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Gemcitabine aerosol: in vitro antitumor activity and deposition imaging for preclinical safety assessment in baboons.

AIM: To characterize gemcitabine aerosol, its in vitro activity against lung cancer cells, its deposition, and tolerance in a non-human primate model. METHODS: In vitro cytotoxicity of nebulized gemcitabine against NCI-H460 and A549 lung cancer cells was tested using a growth inhibition assay and compared with non-nebulized gemcitabine. The (99m)Tc-DTPA-radiolabeled gemcitabine aerosol was characterized by cascade impaction and the gemcitabine mass/(99m)Tc activity relationship was established for further quantitative nuclear imaging. Nine weekly inhalations at a target dose of 1 mg/kg body weight of gemcitabine were performed in three baboons using dynamic scintigraphic acquisitions for continuous monitoring of gemcitabine delivery during inhalation. Gemcitabine plasma concentrations were measured during the first inhalation. RESULTS: Growth inhibition assays for both NCI-H460 and A549 cells did not differ between nebulized and non-nebulized gemcitabine. Aerosol characterization showed a particle mass median aerodynamic diameter of 3.7+/-0.8 microm and a linear relationship between gemcitabine mass (y) and (99m)Tc activity (x) (y=0.82x - 10(-5), R (2)=0.88). No toxicity was observed after nine weekly inhalations of a mean dose of gemcitabine of 11.1 mg (88% of the target dose) as assessed from scintigraphic data. A dose-dependent peak plasma concentration of gemcitabine (20-74 ng/ml) was observed by the tenth minute of inhalation. CONCLUSIONS: We have characterized a gemcitabine aerosol suitable for intrathoracic airway deposition and demonstrated that jet nebulization does not alter the cytotoxic properties of the drug. In a primate model, we have developed a scintigraphic procedure for the monitoring of aerosol deposition, and we have demonstrated the safety of nine weekly aerosol administrations of gemcitabine.

Aerosols↗

Aerosols produced by high-speed cutters in cervical spine surgery: extent of environmental contamination.

High-speed cutters are used in the surgery of the cervical spine. Such high-speed devices can produce an aerosol cloud. As a patient can be a reservoir for pathogens, with aerosol-borne paths of transmission, such an aerosol has to be seen as a potential risk of infection for health care professionals present during the surgery and for patients if micro-organisms are transferred through the medical personnel. The study was performed in order to measure the extension of environmental and body contamination through contaminated aerosols produced by a high-speed cutter. Three laminectomies (C4-C6) were performed on an intact human cadaver with a high-speed 0.6-mm ball cutter. A complete surgical setup was arranged, including surgical draping and a barrier drape to the anesthesiologist's workplace. Body and environmental contamination was detected by the use of surveillance cultures. The irrigation solution was artificially contaminated with Staphylococcus aureus ATCC 12600. Following the surgery, staphylococci were detected in the operating room at an extension of 5x7 m. Everybody showed extensive face and body contamination with Staphylococcus aureus. The study showed that the use of high-speed cutters in surgery of the cervical spine produces an aerosol cloud that is spread over the whole surgical room and contaminates the theater and all personnel present. Such aerosols can be contaminated with pathogens if the patient was infected or colonized. Therefore, sufficient protective measures have to be recommended for everyone present in the operating room during such surgeries. In addition, efficient disinfection of the room and all mobile equipment is necessary after each surgery involving high-speed cutting devices.

Aerosols↗

Factors influencing aerosol characteristics over urban environment.

Atmospheric aerosols are an important contributing factor to turbidity in urban areas besides having impact on health. Aerosol characteristics show a high degree of variability in space and time as nthropogenic share of total aerosol loading is quite substantial and is essential to monitor the aerosol features over long time scales. In the present study extensive observations of columnar aerosol optical depth (AOD), total columnar ozone (TCO) and precipitable water content (PWC) have been carried over a tropical urban city of Hyderabad, India. Significant variations of AOD have been observed during course of the day with low values of AOD during morning and evening hours and high values during afternoon hours. Spectral variation of AOD exhibits high AOD at smaller wavelengths and vice versa except a slight enhancement in AOD at 500 nm. Anomalies in AOD, particulate matter and black carbon concentrations have been observed during May, 2003. Back trajectory analysis of air mass during these episodes suggested variation in air mass trajectories. Analysis of the results suggests that air trajectories from land region north of study area cause high loading of atmospheric aerosols. The results are discussed in the paper.

