggest that water solubility may play a role in the efficacy of the scavenging agents under our exposure protocols. We conclude that: (1) hydrogen peroxide may be involved in ozone-induced lung damage; and (2) that lung injury by ozone and by ozone + sulfuric acid aerosol may share common pathways.

Aerosols↗

Pharmacokinetic modeling of the lung burden from repeated inhalation of nickel aerosols.

The saturable nature of the clearance of soluble nickel compounds from the lung was studied by repeated exposures of rats to respirable submicron-size nickel aerosols. Using Michaelis-Menten type kinetics for removal of nickel lung burdens and a constant rate of deposition, the lung nickel burdens were simulated by computer. The computer simulation was used to design a repeated exposure regimen to test further the hypothesis of saturable clearance. Male Sprague-Dawley rats were exposed for 2 h/day to nickel chloride aerosols at either 90 or 400 micrograms Ni/m3 for up to 14 days. During the 22 h between exposures and up to 3 days post-exposure rats were kept in clean air. The particle size of the aerosol ranged from 0.7 to 0.9 micron mass median aerodynamic diameter with a geometric standard deviation of 1.2-1.4. A steady-state nickel lung burden was observed at 90 micrograms/m3, as predicted from computer modeling, while lung burdens continued to increase with repeated exposure to 400 micrograms Ni/m3. The best fit for the experimental data was obtained with a maximum clearance velocity (Vmax) of 34.6 ng Ni/g X h and a Michaelis-Menten constant for transport (Kt) of 1380 ng Ni/g. The percentage of submicron nickel chloride aerosols retained in the lung was 6.9%. These data support the hypothesis of a saturable clearance mechanism for soluble nickel and provide physiological constants useful for estimating human health risks from nickel inhalation.

Administration, Inhalation↗

Thirty month variability of aerosol pulse dispersion and conventional lung function parameters in healthy middle aged smokers and nonsmokers.

Chronic cigarette consumption is a generally accepted reason for the development of chronic obstructive pulmonary disease (COPD). COPD correlates to histomorphological parameters of lung structure as well as pulmonary function tests (PFT). COPD related changes affect PFT determined by conventional methods (bodyplethysmography, spirometry) as well as parameters of convective gas mixing. This study evaluates the diagnostic potential of a non-invasive aerosol method for the discrimination between healthy smokers and nonsmokers in comparison to conventional PFT. The aerosol method is based on the inhalation of small aerosol pulses suspended in particle free air and determines their changes during the breathing maneuver. Changes of aerosol pulse parameters (APP) are used to describe the convective component of gas mixing during ventilation. PFT and APP were determined in 40 healthy subjects (nonsmoker: 51.1 +/- 1.5 years; smoker: 49.6 +/- 1.5 years, 39.1 +/- 2.2 pack years) before and after a time interval of 30 months. Conventional PFT in smokers and nonsmokers showed no relevant differences between the values at the beginning and the end of the observation period. Thirty months later, at the end of the observation interval, a very similar behavior of the APP was obtained, which strongly confirmed the prior observed differences between smokers and nonsmokers. The data suggest that cigarette smoke-induced variations of lung function are also detectable in clinically asymptomatic smokers. Even in cases of normal PFT, most APP are able to discriminate between healthy smokers and nonsmokers. Since PFT showed only minor differences between both groups, it is indicated that APP are superior to PFT in the detection of early disturbances of lung ventilation in healthy smokers. Mean values of PFT and APP in smokers and nonsmokers showed a high reproducibility of the data obtained at the beginning of the study as well as at the end of the observation period. The data of our study further confirm that parameters of pulmonary gas exchange and gas mixing are affected by cigarette smoke at an earlier time than parameters of breathing mechanics.

Aerosols↗

Adaptive assay of radioactive pulmonary aerosols with an external detector.

The accuracy of the assay of radioactive pulmonary aerosols is influenced by the spatial distribution of the aerosol in the lungs. In general, there is considerable uncertainty in the spatial distribution of the aerosol beginning a few months after inhalation. This paper develops an adaptive approach for optimizing the assay of non-uniform spatial distributions of pulmonary aerosols. An adaptive assay is one in which the design of the assay system is modified during operation in response to measurements obtained on-line. Experimental results are presented which compare the performance of an adaptive assay with that of the standard measurement procedure. We study the assay of 241Am distributed in the lungs of a Lawrence Livermore realistic phantom using a NaI-CsI Phoswich detector.

