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PubMed1998

The epidemiology of adolescent inhalant drug involvement.

OBJECTIVE: To fill some of the gaps in our knowledge of the epidemiology of inhalant drug use. We examine age, sex, and race or ethnicity variations in the occurrence of inhalant use as well as time trends and the purported transitory nature of inhalant use among adolescents in the United States. DESIGN: The data analyzed in this report were collected as part of the National Household Survey on Drug Abuse from 1990 through 1995. This annual survey is designed to provide cross-sectional information about the patterns of drug use among nationally representative samples of US household residents aged 12 years and older. PARTICIPANTS: The sample included 34826 adolescents aged 12 to 17 years who participated in the National Household Survey on Drug Abuse from 1990 through 1995 (N=2177-8005 per survey year). RESULTS: The use of inhalants, particularly aerosols and glue, increased during the first half of the current decade. Initiation of inhalant use is not limited to early adolescence and is not a transitory behavior among adolescents in the United States. The use of inhalants is equally common among members of both sexes, and non-Hispanic white youths are more likely to report use than are members of other race or ethnic groups. CONCLUSIONS: The increasing use of inhalants, their widespread availability, and the risks involved with their use indicate a need for more focused attention on this public health problem.

Adolescent↗
PubMed2001

Socioeconomic status, drug insurance benefits, and new prescriptions for inhaled corticosteroids in schoolchildren with asthma.

BACKGROUND: Low-income children with asthma are less likely to receive inhaled corticosteroid prescriptions that can prevent asthma morbidity. OBJECTIVE: To determine whether the receipt of inhaled corticosteroids in children with asthma is related to household socioeconomic status and type of drug insurance. DESIGN: Using population-based prescription and health care data from Manitoba, a cohort study of the determinants of receiving new prescriptions for inhaled corticosteroids was conducted in children treated with asthma drugs. PARTICIPANTS: School-aged children (n = 12 481) receiving asthma prescriptions from January 1995 to March 1996 but no inhaled corticosteroid prescriptions in the initial 6-month period. MAIN OUTCOME MEASURES: Household socioeconomic and drug insurance predictors of the probability of receiving a new inhaled corticosteroid prescription from July 1995 to March 1998, following adjustment for disease and health care utilization factors. RESULTS: In comparison with higher-income children insured through a provincial cost-sharing drug plan, the adjusted likelihood ratio for a new inhaled corticosteroid prescription was 0.88 (95% confidence interval, 0.80-0.97) in low-income children insured through the same drug plan and 0.82 (95% confidence interval, 0.76-0.88) in children receiving prescriptions at no charge through provincial income assistance or First Nations benefits programs (Winnipeg, Manitoba). CONCLUSION: Independent of asthma severity, type of drug insurance, or health care utilization patterns, low-income children with asthma are significantly less likely to receive inhaled corticosteroid prescriptions.

Adolescent↗
PubMed1998

Comparison of an inhalant allergy immunoassay with allergen specific IgE determinations in human serum.

The diagnosis of inhalant allergy can be elusive, with symptoms resembling viral or bacterial infection, as well as immunologic deficiency. In this study an inhalant allergy immunoassay was investigated as a possible screen to rule in or out respiratory inhalant allergy in patients with allergic-type symptoms. The results of this screen were compared in 192 serum specimens submitted to our laboratory for specific IgE allergy testing and 73 blood bank samples. When the discrepant results of the inhalant allergy immunoassay were resolved by Western blot, a final sensitivity of 94.7% and specificity of 97.5% was calculated. We have found this inhalant allergy immunoassay to be an effective screen for detecting inhalant allergies, and believe it to be a useful tool for the primary care physician or non-allergist trying to differentiate inhalant allergens from chronic sinusitis or other causes of sinopulmonary congestion.

Allergens↗
PubMed2003

Combined corticosteroid and longacting beta-agonist in one inhaler for chronic obstructive pulmonary disease.

