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PubMed1979

Pulmonary alveolar proteinosis: successful treatment with aerosolized trypsin.

A 37 year old man with pulmonary alveolar proteinosis and severe pulmonary physiologic impairment was treated empirically for 12 months with continuous oxygen, intermittent positive pressure breathing and aerosolized saline solution, heparin and acetylcysteine. Because of progression of disease, he was treated with aerosolized trypsin in a dose of 100,000 U twice daily for six months. This treatment was associated with dramatic symptomatic, chest roentgenographic and pulmonary physiologic improvement that has lasted for two and a half years without remission. The absence of adverse effects of trypsin aerosol allowed its administration in the patient's home. It is suggested that the preferred initial therapy for symptomatic alveolar proteinosis is aerosolized trypsin.

Adult↗
PubMed1983

Bronchodilator response to oral aminophylline and terbutaline versus aerosol albuterol in patients with chronic obstructive pulmonary disease.

Bronchodilator efficacy of oral administration of aminophylline (400 mg) and terbutaline sulfate (5 mg) was compared with inhalation of three puffs of albuterol sulfate in 17 patients with stable chronic obstructive pulmonary disease in a double-blind crossover study. Two hours after either form of therapy, the patients were treated again with three puffs of albuterol. Forced expiratory volume in one second (FEV1) increased significantly more from the baseline value after albuterol aerosol than after oral medication at 30, 60, and 120 minutes (paired t test, p less than 0.01). After three puffs of albuterol at 120 minutes, FEV1 increased to similar values an hour later on both days in 14 of 17 patients. Thirteen patients complained of side effects during oral therapy and none during aerosol therapy. Maximum bronchodilatation was achieved by albuterol aerosol in 14 of 17 patients, and addition of oral therapy produced no further increase of flow rate in these patients. Bronchodilator aerosol is the logical choice for treatment of chronic obstructive pulmonary disease because it is more effective than oral therapy and because it is free from side effects.

Aerosols↗
PubMed1985

Pulmonary function in elastase-treated guinea pigs and rats exposed to ammonium sulfate or ammonium nitrate aerosols.

Three weeks following intratracheal instillations of elastase dissolved in saline, or saline alone, guinea pigs and rats were exposed for 5 or 20 days, 6 hr/day, 5 days/week to filtered room air, 1 mg/m3 ammonium sulfate [NH4)2SO4) or 1 mg/m3 ammonium nitrate (NH4NO3) aerosols. Pulmonary function evaluations conducted in guinea pigs showed no detrimental effects of (NH4)2SO4 or NH4NO3 exposure and very little effect of elastase treatment. Lung function changes in elastase-treated rats were consistent with a condition of experimentally induced pulmonary emphysema. Rats exposed to NH4NO3 aerosols showed no consistent exposure-related changes. Compared with air-exposed animals, rats exposed to (NH4)2SO4 aerosols had increased values of residual volume and functional residual capacity and decreased slope of single-breath N2 washout curves. We conclude that elastase treatment had no significant effect on lung function changes resulting from inhalation of (NH4)2SO4 aerosols. Lung function was more affected by (NH4)2SO4 exposure than by NH4NO3 exposure, and lung function changes were more pronounced in rats than in guinea pigs.

Aerosols↗
PubMed1991

Fowlpox virus: pathogenicity and vaccination of day-old chickens via the aerosol route.

Day-old chickens were given a single fowlpox virus vaccination (strain HP201) either via the aerosol or wing-web route. Both methods induced protective immunity against a wing-web or intravenous challenge with virulent fowlpox virus at 47 days old, although high titred virus preparations were required for successful aerosol vaccination. However, no clinical signs of infection were observed as a result of aerosol vaccination even if invasive strains of Escherichia coli were administered simultaneously. The use of aerosol fowlpox virus vaccination of day-old chicks has been shown to be a possible means of mass vaccination and could be applied to the use of fowlpox virus in recombinant vaccines.

Aerosols↗
PubMed1986

Hexamethonium aerosol prevents pulmonary reflexes induced by cigarette smoke in dogs.