Aerosols↗

Comparison of oral aminophylline and aerosol metaproterenol in asthma.

The bronchodilator efficacy of oral aminophylline and aerosol metaproterenol was compared in 18 asthmatic patients in a stable clinical condition. Treatment consisted of four regimens in a double-blind random sequence on four different days after withholding bronchodilators: (1) the administration of aminophylline tablets, 0.4 to 0.6 g, orally, (2) 3 puffs of aerosol metaproterenol administered in a sequential manner, (3) a combination of both, (4) placebos. Both oral aminophylline and aerosol metaproterenol produced significant bronchodilatation measured by forced expiratory volume in 1 second (FEV1). After the administration of aerosol metaproterenol, there was a more prompt and larger improvement in FEV1 than after the administration of aminophylline (p less than 0.01). The combined therapy produced a response which was larger, but not significantly, than the effect of metaproterenol. Side effects were frequent after the administration of aminophylline but absent after aerosol metaproterenol. The advantages of the aerosol adrenergic agonists are the prompt onset of action and efficacy, small dosage preferentially delivered to the bronchial tree and lack of side effects.

Administration, Oral↗

Inhalation of 1-nitropyrene associated with ultrafine insoluble particles or as a pure aerosol: a comparison of deposition and biological fate.

A large number of the environmental particulate pollutants in the atmosphere, including diesel engine exhaust, have a complex mixture of organic compounds associated with them. Organic solvent extracts of many of these particulate pollutants have been shown to contain mutagenic activity which does not require metabolic activation in the Ames bioassay. Much of this direct-acting mutagenic activity has been attributed to nitroaromatic compounds present in these extracts. In the studies reported here, the direct-acting mutagen, [3H]nitropyrene (3H-NP), was used as a model nitroaromatic compound. Rats were exposed to this radiolabeled compound by nose-only inhalation either as a coating (approximately 6% by mass) on relatively inert, ultrafine 67Ga2O3 particles or as a homogeneous ultrafine aerosol. The tissue deposition, retention, and biological fate of each aerosol were investigated and compared. Respiratory tract clearance of 3H radioactivity from each exposure was very rapid with no apparent differences seen in the lung retention of this inhaled compound between each exposure over the course of these studies. Higher 3H-radioactivity levels were seen in stomach and large intestines of rats exposed to the 67Ga2O3-associated 3H-NP than in the same tissues from rats exposed to the pure 3H-NP aerosol. Rats exposed to the 3H-NP-67Ga2O3 aerosol excreted the majority of the deposited 3H radioactivity in the feces (75 +/- 18%), whereas pure 3H-NP exposed animals excreted a major portion of the radiolabeled in the urine (76 +/- 18%). It appeared that the major portion of the pure 3H-NP aerosol was cleared from the respiratory tract by direct absorption into blood, while the 67Ga2O3-associated 3H-NP was cleared by both blood absorption and mucociliary clearance followed by ingestion and fecal excretion. These differences in the deposition and biological fate between the particle-associated NP and the pure NP aerosol may have important implications in terms of the metabolic fate of inhaled nitroaromatic compounds and the health risks associated with human exposures to particulate environmental pollutants that contain this class of compounds.

Aerosols↗

Evaluation of quantitative aerosol techniques for use in bronchoprovocation studies.

To investigate airway physiology by use of inhaled aerosols, it is frequently necessary to measure the actual amount of material deposited on the airway wall as well as the site of particle deposition. To satisfy these needs, radiolabeled aerosols and gamma camera techniques have been used to measure regional deposition of inhaled particles. To make quantitative measurements of the amount deposited, previous investigators have used a "phantom" technique to indirectly calibrate the gamma camera for the attenuation of gamma rays through the lungs and chest wall. For this calibration, the phantom is a simulated lung containing a known amount of radioactivity. Radioactive counts emitted from the phantom are assumed to be attenuated in the same manner as the intact human lung. The present article describes a technique to determine directly the amount of inhaled aerosol deposited in the lung and simultaneously to calibrate the gamma camera for each individual subject. We used right angle light scattering and a gamma camera to measure individual values of the deposition fraction (DF) of inhaled aerosol deposited in the lung and the coefficient of attenuation (AC) of gamma rays in normal and obstructed lungs of human subjects. Radiolabeled monodisperse aerosols 1 and 2 microns in diameter were used. Knowledge of the activity of the inhaled aerosol (microcurie per liter), the volume inhaled, and the measured DF determined each subject's AC (counts per minute per microcurie). DF varied by an order of magnitude in normal (0.04 to 0.48) and obstructed (0.16 to 0.75) of subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Quantitative assays of pharmacologic aerosols used in studying asthma.

