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Cardiopulmonary effects of aerosolized prostaglandin E1 and nitric oxide inhalation in patients with acute respiratory distress syndrome.

Ten patients with acute respiratory distress syndrome (ARDS) received in random order nitric oxide (NO) inhalation, aerosolized prostaglandin E1 (PGE1), infusion of PGE1, or no intervention. Inhalation of either aerosolized PGE1 (10 +/- 1 ng/kg/min) or NO (7 +/- 1 ppm) reduced pulmonary vascular resistance (PVR) from 158 +/- 14 to 95 +/- 11 dyn . s/cm5/m2 (NO) and 100 +/- 12 dyn . s/cm5/m2 (aerosolized PGE1), and improved PaO2 from 78 +/- 3 to 96 +/- 5 mm Hg (NO) and 95 +/- 4 mm Hg (aerosolized PGE1) (p < 0.05), venous admixture (Q VA/Q T) from 45 +/- 2 to 36 +/- 2% (NO), and 36 +/- 2% (aerosolized PGE1) (p < 0.05), oxygen delivery (DO2) from 711 +/- 34 to 762 +/- 45 ml/min/m2 (NO) and 780 +/- 46 ml/min/m2 (aerosolized PGE1) (p < 0.05), and right ventricular ejection fraction (RVEF) from 32 +/- 6 to 37 +/- 5% (NO), and 36 +/- 4% (aerosolized PGE1) (p < 0.05) at a constant cardiac index (CI). Although infusion of PGE1 (12 +/- 1 ng/kg/min) caused a similar reduction in PVR as aerosolized PGE1 and NO inhalation, it improved RVEF and increased CI but decreased Q VA/Q T and PaO2. These results suggest that in ARDS patients inhalation of aerosolized PGE1 or NO in low concentrations equally improves PVR and gas exchange by selective vasodilation in ventilated areas.

Administration, Inhalation↗

Reconciling in vitro and in vivo measurements of aerosol delivery from a metered-dose inhaler during mechanical ventilation and defining efficiency-enhancing factors.

We attempted to resolve the discrepancies in reported data on aerosol deposition from a chlorofluorocarbon (CFC)-propelled metered-dose inhaler (MDI) during mechanical ventilation, obtained by in vivo and in vitro methodologies. Albuterol delivery to the lower respiratory tract was decreased in a humidified versus a dry circuit (16.2 versus 30.4%, respectively; p < 0.01). In 10 mechanically ventilated patients, 4.8% of the nominal dose was exhaled. When the exhaled aerosol was subtracted from the in vitro delivery of 16.2% achieved in a humidified ventilator circuit, the resulting value (16.2 - 4.8 = 11.4%) was similar to in vivo estimates of aerosol deposition. Having reconciled in vitro with in vivo findings, we then evaluated factors influencing aerosol delivery. A lower inspiratory flow rate (40 versus 80 L/min; p < 0.001), a longer duty cycle (0.50 versus 0.25; p < 0.04), and a shorter interval between successive MDI actuations (15 versus 60 s; p < 0.02) increased aerosol delivery, whereas use of a hydrofluoroalkane (HFA)-propelled MDI decreased aerosol delivery compared with the CFC-propelled MDI. A MDI and actuator combination other than that designed by the manufacturer altered aerosol particle size and decreased drug delivery. In conclusion, aerosol delivery in an in vitro model accurately reflects in vivo delivery, providing a means for investigating methods to improve the efficiency of aerosol therapy during mechanical ventilation.

Aerosols↗

Bronchial effects of aerosolized delta 9-tetrahydrocannabinol in healthy and asthmatic subjects.

