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PubMed2006

Responsiveness to inhaled NO in isolated-perfused lungs from endotoxin-challenged rats is dependent on endogenous nitrite/nitrate synthesis.

BACKGROUND AND OBJECTIVES: In isolated-perfused lungs of lipopolysaccharide (LPS)-challenged rats, vasodilatation to inhaled nitric oxide (NO) is impaired. Inhibition of nitric oxide synthase 2 (NOS2) by aminoguanidine (AG) prevented hyporesponsiveness to inhaled NO. Here, we investigated whether NOS2-mediated nitrite/nitrate synthesis modulates responsiveness to inhaled NO. METHODS: Sprague-Dawley rats received intraperitoneally 0.5 mg kg(-1) LPS. Four hours later, LPS-treated rats received 3, 10 or 30 mg kg(-1) AG or 0.01, 0.1 or 1 mg kg(-1) S-methylisothiourea (SMT) by intraperitoneal injection. Sixteen to eighteen hours later, lungs were isolated and perfused, and pulmonary artery pressure (PAP) was elevated by 6-8 mmHg using the thromboxane analogue U46619. The decrease of PAP in response to inhaled NO and nitrate/nitrite levels in serum and perfusate was measured. RESULTS: In rats treated with LPS alone or 0.01 or 0.1 mg kg(-1) SMT, 40 ppm NO decreased PAP less than in rats treated with AG and 1 mg kg(-1) SMT (-1.8 mmHg (95% confidence interval: -1.5 to -2.1) vs. -6.0 mmHg (-5.7 to -6.3), P < 0.01). Improved NO responsiveness was associated with lower serum and perfusate nitrite/nitrate levels than in rats with hyporesponsiveness to inhaled NO (102 micromol (82-122) vs. 282 micromol (261-303) and 8.1 micromol (6.9-9.3) vs. 19.8 micromol (17.2-22.4), respectively, P < 0.01). CONCLUSIONS: These observations demonstrate that in isolated-perfused lungs of LPS-treated rats, NOS2 inhibition improved responsiveness to inhaled NO. Here, responsiveness to inhaled NO is dependent on the ability of NOS2 inhibitors to reduce nitrite and nitrate levels in serum and released in the lung.

Administration, Inhalation↗
PubMedDate not supplied

Comparison of inhaled metaproterenol via metered-dose and hand-held nebulization in prehospital treatment of bronchospasm.

INTRODUCTION: Although the efficacy of the administration of beta-adrenergic bronchodilators has been demonstrated, the best method available for the delivery of these drugs in the prehospital setting has not been defined. This paper compares the effects of administration of metaproterenol when administered by paramedics using either a metered-dose inhaler (MDI) or a hand-held nebulizer (HHN). HYPOTHESIS: There is no difference in the effects produced in patients suffering from smooth bronchiolar muscle spasm by metaproterenol when delivered either by a standard metered-dose inhaler or with a hand-held nebulizer. PARTICIPANTS: Consecutive prehospital patients complaining of difficulty breathing with clinical evidence of bronchospasm and with a history of asthma, chronic obstructive pulmonary disease, or emphysema who were not in extremis. METHODS: Prior to the administration of metaproterenol, a peak expiratory flow rate (PEFR) was obtained. This measurement was repeated five minutes following the conclusion of the administration of metaproterenol. Patients in Burbank, California, received the treatment using a standard metered-dose inhaler, and those in Madison, Wisconsin, received the drug using a hand-held nebulizer. Peak expiratory flow rates were compared using Student's t-tests with Bonferroni's correction. Statistical significance was set at p < 0.05. RESULTS: Data were collected from 36 consecutive patients by the paramedics of the Burbank Fire Department and from 32 consecutive patients by the paramedics of the Madison Fire Department. For the metered-dose inhaler group, the mean value for peak expiratory flow rate for the pre-treatment test was 95.4 +/- 88.1 l/min, and after treatment was 109.4 +/- 89.3 l/min (p < 0.001). For the hand-held nebulizer group, the mean value for peak expiratory flow rate before the administration of the metaproterenol was 96.1 +/- 76.3 l/min and following the treatment was 149.1 +/- 92.9 l/min (p < 0.001). The mean values for the differences between the control peak expiratory flow rate and the post-treatment peak expiratory flow rate for the metered-dose inhaler group was + 140.0 +/- 27.4 l/min, and for the hand-held nebulizer group was + 53.0 +/- 69.1 l/min (p < 0.003). CONCLUSIONS: In the prehospital setting, the administration of metaproterenol using a hand-held nebulizer is more effective than delivering the drug using a metered-dose inhaler. The hand-held nebulizer is easier to use and delivers a higher dose of the drug than is convenient using the metered-dose inhaler.