To more nearly accurately quantitate the dose of pharmacologic agents delivered to human and animal airways via aerosols, we have developed a monodisperse aerosol containing either methacholine or histamine that permits a light scattering device (tyndallometry) to measure accurately the quantity of inspired and expired particles. These aerosols (described in previous studies) are simultaneously tagged with a radioactive label (technetium 99m) to permit the use of external gamma camera imaging. Present work focuses on the development of assay techniques to measure the quantity of methacholine delivered in these aerosols. The lack of specific radioimmune or radioenzyme assays coupled with the cross-reaction of organic contaminants with conventional chemical reagents for measuring methacholine required the development of separative techniques to isolate the methacholine from the organic aerosol contaminants. With aqueous extraction and column separation we have been able to completely isolate the methacholine from these contaminants. This allows the application of standard spectrophotometric assays for methacholine to quantitate the methacholine in the resulting solution. These separative techniques will permit the use of these aerosols in quantitative studies of airway reactivity.

Aerosols↗

Selection of test methods to assess ecological effects of mixed aerosols.

Components of the mixed aerosols generated during military training are known to be of toxicological and/or ecological significance. There are few studies, however, quantifying mixed aerosol effects on ecosystems. Prompted by our finding that one or more of the compounds in the mixed aerosols commonly encountered in military training areas showed mutagenic effects in several species, a multiyear effort is evaluating the use of ecotoxicity testing methods to assess mixed aerosol ecological impacts. Selection of test methods for ecoepidemiology begins with the identification of the data required to meet defined environmental quality objectives. The data requirements are then matched with appropriate test methods, and testing results are related to important ecological effects resulting from aerosol exposure. The critical element of test system selection is to ensure that toxicity testing results relate to important ecological effects. The procedures developed for identifying test methods to assess mixed aerosols are also applicable to a range of environmental contaminants regulated by air, water, and solid waste regulations.

Aerosols↗

Efficacy of high dose-short duration ribavirin aerosol in the treatment of respiratory syncytial virus infected cotton rats and influenza B virus infected mice.

Fifteen to 20 mg/ml ribavirin administered as a small particle aerosol for 10-18 h per day is currently the regimen generally used to treat experimental or naturally-occurring respiratory syncytial (RS) or influenza virus infections in humans. To determine if such prolonged treatment schedules could be reduced, cotton rats and mice were inoculated with RS or influenza B virus, respectively, and then treated with different concentrations of ribavirin small particle aerosols. Aerosols generated from reservoirs containing 60 mg/ml ribavirin given 2 h twice daily, protected cotton rats from RS virus and mice from influenza B virus as well as aerosols generated from reservoirs containing 20 mg/ml ribavirin given 11 h daily. Aerosols generated from reservoirs containing 40 or 20 mg/ml given 2 h daily were less efficacious. There was no evidence of intolerance or pulmonary histopathology in infected or uninfected animals exposed to any of the doses of ribavirin tested. These studies indicate that use of aerosols containing higher concentrations of ribavirin than generally used to treat respiratory virus diseases may permit significantly shorter treatment schedules without loss of efficacy or increase in toxicity.

Aerosols↗

Small particle aerosols of enviroxime-containing liposomes.

