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Inhalant abuse by adolescents.

The deliberate misuse of volatile substances poses a poorly recognized risk for considerable morbidity and mortality in adolescent populations worldwide. The abuse of inhalants continues to be a significant problem among our country's youth. While many household and industrial chemicals can be inhaled, glues, paints, and aerosol propellants are among the most commonly abused. Adolescents are often unaware of the health threats posed by inhalation of solvents. Inhalation can result in serious organ system dysfunction or even sudden death. This review discusses the prevalence of inhalant abuse in the United States, summarizes the various types of substances used, highlights the major physiologic effects of inhalants, and briefly discusses associated risk behaviors, prevention and medical management.

Administration, Inhalation↗

Clinical applications of inhaled nitric oxide in children with pulmonary hypertension.

We have presented our experience with the use of inhaled nitric oxide in children with congenital heart disease and pulmonary hypertension, which indicates that nitric oxide is a selective pulmonary vasodilator that may improve patient management, particularly after surgical procedures requiring cardiopulmonary bypass. Indeed, we have now seen several patients in whom all resuscitative maneuvers for the treatment of pulmonary hypertensive crises were unsuccessful until inhaled nitric oxide was added to the therapeutic regimen. In addition, our studies using inhaled nitric oxide as an investigational probe point toward endothelial injury as a contributor to post-cardiopulmonary bypass pulmonary vasoconstriction. Inhaled nitric oxide relieves pulmonary vasoconstriction associated both with left atrial or pulmonary venous hypertension and following the relief of mitral valve or pulmonary venous obstruction. Absence of a response on the usually reactive pulmonary vascular bed of the neonate should prompt a careful search for anatomic, and possibly surgically remediable, pulmonary vascular obstruction. In the short term nitric oxide is less effective in the older patient with obliterative pulmonary vascular disease. It is possible that recent experimental work with long-term nitric oxide inhalation might be applicable to this group of patients. Nitric oxide may have a unique role in the management of the patient after lung transplantation, as it both reduces right ventricular afterload and improves intrapulmonary shunting. Is nitric oxide the ideal agent for testing pulmonary vascular reactivity? Nitric oxide is simple to deliver by either mask or ventilator and, as a trial of vasoreactivity over 15 min, remains free of side effects that might be encountered during long-term administration, such as methemoglobinemia or nitrogen dioxide toxicity. Indeed, no patient developed significant methemoglobinemia after a trial of nitric oxide and neither was a level of nitrogen dioxide above 1 ppm registered during the administration. Thus, nitric oxide gas fulfills many of the ideal characteristics, as suggested by Rubin,92 required of a drug to test the acute responsiveness of the pulmonary circulation. It has better pulmonary dilating effects than systemic, a short half-life, and minimal adverse effects and it can be both easily and quickly administered. Whether it is able to reliably predict the effect of long-term administration of orally active agents awaits confirmation. Certainly, inhaled nitric oxide is rapidly becoming the standard agent to test pulmonary vascular reactivity during diagnostic cardiac catheterization at our institution.

Administration, Inhalation↗

Once-daily budesonide inhalation suspension in infants and children < 4 and > or = 4 years of age with persistent asthma.