Effects on airway dynamics, heart rate, and the central nervous system of various doses of delta9-tetrahydrocannabinol administered in a random, double blind fashion using a Freon-propelled, metered-dose nebulizer were evaluated in 11 healthy men and 5 asthmatic subjects. Effects of aerosolized delta9-tetrahydrocannabinol were compared with aerosolized placebo and isoproterenol and with 20 mg of oral and smoked delta9-tetrahydrocannabinol. In the normal subjects, after 5 to 20 mg of aerosolized delta9-tetrahydrocannabinol, specific airway conductance increased immediately, reached a maximum (33 to 41 per cent increase) after 1 to 2 hours, and remained significantly greater than placebo values for 2 to 3 hours. The bronchodilator effect of aerosolized delta9-tetrahydrocannabinol was less than that of isoproterenol after 5 min, but significantly greater than that of isoproterenol after 1 to 3 hours. The magnitude of bronchodilatation after all doses of aerosolized delta9-tetrahydrocannabinol was comparable, but 5 mg of delta9-tetrahydrocannabinol caused a significantly smaller increase in heart rate and level of intoxication than the 20-mg dose. Smoked delta9-tetrahydrocannabinol produced greater cardiac and intoxicating effects than either aerosolized or oral delta9-tetrahydrocannabinol. Side effects of aerosolized delta9-tetrahydrocannabinol included slight cough and/or chest discomfort in 3 of the 11 normal subjects. Aerosolized delta9-tetrahydrocannabinol caused significant bronchodilatation in 3 of 5 asthmatic subjects, but caused moderate to severe bronchoconstriction associated with cough and chest discomfort in the other 2. These findings indicate that aerosolized delat9-tetrahydrocannabinol, although capable of causing significant bronchodilatation with minimal systemic side effects, has a local irritating effect on the airways, which may make it unsuitable for therapeutic use.

Adult↗

Effects of sulfuric acid aerosol on cardiopulmonary function of dogs, sheep, and humans.

Submicronic aerosol of sulfuric acid (H2SO4) originates from the burning of fossil fuels and discharge of vapor from the automobile engine equipped with the catalytic converter. This study was conducted to determine whether brief exposure to this aerosol in high concentrations adversely affects the cardiopulmonary system. In all studies, submicronic aerosol of sodium chloride was used as a control. Anesthetized dogs that breathed H2SO4 aerosol in concentrations up to 8 mg per m3 showed no effects on respiratory resistance, static lung compliance, and functional residual capacity. A 4-hour exposure to H2SO4 aerosol (4 mg per m3) produced no significant changes in mechanics of breathing, functional residual capacity, pulmonary and systemic arterial blood pressures, cardiac output, heart rate, and arterial blood gas tensions. Conscious sheep that breathed H2SO4 aerosol in concentrations up to 14 mg per m3 for 20 min had no alteration of tracheal mucous velocity in an immediate 3-hour follow-up period or 5 to 10 days later. Conscious sheep that breathed H2SO4 aerosol (4 mg per m3) for 4 hours had no significant alteration of tracheal mucous velocity immediately and 2 hours thereafter. Both normal and asthmatic adults breathing H2SO4 aerosol in concentrations up to 1 mg per m3 for 10 min showed no significant alteration of lung volumes, distribution of ventilation, ear oximetry, dynamic mechanics of breathing, oscillation mechanics of the chest-lung system, pulmonary capillary blood flow, diffusing capacity, O2 consumption, and pulmonary tissue volume. No delayed effects in pulmonary function nor exacerbation of bronchial asthma were observe during a follow-up period of a few weeks. The present study indicates that single exposure to submicronic H2SO4 aerosol does not produce an immediate or a delayed adverse effect on cardiopulmonary function in anesthetized dogs, conscious sheep, and normal and asthmatic adults.

Aerosols↗

Clinical indications for and effects of bland, mucolytic, and antimicrobial aerosols.

The clinical usefulness of bland, mucolytic, and antimicrobial aerosols in the management of obstructive airway disease or bronchopulmonary infections was critically reviewed at th last Conference on th Scientific Basis of Respiratory Therapy in 1974. From the information available at that time, it was cocluded that there was little scientific basis for these therapeutic modalities. It was also suggested that the value of aerosol therapy should be evaluated by objective tests. The relatively few studies reported during the last 5 years have not generated new data in support of such aerosol therapy. Three criteria have been used to assess the efficacy of bland and mucolytic aerosols: respiratory function, mucociliary function, and subjective symptoms. Although respiratory and mucociliary function have generally been found to remain unaltered or to deteriorate after administration of bland or mucolytic aerosols, some investigators have observed facilitated expectoration or improved cough efficiency. The effectiveness of antimicrobial aerosols is more difficult to evaluate, and their value in patients with bacterial or fungal pulmonary infections remains to be demonstrated. Considering the cost and potential hazards of aerosol therapy, its use should be restricted to forms of aerosols whos clinical value has been objectively demonstrated; a reassessment of the literature suggests that bland and currently used mucolytic and antimicrobial aerosols do not meet this requirement.

