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PubMed2001

Diagnostic concordance of DSM-III-R, DSM-IV, and ICD-10 inhalant use disorders.

The diagnostic concordance of DSM-III-R, DSM-IV, and ICD-10 inhalant use disorders was assessed using the sample of lifetime inhalant users (n=76) participating in the DSM-IV Field Trial for Substance Use Disorders. Substantially smaller proportions of lifetime inhalant users met DSM-IV inhalant abuse or dependence criteria than met comparable DSM-III-R or ICD-10 criteria. DSM-III-R and ICD-10 performed similarly, although DSM-III-R tended to be more inclusive vis-à-vis diagnoses of inhalant dependence. Kappa coefficients indicated a moderate degree of concordance between the three nosologies for inhalant use disorder diagnosis rates. Inclusion of possible withdrawal symptomatology criteria (that are not normally included) in the DSM-IV and ICD-10 criteria sets for inhalant dependence exerted little effect on diagnosis rates.

Adolescent↗
PubMed2001

Educational intervention for correct pressurised metered dose inhaler technique in Trinidadian patients with asthma.

Correct pressurised metered dose inhalers (pMDI) usage is reportedly sub-optimal in patients and data for Caribbean populations is not available. We studied proficiency of inhaler use in Trinidadian patients, and determined sub-groups to be targeted for educational interventions. Inhaler use by 331 consecutive stable patients with airway disease (over 7 years) was observed and marked on a standard checklist. From direct observation only 41% of patients correctly inhaled, though 92% were confident of accurate technique. Few elderly patients (6%) received appropriate instructions on inhaler technique and only 35% (n = 23/66) understood the rationale for two different inhaler therapies (P < 0.001). More children (33%) and elderly patients (21%) reported escaping drug with use. Multiple regression analysis indicated the independent predictors of correct pMDI were age (P < 0.01) and correct understanding of different inhalers. Intensive patient education in Trinidadian children and elderly patients with airway disorders can enable active participation in disease management and maximal benefit from medication.

Adolescent↗
PubMed1992

A clinically relevant modification to existing inhaler therapy.

A modified formulation of inhaled salbutamol and a new inhaler device were studied in a group of 11 moderate-to-severe asthmatic patients. Changes in airway calibre (FEV1, Vmax30) were measured before and after inhalation of the new formulation, and compared with changes following inhalation of conventional salbutamol. A standard Rotahaler was used as a reference for the new inhaler. The study was conducted as a two-part randomized, double-blind cross-over trial. We found a significantly greater bronchodilatation of the larger airways using the modified drug in the Rotahaler. The new inhaler did not show any superiority over the Rotahaler, contrary to expectations from in vitro work. A slightly shorter model may better reflect the in vitro results. The study has implications for inhalation therapy in general.

Adult↗
PubMed1999

Inhaled corticosteroids for adult asthma: impact of formulation and delivery device on relative pharmacokinetics, efficacy and safety.

Metered dose inhalers (MDIs) are the mainstay of inhaled steroid therapy for asthma. With the phasing out of traditional chlorofluorocarbon (CFC) propellants and their replacement with a new generation of CFC-free products, it is becoming clear that formulation and inhaler characteristics can markedly affect the drug delivery. It now seems necessary to compare inhalers not only on the basis of the properties of the steroid molecules but also to take into account the effect of propellants and other inhaler characteristics. The impact of formulation and delivery device on relative pharmacokinetics, therapeutic efficacy and tolerability is illustrated by a new preparation of beclomethasone dipropionate (BDP) in an inhaler containing hydrofluoroalkane (HFA) propellant, called Qvar (3M Health Care, U.K.). This drug preparation delivers the majority of particles (60%) in the fine particle range. This appears to be associated with improved lung deposition, a halving of dose requirements of BDP, but no evidence of clinically relevant adrenal suppression when used in therapeutic doses. Prescribers need to be aware of the impact of formulation on pharmacokinetics of inhaled steroids in order to offer the lowest effective dose and give clear instructions to patients who are changing to a CFC-free product.

Adrenal Cortex Hormones↗
PubMed2003

The effect of a steroid "burst" and long-term, inhaled fluticasone propionate on adrenal reserve.