Enviroxime inhibits the replication of all rhinoviruses tested in vitro at very low concentrations (10-100 ng/ml), but evaluations in humans have not consistently shown efficacy. Lack of an appropriate method for administering this water-insoluble drug may have contributed to the latter result. The present report describes the characteristics and utilization of small particle aerosols to continuously deliver enviroxime-containing liposomes (LE) throughout the respiratory tract. The enviroxime content of liposomes and biological fluids of exposed individuals was quantified by high performance liquid chromatography using C18 resin, a mobile phase of 60:40 acetonitrile:water, and monitoring at 215 nm. Small particle aerosols of LE generated by Puritan-Bennett nebulizers had mass median diameters ranging from 2.4 to 3.1 microns. The concentration of enviroxime in aerosol particles was proportional to the reservoir concentration; during the first hour of operation, the mean concentration was 20 micrograms of enviroxime/l of aerosol. Liposome particles in the reservoir, although initially heterogeneous in size (less than 0.1 to greater than 1 micron), were processed by passage through the nebulizer to smaller, more homogeneous particles; the majority were less than 0.2 micron. In a preliminary study to evaluate short term tolerance and toxicity, five volunteers were exposed to small particle aerosol of LE for 1 h. At 1 h post-treatment, large amounts of enviroxime were still present in the nasal wash as determined both by HPLC and biological assay. Enviroxime was not detected in any urine sample and was detected in only 1 of 5 serum samples. No side effects were noted. This data suggest that liposome aerosols offer a method for the delivery of hydrophobic compounds for the treatment of respiratory diseases.

Adult↗

Acute respiratory effects of endotoxin-contaminated machining fluid aerosols in guinea pigs.

Exposure to machining fluid aerosols in the automotive industry is associated with a variety of respiratory symptoms including cross-shift changes in pulmonary function, cough, asthma, and phlegm. Lubricating and cooling fluids used in machining operations are predominantly water and thus are susceptible to microbial growth. In the present study, the role of endotoxin in the acute pulmonary injury produced by machining fluid aerosols was examined in guinea pigs. Animals were exposed to nebulized water, unused machining fluid, or used machining fluid. At the end of a 3-hr exposure, specific airway conductance (SGaw) was not affected by exposure to the vehicle water, but was decreased in a dose-dependent manner by exposure to aerosols of the used machining fluid. SGaw decreased from preexposure baseline values by 0, 7, and 40% in animals exposed to 1, 10, and 100 mg/m3 used machining fluid, respectively. These exposure levels also produced acute lung injury as evidenced by changes in cellular and biochemical indices in lavage fluid. These adverse respiratory effects may have been due to microbial contamination of the used machining fluid as the aerosol exposures were associated with airborne endotoxin concentrations of 0.3, 1.9, and 5.3 micrograms/m3, respectively. Animals exposed to aerosols of the endotoxin-free unused machining fluid had no statistically significant adverse functional, cellular, or biochemical effects except for a fourfold increase in neutrophils at 100 mg/m3. These results suggest that contamination of machining fluid during use or storage may lead to the adverse respiratory effects of aerosolized machining fluids.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Development of a citric acid aerosol as a smoking cessation aid.

The satisfaction derived from smoking depends not only on the pharmacological effects of nicotine but also the sensory stimulation from smoke inhalation, particularly the tracheal 'scratch'. In a previous study, we found that a citric acid aerosol produces a tracheal 'scratch' and provides some of the same satisfaction as cigarette smoke. In the present study, we evaluated a new pocket-sized device for delivering a citric acid aerosol and examined some of the important variables for providing a satisfying substitute for cigarettes. In the first experiment, volunteers who smoked at least 10 cigarettes per day compared a citric acid aerosol (either alone or with flavor additives) to a cigarette and a placebo. The addition of cigarette smoke flavor was found to best enhance the satisfaction provided by the citric acid aerosol. In the second experiment, smokers were given compact citric acid inhalers to use throughout 8 h of cigarette deprivation. The degree of satisfaction was highly correlated with the intensity of throat sensation provided by the aerosol. This citric acid aerosol inhaler may provide a useful tool for smokers while trying to quit smoking.

Aerosols↗

Immunosuppression with aerosolized cyclosporine for prevention of lung rejection in a rat model.