BACKGROUND: Long-acting beta-agonists and inhaled corticosteroids have been recommended in guidelines for the treatment of chronic obstructive pulmonary disease. However, they have only been available until recently via separate administration. They have been developed in order to facilitate adherence to medication regimens, and to improve efficacy. OBJECTIVES: To assess the efficacy of combined inhaled corticosteroid and long-acting beta-agonist preparations in the treatment of adults with chronic obstructive pulmonary disease. SEARCH STRATEGY: We searched the Cochrane Airways Group chronic obstructive pulmonary disease (COPD) trials register (March 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2003), LILACS (all years to March 2003) and reference lists of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: Studies were included if they were randomised, with adequate blinding procedures in place. Studies could compare a combined inhaled corticosteroids and long-acting beta-agonist preparation with either component preparation or placebo. Studies comparing different members of each class of combined therapies were included DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Four randomised trials with 2986 participants were included. Two different combination preparations (fluticasone/salmeterol and budesonide/formoterol) were studied in the trials. No meta-analysis on clinical outcomes was possible due to different outcome assessment across studies. All studies demonstrated a reduction in exacerbation rates versus placebo. Budesonide/formoterol was more effective than formoterol in reducing exacerbations in one study from 1.84 to 1.42 exacerbations per year. Fluticasone/salmeterol did not significantly reduce exacerbations compared with either of its component treatments. Fluticasone/salmeterol led to better quality of life compared with placebo (two studies), although there were conflicting results when compared with inhaled corticosteroid alone (two studies). There was no significant difference between fluticasone/salmeterol and long-acting beta-agonist (two studies). Budesonide/formoterol led to statistically significant differences in quality of life compared with placebo, but not when compared with component inhaled corticosteroid or beta-agonist (one study). REVIEWER'S CONCLUSIONS: For the primary outcome of exacerbations, budesonide/formoterol had a modest advantage over a component medication, formoterol, in a single trial, but fluticasone/salmeterol did not result in a significant reduction in exacerbations compared to either of its components. The combination of steroids and long-acting beta-agonist in one inhaler was effective in improving symptoms compared with placebo and on certain clinical outcomes compared with one of the individual components alone. In order to draw firmer conclusions about the effects of combination therapy in a single inhaler more data are necessary, including the assessment of the comparative effects with separate administration of the two drugs in double-dummy trials.

Adrenergic beta-Agonists↗
PubMed1993

Inhalation of particulate lead oxide disrupts pulmonary macrophage-mediated functions important for host defense and tumor surveillance in the lung.

Lead, an immunomodulator and potential human carcinogen, is a major airborne pollutant in industrial environments which poses a serious threat to human health. Despite the wide-spread occurrence of respirable lead particles in the air, and the potential human health risks, effects associated with inhalation of particulate lead on the the lung have been poorly studied. This study was performed to determine whether inhalation of particulate lead oxide (PbO), at a concentration below the currently acceptable air lead standard for occupational exposure, disrupts macrophage (M phi) functions important for maintaining pulmonary immunocompetence. These functions include phagocytosis, production of reactive oxygen intermediates, and the biological activity of tumor necrosis factor-alpha (TNF-alpha). Rabbits exposed to PbO at 30 micrograms/m3 for 4 days (3 hr/day) were sacrificed and their lungs lavaged immediately, 24 hr, and 72 hr after the final exposure. Lactate dehydrogenase (a marker of lung cell damage) and lysozyme activity (a marker of lysosome permeability), measured in the lavage fluid, were significantly increased 24 and 72 hr after exposure. PbO produced neutrophil infiltration nor effects on M phi viability or total numbers. Effects on M phi functions were as follows. Phagocytic uptake of latex particles was reduced with increasing post-exposure time reaching a maximum inhibition at 72 hr. Inhalation of PbO enhanced hydrogen peroxide (H2O2) and superoxide anion radical (O2-) production in a time-dependent manner; effects on H2O2 began at 24 hr and were persistent up to 72 hr. Effects on TNF-alpha release/activity appeared earliest and were persistent up to 72 hr. Immediately and 24 hr after exposure, lipopolysaccharide-stimulated activity of TNF-alpha was depressed by 62 and 50%, respectively; after 72 hr, TNF-alpha release was significantly enhanced compared to control levels. Results demonstrate that the lung is a sensitive target for the toxic effects of inhaled lead. This study provides the first evidence that inhalation of particulate lead, at an occupationally relevant concentration, and in the absence of elevated blood lead levels, alters pulmonary M phi functions critical for lung defense against inhaled antigens. Our findings may have important implications for human health and should be considered when evaluating the health risks associated with inhaled lead.