BACKGROUND: Budesonide inhalation suspension (Pulmicort Respules; AstraZeneca LP, Wilmington, DE), a nebulized corticosteroid, was developed for use in infants and young children with persistent asthma. OBJECTIVE: To compare the efficacy and safety of once-daily budesonide inhalation suspension in children < 4 years of age and in those > or = 4 years of age with persistent asthma. METHODS: A retrospective analysis stratified by age group was performed on data from two randomized, double-blind, placebo-controlled, parallel-group studies that evaluated the efficacy and safety of budesonide inhalation suspension 0.25 mg, 0.5 mg, or 1.0 mg once daily for 12 weeks in children 6 months to 8 years of age with persistent asthma. Clinical assessments included nighttime and daytime asthma symptoms, breakthrough medication use, adverse events, and hypothalamic-pituitary-adrenal-axis function. RESULTS: In both randomized studies, budesonide inhalation suspension demonstrated statistically significant improvement in nighttime and daytime asthma symptom scores compared with placebo. In the retrospective analysis of pooled data from these studies, the efficacy of budesonide was maintained when children were stratified by age group. Clinical improvements from baseline in nighttime and daytime asthma symptom scores were observed in both age groups at all budesonide inhalation suspension dose levels. No significant differences were observed between age groups in breakthrough medication use in any of the treatment groups. No differences were observed in the incidence of adverse events between the two age groups, and significant (P < 0.01) effect on hypothalamic-pituitary-adrenal-axis function was apparent only in children < 4 years of age at the 0.25-mg dose level. CONCLUSIONS: Once-daily budesonide inhalation suspension is effective in the treatment of persistent asthma in children aged < 4 and > or = 4 years of age.

Administration, Inhalation↗

Body composition and growth in asthmatic children treated with inhaled steroids.

BACKGROUND: Prolonged treatment with inhaled steroids is recommended for long-term control of asthma in children; however, it can interfere with growth and body composition. OBJECTIVE: The aim of this study is to answer the question whether 6 months treatment with inhaled steroids causes body fat accumulation and growth velocity reduction. METHODS: Hospital-based, open study of body composition [by dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA) and skinfolds] and growth of 26 asthmatic children, treated for 6 months with inhaled steroids [budesonide (BUD) 400 microg/day (group 1) or fluticasone proprionate (FP) 200 microg/day (group 2)], sodium cromoglycate and beta2-agonist (salbutamol) compared with a control group of 16 asthmatic children treated only with sodium cromoglycate and beta2-agonist. RESULTS: On average, total and regional fat mass, adjusted for pubertal stage and gender, and growth velocity were similar in all three groups of patients and were not influenced by treatment (% mean change +/- 1 SD of fat mass during treatment in BUD 0.1 +/- 3.0%, FP -1.1 +/- 3%, and control -2.8 +/- 3.5%; ANOVA P > or = .05); however seven patients, two in group 1 (1 preschool child), three in group 2 (2 preschool children) and two in the control group (two prepubertal boys aged 8.5 and 9.5 year), during treatment, showed a growth velocity standard deviation score below the third percentile. CONCLUSION: A 6-month treatment with inhaled BUD and FP does not induce body fat accumulation; however, in a few preschool children the treatment was associated with growth velocity below the third percentile. Our results suggest the need for constant monitoring of growth in all asthmatic children on chronic treatment with inhaled steroids. Further studies devoted to the effects of inhaled steroids use in preschool children are needed.

Administration, Inhalation↗

Analysis of induced sputum to examine the effects of inhaled corticosteroid on airway inflammation in children with asthma.

BACKGROUND: Analysis of induced sputum can be performed safely in children with asthma and is useful for both cellular and biochemical markers of inflammation. Glucocorticosteroid inhalation has become the first line therapy for chronic asthma by suppressing airway inflammation, which produces the decrease of bronchial hyperreactivity and reduces the number of eosinophil in bronchial submucosa. OBJECTIVE: To determine the characteristics of the inflammatory cells and their markers in sputum and to examine the pharmacokinetic effects of glucocorticoid within 3 hours after inhalation therapy on FEV1 and sputum inflammatory indices in children with clinically defined chronic asthma. METHODS: Thirty subjects with asthma included 14 current symptomatic asthmatics and 14 normal controls inhaled 4.5% hypertonic saline for 10 minutes by nebulizer. The expectorated sputum were collected from all asthmatics before and 3 hours after corticosteroid inhalation for children with asthma and were reduced by dithiotreitol. Total cell counts and differentials were determined. ECP was measured by CAP system. Interleukin-5, GM-CSF and albumin were measured by double sandwich ELISA. RESULTS: The mean eosinophil percentage and ECP in induced sputum of asthmatics were significantly higher than that of controls. The induced sputum samples obtained after glucocorticoid inhalation showed a significant reduction in mean eosinophil percentage, but FEV1, IL-5, GM-CSF, albumin, and ECP values were not significantly decreased. CONCLUSION: The present results in induced sputum may be interpreted to reflect direct steroid action on airways and lack of effect on bone marrow effectors at 3 hours after glucocorticoid inhalation.