Aerosols↗

Chemical composition and hygroscopic properties of size-segregated aerosol particles collected at the Adriatic coast of Slovenia.

The chemical composition as well as the water uptake characteristics of aerosols was determined in size-segregated samples collected during November 2002 on the Slovenian coast. Major ions, water-soluble organic compounds (WSOC), short-chain carboxylic acids and trace elements were determined in the water-soluble fraction of the aerosol. Total aerosol black carbon (BC) was measured from filter samples. Our results showed that the origin of air masses is an important factor that controls the variation in the size distribution of the main components. Very high concentrations of WSOC as well as higher concentrations of BC were found under mostly continental influence. Besides the main ionic species (SO4(2-), NH4(+), K+) in the finest size fraction (0.17-0.53 microm), the concentration of NO3(-) was also high. The difference between the two different air mass origins is particularly expressed for Cl-, Na+, Mg2+ and Ca2+ determined in particles larger than 1.6 microm. As expected, a very good correlation was found between Na+ and Cl-. A good correlation was found between sea salt elements and elements of crustal origin (Na+, Cl-, Mg2+, Ca2+, Sr). A good relationship between typical anthropogenic tracers (K, V and Pb) was also observed. The mass growth factors, for all size fractions of aerosols collected under continental influence were very low (maximum 2.23 at 94%, 1.6-5.1 microm), while under marine influence the mass growth factors increased significantly with the particle size. At 97% humidity, the mass growth factors were 6.95 for the size fraction 0.53-1.6 microm and 9.78 for larger particles (1.6-5.1 microm).

Aerosols↗

Determination of sugar compounds in atmospheric aerosols by liquid chromatography combined with positive electrospray ionization mass spectrometry.

We here report a method for the determination of sugar compounds of known presence in atmospheric aerosols using liquid chromatography (LC) combined with positive electrospray ionization mass spectrometry (MS). The target analytes include C(3)-C(6) monosaccharide alcohols (glycerol, erythritol, xylitol, mannitol), C(5)-C(6) monosaccharides (xylose, glucose, and levoglucosan), a disaccharide (sucrose), and a trisaccharide (melezitose). A mobile phase consisting of 20% 10 mM aqueous ammonium acetate, 8% methanol, and 72% water was found to provide abundant [M+NH(4)](+) adduct ions when coupled with electrospray ionization. Use of a polymer-based amino analytical column resolved the target compounds from the bulk solvent and provided limited separation among the target compounds. The target analytes were quantified using their [M+NH(4)](+) ions. Sample pretreatment was greatly simplified in comparison with the more commonly used gas chromatographic methods. It involved extraction of aerosol filters in methanol, evaporation of the solvent, and reconstitution with 5 mM ammonium acetate in water prior to the LC-MS analysis. The analyte recoveries were measured at the levels of 100, 500 and 1000 microg/L to be in the range of 78-102%, 94-112%, and 92-110%, respectively. The detection limits were lower than 10 pmol/injection for the tested target compounds except for xylose. Xylose had a detection limit of 95 pmol/injection. The method was applied to analyze 30 atmospheric aerosol samples to demonstrate its feasibility. The LC-MS method made possible the detection of trisaccharides as aerosol constituents for the first time.

Aerosols↗

Powder specific active dispersion for generation of pharmaceutical aerosols.

Dry powder inhalers are increasingly employed to deliver pharmaceutical aerosols. Efficient mechanisms of particle dispersion are central to their success in disease therapy. Creation of a powder aerosol requires the input of energy to transition the static powder bed into an entrained aerosol. The purpose of this study was to investigate the effects of input of vibrational energy into a powder on aerosol entrainment. Rotating drum characterization of powder flow was performed on lactose and maltodextrin excipients blended with albuterol sulfate. Dispersion experiments were conducted using an entrainment tube and a vibration actuator, vibrational energy input being derived from analysis of powder flow data from rotating drum analysis. Results of analysis of the rotating drum data showed that with increasing rotational speed powders reached a constant state of fluidization with a mean avalanche time dependent on the powder. Dispersion experiments demonstrated that the input of vibrational energy increased the dose emission while the input of frequencies specific to the powders improved the reproducibility. Frequency analysis of the vibration signals indicated that the reproducibility was determined by the bandwidth of the signal. This work suggests that an ability to tailor energy input to match the flow properties of a given powder formulation may significantly improve reproducibility of dose delivery from active dry powder inhalers.