Adult↗

Hypotonic and isotonic aerosols increase bronchial reactivity in basenji-greyhound dogs.

Because basenji-greyhound dogs have greater bronchial reactivity to a range of inhaled stimuli than mongrel dogs do, and because bronchial hyperreactivity to nonspecific stimuli is characteristic of asthma, we asked whether basenji-greyhound dogs have greater bronchial reactivity to hypotonic and isotonic aerosols than mongrel dogs do. We assessed bronchial reactivity by measuring both the total pulmonary resistance and the bronchial response to an acetylcholine aerosol, before and after delivery of hypotonic and isotonic aerosols. Bronchial reactivity as measured by a change in total pulmonary resistance increased 9-fold after delivery of hypotonic and 5-fold after delivery of isotonic aerosols in 5 anesthetized basenji-greyhound dogs, but not in 3 similarly challenged mongrel dogs (p less than 0.01). Bronchial reactivity as measured by an increased bronchial response to acetylcholine aerosol increased 3-fold in basenji-greyhound dogs but not in mongrel dogs. Thus, hypotonic and isotonic aerosols increase bronchial reactivity in basenji-greyhound dogs. We also asked whether vagal or nonvagal pathways are involved in the increase in total pulmonary resistance induced by a hypotonic aerosol. Both vagal and nonvagal pathways appear to be involved, since blockade of the vagal pathway by intravenously administered atropine only partially inhibited the bronchoconstriction induced by a hypotonic aerosol (54%). Disodium cromoglycate, which inhibits vagal and nonvagal pathways, partially inhibited the bronchoconstriction (57%), but even in combination with atropine, did not completely inhibit it (68%). Our observations in basenji-greyhound dogs are similar to results in asthmatic subjects, suggesting that basenji-greyhound dogs are useful experimental animals in which to study the mechanisms by which hypotonic and isotonic aerosols increase bronchial reactivity.

Aerosols↗

Aerosolized pentamidine and Pneumocystis carinii pneumonia: patient compliance and outcomes.

OBJECTIVE: The study objectives were to compare compliance between every-two-week and every-four-week aerosolized pentamidine regimens, and to determine if patients who were more compliant with the use of aerosolized pentamidine were at decreased risk for developing Pneumocystis carinii pneumonia (PCP). DESIGN: Nonrandomized observational study of patients receiving aerosolized pentamidine for PCP prophylaxis using the hospital pharmacy computer system to document aerosolized pentamidine use and compliance, and the Patient Administration Division's computer to document cases of PCP. SETTING: Tertiary care, US Army medical center. PATIENTS: All patients who were prescribed aerosolized pentamidine (60 mg every two weeks, 300 mg every four weeks, or both) over a 3.5-year period. MAIN OUTCOME MEASURES: Mean percent compliance was determined and compared between every-two-week and every-four-week regimens. The relationship between compliance and cases of PCP as determined using nonparametric statistics. RESULTS: Patients (n = 146) who were prescribed aerosolized pentamidine 60 mg every two weeks were more compliant (p = 0.006) than those prescribed 300 mg every four weeks. In addition, those patients who initially received the 60-mg regimen and were switched to the 300-mg regimen were more compliant when taking the 60-mg dose (p = 0.027). There was no association between compliance with either regimen and cases of PCP. Compliance generally was poor with both regimens. CONCLUSIONS: Patients on every-two-week regimens of aerosolized pentamidine were more compliant than those on every-four-week regimens. However, regardless of compliance, some patients failed aerosolized pentamidine over the 3.5-year period. Other agents that lend themselves to compliance may be more appropriate for PCP prophylaxis than aerosolized pentamidine.

Administration, Inhalation↗

The effectiveness of an aerosol reduction device for ultrasonic scalers.