Administration, Inhalation↗

Increased perception of dyspnea by inhalation of short acting beta2 agonist in patients with asthma of varying severity.

BACKGROUND: Poor perception of dyspnea in asthma may lead to a delay in starting appropriate treatment which is probably one of the factors contributing to death from asthma. OBJECTIVE: This study was carried out to determine whether impaired perception of dyspnea in patients with asthma of varying severity can be corrected by inhalation of short acting beta2 agonist treatment. METHODS: We enrolled 20 patients with asthma of varying severity. Forced expiratory volume in one second (FEV1) was measured before and 10 minutes after two puffs of salbutamol administered by metered dose inhaler. Perception of dyspnea was scored on the Borg scale during breathing through an inspiratory muscle trainer. RESULTS: After inhalation of short acting beta2 agonist treatment, the baseline Borg score was decreased significantly from 2.20 +/- 0.32 to 1.80 +/- 0.31 (P < .01). The Borg score during breathing with the highest resistance, on the contrary, was increased significantly from 6.25 +/- 0.35 to 6.90 +/- 0.35 after inhalation of short acting beta2 agonist treatment (P < .01). Highest resistance-induced score difference from the baseline value (highest resistance-load score) was increased significantly from 4.10 +/- 0.46 to 5.25 +/- 0.42 (P < .01). There was no relationship between the change of Borg score from baseline value at each resistive load and the % change of FEV1 after inhalation of short acting beta2 agonist treatment. CONCLUSION: These studies demonstrate that inhalation of short acting beta2 agonist treatment decrease dyspnea, but increase perception of dyspnea induced by a resistive load in patients with asthma, and the mechanism of the increased perception may not be related to the increased airflow rate. It may be due to some local or central effects of bronchodilator drug on perception of asthma.

Administration, Inhalation↗

Clinical adverse effects of inhaled corticosteroids: results of a questionnaire survey of asthma specialists.

BACKGROUND: Inhaled corticosteroids are recognized as the mainstay of prophylactic anti-inflammatory therapy in patients with persistent asthma. In large multiclinic trials, the clinical adverse event profiles have been not significantly different than patients treated with placebo or other medications; however, in small studies evaluating very sensitive in vitro measurements of the hypothalamic pituitary adrenal axis there have been adverse laboratory events noted with moderate and high doses of inhaled steroids. OBJECTIVE: To survey asthma specialists in North America with regard to their personal clinical experience of adverse events with the use of inhaled corticosteroids. METHODS: Two hundred thirteen physicians specializing in the treatment of asthma responded to questionnaires asking their experiences with specific adverse clinical events that have the potential to occur after the use of inhaled corticosteroids (see appendix A for questionnaire). RESULTS: There was a 67% response rate for the questionnaire. Eighty percent of the respondents were allergists/immunologists and 20% were pulmonologists. The average length of time they had been in practice was 16 years. In general, side effects from inhaled steroids were seen very infrequently in the hands of these physicians in spite of the fact that they were primarily secondary or tertiary referral physicians for the treatment of asthma. The local oropharyngeal adverse events were seen 48% of the time on an occasional basis but only 3% of the time on a frequent basis. When spacers were used the oropharyngeal symptoms were reduced significantly. Skin changes such as bruising or thin skin were seen frequently 6% of the time and occasionally 24% of the time only. In general, these skin changes were found in elderly or middle-aged individuals. Weight gain was very unusually seen, as were adverse effects on bone (osteoporosis, fractures, growth problems, etc.). Hypothalamic pituitary axis abnormalities were seen quite infrequently and primarily in patients who had also received oral corticosteroids. CONCLUSIONS: This study shows that inhaled corticosteroids are generally safe in the treatment of asthma and are rarely associated with systemic side effects, as detected in routine clinical practice.