BACKGROUND: Although widely used, the effects of steroid "bursts" on the hypothalamic-pituitary-adrenal axis, especially with long-term, concomitant topical steroids use, have not been studied. OBJECTIVE: To examine the effect of a prednisone burst, long-term intranasal steroids, and inhaled fluticasone propionate on the suppression and recovery of adrenal function. METHODS: Adult patients taking long-term intranasal steroids, either moderate-dose (440 microg/d) or high-dose (880 microg/d) inhaled fluticasone propionate, underwent a low-dose cosyntropin stimulation test (LDCST) before and 2 days after a prednisone burst. Suppressed adrenal responses were monitored with a weekly LDCST. Persistent abnormal LDCST results were confirmed by 8-hour cosyntropin infusion. Inhaled fluticasone dosages were decreased; adrenal recovery was evaluated by a monthly LDCST. Adverse effects of steroids were monitored by questionnaires. RESULTS: Sixty-three patients participated in the study. Three of 31 patients not taking inhaled steroids and 1 of 13 patients taking moderate-dose fluticasone had abnormal LDCST results on day 2 after the prednisone burst, which normalized by the second week. In the high-dose fluticasone group, 14 of 19 patients had suppressed LDCST responses on day 2 and adrenal function recovered in 10 of 19 patients by the fourth week. These patients complained significantly of decreased libido (P = 0.02), listlessness (P = 0.03), and weight loss (P = 0.05). High-dose fluticasone (r = 0.66, P < 0.001) and duration of use (r = 0.32, P = 0.01) were statistically correlated with adrenal impairment. Of the 4 patients with persistent adrenal impairment, 3 patients successfully reduced dosages of inhaled fluticasone and adrenal function recovered in 2 to 10 months. CONCLUSIONS: Prednisone bursts induce brief adrenal impairment. Intranasal steroids and moderate-dose fluticasone had no effect on adrenal function. High-dose, inhaled fluticasone caused mild-to-significant adrenal suppression and delayed the recovery after a steroid burst. Avoiding or limiting the duration of high-dose inhaled steroids would minimize systemic adverse effects.

Administration, Intranasal↗
PubMed2003

Inhaled glucocorticoids and adrenal function: an update.

For the vast majority of asthmatic children, treatment with inhaled glucocorticoids is safe and effective. Mild impairment of adrenal function of doubtful clinical significance is known to occur in some children inhaling > or = 400 micro g/day budesonide and beclomethasone or > or = 200 micro g fluticasone. Recent reports of life-threatening adrenal failure in asthmatic children inhaling glucocorticoids, some of whom were prescribed licensed doses, have prompted the recommendation that the use of high-dose inhaled glucocorticoids, particularly fluticasone, should be avoided. However, the importance of correctly diagnosing asthma, of using the minimum dose of inhaled glucocorticoid required for symptom control and of regular growth-velocity assessment cannot be over-emphasised. Appropriate asthma management including the early introduction of steroid-sparing agents such as a long-acting beta-agonist or leukotriene antagonist may reduce the morbidity associated with inhaled glucocorticoid use but some children, for reasons as yet unknown, may exhibit increased sensitivity to the systemic effects of inhaled glucocorticoid treatment. Possible explanations for this, with reference to the pharmacology and molecular mechanisms of glucocorticoid action, are accompanied in this review by a summary of the recent case reports and discussion of assessment of adrenal function.

Administration, Topical↗
PubMed1997

Aerosol electrostatics. I: Properties of fine powders before and after aerosolization by dry powder inhalers.

PURPOSE: To evaluate the dependence of fine particle dose charge (FPD charge) generated from powder inhalers on physico-chemical properties of the inhalation powder, inhaler type, deaggregation mechanism, dose number and/or retained powder. METHODS: Electrostatic charges were determined on micronized powders and aerosolized fine particle doses withdrawn from two, high efficiency, multidose powder inhalers, Turbohaler and prototype Dryhaler. The behavior of terbutaline sulfate, budesonide, albuterol (sulfate and base), beclomethasone dipropionate and lactose was assessed before and after aerosolization. RESULTS: Both inhalers conferred triboelectric FPD charges during aerosolization in the range -400 pC through +200 pC. Specific charges (charge/unit mass) on the fine particle doses of budesonide from Dryhaler were significantly less than those from Turbohaler (p < 0.01). Electrostatic charges on the potentially respirable cloud of terbutaline sulfate generated by Bricanyl Turbohaler were positive and/or negative and unpredictable. With Pulmicort Turbohaler, FPD charges on budesonide were always positive. Dryhaler was used to determine the chemical dependence of fine particle triboelectrification during the aerosolization of pure materials. A triboelectric series was constructed from the Dryhaler results ranking the powders from positive to negative as budesonide > lactose > albuterol sulfate > terbutaline sulfate > or = albuterol > or = beclomethasone dipropionate. CONCLUSIONS: While there was no evidence of FPD charge dependence upon dose number with either inhaler, FPD charges were dependent upon the powder under investigation, as well as the construction and deaggregation mechanism of the inhaler. The specific charge on the fine particle dose of budesonide from Turbohaler corresponded to approximately 200 electronic charges per particle, a value which is known to affect both total and regional aerosol deposition in the human lung. Electrostatic charge effects may be important determinants of aerosol behavior and should not be neglected.