Administration, Inhalation↗
PubMed1990

A method for determination of the absolute pulmonary bioavailability of inhaled drugs: terbutaline.

Terbutaline sulfate (4 X 0.250 mg) was given to 11 healthy volunteers by inhalation from a metered dose inhaler (MDI), with and without oral administration of a charcoal slurry. Before the inhalations, the adsorbing capacity of the charcoal slurry was tested. Deuterated terbutaline, 0.125 mg, was given intravenously at the same time as the test doses. The charcoal slurry adsorbed 97% of an oral dose. The oral contribution to the overall systemic bioavailability after inhalation, when charcoal was coadministered, could thus be neglected. After inhalation of terbutaline, 9.1% of the dose was deposited in the lungs and an additional 6.7% was systemically available via the oral route. The method presented measures the absolute pulmonary bioavailability after inhalation from a MDI. Since a deuterated analogue is given intravenously together with the inhalations, fewer subjects are needed to obtain reliable data.

Administration, Inhalation↗
PubMed1999

The effect of intranasal and inhaled corticosteroids in healthy volunteers on the number of circulating lymphocytes and lymphocyte subsets.

BACKGROUND: There has been an increasing interest in the potential systemic effects of inhaled corticosteroids. METHODS: The effect of locally inhaled corticosteroids in the nose and lung on blood lymphocytes was measured in two studies. In the first study, budesonide (BUD) (200 and 800 microg), fluticasone propionate (FP) (200 and 800 microg), and placebo were administered in the nose, and BUD (1600 microg) and FP (1500 microg) were inhaled into the lungs in a blinded, randomized fashion by 12 healthy volunteers. Blood samples were taken before and 4 h after the administration of the drug, and total lymphocyte count and different subpopulations were determined. In the second study, 15 healthy volunteers were randomized to BUD (1600 microg), FP (1600 microg), or placebo inhaled into the lungs. Blood samples were taken before and 4, 8, 24, 48, and 148 h (=7 days) after inhalation of the medication. RESULTS: Neither the nasal applications nor the inhalation of FP (1500 microg/1600 microg) showed significant differences in total lymphocyte count or different subpopulations between baseline and 4 h after the administration. In both studies, a significant reduction was found in the total lymphocyte count, B cells, T cells, and the CD4+ and the CD8+ fractions 4 h after application of BUD 1600 microg. CONCLUSIONS: Nasal application of BUD or FP in doses up to 800 microg do not induce lymphopenia. BUD 1600 microg inhalation in the lung reduces lymphocytes and their subfractions. Further studies have to be done to determine whether the results obtained in this study in healthy volunteers will also be found in patients with diseased mucosa and whether there is any correlation with adverse effects such as growth inhibition or osteoporosis.

Administration, Inhalation↗
PubMed2002

The inhaled ET(A) receptor antagonist LU-135252 acts as a selective pulmonary vasodilator.