The efficacy of local delivery of aerosol cyclosporine (CsA) for prevention of lung rejection was compared with the intramuscular route (IM) in a fully allogeneic rat model (BN/LEW) of lung transplantation (LTx). Control rats (group 1, n = 6) received no CsA after LTx. Rats in group 2 (n = 10) received 4 doses of CsA in olive oil (25 mg/kg) intramuscularly starting on postoperative day (POD) 0. Group 3 (n = 9) was treated with aerosolized CsA for 3 h/day for 7 days starting on POD 0. All animals were sacrificed on POD 6. Transplanted lungs were graded histologically in a blind manner on a 0-4 scale. Control animals all showed grade 4 rejection. i.m. CsA therapy reduced lung rejection with a rejection grade of 1.8 +/- 0.35 (mean +/- SD) but was associated with a 50% incidence of pneumonia. Aerosol CsA provided better control of rejection with a rejection grade of 1.2 +/- 0.4 (group 3 vs. group 2: P less than 0.05 Wilcoxon) and none of these animals had penumonia. Trough blood levels of CsA were significantly lower in the group treated with aerosolized CsA when compared with the IM group (P less than 0.05). Therefore we conclude that: (1) aerosol CsA is effective in preventing lung allograft rejection following lung transplantation in rats, and (2) local delivery of aerosol CsA is superior to the i.m. route because better control of rejection is achieved with a lower systemic delivery of CsA.

Aerosols↗

In-injection port thermal desorption and subsequent gas chromatography-mass spectrometric analysis of polycyclic aromatic hydrocarbons and n-alkanes in atmospheric aerosol samples.

The traditional approach for analysis of aerosol organics is to extract aerosol materials collected on filter substrates with organic solvents followed by solvent evaporation and analytical separation and detection. This approach has the weaknesses of being labor intensive and being prone to contamination from the extracting solvents. We describe here an alternative approach for the analysis of aerosol alkanes and polycyclic aromatic hydrocarbons (PAHs) that obviates the use of solvents. In our approach, small strips of aerosol-laden filter materials are packed into a GC split/splitless injector liner. Alkanes and PAHs on the filter are thermally desorbed in the injection port and focused onto the head of a GC column for subsequent separation and detection. No instrument modification is necessary to accommodate the introduction of the aerosol organics into the GC-MS system. Comparison studies were carried out on a set of 16 ambient aerosol samples using our in-injection port thermal desorption (TD) method and the traditional solvent extraction method. Reasonably good agreement of individual alkanes and PAHs by the two methods was demonstrated for the ambient samples. The in-injection port thermal desorption method requires much less filter material for detecting the same air concentrations of alkanes and PAHs.

Aerosols↗

Variations of Cd/Pb and Zn/Pb ratios in Taipei aerosols reflecting long-range transport or local pollution emissions.

Along with windblown dust, large quantities of pollutants are annually brought out of continental China by the westerlies in winter and spring; thereafter, they are partly subjected to transport by northeastern monsoon winds to Taiwan. To characterize the heavy metal composition differences between long-range transported and local aerosols and to evaluate metal contributions from long-range transported aerosols during the northeastern monsoon season, both PM(10) and PM(2.5) aerosols collected from Taipei, Taiwan from February 2002 to March 2003 were analyzed for three selected heavy metals, namely Pb, Cd and Zn using ICP-MS. Monthly patterns show that Pb concentrations in winter (62 ng/m(3)) were over two times higher than those in the other seasons, which is attributed to long-range transport from areas under development in China. Low Cd/Pb (0.017) and Zn/Pb (1.82) ratios were measured in aerosols collected during the Asian dust period, in which the ambient aerosols consisted predominantly of long-range transported pollutants. By contrast, high Cd/Pb (0.030) and Zn/Pb (3.44) ratios were observed during the summer monsoon season, in which aerosols were dominated by local pollutant emissions. Cd/Pb and Zn/Pb ratios appear to be successfully applied to identify the pollutants originating principally from the long-range transport or from local emissions. In addition, by assuming that a significant fraction of heavy metals associated with coarse airborne dust have settled to the sea prior to reaching Taiwan in spring, a mechanism is suggested to explain why higher anthropogenic metal concentrations occurred in winter than those in dust-rich spring.

Aerosols↗

Worker exposures to inhalable and total aerosol during nickel alloy production.

This paper describes a study that was carried out at a North American nickel alloy production facility to compare the levels of personal exposures to inhalable and total nickel-containing aerosols. It is part of a large body of work aimed at assessing the impact of introducing new personal sampling instrumentation with performance consistent with the latest criteria proposed by the International Standards Organization (ISO), the Comité Européen Normalisation (CEN) and the American Conference of Governmental Industrial Hygienists (ACGIH). Side-by-side sampling using the 37-mm filter holder (for total aerosol) and the so-called IOM inhalable aerosol sampler was conducted for the personal exposures of workers in a range of workplaces throughout the facility. The results showed that inhalable aerosol exposure levels-for both overall aerosol and for total nickel-were consistently and significantly higher than the corresponding total aerosol levels. Weighted least-squares linear regression yielded factors ranging from about 1.3 to 2.4 for overall dust and from about 1.5 to 3.5 for nickel. Inspection of the statistical distribution of the exposures for the whole plant suggested that it was log-normal.