Aerosols↗

Poly(ether-anhydride) dry powder aerosols for sustained drug delivery in the lungs.

A new family of biodegradable ether-anhydride polymers was used to develop microparticles capable of controlled drug release and inhalation as a dry powder. The polymers are composed of various ratios of sebacic acid (SA) (to render the polymer insoluble in water) and poly(ethylene glycol) (PEG) (to reduce particle clearance by macrophages and improve aerosolization). Particle aerodynamic diameter was controlled within the respirable range by producing geometrically large, but low density particles as a first step toward reducing particle adhesion forces that limit efficient aerosolization of dry powders. Particles made from a variety of polymer compositions possessed high emitted doses (>80%) from a Spinhaler dry powder inhaler (DPI). Control over particle surface and bulk properties (surface roughness, surface charge, density and water retention) was achieved by varying the percentage of PEG in the polymer backbone. The addition of 10% PEG into the polymer backbone significantly enhanced deposition in the lower stages of an in vitro lung model following aerosolization from the DPI (fine particle fractions [FPF] reached 30%). Efficient aerosolization from an obsolete DPI combined with the ability to evade phagocytic clearance and provide controlled release of various drug molecules make these particles promising for prolonged drug delivery in the lung.

Aerosols↗

Evaluation of pulmonary alveolo-capillary permeability in Type 2 diabetes mellitus: using technetium 99mTc-DTPA aerosol scintigraphy and carbon monoxide diffusion capacity.

The thickening of alveolar basement membrane is found in autopsies, along with microvascular pathologies, in Type 1 and 2 diabetes mellitus (DM). To detect the function and permeability of alveolar basement membrane, carbon monoxide diffusion capacity (DLCO) and technetium 99m-diethyltriaminepentaaceticacid ((99m)Tc-DTPA) aerosol scintigraphy methods can be used. The aim of this study was to determine alveolar basement membrane damage using these two methods. Nineteen women and 6 men, nonsmoking, Type 2 DM cases, without any lung and/or heart disease and who had neither anemia nor obesity, made up the patient group. They were compared with six female and nine male healthy cases who had the same characteristics with the diabetes cases. All of the cases DLCO were measured by single-breath method and (99m)Tc-DTPA aerosol scintigraphy was performed. DLCO showed no difference between the two groups. Aerosol scintigraphy was significantly decreased in the diabetic group (P=.01). In cases with >5 years of diabetic duration (P<.01), in cases with glycolized hemoglobin (HbA(1c)) </=8% (P<.05) and >8% (P<.05), and in microangiopathic cases (P<.01), alveolo-capillary permeability was significantly decreased than in the control group. Among the same groups, no significant difference could be detected for DLCO. The permeability of alveolar basement membrane can reduce in respect to diabetes duration and poor metabolic control. According to our investigation, (99m)Tc-DTPA aerosol scintigraphy method is more sensitive than DLCO method for determining these pathologies.

Administration, Inhalation↗

Atmospheric fate of OH initiated oxidation of terpenes. Reaction mechanism of alpha-pinene degradation and secondary organic aerosol formation.