To investigate the hypothesis that the inhaled ET(A) receptor antagonist LU-135252 acts as selective pulmonary vasodilator, we compared inhaled LU-135252 and inhaled nitric oxide (iNO) in an experimental model of acute lung injury (ALI), in a prospective, randomized, controlled animal study. A total of 30 anaesthetized, tracheotomized and mechanically ventilated pigs underwent induction of ALI by repeated saline washout of surfactant. The animals were then randomly assigned to receive the nebulized ET(A) receptor antagonist LU-135252 (0.3 mg x kg(-1), inhaled over 20 min; ET(A)-A group; n=10), inhaled NO (30 p.p.m. continuously; iNO group; n=10) or nebulized saline buffer (5 ml inhaled over 20 min; control group; n=10). Measurements of pulmonary gas exchange and haemodynamics were performed hourly over a 4 h period after induction of ALI. In the ET(A)-A group, the arterial oxygen tension (Pa(2)) increased from 58+/-3 to 377+/-39 mmHg at 4 h after intervention, while the intrapulmonary shunt (Q(S)/Q(T)) decreased from 53+/-4% to 18+/-2% (P<0.01 compared with controls). In the iNO group, Pa(2) increased from 62+/-4 to 224+/-48 mmHg, and Q(S)/Q(T) decreased from 47+/-2% to 27+/-5%, at 4 h after induction of ALI (P<0.05 compared with controls). In the ET(A)-A and iNO groups, the increase in mean pulmonary artery pressure was significantly attenuated compared with controls (ETA-A group, 14+/-4%; iNO group, 6+/-4%; values at 4 h; P<0.01 compared with controls). In contrast, there were no significant differences in changes of mean arterial pressure and cardiac output between groups. Thus, in this experimental model of ALI, both inhaled LU-135252 and iNO significantly improved gas exchange and prevented an increase in mean pulmonary artery pressure, without significant systemic effects, when compared with controls. Our results indicate the occurrence of selective pulmonary vasodilation in both treatment groups.

Administration, Inhalation↗
PubMed1999

Efficacy and economy of inhaled nitric oxide in neonates accepted for extra-corporeal membrane oxygenation.

OBJECTIVE: To study the clinical efficacy as well as the cost-effectiveness of inhaled nitric oxide (NO) compared with extra-corporeal membrane oxygenation (ECMO) in neonates with pulmonary hypertension and hypoxic respiratory failure accepted for ECMO treatment. DESIGN: Retrospective study of the first 10 consecutive neonatal patients treated with inhaled NO during 1992-94. Inhaled NO was administered after failure of conventional treatment as a last resort before initiating ECMO. For cost-effectiveness calculations the above-described patient population was compared with ECMO patients having a very favourable ECMO course. SETTING: Twelve-bed neonatal and paediatric intensive care unit with ECMO capabilities at a tertiary university referral hospital. RESULTS: Inhaled NO was found to significantly decrease the oxygenation index (OI pre-NO: median 80.5; OI post-NO: median 22.5; P=0.003) and five of the patients could successfully be handled without the use of ECMO. ECMO was found to be more than four times as expensive as inhaled NO treatment on a per hour basis ($244 vs. $53 per hour) and the net savings from being able to avoid ECMO in five patients was calculated to be $156 200. CONCLUSION: Initiation of inhaled NO caused a significant improvement in oxygenation index and reduced the need for ECMO by 50% in critically ill neonatal patients with hypoxic respiratory failure. Inhaled NO was also found to compare very favourably with ECMO regarding cost-effectiveness ($53 vs. $244 per treatment hour).

Administration, Inhalation↗
PubMed2000

Relative bioavailability of salbutamol to the lung following inhalation when administration is prolonged.