The reflexogenic respiratory responses to spontaneous inhalation of cigarette smoke (500-750 ml, 12-20% concentration) were studied in chloralose anesthetized dogs before and after hexamethonium aerosol, a nicotinic receptor antagonist, was administered into the lungs. In 11 of 13 dogs studied, reproducible responses of either apnea (n = 9) or rapid shallow breathing (n = 2) were elicited immediately after the first or second breath of smoke inhalation: apneic duration reached 398 +/- 47% (mean +/- SEM) of the mean baseline expiratory duration. Pretreatment with hexamethonium aerosol (3-5 breaths, 10% concentration) completely abolished these immediate changes in breathing patterns, but did not significantly reduce the delayed hyperpnea induced by smoke inhalation. Hexamethonium aerosol alone did not cause any detectable systemic effects. To examine if a bronchoconstrictive effect of nicotine was involved, the response to cigarette smoke was also studied after bronchodilation was induced by isoproterenol aerosol (15 breaths, 0.5% concentration) in 6 of these dogs. However, neither immediate nor delayed responses to smoke inhalation was significantly affected. These results suggest that: (1) these immediate respiratory responses to smoke inhalation are elicited by a nicotine-induced stimulation of vagal sensory receptors in the lungs, and (2) bronchoconstriction is not responsible for causing these reflex effects.

Aerosols↗
PubMed1987

In vivo hysteresis of airspace dimensions measured by aerosol recovery.

In anesthetized mongrel dogs, we made measurements of single breath aerosol recovery (RC) at equal volume points on the inflation and deflation limb of the quasi-static pressure-volume (P-V) curve of the lungs. Using a 1.2 micron monodisperse aerosol, a large aerosol tidal volume (Vt), and a breathing period of 5 sec, we found that losses of particles were primarily due to sedimentation in pulmonary airspaces distal to anatomic dead space. Thus, the RC measurements could be related to a mean radius (R) of airspaces filled with aerosol over the course of the breath. Furthermore, at a given volume, differences between inflation and deflation limb RC could be attributed to differences in R for the two measurements (i.e., RI vs RD). We found that at isovolume, RC as measured from the inflation limb was larger than that measured from the deflation limb for low lung volumes (less than 0.75 TLC). However, the recoveries were similar as lung volume approached TLC (greater than 0.75 TLC). These results implied that at the same volume, RI greater than RD expect at volumes approaching TLC, i.e. a larger mean airspace dimension on the inflation limb than on the deflation limb at equal volume. The findings of this study support a model of nonuniform changes in airspace dimensions associated with in vivo inflation and deflation of the lungs.

Aerosols↗
PubMed1995

Effect of bronchoconstrictive aerosols on pulmonary gas trapping in the A/J mouse.

We exposed A/J mice to several challenge aerosols and measured gas trapped within excised lungs by quantitating their buoyancy in saline (Archimedes' principle). The temporal stability of the excised lung gas volume (ELGV) measurement was also examined. ELGV increased in a dose proportional manner with increasing concentrations of methacholine and reached a maximum of 338 +/- 33% above vehicle-exposed controls. The A/J mice were 100 times more responsive to aerosol methacholine compared to hyporesponsive C3H/HeJ mice. Aerosol challenges of U-46619, a thromboxane A2 mimetic, and serotonin resulted in a 40% and 135% increase in ELGV's versus their controls, respectively. ELGV's were not increased after aerosols of leukotriene C4, histamine, substance P, N-formyl-methionyl-leucyl-phenyl-alanine and platelet activating factor. Both normal (filtered air-exposed) and hyperinflated (methacholine-exposed) excised lungs lost about 10% of their initial volume by 30 min and 40-65% of initial volume by 4 h. Occlusion of the trachea in either group did not affect the total gas lost, suggesting that majority of the gas loss was via transpleural diffusion. We conclude that determination of ELGV in mice, when performed soon after challenge testing, is a simple, rapid and reliable estimate of airway obstruction.

Aerosols↗
PubMed1983

A method to rapidly evaluate the acute pulmonary effects of aerosols in unanesthetized guinea pigs.

A method was developed to rapidly evaluate the acute effects of aerosols on the respiratory tract in unanesthetized but slightly restrained guinea pigs. Each animal was placed in a whole body plethysmograph and was fitted with a head chamber. From the head chamber, inspiratory volume (VI) was measured by integration with time of airflow rate obtained via a pneumotachograph. From the whole body plethysmograph a pressure (delta P) proportional to inspiratory volume was measured. Both VI and delta P were measured while the animal breathed a mixture of 10% CO2, 18% O2, and 72% N2. This procedure resulted in a stable and sustained increase in both VI and delta P. With the animals still breathing 10% CO2, the aerosols to be tested were then introduced. Both sulfuric acid and histamine aerosols produced a significant decrease in VI and delta P. The method is simple and does not necessitate anesthesia or invasive techniques. It should be useful to rapidly evaluate the possible acute effects of airborne contaminants. Furthermore, measurement of delta P alone with the animal in the whole body plethysmograph, obviating the need for the head chamber and the restraint imposed by it, was found to indicate an effect similar to the measurement of VI. This step further simplifies the method to evaluate an acute effect of aerosols on the respiratory tract.