Administration, Inhalation↗

Esophageal candidiasis as a complication of inhaled corticosteroids.

BACKGROUND: Oropharyngeal candidiasis is a well-described side effect of inhaled corticosteroids. Nevertheless, few cases of esophageal candidiasis have been reported. OBJECTIVE: To present a patient with esophageal candidiasis associated with inhaled corticosteroids. METHODS: Case report. RESULTS: Our patient is a 70-year-old white woman with a 20-year history of intrinsic asthma, well controlled on triamcinolone acetonide 400 micrograms, ipratropium bromide 36 micrograms, and pirbuterol acetate 400 micrograms, each inhaled four times daily. She reported no oral steroid use for > 4 years and that she always rinsed her mouth following triamcinolone acetonide inhalation. The patient had gastritis with peptic ulcer disease in the past and developed worsening dyspeptic pain and heartburn. Following discontinuation of cimetidine and initiation of ranitidine without improvement, esophagogastroduodenoscopy was performed. Several small white patches in the mid and distal esophagus could not be removed with pressure. A biopsy confirmed the diagnosis of candidal esophagitis. Following a 4-week course of fluconazole, the patient was clinically improved and follow-up esophagogastroduodenoscopy was normal. There was no evidence of underlying cellular immunosuppression, malignancy, or diabetes mellitus and no history of recent antibiotic usage. Delayed skin tests revealed 5 x 5 mm induration to dermatophytin. Delayed hypersensitivity to Candida and mumps tests was absent. There was strong in vitro lymphocyte transformation and a positive immediate skin test response to Candida. ELISA for human immunodeficiency virus was negative. T and B cell counts were normal with CD4 = 630/mm3, CD8 = 520/mm3, and absolute B cell = 120/mm3. It is possible that this patient's immediate hypersensitivity response to Candida suppressed her delayed response. Candidal esophagitis is a rare, yet important, complication of inhaled corticosteroid use. CONCLUSION: Immunocompetent patients on inhaled corticosteroids with medically unresponsive symptoms of esophagitis should be investigated for esophageal candidiasis.

Administration, Inhalation↗

Comparison of three treatment regimens of inhaled sodium cromoglycate in the management of adult patients with severe, steroid-dependent asthma.

BACKGROUND: Asthmatic patients whose asthma remains poorly controlled despite treatment with high doses of inhaled corticosteroids and co-administration of oral corticosteroids are a difficult problem in therapeutics. OBJECTIVE: To investigate the relative efficacy of three treatment regimens of inhaled sodium cromoglycate in the treatment of adult, severe, corticosteroid-dependent patients as determined by the reduction in the dose of oral corticosteroids and change in lung function. METHODS: Open, randomized, group comparative trial of 12 weeks duration in asthmatic patients attending a hospital outpatient department. Patients whose asthma is (1) severe according to the classification of the Japanese Society of Allergology, (2) stable, and (3) needing treatment with at least 1600 microg of inhaled beclomethasone dipropionate and 5 mg or greater of oral prednisolone per day. The three treatment regimens of inhaled sodium cromoglycate were group A received sodium cromoglycate powder at a dose of 16 mg/day administered by a metered dose inhaler. Group N received sodium cromoglycate aqueous solution at a dose of 80 mg/day administered by a nebulizer. Group C received sodium cromoglycate aqueous solution (80 mg/day) combined with salbutamol (3 mg/day) administered by a nebulizer. The main outcome measures were a change in the daily dose of oral corticosteroids and in lung function with twice daily measurements of peak expiratory flow (PEF) recorded in the morning (PEF AM) and in the evening (PEF PM). RESULTS: Mean reduction in oral corticosteroid dose/day was group A, 3.68 mg (95% CI 1.35,5.95); group N, 3.59 mg (95% CI 0.73,6.45); and group C, 3.97 mg (95% CI 1.81,6.13). The dosage reductions are all significant but with no differences between the groups. The mean increase in PEF over the last 4 weeks of treatment compared with baseline values was significant in all groups. The increases in group C are significantly greater than those in the other groups. These changes are all significant and the increases in group C are significantly greater than those in the other groups. CONCLUSIONS: Inhaled sodium cromoglycate may be a useful additional treatment in the management of adult patients with severe, oral steroid-dependent asthma. Of the three methods of administration compared in this trial the most useful immediate results were obtained when the drug was administered as an aqueous solution mixed with salbutamol and delivered by a powered nebulizer.