This paper studies the reaction products of alpha-pinene, beta-pinene, sabinene, 3-carene and limonene with OH radicals and of alpha-pinene with ozone using FT-IR spectroscopy for measuring gas phase products and HPLC-MS-MS to measure products in the aerosol phase. These techniques were used to investigate the secondary organic aerosol (SOA) formation from the terpenes. The gas phase reaction products were all quantified using reference compounds. At low terpene concentrations (0.9-2.1 ppm), the molar yields of gas phase reaction products were: HCHO 16-92%, HCOOH 10-54% (OH source: H2O2, 6-25 ppm); HCHO 127-148%, HCOOH 4-6% (OH source: CH3ONO, 5-8 ppm). At high terpene concentrations (4.1-13.2 ppm) the results were: HCHO 9-27%, HCOOH 15-23%, CH3(CO)CH3 0-14%, CH3COOH 0-5%, nopinone 24% (only from beta-pinene oxidation), limona ketone 61% (only from limonene oxidation), pinonaldehyde was identified during alpha-pinene degradation (OH source H2O2, 23-30 ppm); HCHO 76-183%, HCOOH 12-15%, CH3(CO)CH3 0-12%, nopinone 17% (from beta-pinene oxidation), limona ketone 48% (from limonene oxidation), pinonaldehyde was identified during alpha-pinene degradation (OH source CH3ONO, 14-16 ppm). Pinic acid, pinonic acid, limonic acid, limoninic acid, 3-caric acid, 3-caronic acid and sabinic acid were identified in the aerosol phase. On the basis of these results, we propose a formation mechanism for pinonic and pinic acid in the aerosol phase explaining how degradation products could influence SOA formation and growth in the troposphere.

Aerosols↗

Limitations of monoclonal antibodies for monitoring of fungal aerosols using Penicillium brevicompactum as a model fungus.

Molds are ubiquitous in every environment and many species have been recently associated with an increase in opportunistic infections in immunocompromised patients or the exacerbation of asthmatic episodes in allergic patients. The degree of environmental contamination with fungi thus needs to be monitored and in this study we report the development of a monoclonal antibody (mAb)-mediated enzyme-linked immunosorbent assay (ELISA) for the detection of spores of Penicillium brevicompactum in experimental model aerosols. In addition, we have investigated the influence of different parameters of air sampling and sample recovery on ELISA performance. MAbs were produced with standard hybridoma techniques and cross-reactivities were determined against spores of 53 fungal species by indirect ELISA. Standardized experimental fungal aerosols were collected with the Button Personal Inhalable Aerosol Sampler onto polycarbonate or polytetrafluoroethylene filters (PTFE) and the effects of different extraction buffers and filter agitation methods during sample processing on spore recovery and ELISA detection were investigated. Five mAbs were produced and all of them cross-reacted with several of 31 related Aspergillus, Penicillium and Eurotium species. However, cross-reactivities with 21 non-related fungi were rare. Spores were recovered in much higher numbers from polycarbonate filters (PFs) than from polytetrafluoroethylene filters. Optical densities (ODs) in ELISA were higher for spores collected into carbonate coating buffer (CCB) than phosphate-buffered saline (PBS). Filter bath sonication following filter vortexing had no positive effects on ELISA sensitivity. The cross-reactivity patterns of mAbs suggest that Aspergillus and Penicillium species share multiple antigens. Quantitative ELISA results for fungal aerosols were found to be influenced by differential sample processing and thus method standardization will be essential to maintain the comparability of immunometric monitoring results.

Aerosols↗

Second-hand exposure to aerosolized intravenous anesthetics propofol and fentanyl may cause sensitization and subsequent opiate addiction among anesthesiologists and surgeons.

We hypothesize that aerosolization of anesthetics administered intravenously to patients in the operating room may be an unintended source of exposure to physicians. This may lead to inadvertent sensitization, which is associated with an increased risk for developing addiction. This may contribute to the over-representation of certain specialties among physicians with addiction. We retrospectively reviewed the de-identified demographic information of all licensed physicians treated for substance abuse in the State of Florida since 1980, to determine if medical specialty was associated with addiction in this group of individuals. Then, to identify the potential for exposure, two mass spectrometry assays were developed to detect two intravenously administered drugs, fentanyl and propofol, in air. Since 1980, 7.6% of licensed Florida physicians underwent treatment for addiction. Addiction in anesthesiologists was higher than expected. Opiate abuse was greater in anesthesiologists and surgeons compared to other specialties. Aerosolized fentanyl was detected in the air of the cardiothoracic operating room, in patients' expiratory circuits, and in the headspace above sharps boxes, but not in adjoining hallways. Aerosolized propofol was detected in the expirations of a patient undergoing transurethral prostatectomy. While access and stress may place anesthesiologists and surgeons at greater risk for substance abuse, an additional risk factor may be unintended occupational exposure to addictive drugs. This report provides preliminary evidence of detection of aerosolized intravenous anesthetics using two newly developed analytical methods. We conclude that the potential exists for chronic exposure to low levels of airborne intravenously administered drugs. Further studies are under way to determine the significance of this exposure.