Aerosols↗
PubMed1986

Inhaled smoke volume, puffing indices and carbon monoxide uptake in asymptomatic cigarette smokers.

Nine asymptomatic smokers each smoked one cigarette of their usual brand on four separate occasions. The inhaled smoke volume was measured by tracing the smoke with the inert gas 81Krm. Puffing indices were recorded by using an electronic smoking analyser and flowhead/cigarette holder. The expired air carbon monoxide concentration was measured immediately before and within 5 min of finishing smoking. The inhaled smoke percentage (total inhaled smoke volume/total puff volume) averaged 46% to 85% in different subjects. Neither the mean inhaled smoke volume per puff nor the total inhaled smoke volume per cigarette was significantly correlated with any of the puffing indices. Smokers took significantly smaller and shorter puffs, left longer between puffs and inhaled less smoke as the cigarette was smoked (P less than 0.01), although the proportion of the puff which was subsequently inhaled did not change significantly. There was no significant intra-subject difference in any index from one visit to another.

Adolescent↗
PubMed2003

The use of inhaled corticosteroids in the United Kingdom and the Netherlands.

This study examined the utilisation patterns of inhaled corticosteroids in England/Wales and the Netherlands. Computerised medical records from the GPRD (U.K.) and PHARMO (the Netherlands) databases were used. It included 284733 English/Welsh and 27761 Dutch adult patients who were prescribed inhaled corticosteroids during the 10-year study period. Our results showed that, in both study populations, overall use of inhaled corticosteroids increased over the period studied, with its prevalence rising steeply with age and declining in extreme old age. Decreased use of bronchodilators and oral corticosteroids in the early treatment of asthma was noted in our findings. In addition, a trend towards the decreasing use of oral corticosteroids concomitant with inhaled corticosteroid therapy was also observed for both groups. Our study found that only 42.1% of the GPRD and 31.1% of the PHARMO patients received a repeat prescription within the expected duration ofthe preceding inhaled corticosteroid prescription. In conclusion, our study found many similarities in the prescribing and use of inhaled corticosteroids between the two study populations. The observation of irregular use of inhaled corticosteroid among a substantial number of patients highlights a need for further study into the reasons for irregular use and its consequences on the effectiveness of treatment.

Adult↗
PubMed1984

Therapeutic inhalation agents and devices. Effectiveness in asthma and bronchitis.

Although a variety of therapeutic agents can be given as aerosols, the physical problems involved in delivering the drug to the peripheral airways have often been ignored. Therapeutic aerosols are deposited in the respiratory tract by two chief mechanisms--inertial impaction (in the oropharynx and in large conducting airways) and gravitational sedimentation (in small conducting airways and in alveoli). In practice, only about 10% of the aerosol dose reaches the lungs from metered-dose inhalers (MDIs) and nebulizers, and rather less from dry-powder inhalers. Changes in either aerosol particle size or inhalation mode can optimize the amount of aerosol delivered to the peripheral lung regions by each device. The inhaled route has several advantages over oral and intravenous administration for the treatment of asthma and bronchitis, ie, a rapid onset of drug action, a small drug dose, and a low incidence of systemic side effects. Although various disadvantages or problems have been proposed for the inhaled route, these seem to be of minor importance. Drugs inhaled from MDIs, dry-powder inhalers, or nebulizers are thought to be safe if used in the recommended manner.

Administration, Oral↗
PubMed2001

Comparison of gene expression of cytokines mRNA in lungs of rats induced by intratracheal instillation and inhalation of mineral fibers.