Administration, Inhalation↗

A single dose of zafirlukast reduces LTD4-induced bronchoconstriction in patients on maintenance inhaled corticosteroid therapy.

BACKGROUND: Previous studies demonstrated that leukotriene receptor antagonists (LTRAs) are effective in reducing asthma symptoms and the airway response to inhaled leukotriene D4 (LTD4) in asthmatic patients receiving inhaled beta2-agonists alone. OBJECTIVE: To investigate the efficacy of a single 20-mg dose of the oral LTRA zafirlukast in reducing the airway response to inhaled LTD4 in mild-to-moderate asthmatic patients receiving inhaled beta2-agonists and inhaled corticosteroids (ICS). METHODS: In this double-blind, crossover trial, six patients on maintenance ICS (median dose 800 microg/day; range 336 to 1600 microg/day), who had a 20% decrease in FEV1 following inhalation of a maximal concentration of 50 microg/mL LTD4, received either zafirlukast or placebo on each of two study days. Two hours after dosing, patients underwent bronchoprovocation challenges with increasing concentrations of LTD4 (0.1 to 1000 microg/mL) at 10-minute intervals until either the patient's FEV1 decreased by 20% or the maximum concentration of LTD4 was given. Spirometric tests were done just before (baseline) and throughout the challenge phase until the patient's FEV1 returned to within 5% of baseline. Blood samples were collected two hours after dosing to determine plasma concentrations of zafirlukast. RESULTS: Compared with placebo, zafirlukast produced a 1.82-unit increase in logPC20FEV1 and a 1.88-unit increase in logPD20FEV1, representing a 66-fold higher concentration and a 76-fold higher dose of LTD4, respectively, to produce a 20% decrease in FEV1 (P < .001). Mean time to recovery after challenge was 36.7 versus 51.7 minutes when patients received zafirlukast and placebo, respectively. No correlation between clinical effects and plasma drug levels was observed. CONCLUSIONS: This trial demonstrated that asthmatic patients on maintenance ICS can respond to exogenously administered LTD4 and that zafirlukast reduced the airway response to LTD4 in these patients.

Administration, Inhalation↗

Adrenal suppression among asthmatic children receiving chronic therapy with inhaled corticosteroid with and without spacer device.