Aerosols↗
PubMed1987

Functional changes in the lungs of guinea pigs exposed to sodium sulfite aerosols.

Guinea pigs were exposed head only for 1 hr to submicrometer sodium sulfite aerosols (mass median aerodynamic diameter = 0.36 micron, sigma g = 2.96) at 474, 669, and 972 micrograms SO3(2-)/m3. Respiratory mechanics were measured in unanaesthetized animals before, during, and after exposure. Dose-related increases in resistance and decreases in compliance were observed. At 972 micrograms SO3(2-)/m3, the sodium sulfite aerosol caused a 50% increase in resistance and a 19% decrease in compliance. These changes were still present 1 hr after the end of exposure. The results were used to assess the irritant potency of sodium sulfite aerosol. Another group of guinea pigs was exposed whole body for 1 hr to the same aerosol at 0, 204, 395, and 1152 micrograms SO3(2-)/m3. Immediately after the exposures, lung volume, diffusion capacity for carbon monoxide (DLCO), and wet lung weight were evaluated in anesthetized, tracheotomized animals. As compared to controls, total lung capacity, vital capacity, functional residual capacity, residual volume, and DLCO were all decreased with increasing concentrations of sodium sulfite. Dose-related increases in wet lung weights were also observed. These results were compared with the irritant responses of animals exposed to zinc oxide and sulfur dioxide mixed under different conditions of temperature and humidity.

Aerosols↗
PubMed1987

Acute cardiovascular and pulmonary effects of intravenous and aerosolized amiloride in the dog.

Active Na+ absorption by the epithelia that line the airways can drive volume from the airway surface. Exposure of the lumen-facing surface of airway epithelia to amiloride inhibits Na+ transport. Consequently, aerosolized amiloride may help hydrate the desiccated surface liquid that characterizes lung diseases such as cystic fibrosis. We studied the acute cardiovascular and pulmonary effects of amiloride in anesthetized dogs. Intravenous amiloride reduced blood pressure and increased ventilation frequency and airways resistance of the dog. The effects were dose-related (ED50 = 1.3 X 10(-6) mol/kg), resembled those of injected histamine, and were antagonized by methapyrilene. These results were compatible with the release of endogenous histamine by amiloride, but the graded dose-effect relationship for amiloride differed from the quantal relationship induced by the prototypical releaser, 48/80. Aerosolization of a Ringer's solution that was nearly saturated with amiloride deposited, in upper airway surface liquid, drug concentrations which in previous studies, were sufficient to inhibit Na+ transport by canine airways (ED50 approximately 10(-6) M). Cardiovascular function, airways resistance, and indices of pulmonary tissue water, gas exchange, and perfusion were not affected. Since circulating amiloride after aerosolization was estimated to fall below the concentration that induced vasodepression and correct circled bronchoconstriction after intravenous injection, we conclude that the potency of aerosolized amiloride to induce acute effects in tissues other than airway epithelia is no greater than that of intravenous drug.

Administration, Inhalation↗
PubMed1989

Establishing aerosol exposure concentrations for inhalation toxicity studies.

Criteria for the selection of aerosol concentrations to be used in inhalation studies assessing the toxicity and carcinogenicity of chemical substances were discussed by the authors in a meeting sponsored by the National Toxicology Program. Concepts in the design of aerosol inhalation studies emerged from that meeting and are being communicated through this publication. Inhalation studies assessing the toxicity and carcinogenicity of aerosols have often used maximum exposure levels on the basis of technological feasibility. Evidence has now accumulated that the amount of pulmonary burden of deposited particles impacts on particle clearance above some as yet not well-defined exposure concentration. The sequelae are such that lung clearance decreases with increased particulate burden to the point of approaching complete cessation. This paper focuses on the major determinants in establishing maximal aerosol concentrations for use in inhalation toxicity studies with special emphasis on experimental design features to assess lung retention. The subject matter of this paper is a rapidly developing area in terms of knowledge. Accordingly, the contents of this article are intended as guidelines and not as absolute rules for the conduct and interpretation of inhalation exposure studies.