Aerosols↗

Susceptibility of immunodeficient mice to aerosol and systemic infection with virulent strains of Francisella tularensis.

Previous studies have shown that IFN-gamma, TNF-alpha and NOS-2, but not B cells, are crucial for host defense against primary systemic infection with the attenuated live vaccine strain (LVS) of Francisella tularensis. In this study, we examined the importance of these and additional immune components in host resistance against infection with virulent strains of F. tularensis initiated by systemic and airborne routes. Wild-type (WT) mice and mice deficient in IFN-gamma, TNFR1R2, NOS-2, or B cells were equally susceptible to low dose ( approximately 10 colony forming units) aerosol or intradermal challenge with virulent type B F. tularensis, and succumbed to the infection between days 6 and 8 post-inoculation. Quantitative bacteriology showed that IFN-gamma-/- and B cell-/- mice consistently harbored up to one log(10) more bacteria in their lungs, spleens and livers than WT mice at day 5 post aerosol exposure. Surprisingly, however, compared to other strains of KO mice and WT control mice, IFN-gamma-/- mice showed only mild liver damage as assessed by histopathology and liver function tests. Additional experiments established that even mice with broad immunodeficiency (SCID, neutropenic, splenectomized or thymectomized mice and mice treated with corticosteroid) were no more susceptible to aerosol-initiated infection with virulent type B or type A F. tularensis than immunosufficient control mice. Combined, our results indicate that, unlike LVS, normal type A and type B F. tularensis strains are so extremely virulent that even immunocompetent mice are virtually defenseless to low dose aerosol and intradermal challenges with them.

Aerosols↗

Trends in aerosol optical depth in the Russian Arctic and their links with synoptic climatology.

Temporal and spatial variability of aerosol optical depth (AOD) are examined using observations of direct solar radiation in the Eurasian Arctic for 1940-1990. AOD is estimated using empirical methods for 14 stations located between 66.2 degrees N and 80.6 degrees N, from the Kara Sea to the Chukchi Sea. While AOD exhibits a well-known springtime maximum and summertime minimum at all stations, atmospheric turbidity is higher in spring in the western (Kara-Laptev) part of the Eurasian Arctic. Between June and August, the eastern (East Siberian-Chukchi) sector experiences higher transparency than the western part. A statistically significant positive trend in AOD was observed in the Kara-Laptev sector between the late 1950s and the early 1980s predominantly in spring when pollution-derived aerosol dominates the Arctic atmosphere but not in the eastern sector. Although all stations are remote, those with positive trends are located closer to the anthropogenic sources of air pollution. By contrast, a widespread decline in AOD was observed between 1982 and 1990 in the eastern Arctic in spring but was limited to two sites in the western Arctic. These results suggest that the post-1982 decline in anthropogenic emissions in Europe and the former Soviet Union has had a limited effect on aerosol load in the Arctic. The post-1982 negative trends in AOD in summer, when marine aerosol is present in the atmosphere, were more common in the west. The relationships between AOD and atmospheric circulation are examined using a synoptic climatology approach. In spring, AOD depends primarily on the strength and direction of air flow. Thus strong westerly and northerly flows result in low AOD values in the East Siberian-Chukchi sector. By contrast, strong southerly flow associated with the passage of depressions results in high AOD in the Kara-Laptev sector and trajectory analysis points to the contribution of industrial regions of the sub-Arctic. In summer, low pressure gradient or anticyclonic conditions result in high atmospheric turbidity. The frequency of this weather type has declined significantly since the early 1980s in the Kara-Laptev sector, which partly explains the decline in summer AOD values.

Aerosols↗

Contribution of marine and continental aerosols to the content of major ions in the precipitation of the central Mediterranean.