BACKGROUND: Inhaled corticosteroids have become a first-line treatment for chronic asthma. It has been shown that inhaled corticosteroids can have a measurable effect on the hypothalamic-pituitary-adrenal axis in asthmatic children. OBJECTIVE: To investigate the prevalence of adrenal suppression among asthmatic children receiving chronic therapy with low to moderate doses (up to 1000 micrograms) of inhaled beclomethasone dipropionate via a metered dose inhaler (MDI) and via MDI attached to a spacer device (MDI-spacer). METHODS: The study included 39 asthmatic children currently undergoing therapy; 24 received beclomethasone dipropionate by MDI attached to a spacer, and 15 directly by MDI. All the patients had been treated for at least 4 months. Another 21 children were normal controls. The 24-hour urinary free cortisol excretion was measured to evaluate hypothalamic-pituitary-adrenal axis function. RESULTS: Seven of 15 (47%) patients from the MDI group had reduced 24 hour-urinary free cortisol excretion and 2 of 24 (8%) in the MDI-spacer group (P = .006). The mean 24-hour urinary free cortisol excretion of the MDI group was 0.0185 +/- 0.0089 microgram/gram creatinine, and the MDI-spacer and the control groups were, 0.0290 +/- 0.0138 microgram/gram creatinine and 0.0270 +/- 0.0118 microgram/gram creatinine, respectively, (P = 0.37, f = 3.51 ANOVA). CONCLUSION: Chronic inhalation of low to moderate doses of corticosteroids is associated with adrenal suppression in some asthmatic children. This side effect is more common among patients inhaling directly from the MDI and is less frequent when a large volume spacer is attached to the MDI.

Administration, Inhalation↗

A new powder design method to improve inhalation efficiency of pranlukast hydrate dry powder aerosols by surface modification with hydroxypropylmethylcellulose phthalate nanospheres.

PURPOSE: A new particle design method to improve the aerosolization properties of a dry powder inhalation system was developed using surface modification of hydrophobic drug powders (pranlukast hydrate) with ultrafine hydrophilic particles, hydroxypropylmethylcellulose phthalate (HPMCP) nanospheres. The mechanism of the improved inhalation properties of the surface-modified particles and their deposits on carrier particles (lactose) was clarified in vitro. METHODS: Drug particles were introduced to aqueous colloidal HPMCP dispersions prepared by emulsion-solvent diffusion techniques followed by freeze- or spray-drying of the resultant aqueous dispersions. The surface-modified powders obtained with HPMCP nanospheres and their mixture with lactose powders were aerosolized by Spinhaler and their mode of deposition in lung was evaluated in vitro using a twin impinger. To elucidate the inhalation mechanism of these surface modified particles, we measured their modified micromeritic properties, such as surface topography, specific surface area, dissolution rate, and dispersibility in air. RESULTS: Dramatically improved inhalation properties of the surface modified powder, i.e. a two-fold increase in emission and a three-fold increase in delivery to deep lung, were found in vitro compared with the original unmodified powder. Improved inhalation was also found with the surface-modified drug deposited on lactose particles. Those improvements were attributed to the increased surface roughness and hydrophilicity of the surface-modified particles, and the resultant increased dispersibility in air. CONCLUSIONS: Surface modification of hydrophobic drug particles with HPMCP nanospheres to improve hydrophilicity was extremely useful in increasing the inhalation efficiency of the drug itself and the drug deposited on carrier; this was attributed to increased dispersibility in air and emission from the device, for spray- and freeze-dried particles, respectively.

Administration, Inhalation↗

Pharmacodynamic effects of inhaled dry powder formulations of fenoterol and colforsin in asthma.

The airway and tremor response and cardiovascular and hypokalemic effects of single doses of inhalative fenoterol dry powder capsules (0.4 mg) were compared with the fenoterol metered dose inhaler (0.4 mg) and colforsin (forskolin) dry powder capsules (10.0 mg), a direct activator of the adenylate cyclase system, in 16 patients with asthma. Subjects (FEV1 < or = 60% predicted) were investigated in a randomized, double-masked, placebo-controlled, four-period, crossover trial for a 120 minute period. All active drugs caused a significant increase in specific airway conductance (p < 0.05); the order of potency (mean +/- SEM maximum increase from baseline) was fenoterol metered dose inhaler (0.51 +/- 0.06 sec-1 x kPa-1), fenoterol dry powder capsules (0.49 +/- 0.07), and colforsin dry powder capsules (0.30 +/- 0.03). A marked increase in finger tremor amplitude resulted after fenoterol metered dose inhaler only (62.93% +/- 10.21%; p < 0.05) in contrast to fenoterol dry powder capsules (15.84% +/- 4.35%; p < 0.05) and colforsin dry powder capsules (12.87% +/- 10.44%; p > 0.05). A decrease in plasma potassium was found after fenoterol (metered dose inhaler > dry powder capsules; p < 0.05). In conclusion, fenoterol dry powder capsules caused less tremor response and hypokalemic effects than the metered dose inhaler, although the bronchodilator capacity was similar. Colforsin dry powder capsules resulted in a measurable bronchodilatation in patients with asthma.