AIMS: Urinary salbutamol post-inhalation has been shown to be an index of lung deposition. The possibility of using the urinary method for prolonged periods of inhalation (such as nebulized therapy) has been evaluated. METHODS: On separate study days volunteers received salbutamol 5 x 100 microg via either oral administration (ORAL), oral with 5 g oral charcoal (ORAL + C), inhaled from a metered dose inhaler (MDI) or MDI plus 5 g oral charcoal (MDI + C). Each dose was separated by 2 min, i.e. administration time of 8 min. Urine samples were provided at 0, 30, 40, 60 and 120 min postdose. Also seven subjects inhaled 5x100 microg doses from the MDI on five separate occasions and provided urine 0-30 min post dose. RESULTS: No salbutamol was detected in urine samples following ORAL + C. The mean (s.d.) amounts of salbutamol excreted in the urine in the first 30 min post ORAL, MDI and MDI + C were 0.42 (0.55), 11.01 (3.77) and 11.60 (3.68) microg, respectively. The ratio of urinary salbutamol following MDI and MDI + C to ORAL in the 0-30 min collection period was 26.2 and 27.8, and between 30 and 40 min postdose was 5.1 and 4.7, respectively. There was no difference between urinary salbutamol over the first 30 min following MDI and MDI + C with a mean ratio (90% confidence interval) of 95.6 (84.0, 107.2). The mean (s.d.) coefficient of variation for the 30 min urinary salbutamol elimination following inhalation of 5 x 100 microg doses from the MDI by seven subjects (on 5 separate study days) was 9.4 (2.3)%. CONCLUSIONS: The 30 min urinary salbutamol method can be used for an inhalation period of up to 8 min to identify the relative bioavailability to the lung. Samples taken after this time period are affected by excretion of the oral absorbed fraction. Most nebulisers deliver their dose within this administration time.

Administration, Inhalation↗
PubMed1999

Effects of inhaled beclomethasone dipropionate on serum IgE levels and clinical symptoms in atopic asthma.

BACKGROUND: A high serum immunoglobulin (Ig)E level is considered a potent predictor for the development of asthma and IgE is targeted for treatment of asthma. Although inhaled corticosteroids are well established in the treatment of asthma, the effects of inhaled corticosteroids on serum IgE levels in asthma remain uncertain. METHODS: We therefore examined asthma symptoms, concentrations of total serum IgE and specific IgE antibodies to selected allergens, blood eosinophil counts and lung functions before and 3 months after treatment with either inhaled beclomethasone dipropionate (BDP; 800 microg/day) (n = 7) or inhaled beta2-agonists alone (n = 7) in patients with atopic asthma in a randomized, double-blind, parallel-group controlled trial. RESULTS: Inhaled BDP significantly improved asthma symptom scores and forced expiratory volume in 1 s, and decreased blood eosinophil counts, total serum IgE levels and specific IgE antibodies to house dust mite and cedar. Decreases in total serum IgE significantly correlated with an improvement in asthma symptom scores. In contrast, none of parameters altered in patients with atopic asthma treated with inhaled beta2-agonists alone. CONCLUSIONS: Inhaled corticosteroids may improve the subsequent clinical course of atopic asthma in association with a reduction of serum IgE levels.

Administration, Inhalation↗
PubMed2003

Inhaled endotoxin and organic dust particulates have synergistic proinflammatory effects in equine heaves (organic dust-induced asthma).