Intraoral use of ultrasonic scalers may generate aerosols that contain infectious microorganisms and therefore pose a hazard to the health of the dental professional. The purpose of this in vivo study was to determine if an aerosol reduction device for an ultrasonic scaler would be effective in reducing the amount of contaminated aerosols produced during ultrasonic instrumentation. Twelve adult subjects participated in the study. A split-mouth design was utilized, and two treatments (in separate rooms) were performed on each subject: 1) ultrasonic scaling for 5 minutes with the aerosol reduction device; and 2) ultrasonic scaling for 5 minutes without the aerosol reduction device. The right or left side of the subject's mouth was randomly assigned to one of the two treatment groups. After instrumentation, the subject and operator remained motionless for 25 minutes during collection of aerosol particles. Air samples were collected on blood agar plates 6 inches from the subject's mouth. Replicate organism detection and counting plates were used to sample microorganisms present on the investigator's face shield. All plates were incubated for 3 days at 37 degrees C. The results, using the paired t-test (P < 0.001), indicate that the ultrasonic scaler without the aerosol reduction device had a significantly greater quantity of mean colony forming units (CFUs) 6 inches from the subject's mouth (45.1 +/- 28.9) than the ultrasonic scaler with the aerosol reduction device (2.6 +/- 3.6). No significant difference was evident in the number of CFUs found on the investigator's face shield. These data suggest that an aerosol reduction device is effective in reducing the number of microorganisms generated during ultrasonic scaling, therefore decreasing the risk of disease transmission.

Adult↗

Aerosolization of Newcastle disease vaccine virus and Enterococcus faecalis.

In order to study the aerosol transmission of arthropathic and amyloidogenic Enterococcus faecalis strains, preliminary aerosol experiments were performed. The experiments were carried out in empty isolators to assess the yield and viability of E. faecalis and Newcastle disease vaccine virus (NDVV) aerosol particles with time. NDVV was aerosolized because this virus would be used in combination with E. faecalis in a subsequent study. Concentrations of about 10(5) colony-forming units (CFU) of E. faecalis/ml of air were still found 30 min after the aerosol application. At 45 min, however, E. faecalis concentrations dropped below the detection level. The average E. faecalis concentration during the aerosol experiment was estimated at 10(5) CFU/liter. The NDVV aerosol generated an average of 10(4)-10(5) 50% embryo infective dose per liter of air. In these experiments, E. faecalis and NDVV aerosols were successfully generated despite considerable initial particle loss. The bacteria and virus uptakes per chick are discussed in case day-old chicks would be exposed to these aerosols.

Aerosols↗

Characterization of antimicrobial aerosols for administration to horses.

A study was conducted to characterize the aerosols produced by a medical ultrasonic nebulizer using solutions containing antimicrobials appropriate for therapy of equine lower respiratory bacterial infections (gentamicin sulfate and ceftiofur sodium). Test aerosols were generated using an ultrasonic nebulizer and were analyzed using a laser diffraction aerosol particle analyzer. The aerosol was described in terms of the particle size distribution (volume median diameter), span (sample dispersion), and aerosol density (% volume). The particle size distribution and aerosol density of gentamicin and ceftiofur aerosols were affected by the antimicrobial concentration of the solution. All solutions produced aerosols appropriate for delivery of antimicrobials to the intrathoracic airways of the horse, but the gentamicin (50 mg/ml) and ceftiofur (25 mg/ml) solutions offered the optimal combinations of particle size and aerosol density.

Aerosols↗

Aerosol delivery to ventilated infant and pediatric patients.

Infants have low tidal volume, vital capacity, and functional residual capacity, and short respiratory cycles (low I:E ratio), which result in a low residence time for aerosol particles and, thus, low pulmonary deposition of aerosol particles (< 1% of the nominal dose), compared to adults (8-22%). Scintigraphy data suggest aerosol deposition of < 1% in both intubated and nonintubated infants. In vitro testing appears to overestimate pulmonary deposition, partly because in vitro testing does not account for exhaled aerosol. Animal models of infant ventilation tend to agree with data from human studies. However, though only a small percentage of the aerosol deposits in the lung, infants nevertheless receive considerably more aerosolized drug per kilogram of body weight than do adults. Efficient aerosol delivery to infants is challenging because of low deposition and high inter-patient and intra-patient variability, but existing systems can effectively delivery various aerosolized drugs, including bronchodilators, anti-inflammatories, and anti-infectives. Use of a nebulizer that has a low residual volume (of drug remaining in the device after nebulization) delivers up to 13%. Awareness of the variables that impact aerosol delivery efficiency can result in more effective treatment of mechanically ventilated infants.