Air Pollutants↗
PubMed2002

Multiple-deep-breath inhalation induction with 5% sevoflurane and 67% nitrous oxide: comparison with intravenous injection of propofol.

PURPOSE: To evaluate the clinical characteristics of multiple-deep-breath inhalation induction with sevoflurane and nitrous oxide followed by the same inhalational anesthetics for maintenance, we compared the technique with intravenous propofol anesthesia. METHODS: Forty patients scheduled for ophthalmic surgery under general anesthesia with a laryngeal mask airway (LMA) were assigned to two groups. Anesthesia was induced with multiple-deep-breath inhalation of 5% sevoflurane and 67% nitrous oxide in oxygen (group S: n = 20) or intravenous injection of 1% propofol at the rate of 1200 ml.h(-1) with spontaneous inhalation of 67% nitrous oxide in oxygen until the patient lost consciousness or received propofol up to 2 mg.kg(-1) (group P: n = 20). We attempted to insert an LMA when the patient's jaw relaxation was adequate. We compared induction times, recovery times, occurrence of adverse events, and patient satisfaction between the two groups. RESULTS: The mean time to insertion of the LMA was significantly shorter in group P (209 +/- 118 s) than in group S (302 +/- 102 s; P < 0.05). The recovery times did not differ significantly between the groups. There were no serious side effects during the induction and recovery period in either group. Significantly more patients in group P than in group S wanted to have the same anesthetic method (90% vs 50%; P < 0.05). CONCLUSION: Multiple-deep-breath inhalation induction with 5% sevoflurane and 67% nitrous oxide followed by the same inhalational anesthetics for maintenance was safely performed without serious adverse events. However, the induction time was shorter and patient satisfaction was higher in propofol group than in the inhalational group.

Journal Article↗
PubMed1994

Endothelin release and enhanced regional myocardial ischemia induced by cold-air inhalation in patients with stable angina.

This study was designed to determine the influence of cold-air inhalation on regional myocardial perfusion in patients with ischemic heart disease. A selected group of vasoactive hormones was measured to investigate their possible roles as ischemic agents. Ten men who had recently had a myocardial infarction and anginal symptoms and with verified pathologic ST deviations during a preceding exercise test volunteered to participate in this randomized cross-over study. Two identical exercise tests were performed on different days; one with inhalation of cold (-22 degrees C) air and the other one with inhalation of thermoneutral air (22 degrees C). Scintigraphic imaging (single-photon emission computed tomography) of regional myocardial blood flow was performed with technetium 99m isonitrile flowtracer and a Bull's eye visual display with calculation of the scintigraphic ischemic severity score. The score was significantly higher during exercise with inhalation of cold air as compared to exercise with inhalation of thermoneutral air. Furthermore, only with cold-air inhalation did arterial plasma endothelin concentration increase significantly from rest to exercise and correlate with the change of ischemic severity score. In contrast, no change was observed under thermoneutral conditions. There was no significant difference between peak values of heart rate, systolic blood pressure, adrenaline, and noradrenaline concentrations in the two situations. We conclude that inhalation of cold air during exercise increases the degree of regional myocardial ischemia and that this is not caused by an increased myocardial oxygen demand. We suggest that cold air directly influences the vasomotor tone of the myocardial resistance vessels and that endothelin may be involved in the ischemic response.

Adult↗
PubMed1983

Interactions between selenium and mercury in mice: marked retention in the lung after inhalation of metallic mercury.