BACKGROUND: Equine heaves is a naturally occurring organic dust-induced asthma characterized by airway neutrophilia, mucus hypersecretion and obstructive lung dysfunction. However, the relative role of different dust components in disease severity remains unclear. OBJECTIVE: This study investigated the relative contribution of inhaled endotoxin and organic dust particulates (mainly mould spores) in inducing heaves in heaves-susceptible horses. METHODS: Control and heaves-susceptible horses received inhalation challenges with hay dust suspension (HDS) before and after lipopolysaccharide (LPS) depletion. Heaves-susceptible horses also received inhalation challenge with HDS particulates with and without the addition of LPS and were housed in two separate dusty environments during which mould and endotoxin exposure was measured. The airway inflammatory and functional response to each challenge was measured. RESULTS: Depletion of endotoxin from HDS attenuated the airway neutrophilia and abrogated the airway dysfunction induced in heaves horses by inhaled HDS. The airway response was re-established by adding back LPS to the depleted HDS, confirming that the attenuation in airway response was due specifically to endotoxin depletion. Interestingly, the magnitude of alteration in airway response following endotoxin depletion and add-back was greater than that which could be attributed solely to endotoxin per se, indicating that the LPS activity was enhanced by the other dust components. Consistent with this possibility, washed particulates harvested from HDS enhanced the airway response to inhaled LPS in heaves horses. Heaves horses given two different hay/straw challenges had a significantly different severity of airway inflammation and dysfunction, despite airborne dust and endotoxin concentrations in the horses' breathing zones being similar. CONCLUSION: Although inhaled endotoxin appears not to be the only determinant of disease severity in heaves, it does contribute significantly to the induction of airway inflammation and dysfunction. This contribution is largely via the synergistic action of inhaled endotoxin and organic dust particulates, although other soluble dust components also contribute to a lesser degree.

Animals↗
PubMed1999

Improved targeting of beclomethasone diproprionate (250 micrograms metered dose inhaler) to the lungs of asthmatics with the Spacehaler.

The Spacehaler (Evans Medical Ltd, Leatherhead, U.K.) is a new, compact, inhaler device containing the same aerosol canister as a conventional metered dose inhaler (MDI). However, the design of the Spacehaler has been shown to reduce the velocity of the aerosol, thus reducing the proportion of non-respirable particles delivered to the patient. This study compared radioaerosol deposition patterns following inhalation of 250 micrograms of beclomethasone dipropionate from the Spacehaler and a conventional MDI (Beclazone, Norton Health Care, Harlow, U.K.). After rigorous in vitro validation of the radiolabelling technique, 12 asthmatic subjects (seven men aged 20-69 years, mean baseline FEV1 2.59 1 (SD 0.55 1) received one dose of 99mTc-labelled beclomethasone dipropionate 250 micrograms via either a Spacehaler or MDI on each of two study days in a randomized cross-over manner. All subjects had been taught the required inhalation technique before the dose was administered. Inhalation details were recorded using a spirometer connected in series with the device. Lung and oropharyngeal depositions were measured by gamma scintigraphy. The mean percentage of the metered dose deposited in the lungs was 23.0% (SD 8.3%) for the Spacehaler and 12.8% (SD 6.8%) for the MDI (P < 0.01). However, there was no significant difference in the distribution patterns within the lungs between the two devices. Oropharyngeal deposition was significantly lower (P < 0.01) for the Spacehaler than for the MDI [mean (SD) 27.9% (16.4%) and 73.6% (8.7%), respectively] whilst the percentage of the metered dose remaining on the Spacehaler actuator was significantly greater than that on the MDI actuator [mean (SD) 48.0% (11.8%) and 12.4% (8.5%) respectively, P < 0.01]. There was evidence from the inhalation recordings that some patients experienced the 'cold Freon effect' whilst using the metered dose inhaler which may have contributed to the lower lung deposition seen with this device. This study demonstrates that the proportion of a 250 micrograms dose of beclomethasone dipropionate that is delivered to the lungs is significantly greater with the Spacehaler than the MDI. The Spacehaler also reduces the proportion of the does that is deposited in the oropharynx to less than half that observed with the MDI, and reduces the total dose of drug received by the patient.

Administration, Inhalation↗
PubMed2004

Inhaled salbutamol and endurance cycling performance in non-asthmatic athletes.