Administration, Inhalation↗

Risk of acute bronchospasm and bronchial hyperreactivity from inhaled acid aerosol in healthy subjects: randomized, double-blind controlled trial.

AIM: To determine the risk of developing acute bronchial spasm and bronchial hyperreactivity in healthy subjects after inhaling hydrochloric acid aerosol of different pH, since various characteristics of inhaled aerosol, particularly its acidity, contribute to the reduction in lung function in patients with a pre-existing disease. METHODS: Randomized, double-blind, placebo-controlled trial included 79 healthy volunteers. After submitting a written consent, they were randomized in 4 groups with approximately equal number of participants. Each group was exposed to acid aerosol of different pH. The respiratory lung function expressed by forced expiratory volume (FEV1), forced expiratory flow at 50% (FEF50), 75% (FEF25), and between 25% and 75% of vital capacity (FEF25/75), and non-specific bronchial reactivity were measured after inhalation of hydrochloric acid aerosol of pH 7.0, pH 5.0, pH 3.0, and pH 2.0 and compared with baseline values. Twelve subjects, who reached the threshold doses in both bronchial challenges, were tested again after receiving a systemic beta-blockade with a single oral dose of propranolol. RESULTS: Significant bronchospasm developed after the inhalation of hydrochloric acid aerosol of pH 5.0, 3.0, and 2.0. After the inhalation of aerosols of pH 5.0 and pH 2.0, all parameters of respiratory lung function (FEV1, FEF50, FEF25, and FEF25/75) significantly decreased. After the inhalation of aerosol of pH 3.0, all parameters significantly decreased except for FEF25, which showed no significant difference (1.84+/-0.46 before vs 1.58+/-0.49 after inhalation; p=0.07). The inhalation of hydrochloric acid aerosol had no significant effect on the level of non-specific bronchial reactivity irrespective of its pH. Eight out of 12 subjects tested again after pretreatment with propranolol and with no significant change in the heart rate showed no change in non-specific bronchial reactivity in comparison with the 4 subjects who reacted with a significant decrease in the heart rate (>10%), as well as in non-specific bronchial reactivity (p=0.023). CONCLUSION: Inhalation of acid aerosol in healthy subjects induced a bronchial spasm, but had no effect on non-specific bronchial reactivity except in subjects under systemic adrenergic inhibition.

Adrenergic beta-Antagonists↗

Sites of deposition of aqueous aerosols: a study of efficiency of delivery systems for lung ventilation imaging in man.

A study was made of the deposition of 99Tcm-DTPA aerosol in the components of a jet nebulizer-based aerosol production system. Three impaction devices were compared: a ball-bearing separator, a virtual impactor and a step separator. In addition a comparison was made of two types of tubing which carried aerosol from nebulizer to mouthpiece: corrugated and smooth-walled tubing. The retention of aerosol following inhalation was measured in five normal volunteers using different patterns of breathing. Using an aerosol production system which included a ball-bearing separator only a mean of 11% of the radioactivity loaded into the nebulizer was emitted as an aerosol. Some 18% remained in the ball-bearing separator. The ball-bearing and step separators produced similar total outputs (7% and 6% minimum), the step separator producing marginally higher mean output/min. The virtual impactor produced a lower output than the other two impactors studied, only 1%. A larger proportion of the aerosol output was deposited on corrugated tubing (7%) compared with smooth-walled tubing (1%). The retained fraction of the aerosol inhaled by subjects ranged from 16% to 43%. A higher fraction was retained when subjects inhaled deeply and held their breath for 10 s between each breath. The efficiency of radionuclide deposition from aerosol generator to patient ranged from 1.1% to 6% and was determined more by the retention in the subject than by choice of separator or tubing.

Aerosols↗

Lidocaine aerosols do not prevent allergic bronchoconstriction.