Administration, Inhalation↗

Inhaling medicines: delivering drugs to the body through the lungs.

Remarkably, with the exception of anaesthetic gases, the ancient human practice of inhaling substances into the lungs for systemic effect has only just begun to be adopted by modern medicine. Treatment of asthma by inhaled drugs began in earnest in the 1950s, and now such 'topical' or targeted treatment with inhaled drugs is considered for treating many other lung diseases. More recently, major advances have led to increasing interest in systemic delivery of drugs by inhalation. Small molecules can be delivered with very rapid action, low metabolism and high bioavailability; and macromolecules can be delivered without injections, as highlighted by the recent approval of the first inhaled insulin product. Here, we review these advances, and discuss aspects of lung physiology and formulation composition that influence the systemic delivery of inhaled therapeutics.

Absorption↗

Orthodontic extractions: a comparative study of inhalation sedation and general anaesthesia.

OBJECTIVE: To compare directly inhalation sedation and general anaesthesia in terms of treatment success rate, various aspects of morbidity and time taken, when used for patients having orthodontic extractions. DESIGN: Patients requiring orthodontic extractions were treated with either inhalation sedation or general anaesthesia. The two groups were matched for age, sex, number of teeth extracted and pre-operative anxiety. Data were collected by questionnaires. SETTING: Unit of Paediatric Dentistry at the University Dental Hospital of Manchester. SUBJECTS: All patients referred for orthodontic extractions between November 1994 and May 1996 were invited to take part in the study. Total number of patients = 101. INTERVENTIONS: Sixty-six patients commenced treatment with inhalation sedation and 35 with general anaesthesia. Routine orthodontic extractions were carried out. OUTCOME MEASURES: Treatment success rate, various aspects of morbidity and total time taken were measured and compared for the two groups. RESULTS: Treatment success rates were high for both groups. Significantly less morbidity was found to be associated with inhalation sedation and the total time taken was significantly shorter with inhalation sedation than with general anaesthesia. CONCLUSIONS: Inhalation sedation is a successful alternative to general anaesthesia for orthodontic extractions with patients experiencing less morbidity and the time taken being shorter.

Anesthesia, Dental↗

Inhalation of activated protein C inhibits endotoxin-induced pulmonary inflammation in mice independent of neutrophil recruitment.

BACKGROUND AND PURPOSE: Intravenous administration of recombinant human activated protein C (rhAPC) is known to reduce lipopolysaccharide (LPS)-induced pulmonary inflammation by attenuating neutrophil chemotaxis towards the alveolar compartment. Ideally, one would administer rhAPC in pulmonary inflammation at the site of infection to minimize the risk of systemic bleeding complications. In this study, we therefore assessed the effect of inhaled rhAPC in a murine model of acute lung injury. EXPERIMENTAL APPROACH: Mice were exposed to LPS (0.5 mg kg(-1): intranasally) to induce acute lung injury. 30 minutes before and 3 hours after LPS exposure mice were subjected to vehicle or rhAPC inhalation (25 or 100 microg per mouse in each nebulization). In order to establish whether rhAPC inhalation affects neutrophil recruitment, neutrophil migration was determined in vitro using a trans-well migration assay. KEY RESULTS: rhAPC inhalation dose-dependently decreased LPS-induced coagulation and inflammation markers in bronchoalveolar lavage fluid (BALF), reduced protein leakage into the alveolar space and improved lung function. In contrast, rhAPC did not prevent LPS-induced neutrophil recruitment into the alveolar space. Neutrophil migration in vitro towards FCS or interleukin (IL)-8 was significantly inhibited by pretreatment with rhAPC (0.01-10 microg ml(-1)], whereas rhAPC (10 microg ml(-1)) added to the chemoattractant (modelling for topical rhAPC administration) did not affect neutrophil migration towards FCS or IL-8. CONCLUSIONS AND IMPLICATIONS: rhAPC inhalation significantly diminished LPS-induced pulmonary inflammation. The benefit of inhaled rhAPC appeared not to involve attenuation of neutrophil recruitment, in contrast to its effects after intravenous administration.