Beta(2)-adrenergic agonists are important therapeutic agents for the prevention and treatment of (exercise-induced) asthma in athletes, but may have ergogenic effects. In this study we investigated whether inhalation of a supra-therapeutic dose of 800 microg salbutamol before exercise affects endurance performance during a cycling trial in non-asthmatic athletes. In a double-blind, randomized cross-over study, 16 athletes performed two trials, where they had to perform a certain amount of work as fast as possible on a cycle ergometer, 30 minutes after inhalation of 800 micro g salbutamol or placebo. Peak expiratory flow (PEF), forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV(1)) were measured before and after exercise and blood samples were obtained before and during exercise. Cycling performance time was 4010.2 +/- 327.7 s after placebo inhalation and 3927.6 +/- 231.3 s after inhalation salbutamol (p < 0.05). Although salbutamol inhalation increased plasma free fatty acids, glycerol and lactate concentrations and decreased plasma potassium concentrations at rest, no differences between placebo and salbutamol in these variables were found during exercise. PEF and FEV(1) were increased after salbutamol inhalation at rest compared with placebo, but the difference between placebo and salbutamol after exercise was no longer significant. Inhalation of a supratherapeutic dose of 800 micro g salbutamol improved endurance cycling performance by 1.9 +/- 1.8 % in non-asthmatic athletes, which indicates that this route of administration does not exclude the possibility of an ergogenic effect of beta(2)-adrenergic agents in athletes. The increase in performance was not explained by changes in plasma concentrations of free fatty acids, glycerol, lactate, and potassium during exercise or by changes in ventilatory parameters at rest and after exercise. Therefore, the mechanism of the increase in performance remains to be determined.

Administration, Inhalation↗
PubMed2001

Effects of inhaled glucocorticoids on bone density in premenopausal women.

BACKGROUND: Inhaled glucocorticoids are the most commonly used medications for the long-term treatment of patients with asthma. Whether long-term therapy with inhaled glucocorticoids reduces bone mass, as oral glucocorticoid therapy does, is controversial. In a three-year prospective study, we examined the relation between the dose of inhaled glucocorticoids and the rate of bone loss in premenopausal women with asthma. METHODS: We studied 109 premenopausal women, 18 to 45 years of age, who had asthma and no known conditions that cause bone loss and who were treated with inhaled triamcinolone acetonide (100 microg per puff). We measured bone density by dual-photon absorptiometry at base line, at six months, and at one, two, and three years. Serum osteocalcin and parathyroid hormone and urinary N-telopeptide, cortisol, and calcium excretion were measured serially. We measured inhaled glucocorticoid use by means of monthly diaries, supported by the use of an automated actuator-monitoring device. RESULTS: Inhaled glucocorticoid therapy was associated with a dose-related decline in bone density at both the total hip and the trochanter of 0.00044 g per square centimeter per puff per year of treatment (P= 0.01 and P=0.005, respectively). No dose-related effect was noted at the femoral neck or the spine. Even after the exclusion of all women who received oral or parenteral glucocorticoids at any time during the study, there was still an association between the decline in bone density and the number of puffs per year of use. Serum and urinary markers of bone turnover or adrenal function did not predict the degree of bone loss. CONCLUSIONS: Inhaled glucocorticoids lead to a dose-related loss of bone at the hip in premenopausal women.

Administration, Inhalation↗
PubMed2001

Inhaled corticosteroids: impact on asthma morbidity and mortality.

Inhaled corticosteroids are now recommended as first-line therapy for asthma. Although these drugs clearly improve the symptoms of the disease and the associated physiologic abnormalities, epidemiologic studies provide important information on their effectiveness in preventing asthma morbidity and mortality. We review the evidence regarding the role of inhaled corticosteroids in the prevention of asthma fatality and hospitalization. In the process, we discuss the methodologic complexities of the nonexperimental studies and the implications of the methodologic issues on the evaluation of the impact of these drugs. Eight of the cohort and ecologic studies conducted to date strongly suggest that inhaled corticosteroids, when taken regularly, decrease the number of hospitalizations for asthma by up to 80%. For asthma death, the results of 11 investigations appear less consistent, especially those of several cohort and case-control studies whose principal objective was to examine not the benefit of inhaled corticosteroids but the adverse effects of other drug classes. Much of the inconsistency in the results, however, can be explained by weaknesses in study design and analysis-in particular, the failure to consider exposure in terms of regular use of inhaled corticosteroids. When the most recent study involving the use of the Saskatchewan databases is considered, it is evident that regular treatment with conventional or low-dose inhaled cortico-steroids results in a significant reduction in fatalities due to asthma. In all, the evidence to date strongly indicates that regular use of inhaled corticosteroids, even at low doses, would prevent the major portion of asthma hospitalizations and deaths.