To test the effectiveness of local anesthetic aerosols in asthma, we compared the protection afforded by lidocaine and saline aerosols to bronchoconstriction provoked by inhalation of Ascaris antigen aerosols in five previously sensitized, anesthetized Basenji-Greyhound, crossbred dogs. Pulmonary resistance (RL) was determined by the method of Von Neergaard and Wirz, and blood lidocaine levels were determined by gas chromatography. Lidocaine, 4%, was administered as an aerosol for 10 minutes before challenge with Ascaris antigen and again during the 10-minute challenge with Ascaris antigen. Lidocaine aerosols frequently elicited a slight increase in RL before antigen challenge, whereas saline aerosols did not alter RL. Despite a large dose (approximately 10 mg/kg), which produced blood levels of 0.6 to 3.3 micrograms/ml, lidocaine afforded no protection against antigen challenge: RL increased from a control mean of 4.2 +/- 1.7 (SEM) cm H2O/liters/sec to 26.9 +/- 9.3 after challenge in lidocaine-treated dogs, and from 2.9 +/- 0.6 to 22.8 +/- 5.1 in saline-treated dogs. In contrast, lidocaine aerosols prevented the 7-fold increase in RL elicited by challenge with citric acid aerosols, demonstrating an adequate block of irritant reflexes. The failure of lidocaine aerosols to protect against antigen-induced bronchoconstriction indicates that the concentrations achieved in lung by this route are inadequate to relax smooth muscle directly.

Aerosols↗

Chemoprevention of pulmonary carcinogenesis by aerosolized budesonide in female A/J mice.

This investigation is part of a continuing effort to develop effective chemoprevention for carcinogenesis of the lung. The present study explores the use of aerosol administrations for this purpose. The agent selected for initial study was the synthetic glucocorticoid budesonide. This selection was based on previous work in which budesonide added to the diet was found to inhibit pulmonary adenoma formation in female A/J mice. However, high dose levels were required, i.e., of the order of 300 microg/kg, of body weight [L. W. Wattenberg and R. D. Estensen, Carcinogenesis (Lond.), 18: 2015-2017, 1997]. For aerosol administration of budesonide, a nose-only technique has been developed that entails nebulization of the compound dissolved in ethanol and subsequent stripping off of the solvent (less than 3 microl ethanol/liter of air remaining at the site of inhalation). The budesonide particles produced by the apparatus had a mass median aerodynamic diameter of less than 1 microm. An experiment has been carried out in which the inhibitory effects of aerosolized budesonide, given for 1 min six times a week, were studied. Concentrations of budesonide of 26, 81, and 148 microg/liter of air (calculated doses of 23, 72, and 126 microg/kg of body weight) were used. The aerosols were started 1 week after three oral administrations of benzo(a)pyrene (2 mg/20 g of body weight) to female A/J mice. All three doses of budesonide resulted in more than 80% inhibition of pulmonary tumor formation compared to the aerosol control and 90% or greater compared to mice not exposed to aerosol. The difference in inhibition is due to the aerosol procedure itself, which produces a reduction in tumor formation. A decrease in splenic weight (evidence of a systemic effect) occurred at all doses of budesonide. To the best of our knowledge, this is the first published effort at the use of aerosol administration to prevent neoplasia of the respiratory tract. The results of the present study show that administration of a potential chemopreventive agent by aerosol at a low dose can inhibit the occurrence of pulmonary carcinogenesis in female A/J mice.

Administration, Inhalation↗

Aerosol therapy in cystic fibrosis: a survey of 54 CF centers.

Aerosol therapy has become increasingly important in the treatment of lung disease of patients with cystic fibrosis (CF). Still, many questions concerning this therapy remain unanswered. It is unclear at what age aerosol therapy should be started; which aerosolized drugs are essential in the treatment of CF lung disease; which delivery system(s) should be used; and how aerosol therapy should be timed in relation to physiotherapy. We hypothesized that large differences in aerosol treatment practices between CF centers would be present. To investigate this, we performed an observational survey to evaluate different aspects of aerosol therapy. A questionnaire was sent to 102 CF centers in 28 different countries. A completed questionnaire was returned by 54 out of 94 centers (57%). In these 54 centers, 7,324 CF patients were treated. Substantial differences were found in aerosol therapy between centers. Patients below age 1 year were not treated with any form of aerosol therapy in 10% of the centers, while 37.5% of the centers treated all of these patients. The timing of nebulization and physiotherapy varied substantially for many important and expensive drugs. We conclude that many aspects of aerosol therapy in cystic fibrosis need to be executed in a more rational and evidence-based manner than is currently the case.