Aerosols↗

Aerosolized adrenomedullin suppresses pulmonary transforming growth factor-beta1 and interleukin-1 beta gene expression in vivo.

The effect of aerosolized adrenomedullin on interleukin-1 beta and transforming growth factor (TGF)-beta1 mRNA and protein expression was studied in surfactant depleted piglets, receiving aerosolized adrenomedullin (adrenomedullin, n=6), aerosolized adrenomedullin plus i.v. N(G)-nitro-L-arginine-methylester (adrenomedullin+L-NAME, n=5), or aerosolized saline solution (control, n=6). After 8 h of aerosol interval therapy, mRNA expression of interleukin-1 beta and TGF-beta1 in lung tissue was quantified normalized to beta-actin and hypoxanthine-guanine-phosphoribosyl-transferase by real-time polymerase chain reaction (PCR). Interleukin-1 beta and TGF-beta1 protein concentration in lung tissue was quantified by enzyme-linked immunosorbent assay (ELISA). In the adrenomedullin group, interleukin-1 beta and TGF-beta1 mRNA expression was lower than in controls. Reduction for interleukin-1 beta/beta-actin was 56% (p<0.001), for interleukin-1 beta/hypoxanthine-guanine-phosphoribosyl-transferase 60% (p<0.001), for TGF-beta1/beta-actin 65.5% (p<0.001), and for TGF-beta1/hypoxanthine-guanine-phosphoribosyl-transferase 56.2% (p<0.001). Mean interleukin-1 beta protein expression was different between the groups, p<0.05 (adrenomedullin 601+/-61, Control 836+/-88 pg/mg protein). L-NAME did not antagonize adrenomedullin effect on TGF-beta1 mRNA. In conclusion, aerosolized adrenomedullin reduced pulmonary inflammatory and pro-fibrotic response.

Adrenomedullin↗

Aerosol delivery of diethylenetriamine/nitric oxide, a nitric oxide adduct, causes selective pulmonary vasodilation in perinatal lambs.

Postnatal adaptation of the pulmonary circulation is mediated partly by endothelium-derived nitric oxide (NO). Recent studies have demonstrated that inhaled NO causes selective and sustained vasodilation in infants with persistent pulmonary hypertension of the newborn. Because the short half-life of NO limits its clinical application, we hypothesized that aerosol delivery of an NO-adduct, diethylenetriamine (DETANO), can cause sustained and selective pulmonary vasodilation. To test the acute effects of DETANO, we studied the pulmonary vascular response of late-gestation fetal lambs (n = 8; age = 138 days; term = 147) to aerosolized DETANO in the presence of an endothelium-derived NO inhibitor, nitro-L-arginine. To determine whether DETANO has a sustained effect, fetal lambs were ventilated with FiO2 0.10 before and 15 minutes after they were treated with aerosolized DETANO. Fetal lambs were acutely prepared. Nitro-L-arginine (1 mg/min x 30 minutes) was infused into the left pulmonary artery before ventilation with FiO2 1.00 for 30 minutes, followed by continued ventilation with FiO2 0.10 for 10 minutes. This represented the control period. Ventilation was continued with FiO2 1.00, and aerosolized DETANO was given in doses of 0.1, 0.4, and 1.0 mg. Fifteen minutes after the last dose of DETANO was administered, animals were ventilated with FiO2 0.10. In the control period, during ventilation with FiO2 0.10, left pulmonary artery flow was 122+/-33 mL/min and decreased to 104+/-22 mL/min. Aerosol delivery of DETANO increased left pulmonary artery flow to 176+/-26 mL/min (P<.05) and had no effect on aortic pressure or heart rate. After DETANO was administered, ventilation with FiO2 0.10 did not cause any change in left pulmonary artery flow. We conclude that DETANO can cause selective fetal pulmonary vasodilation. Aerosol delivery of DETANO may increase the clinical applications of NO.

Aerosols↗