Administration, Inhalation↗
PubMedDate not supplied

Effects of an L-selectin antibody on the pulmonary and systemic manifestations of severe smoke inhalation injuries in sheep.

Sheep were treated with either lymphocyte adhesion molecule (LAM)1-3, an antibody against L-selectin, (40 mg 1 hour before smoke inhalation and 35 mg 24 hours after smoke inhalation; n = 6) or equivalent volumes of 0.9% saline solution (n = 6). After the smoke inhalation injuries, the PaO2/FIO2 ratio declined in both groups until 40 hours after the injuries, when a trend toward improvement was noted in the group that received LAM1-3. Lung lymph flow increased in both groups until 36 hours after the smoke inhalation injuries and then significantly decreased in the group that received LAM1-3. Forty-eight hours after the smoke inhalation injuries, there was a significant decrease in the ratio of wet-dry lung weight and in preservation of the reflection coefficient in the group that received LAM1-3 (P < .05). Histopathologic examination showed no differences between the groups in the pulmonary morphology associated with smoke inhalation. A reduction in splanchnic blood flow was noted in the control group (P < .05); this reduction was attenuated by treatment with LAM1-3. The delayed pulmonary effects and improved splanchnic blood flow suggested that LAM1-3 attenuated the development of a systemically induced secondary lung injury rather than of the primary lung injury associated with smoke inhalation.

Animals↗
PubMed2006

Adolescent inhalant use among male patients in treatment for substance and behavior problems: two-year outcome.

UNLABELLED: Adolescent inhalant users are significantly more likely than other patients to have conduct disorder, to report abuse and neglect, and to have previously attempted suicide. Yet little has been published regarding treatment outcome for inhalant users. METHODS: Eighty male adolescents admitted to a residential treatment program underwent baseline assessment during treatment, and follow-up assessment at two-years post admission. Subjects reporting any lifetime inhalant use at baseline (n = 34) were compared to the other patients (n = 46) on 4 outcome variables. RESULTS: Adolescents reporting any lifetime inhalant use at baseline assessment reported twice as many past-year conduct disorder symptoms at two-year follow up (p = 0.03). The relationship between inhalant use and conduct disorder symptoms remained significant (p = 0.03) in analyses that controlled for age, time in jail or restricted environments in the 6-months preceding follow-up, as well as baseline-reported lifetime number of conduct disorder symptoms. Inhalant users were not significantly worse on these other outcome measures: crime in the last month (p = 0.60), days of nontobacco substance use in the last 6 months (p = 0.65), or, commission of selected crimes in the last 6 months (p = 0.06). CONCLUSIONS: Inhalant use among adolescent males in treatment for substance and behavior problems may predict more severe conduct disorder symptoms after treatment.

Administration, Inhalation↗
PubMed2006

Axis I psychiatric comorbidity among adult inhalant dependents seeking treatment.