Administration, Inhalation↗

Effects of aerosol-applied capsaicin, histamine and prostaglandin E2 on airway sensory receptors of anaesthetized cats.

1. Capsaicin, prostaglandin E2 (PGE2) and histamine are potent stimuli for reflex coughing and bronchoconstriction in many species including man. We have studied the effects of solutions of capsaicin, PGE2 and histamine on airway sensory receptors when administered as inhaled aerosols to the lower respiratory tract in anaesthetized, paralysed and artificially ventilated cats. 2. Histamine, administered by aerosol (6 breaths of a 1 mg ml-1 solution) and intravenously (10 micrograms kg-1), caused an increase in the rate of discharge from rapidly adapting stretch receptors (RARs) and caused bronchoconstriction. 3. Six breaths of a capsaicin aerosol generated from solutions of 0.1 or 1 mg ml-1 stimulated six out of nine RARs tested. Bronchoconstriction occurred with and without RAR stimulation. The diluent for the capsaicin aerosol had no significant effect on pulmonary mechanics or rate of RAR discharge. 4. Administration of increasing concentrations (0.001-1 mg ml-1) of PGE2 aerosol given in six breaths (at 6 min intervals) caused a dose-dependent increase in the rate of discharge of eight RARs tested and caused bronchoconstriction. The diluent for the PGE2 aerosol had no effect on pulmonary mechanics or rate of RAR discharge. 5. Inhalation of aerosols of histamine (6 breaths of 1 mg ml-1 solution) and capsaicin (3 breaths of 0.1 mg ml-1 solution) stimulated all six lung C fibre endings studied (3 pulmonary and 3 bronchial). These aerosols of capsaicin and histamine also caused bronchoconstriction. 6. We conclude that solutions of capsaicin and PGE2, when delivered by aerosol to the airway epithelial surface, are not selective stimulants of C fibres. Both agents can stimulate RARs. Activation of some but not all RARs tested, by inhaled capsaicin, suggests that there are subpopulations of capsaicin-sensitive and -insensitive receptors. Stimulation of airway RARs by a range of pharmacologically active agents released by airway inflammation may contribute to reflex coughing and bronchoconstriction in man.

Administration, Inhalation↗

Optimal eigenanalysis for the treatment of aerosols in the retrieval of atmospheric composition from transmission measurements.

The separation of the individual contributions of aerosol and gases to the total attenuation of radiation through the atmosphere has been the subject of much scientific investigation since remote sensing experiments first began. We describe a new scheme to account for the spectral variation of the aerosol extinction in the inversion of transmission data from occultation measurements. Because the spectral variation of the aerosol extinction is generally unknown,the inversion problem is underdetermined and cannot be solved without a reduction in the number of unknowns in the set of equations used to describe the attenuation at each wavelength. This reduction can be accomplished by a variety of methods, including use of a priori information, the parameterization of the aerosol spectral attenuation, and the specification of the form of the aerosol size distribution. We have developed and implemented a parameterization scheme based on existing empirical and modeled information about the microphysical properties of aerosols. This scheme employs the eigenvectors from an extensive set of simulations to parameterize the aerosol extinction coefficient for incorporation into the inversion algorithm. We examine the accuracy of our method using data sets containing over 24,000 extinction spectra and compare it with that of another scheme that is currently implemented in the Polar Ozone and Aerosol Measurement (POAM) satellite experiment. In simulations using 80 wavelengths in the UV-visible-near-IR spectral range of the Stratospheric Aerosol and Gas Experiment III (SAGE) instrument, we show that, for our optimal parameterization, errors below 1% are observed in 80% of cases, whereas only approximately 20% of all cases are as accurate as this in a quadratic parameterization employing the logarithm of the wavelength.

Journal Article↗