The distribution of 203Hg after inhalation of radioactive metallic mercury (4.3 mumol 203Hg0/kg body wt. for 1 h) was studied in saline (control) and selenite (10 mumol/kg body wt. intraperitoneally, i.p.) pretreated male C57BL mice by means of whole-body autoradiography and scintillation counting. Selenite pretreatment did not apparently change the immediate uptake and distribution of 203Hg (presumably inorganic Hg after oxidation in the different organs) but markedly increased the retention time in the whole body. The most marked retention was seen in the lungs where the selenite-pretreated animals had 200 times higher concentration as compared to control animals 14 days after inhalation. In other organs the corresponding value ranged between 1 (brain) and 12 (spleen). Selenite-pretreated and control animals showed the same low rate of exhalation of 203Hg after the inhalation period, while the latter animals eliminated significantly more through the urine and faeces (measured only during the first 24 h). When inversely radioactive selenite (75Se-selenite) was injected i.v. into animals 1 h earlier exposed to non-radioactive Hg0 (by inhalation), the lung concentration of 75Se after 24 h was 4 times higher than that of control animals. When radioactive mercury was injected i.v. in the form of 203HgCl2 (4.3 mumol/kg body wt.), selenite (10 mumol/kg body wt., i.p.) increased the retention time in the body, more so than after 203Hg0 inhalation. In this case the mercury was retained especially in the serum, red pulp of the spleen and liver (reticulo-endothelial system). 75Se-selenite injected i.v. after i.p. administration of non-radioactive HgCl2 in the same doses as above similarly accumulated more in serum, spleen and liver as compared to control animals. It is presumed that while injected selenite and inorganic mercury (Hg2+) interact strongly in the serum, increasing each other's uptake and retention especially in the reticulo-endothelial system, inorganic mercury retained in various organs after oxidation of Hg0 upon inhalation interacts with selenium mainly intracellularly. This occurs especially in the lungs, where initially high concentrations of mercury are found after inhalation.

Animals↗
PubMed1984

Lung retention and metabolic fate of inhaled benzo(a)pyrene associated with diesel exhaust particles.

Polycyclic aromatic hydrocarbons (PAHs) are a class of compounds considered to have human carcinogenic potential and have been found associated with many respirable, environmental particle pollutants. The effect of these ultrafine, insoluble, carrier particles on the lung retention and metabolic fate of inhaled PAHs was investigated with a radiolabeled model PAH, [3H]benzo(a)pyrene (3H-BaP). Fischer-344 rats were exposed (30 min) by nose-only inhalation to 3H-BaP adsorbed (approximately 0.1% by mass) onto diesel engine exhaust particles. These aerosols were generated in a dynamic aerosol generation system by vapor condensation methods. The total mass concentration of these aerosols was 4-6 micrograms/liter of air with a mass median diameter of 0.14 micron. Lung clearance of the inhaled particle-associated 3H radioactivity occurred in two phases. The initially rapid clearance of this inhaled radiolabel had a half-time of less than 1 hr. The second, long-term component of lung clearance had a half-time of 18 +/- 2 days and represented 50 +/- 2% of the 3H radioactivity that had initially deposited in lungs. In contrast, previous inhalation studies with a pure 3H-BaP aerosol showed that greater than 99% of the 3H radioactivity deposited in lungs was cleared within 2 hr after exposure (Sun et al., Toxicol. Appl. Pharmacol. 65, 231-244, 1982). By HPLC analysis, the majority of diesel soot-associated 3H radioactivity retained in lungs was BaP (65-76%) with smaller amounts of BaP-phenol (13-17%) and BaP-quinone (5-18%) metabolites also being detected. No other metabolites of BaP were detected in lungs of exposed rats. Tissue distribution and excretion patterns of 3H radioactivity were qualitatively similar to previous inhalation studies with 3H-BaP coated Ga2O3 aerosols (Sun et al., 1982). These findings suggest that inhaled PAHs may be retained in lungs for a greater period of time when these compounds are associated with diesel engine exhaust particles. In addition, these compounds retained in lungs can be metabolized in lungs. These results may have significant implications for the health risks that may be involved with human exposure to particle-associated organic pollutants.