To investigate whether the results of intratracheal instillation studies on mineral fibers reflect the findings obtained by long-term inhalation data on mineral fibers, we have examined gene expression of cytokines and pathological features in lungs induced by intratracheal instillation and inhalation of mineral fibers. Male Wistar rats were given a single intratracheal instillation of 2 mg alumina silicate refractory fiber (RF1) or potassium octatitanate whisker (PT1), and were sacrificed 4 wk after the fiber instillation. Long-term inhalation studies were also performed. In these, animals were exposed to fiber aerosol of RF1 or PT1 for 5 days/wk for 1 yr, and sacrificed after 1 yr of inhalation. Expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and transforming growth factor-beta1 (TGF-beta1) from lungs was observed by reverse-transcription polymerase chain reaction (RT-PCR). The expression of TNF-alpha, IL-6, and TGF-beta1 mRNA in PT1-exposed lung was significantly higher than for those exposed to RF1 in both intratracheal instillation and inhalation studies. Pathological findings revealed that mild pulmonary fibrosis was seen in the lungs after intratracheal instillation and inhalation of PT1 but not RF1. Similarities were observed not only in gene expression of cytokines but in pathological features between both studies. These data suggested that the results of intratracheal instillation reflect the findings obtained from long-term inhalation data.

Aluminum Silicates↗
PubMed2003

Budesonide inhalation suspension reduces the need for emergency intervention in pediatric asthma: a named-patient case series.

This report describes 15 children aged 10-35 months frequently hospitalized with uncontrolled asthma who were monitored for a mean of 26.9 months to assess the efficacy of budesonide inhalation suspension (AstraZeneca LP, Wilmington, DE) in reducing emergency interventions. Budesonide inhalation suspension was previously shown to relieve asthma symptoms, improve pulmonary function, and reduce rescue medication use in children as young as 6 months with mild to severe persistent asthma. We now show that > or = 1 year of treatment with budesonide inhalation suspension at doses between 0.25 and 1.5 mg/d decreased the burden of asthma. The mean number of hospitalizations caused by asthma or respiratory illness decreased from 1.8 +/- 1.37 in the period before initiation of treatment with budesonide inhalation suspension to 0.33 +/- 0.62 during treatment. Likewise, the mean number of oral prednisone courses decreased from 8.1 +/- 13.7 to 1.8 +/- 2.1, and the mean number of acute respiratory illnesses requiring additional therapy decreased from 2.7 +/- 2.3 before treatment with budesonide inhalation suspension to 0.87 +/- 0.74 during treatment. Numbers of emergency department visits decreased or remained the same after initiation of budesonide inhalation suspension treatment in all but two children. There was no effect on growth rate in this group of children with moderate to severe asthma. In this case series, budesonide inhalation suspension represents a safe, effective treatment option to prevent recurrent emergency intervention for patients < 3 years of age with poorly controlled asthma.

Anti-Inflammatory Agents↗
PubMed2000

Validation of a new breathing simulator generating and measuring inhaled aerosol with adult breathing patterns.

The use of breathing simulators for the in vitro determination of the inhaled mass of drug from nebulizers has become widely accepted. Their use is, however, based on the assumption that there is a correlation between the in vitro and in vivo inhaled mass of drug. The aim of the study was therefore to investigate whether a new breathing simulator--the MIMIC Breathing Emulator (Medic-Aid Limited, Bognor Regis, UK)--could accurately emulate the in vivo inhaled mass of budesonide suspension for nebulization. Eight adult healthy subjects were included. Each subject inhaled for 2 min from a Spira Module 1 jet nebulizer (Respiratory Care Center, Hämeenlinna, Finland), charged with 1.0 mg of budesonide suspension for nebulization (0.5 mg mL-1, 2 mL suspension, AstraZeneca, Sweden) and supplied with an inhaled mass filter between the nebulizer and the subject. The breathing patterns were recorded during the nebulization and simulated in vitro at two different experimental sites (simulations A and B) with the breathing simulator. With the patients breathing through the filters (in vivo test), inhaled mass of budesonide averaged 103.6 micrograms. The two in vitro experiments using the simulator revealed similar results with in vitro simulation A equal to 101.0 micrograms and simulation B 99.1 micrograms. There were no statistically significant differences between the in vivo results and those of in vitro simulation A. Results were significantly different for simulation B (p = 0.032) although the difference was less than 4.5%. These data indicate that the breathing simulator can be used to accurately simulate sine waveforms, human breathing patterns, and the in vitro and in vivo inhaled mass of budesonide suspension for nebulization.