The present study aimed to investigate the prevalence of Axis I disorders in adult inhalant-dependent patients in comparison to other substance-dependent patients and subjects without substance use disorders. The inhalant-dependent group consisted of 83 male inpatient and outpatient adults diagnosed according to DSM-IV criteria. This group was compared with 74 other substance-dependent patients and with 70 subjects without alcohol and substance use disorder diagnoses. Ninety-three percent of the inhalant dependents had a lifetime history of at least one type of comorbid Axis I disorder, while 77% of the same subjects had at least one type of any affective disorder and 75.9% of them had at least one type of anxiety disorder. Prevalence of Axis I disorders among inhalant dependents was 72.3% for lifetime major depression, 41% for major depression during the past month, 24% for dysthymic disorder, 20.5% for inhalant-induced depressive disorder, 27.7% for panic disorder, 30% for PTSD, 36.1% for social phobia and 20.5% for generalized anxiety disorder. The rate of lifetime axis I disorders was higher in patients with inhalant dependency in comparison to the other two groups. This finding suggests that inhalant-dependent adults have high rates of comorbid psychiatric problems, and that it is important to determine Axis I disorder comorbidity in this population before making an inpatient or outpatient treatment plan.

Administration, Inhalation↗
PubMedDate not supplied

Short-term lower leg growth in asthmatic children treated with inhaled beta2-agonists.

BACKGROUND: Knemometry studies of growth suppressive effects of inhaled glucocorticoids in children with asthma usually allow participating children to use concomitant inhaled beta2-agonists. Systemic beta2-agonists, however, have been found to suppress growth hormone secretion and this has caused concern about a possible confounding effect of inhaled beta2-agonists on results of growth studies of exogenous glucocorticoids. AIM: The study evaluated whether inhaled salbutamol adversely affects short-term growth. SUBJECTS AND METHODS: Fifteen children aged 6-12 years with mild asthma were enrolled in a single-blind, randomized crossover study with two 2-week treatment periods and a 1-week run-in. During the active period treatment dry powder salbutamol (Ventoline Diskhaler) 200 microg was inhaled three times a day. During the comparative period no treatment was given. Knemometry of the right lower leg was performed on the first and the last day of each period. RESULTS: Mean lower leg growth rates (SEM) during no-treatment and salbutamol periods were 0.35 (0.06) and 0.42 (0.07) mm per week, respectively (P = 0.35, t = -0.98, 95% CI: 0.25-0.93 mm per week). CONCLUSIONS: Inhaled salbutamol 200 microg three times daily does not suppress short-term growth in asthmatic children. Inhaled beta2-agonists in equipotent doses and regimens can be safely used in short-term knemometric growth studies of exogenous glucocorticoids without any risk of confounding the results.

Administration, Inhalation↗
PubMed1999

Nitric oxide inhalation inhibits pulmonary apoptosis but not inflammatory injury in porcine meconium aspiration.

To investigate the possible protective effects of nitric oxide (NO) inhalation in newborns with meconium aspiration, 18 10-12-d-old piglets were studied for 6h after an intratracheal bolus (3 ml/kg) of a 65-mg/ml mixture of human meconium. Twelve of the piglets were treated with continuous NO inhalation at a dose of 1 ppm (n = 6) or 10 ppm (n = 6), started 30 min before the insult. Pulmonary haemodynamics and systemic oxygenation were followed, and lung tissue samples were studied for signs of inflammation, evidence of ultrastructural injury and apoptotic cell changes. Inhalation of 10 ppm NO, in contrast to 1 ppm NO, significantly delayed the meconium-induced pulmonary pressure rise and the increase in intrapulmonary shunt fraction, and maintained better oxygenation in the piglets. Histologically and biochemically, treatment with 1 or 10 ppm NO inhalation did not protect the lungs against meconium-induced inflammatory injury. Further, ultrastructural lung tissue analysis revealed a significant amount of alveolar exudate and oedematous alveolar epithelium and endothelium after meconium instillation, also in the lungs treated with NO inhalation. However, the increase in apoptotic epithelial cell deaths, previously shown to be stimulated by intratracheal meconium, was significantly impeded after inhalation of 10 ppm. These results thus show that early continuous NO inhalation controls the rise in pulmonary artery pressure and improves the efficiency of arterial oxygenation, and further prevents the increase in epithelial apoptosis, but does not protect against early inflammatory damage caused by meconium aspiration.

Administration, Inhalation↗