Aerosols↗
PubMed1984

A physiologically based description of the inhalation pharmacokinetics of styrene in rats and humans.

A physiologically based pharmacokinetic model which describes the behavior of inhaled styrene in rats accurately predicts the behavior of inhaled styrene in humans. The model consists of a series of mass-balance differential equations which quantify the time course of styrene concentration within four tissue groups representing (1) highly perfused organs, (2) moderately perfused tissues such as muscle, (3) slowly perfused fat tissue, and (4) organs with high capacity to metabolize styrene (principally liver). The pulmonary compartment of the model incorporates uptake of styrene controlled by ventilation and perfusion rates and the blood:air partition coefficient. The metabolizing tissue group incorporates saturable Michaelis-Menten metabolism controlled by the biochemical constants Vmax and Km. With a single set of physiological and biochemical constants, the model adequately simulates styrene concentrations in blood and fat of rats exposed to 80, 200, 600, or 1200 ppm styrene (data from previously published studies). The simulated behavior of styrene is particularly sensitive to changes in the constants describing the fat tissue group, and to the maximum metabolic rate described by Vmax. The constants used to simulate the fate of styrene in rats were scaled up to represent humans. Simulated styrene concentrations in blood and exhaled air of humans are in good agreement with previously published data. Model simulations show that styrene metabolism is saturated at inhaled concentrations above approximately 200 ppm in mice, rats, and humans. At inhaled concentrations below 200 ppm, the ratio of styrene concentration in blood to inhaled air is controlled by perfusion limited metabolism. At inhaled concentrations above 200 ppm, this ratio is controlled by the blood:air partition coefficient and is not linearly related to the ratio attained at lower (nonsaturating) exposure concentrations. These results show that physiologically based pharmacokinetic models provide a rational basis with which (1) to explain the relationship between blood concentration and air concentration of an inhaled chemical, and (2) to extrapolate this relationship from experimental animals to humans.

Administration, Oral↗
PubMed1976

Betamethasone valerate compared by the oral and inhaled routes in childhood asthma.

The value of betamethasone valerate by inhalation in the prophylactic therapy of severe childhood asthma has been established. To determine whether the efficacy of this drug is due to a local or a systemic action a double-blind crossover study of 28 days' treatment with oral betamethasone valerate and 28 days' treatment with inhaled steroid was carried out in 10 asthmatic children. Daily doses used were 1 mg orally and 800 mug by inhalation. Nine patients had fewer symptoms, higher peak expiratory flow rates, and a lower bronchodilator requirement on inhaled than on oral therapy. Exercise-induced bronchoconstriction was diminished on inhaled therapy. Five children requested early termination of the oral therapy period because of unacceptable symptoms. Nine parents stated a preference for the period of inhaled therapy. It is concluded that betamethasone valerate is highly effective by inhalation but that a comparable oral dose has no appreciable clinical effect.

Administration, Intranasal↗
PubMed1983

Inhaled verapamil in histamine-induced bronchoconstriction.

Fifteen asthmatic subjects participated in a double-blind trial comparing the protective effects of inhaled verapamil, salbutamol, and saline against inhaled histamine. Inhaling verapamil between four repeated histamine inhalation tests produced no significant protection against histamine-induced bronchoconstriction, while there was significant protection with salbutamol (p less than 0.001). Inhaling verapamil before a single inhalation test produced limited but significant protection (p less than 0.05) compared with a saline control in eight asthmatic subjects. This small protective effect in the two-treatment study of eight asthmatics suggests that either the protective effect of verapamil is variable among subjects or a preceding histamine inhalation test blocks the verapamil effect.

Adult↗
PubMed1985

Inhaled corticosteroid therapy: a substitute for theophylline as well as prednisolone?