Administration, Inhalation↗
PubMed1986

Pharmacology of aerosol leukotriene C4- and D4-induced alteration of pulmonary mechanics in anesthetized cynomolgus monkeys.

Aerosol administration of solutions of 900 micrograms/ml of leukotriene C4 (LT) or D4 to cynomolgus monkeys produced dose-dependent, equipotent increases in pulmonary resistance (Rp) and decreases in dynamic lung compliance (Cdyn). Time to peak response was, in part, related to dose and ranged from 4 to 20 min. Both LTC4 and LTD4 were less potent than histamine. Aerosol pretreatment with the cyclooxygenase inhibitor indomethacin had no significant effect on either LTC4 or LTD4 dose-response curves; however, at the highest doses of these agonists a notable, nonsignificant inhibition of effects on both Rp and Cdyn was seen. Intravenous dl-propranolol had no effect on responses to LTD4. Aerosol pretreatment with FPL 55712 significantly (P less than 0.05) inhibited airway responses to both LTC4 and D4. In contrast, an intravenous infusion of FPL 55712 failed to block the bronchospastic activity of LTD4. In conclusion, cynomolgus monkeys are responsive to aerosol administration of LTC4 and LTD4, and the pharmacology of their responses appears to resemble that of man.

Aerosols↗
PubMed1980

In vivo effect of cimetidine on canine pulmonary responsiveness to aerosol histamine.

A series of experiments were designed to discover whether pulmonary histamine H2 receptors might be of physiologic importance in vivo in the dog. Dose-response curves were performed to aerosol histamine in 11 dogs both before and 1 hr after H2 receptor blockade with cimetidine (1 mg/kg as a rapid intravenous infusion). Cimetidine had no significant effect on control values of dynamic compliance or resistance of the lung. In the 11 dogs tested H2 receptor antagonism significantly potentiated (p less than 0.05) the animals' pulmonary responsiveness to aerosol histamine. The potentiation of histamine constrictor e-fects produced by cimetidine were more marked on those dogs initially least responsive to aerosol histamine (p less than 0.01). We have found evidence for the presence of inhibitory H2 receptors in canine airways and for the distribution of these receptors among dogs, explaining in part the previously described differences among dogs in the pulmonary responsiveness to aerosol histamine.

Aerosols↗
PubMed1986

Clinical, rhinomanometric, and cytologic evaluation of seasonal allergic rhinitis treated with beclomethasone dipropionate as aqueous nasal spray or pressurized aerosol.

The currently available beclomethasone dipropionate (BDP) metered-dose nasal aerosol spray is considered uncomfortable by some patients because of the force of delivery. It was compared for efficacy and acceptability in a double-blind study with a new aqueous suspension BDP spray for the treatment of seasonal allergic rhinitis in 44 symptomatic patients aged 12 to 43 years. After 7 days of baseline evaluation, every patient was given both an aerosol canister and an aqueous spray bottle each containing either BDP, 42 mcg per spray, or placebo (P). For 15 days the patient sprayed each nostril twice a day with one spray of suspension (BDP or P) followed 5 minutes later by one spray of aerosol (P or BDP). Patients were evaluated before the study medications were started (day 1) and on days 4, 8, and 15 for nasal and eye symptoms. Nasal cytologic specimens were examined on days 1 and 15, and rhinomanometry was performed on days 1, 8, and 15 of the study. Topical BDP by both methods of delivery was rapidly effective in decreasing mean nasal obstruction, rhinorrhea, sneezing, and itching symptoms as well as mean eye symptoms with no statistically significant differences between them. Nasal airflow increased with both treatments; rhinomanometry significantly correlated with subjective nasal obstruction scores. Of 34 patients with nasal eosinophils, 74% had fewer eosinophils after treatment. Most patients (84%) preferred the aqueous spray over the pressurized aerosol.

Administration, Intranasal↗
PubMed1990

Dilution of nebulised aerosols by air entrainment in children.

Guidelines for use of aerosolised drugs in children are inconsistent. In a study of 14 infants, 22 children, and 4 adults inspired nebulised aerosols were diluted more for large than for small subjects, because of air entrainment which occurred when inspiratory flow exceeded nebuliser flow. Infants under 6 months of age did not entrain air and would receive undiluted aerosols. All other subjects entrained air, which caused up to a 5-fold dilution in inspired aerosol concentration as subject size increased. In subjects who entrained air, the ratio of inspired nebuliser output versus total nebuliser output was relatively constant, and was related to the respiratory pattern. For a given nebuliser solution concentration, infants who do not entrain will inspire more concentrated aerosols than older children. Once entrainment occurs, the mass of drug inspired is largely independent of size. Regimens for nebulised drug delivery in children may require revision.