The region of the investigated receptor is situated in the southern part of the Adriatic Sea in the Mediterranean. The measuring station is located on the seashore, which, being considered as a border area, is representative for the qualitative and quantitative estimation of the influence of marine and continental aerosols on the content of major ions in precipitation. In the sampling period, precipitation in the region of the investigated receptor was more abundant during the summer and autumn than during the winter and spring. The most frequent precipitation heights were up to 20 mm, while high precipitation came exclusively from the continental region. The results of the measurements of ions readily soluble in water were used for the differentiation of marine from continental contributions of primary and secondary aerosols to their content in the precipitation. Using PCA, it was shown that main contribution of Cl(-), Na(+) and Mg(2+) came from primary marine aerosols, while the contribution from continental sources was dominant for the content of SO(4)(2-), NO(3)(-), NH(4)(+) and Ca(2+) in the precipitation. The continental origin of Ca(2+) was from a primary source, while SO(4)(2-), NO(3)(-) and NH(4)(+) were representatives of secondary aerosols produced by reactions between acid oxides and alkaline species in the atmosphere, but SO(4)(2-) and NO(3)(-) also exist in the precipitation as free acids. The origin of the trace elements Cd, Cu, Pb and Zn in the precipitation came from anthropogenic emission sources. The results obtained in this work are based on experimental data from 609 samples collected during the period 1995-2000.

Aerosols↗

Aerogenic vaccination with a Burkholderia mallei auxotroph protects against aerosol-initiated glanders in mice.

Burkholderia mallei is an obligate mammalian pathogen that causes the zoonotic disease glanders. Two live attenuated B. mallei strains, a capsule mutant and a branched-chain amino acid auxotroph, were evaluated for use as vaccines against aerosol-initiated glanders in mice. Animals were aerogenically vaccinated and serum samples were obtained before aerosol challenge with a high-dose (>300 times the LD50) of B. mallei ATCC 23344. Mice vaccinated with the capsule mutant developed a Th2-like Ig subclass antibody response and none survived beyond 5 days. In comparison, the auxotrophic mutant elicited a Th1-like Ig subclass antibody response and 25% of the animals survived for 1 month postchallenge. After a low-dose (5 times the LD50) aerosol challenge, the survival rates of auxotroph-vaccinated and unvaccinated animals were 50 and 0%, respectively. Thus, live attenuated strains that promote a Th1-like Ig response may serve as promising vaccine candidates against aerosol infection with B. mallei.

Aerosols↗

Corneal ulcer associated with contamination of aerosol saline spray tip.

PURPOSE: To report a complication of aerosol saline use in a contact lens wearer. METHODS: Case report. A 57-year-old woman who used soft contact lenses on an extended-wear basis developed a unilateral Pseudomonas corneal ulcer associated with the use of preservative-free aerosol saline. RESULTS: The solution inside the aerosol can was free of microbial contamination. The spray tip, however, was contaminated with P aeruginosa. CONCLUSIONS: Aerosol spray cans may minimize contamination of the solution inside the can. The spray tip is still susceptible to microbial contamination, especially with continued use of the solution over an extended period of time.

Aerosols↗

High-dose, short-duration ribavirin aerosol therapy compared with standard ribavirin therapy in children with suspected respiratory syncytial virus infection.

Children with suspected respiratory syncytial virus infection were examined prospectively in a randomized evaluation of standard ribavirin aerosol therapy (6 gm/300 ml water for 18 hours daily) compared with high-dose, short-duration ribavirin aerosol therapy (6 gm/100 ml water given for a period of 2 hours three times a day) by means of an oxygen hood (n = 20) or a ventilator (n = 12). Viral shedding was quantitated daily; clinical observations were recorded daily by 2 physicians aware and one unaware of treatment assignments. Study characteristics evaluated at entry were not significantly different in the high-dose and the standard-dose groups. Viral titers and clinical scores decreased similarly in both groups during the study; pulmonary function test results were also similar at discharge in children not receiving mechanical ventilation. Potential complications related to aerosol therapy were noted in three patients (one hood patient who was receiving standard therapy; two patients with an endotracheal tube in place who were receiving high-dose therapy); substantial crystallization was noted in the tubing of the patients undergoing intubation and receiving high-dose therapy. Environmental sampling revealed that ribavirin was nearly undetectable near patients supported by mechanical ventilation who were receiving either form of therapy, and was significantly decreased on a daily basis in patients without an endotracheal tube who were receiving high-dose therapy compared with those receiving standard therapy. The effects of high-dose, short-duration aerosol ribavirin therapy were similar to those of standard-dose therapy in our study patients and resulted in a decreased release of ribavirin into the room of patients receiving therapy by means of an oxygen hood.

Aerosols↗