Topical corticosteroid treatment can be successfully achieved by inhaled therapy and can effectively provide a safe substitute for oral steroids. More than 8 million patient years of experience gained over a decade of use of inhaled steroids has shown them to be acceptable to patients and clinicians, with side effects confined to the upper airway. At daily doses of 200 to 1600 micrograms BDP or the equivalent, minor systemic activity may occasionally be demonstrated but no adverse systemic side effects have been reported. The topical anti-inflammatory treatment provided by inhaled steroids thus compares favorably with prednisolone and with other asthma therapy with respect to morbidity and mortality, suggesting that inhaled steroids combined with an inhaled beta-agonist is a safe and comprehensive treatment for chronic asthma. This parallel attack on inflammation and bronchoconstriction can be achieved with a morbidity that is much less than that of asthma and also likely to be less than that of the frequently used combination of theophylline and inhaled beta-agonist. Twice-daily regimens of inhaled steroids over a dose range of 200 to 1600 micrograms BDP or the equivalent should enable most patients with chronic asthma to receive effective therapy without recourse to potentially more toxic oral bronchodilator or steroid therapy.

Adrenal Cortex Hormones↗
PubMed2004

Effect of particle morphology on the triboelectrification in dry powder inhalers.

Electrostatic charge of lactoses of different particle morphology and amorphous contents were measured during actuation from two different dry powder inhalers (DPIs). Triboelectric studies may give important information when new inhaler devices, materials and formulations are designed in order to improve the drug deposition. Two inhalers, Taifun (Focus Inhalation Oy, Finland) and Clickhaler (Innovata Biomed Ltd., UK) were filled with lactose powders which were spray dried from different solutions or suspensions of lactose, ethanol and water. Differences in the amorphous contents were determined with isothermal microcalorimetry (IMC) and X-ray diffraction (XRD) and the particle morphology was examined with laser diffraction and electron microscopy (SEM). Samples were actuated from the inhalers at given intervals into the Faraday pail and the generated charges were recorded. Increase in the water concentration of the feed suspension had negligible effect on the charging until it exceeded 70%. Reproducibility of the measurement was found to be better with samples of homogenous particles and higher crystallinity while more amorphous samples with different morphology and wide particle size distribution showed change in the sign of the charge in addition to higher variations of the magnitude. In this study we show that different inhalers, as well as the morphology of the lactose powder, has noticeable effects on the generated charge which has previously been shown to affect the deposition of the drug and the function of an inhaler.

Crystallization↗
PubMed2006

The effect of carrier surface treatment on drug particle detachment from crystalline carriers in adhesive mixtures for inhalation.

In this study, the effect of lactose carrier surface treatment on drug particle detachment during inhalation has been investigated. Crystals of marketed brands of alpha lactose monohydrate brands normally exhibit a certain surface rugosity and contain natural fines and impurities on their surface, which influence the drug-to-carrier interaction in adhesive mixtures for inhalation. Submersion treatment may change these surface characteristics. Two different sieve fractions (63-90 and 250-355microm) were submerged in mixtures of ethanol and water (96 and 80% v/v, respectively). Microscopic observation and laser diffraction analysis revealed that neither the shape nor the size of the carrier particles was changed by the submersion treatment. However, the specific surface area and the amount of impurities appeared to decrease substantially after submersion, and the magnitude of the decrease was different for the different ethanol-water mixtures. The reduction in specific surface area was attributed particularly to the removal of the adhering lactose fines from the carrier surface. Mixtures with budesonide (in a wide range of carrier payloads) were prepared before and after treatment. Drug particle detachment from the various mixtures was studied with a sieve test and with a cascade impactor analysis at 30 and 60l/min. Two different types of inhalers were used, one generating lift- and drag-forces (ISF inhaler) and one generating inertial forces (test inhaler), respectively. The cascade impactor and sieve test experiments showed that an increase in carrier surface smoothness results in a reduced drug particle detachment during inhalation, which was independent of the type of inhaler used. This reduction could be attributed to the removal of the adhering lactose fines which may provide shelter for the drug particles from press-on forces during mixing.

Bronchodilator Agents↗
PubMed1997

Variable response to inhaled nitric oxide after cardiac surgery.