Adolescent↗
PubMed1983

Genotoxicity of aerosol extracts. Some methodological aspects and the contribution of urban and industrial locations.

The genotoxicity of aerosol extracts was investigated with the Ames test and an SCE test in vitro. In addition to experiments to evaluate current techniques, a so-called gradient study was carried out in an industrialized part of The Netherlands to obtain insight into the contribution of urban and industrial locations to the genotoxicity of aerosol extracts. The influence of variations in the sampling was investigated. The results indicate that moderate variations in the volume of air sampled per unit of time and of the duration of the sampling period do not have a great influence on the effect measured. Experiments with filters impregnated with 14C-labelled benzo[a]pyrene showed that this compound is converted during sampling into directly active mutagens; no evaporation occurred. The results of experiments to evaluate the extraction procedure indicated that an 8-h Soxhlet extraction with methanol is better than, or as good as, Soxhlet extraction with other solvents. The gradient study showed that the aerosol downwind from industrial/urban areas exerted a reproducibly stronger effect in the Ames test and the SCE test when compared with aerosol from sea air.

Aerosols↗
PubMed1994

Evaluation of single-use masks and respirators for protection of health care workers against mycobacterial aerosols.

BACKGROUND: The recent increase in multidrug-resistant tuberculosis has spawned a major controversy concerning the degree of respiratory protection needed by health care workers, particularly during sputum-inducing procedures. The objective of this study was to measure the filtration efficiencies of a single-use submicron surgical mask, two disposable dust/mist respirators, a dust/mist/fume respirator, and a high-efficiency particulate air respirator against aerosolized mycobacteria. Facial fit was not addressed. METHODS: In a specially designed enclosed test apparatus, an aerosol was generated with a Collison nebulizer from a known concentration of Mycobacteria chelonae, used as a surrogate for Mycobacterium tuberculosis. Aerosol concentrations were measured with Anderson samplers upstream and downstream of the test masks and respirators, which were heat sealed to a metal plate. RESULTS: Mean efficiencies ranged from approximately 97% for the surgical mask and a dust/mist respirator to more than 99.99% for the high-efficiency particulate air respirator. Measurements of filter efficiency with an Aerodynamic Particle Sizer for the M. chelonae aerosol and independent challenge tests with latex spheres correlated closely with measurements of M. Chelonae collection efficiency determined with Andersen samplers. CONCLUSIONS: Analysis of variance and Tukey's method for multiple comparisons indicated that the dust/mist/fume respirator and the HEPA respirator collected M. chelonae with significantly greater efficiency than did either the surgical mask or the dust/mist respirator. Even the least efficient mask tested, however, had a filter efficiency of more than 97% against particles averaging less than 1 micron in aerodynamic diameter.

Aerosols↗
PubMed1991

In vivo deposition of ultrafine aerosols in the nasal airway of the rat.

We studied the deposition of ultrafine aerosols, ranging in geometric diameter from 0.005 to 0.1 microns, in the nasal airway of Fischer-344/N rats, at inspiratory flow rates of 200, 300, 400, and 600 ml/min. Simultaneously, we measured the pressure drop across the rat nasal airway. The purpose was to determine whether the in vivo deposition of ultrafine aerosols in the rat nasal airway is the same as the deposition observed in rat nasal casts. At a flow rate of 400 ml/min, corresponding to the normal mean inspiratory flow rate of the rat, deposition efficiency increased from 6 to 58%, when the particle diameter decreased from 0.1 to 0.005 microns. For 0.005-microns-diameter particles, the deposition efficiency decreased from 68 to 52% when the flow rate was increased from 200 to 600 ml/min. These results agree well with those from previous experiments with nasal casts, which indicated that diffusion is the dominant mechanism for deposition of ultrafine aerosols. The pressure drop in the nasal airway of the rat increased almost linearly with flow rate, from 73 Pa at 200 ml/min to 247 Pa at 600 ml/min. These values are within the range of those obtained in previous experiments with nasal casts, although the pressure drop in casts increased as a power greater than 1 with flow rate. The results of our study support the use of nasal airway casts to estimate the in vivo deposition of ultrafine aerosols.

Aerosols↗