Administration, Inhalation↗

Inhaled nitric oxide in term and preterm infants.

Nitric oxide (NO) is a gas that has potent vasodilator properties. It can be administered via inhalation in situations where NO production is impaired and results in vasodilatation of the pulmonary capillaries. In term infants, the administration of inhaled NO, at a dose of 20 parts per million, may reduce the need for extracorporeal membrane oxygenation by reducing pulmonary vascular resistance and improving oxygenation. Inhaled NO is an approved therapy in term babies with severe hypoxemic respiratory failure. In premature infants, inhaled NO may increase bleeding time and decrease platelet aggregation resulting in an increased risk for intraventricular hemorrhage. Early administration of inhaled NO may also potentially decrease the risk for developing chronic lung disease in premature infants. However, since studies show conflicting results, inhaled NO should only be used in premature neonates following investigational review board approved protocols.

Administration, Inhalation↗

Determination of germanium in urine and its usefulness for biomonitoring of inhalation exposure to inorganic germanium in the occupational setting.

The present study aimed to assess whether urinary germanium concentration can be used as a biomarker of inhalation exposure to airborne dust from metallic germanium (Ge) or GeO2 in the occupational setting. A novel hydride generation-based method coupled with fow-injection graphite furnace atomic absorption spectrometry (HG/FI-GFAAS) was developed for the determination of urinary germanium. It was found that urinary germanium concentration could be reliably determined by a standard additions method after thorough digestion of the urine and careful pH adjustment of the digest. The limit of detection (LOD) in urine for the HG/FI-GFAAS method was 0.25 microg Ge L(-1). In Belgian control male subjects, the urinary germanium concentration was below this LOD. In 75 workers currently exposed to inorganic germanium compounds, respirable and inhalable concentrations of germanium in the aerosols were measured on Monday and Friday at the job sites using personal air samplers. Spot-urine samples were collected on the same days before and after the work shift. The germanium concentrations of respirable dust correlated very well with those of inhalable dust and represented 20% of the inhalable fraction. Workers exposed to metallic Ge dust were on average ten times less exposed to germanium than those whose exposure involved GeO2 (3.4 versus 33.8 microg Ge m(-3)). This difference was reflected in the urinary germanium concentrations (3.4 versus 23.4 microg Ge g(-1) creatinine). Regression analysis showed that the concentration of germanium in the inhalable fraction explained 42% of the post-shift urinary germanium concentration either on Monday or on Friday, whereas in a subgroup of 52 workers mainly exposed to metallic germanium dust 57% (r = 0.76) of the Monday post-shift urinary germanium was explained. Urinary elimination kinetics were studied in seven workers exposed to airborne dust of either metallic Ge or GeO2. The urinary elimination rate of germanium was characterised by half-times ranging from 8.2 to 18.1 h (on average 12 h 46 min). The present study did not allow discrimination between the germanium species to which the workers were exposed, but it showed fast urinary elimination kinetics for inhalation exposure to dust of metallic Ge and GeO2. It pointed out that urine samples taken at the end of the work shift can be used for biological monitoring of inorganic germanium exposure in the occupational setting.

Air Pollution, Indoor↗