BACKGROUND: Inhaled nitric oxide (NO) is a promising therapy that may be valuable in the control of pulmonary hypertension in cardiac surgical patients. Patients with valvular heart disease have remodeling of the pulmonary vascular bed that contributes to pulmonary hypertension. The purpose of this study was to compare the efficacy of inhaled NO in cardiac surgical patients with pulmonary hypertension with and without valvular heart disease. METHODS: The effect of inhaled NO (40 ppm) on pulmonary hemodynamics in patients with pulmonary hypertension (mean pulmonary artery pressure > or = 30 mm Hg) was studied in the operating room after cardiac operation. Fifteen patients with valvular heart disease comprised the study group; 25 patients undergoing aortocoronary bypass grafting were controls. RESULTS: In patients undergoing aortocoronary bypass grafting, inhaled NO produced a 24% decrease in mean pulmonary artery pressure (33 +/- 1 to 25 +/- 1 mm Hg; p < 0.05), a 36% decrease in pulmonary vascular resistance (375 +/- 30 to 250 +/- 30 dyne.s.cm-5; p < 0.05), and no change in systemic arterial blood pressure. On the other hand, patients with pulmonary hypertension from valvular heart disease did not respond to inhaled NO: mean pulmonary artery pressure was 39 +/- 3 mm Hg and pulmonary vascular resistance was 620 +/- 30 dyne.s.cm-5 before, during, and after NO. CONCLUSIONS: Among cardiac surgical patients with pulmonary hypertension, the response to inhaled NO is variable. Despite the promise of inhaled NO as a pulmonary vasodilator in cardiac surgical patients, these data suggest that alternative therapies are needed to control pulmonary hypertension in patients with pulmonary hypertension from valvular heart disease.

Aged↗
PubMed1984

Inhaled therapy reduces morning dips in asthma.

14 asthmatic patients with nocturnal symptoms and morning dips in peak expiratory flow rate (PEFR) were treated with regular inhaled salbutamol for 1 or 2 weeks, followed by regular inhaled beclomethasone dipropionate, in addition to salbutamol, for a further 2 weeks. Mean PEFR rose to normal values in all but 1 patient. Morning dips in PEFR were substantially reduced in 8 patients. There was an equivalent rise in mean PEFR in the other 6 patients, but their morning dips did not improve. Inhaled salbutamol reduced the dips in the responsive patients, but addition of inhaled steroid produced further improvement. Inhaled beta agonist alone improved mean PEFR in these patients, but inhaled steroids produced most of the improvement in the other subgroup. No patient experienced side-effects. Thus mean PEFR can be improved and morning dips in PEFR reduced in a high proportion of asthmatic patients by the use of regular inhaled therapy without resorting to less-well-tolerated oral agents.

Adolescent↗
PubMedDate not supplied

Fate of inhaled hexachlorocyclopentadiene in albino rats and comparison to the oral and IV routes of administration.

Hexachlorocyclopentadiene (C56) is extremely toxic when inhaled by rats, but only moderately toxic when administered orally. The difference in toxicity as a function of route of exposure was studied by determining the absorption, distribution, and ultimate fate of C56 following acute oral, inhalation, and iv exposure. For rats treated with a single oral dose (5 micrograms/kg) of 14C-C56, radiocarbon was primarily excreted in the 0-72 hr feces (68.2%). Animals treated with equivalent inhaled and iv doses eliminated 23.1 and 31.4% of the dose in the 0-72 hr feces, respectively. Urinary radiocarbon was equivalent to 24.4, 23.1, and 31.4% of the dose for oral, inhalation and iv treatments, respectively. Biliary excretion following all exposure routes was between 9 and 18% of the dose, indicating that the large amount of radiocarbon in the feces of orally treated rats was due to poor absorption of C56 from the gastrointestinal tract. For all exposure routes, the lungs appeared to be a major site of C56 toxicity upon post-mortem examination. This study suggests that the direct damage to lung tissue by inhaled C56 and low bioavailability of orally administered C56 contribute substantially to the difference in toxicity between oral and inhalation exposure to C56. A recently developed inhalation exposure system which allows quantitative administration of toxicant vapors to rats is also described in this report.

Administration, Oral↗