Adult↗
PubMed1995

Identifying the manifestations of inhalant abuse.

Inhalants are frequently the first mood-altering drugs used by children. They are popular because of peer influences, low cost, availability, and rapid mood-elevation effects. Inhalants cause a fleeting sense of well being, but users frequently are also affected psychologically and physically. Substances such as gasoline and paint thinners are highly toxic and destroy major organs. The abuse of inhalants can cause cardiac arrest, asphyxiation, and accidents. This article focuses on the clinical manifestation of inhalants, altered lab values, the specific agents used, and their effects on the various organs. Health care professionals are in a key position to identify inhalant abusers when clients are seeking treatment for medical problems caused by inhalants. If health care professionals are cognizant of the manifestations of inhalant abuse, they can save a client's life.

Adolescent↗
PubMed1991

A method for bioassay of potency and effectiveness of inhaled bronchodilators in normal subjects.

1. Bioassay of inhaled bronchodilator drugs for potency and effectiveness in normal human subjects is rendered difficult and imprecise because bronchomotor tone is low. When attempting to determine log dose-effect relationships for inhaled, nebulised bronchodilator drugs and measuring increased specific airways conductance (sGaw), the coefficient of variation of each mean response is likely to be so large that an intermediate response is not significantly different from either the maximum or no response. 2. A method is described by which inhaled, nebulised bronchodilator drugs can be bioassayed for potency and effectiveness with high precision. The method involves the use of inhaled, nebulised bronchoconstrictor agents (methacholine or histamine) to provide a highly reproducible, near-constant, background reduction in airway conductance in normal human subjects. The activity of bronchodilators is assessed against this background reduction in airway conductance. 3. Log specific airway conductance (log sGaw) was chosen as the response metameter on grounds of normality of distribution and relative homoscedasticity. A central straight line segment of the bronchoconstrictor drug dose-effect curve extending over a 10-fold dose multiple could be found easily; the upper end of this segment occurred near 67-75% reduction in sGaw and was reproducible. 4. The effect of a dose bronchoconstrictor drug causing 67-75% reduction in sGaw waned linearly with time at first, over the effect segment corresponding to the linear segment of the drug's log dose-effect curve. The rate constant of local elimination of bronchoconstrictor drug from its site of action, in inhaled dose equivalents, was deduced from the ratio of the slopes of the linear segments of the log dose-effect and time-effect curves. 5. The maintenance dose rate to maintain the peak effect (67-75% reduction in sGaw) of the loading dose was calculated. The repeated administration of maintenance doses at regular short intervals, at this calculated dose rate, created a steady state of bronchoconstriction equal in extent to the effect of the loading dose. This steady state bronchoconstriction occurred without undue discomfort for the subject and was reproducible. 6. Against this background bronchoconstriction, inhaled, nebulised salbutamol produced a rapidly developing and slowly waning increase in sGaw. Reproducible log dose-effect curves for the bronchodilator drugs salbutamol and reproterol allowed measurement of their potency and effectiveness; the potency of reproterol relative to salbutamol was 0.082 with 95% confidence limits of 0.0504 and 0.131. 7. Estimation of the subject's pharmacodynamic and pharmacokinetic parameters for inhaled methacholine from just three dosage individualising sessions provides estimates accurate enough to be of practical value.

Adult↗
PubMed1992

Protection of nedocromil sodium on bronchoconstriction induced by inhaled neurokinin A (NKA) in asthmatic patients.

Neurokinin A (NKA) has been shown to exert a potent contractile action on bronchial smooth muscles both in vitro and in vivo. Although this effect seems to be due either to a direct action of this peptide on specific muscular receptors or to an indirect effect on mast cells and/or nerves, its mechanism of action in bronchial asthma is still unknown. In the present study we have investigated the airway response to inhaled NKA in 10 asthmatic subjects and the activity of the novel pyranoquinoline dicarboxylic acid drug, nedocromil sodium, on this response. Ten asthmatic patients with stable asthma took part in the study consisting of four separate visits. On the first two occasions we derived histamine and NKA PD15 values in absence of any drug treatment. On the following two visits the inhalation challenge with NKA was performed after administration of either nedocromil sodium or matched placebo administered as pressurized aerosols via metered dose inhalers in a randomized double-blind order. Inhaled NKA produced a dose-related fall in FEV1 in all the subjects studied. Inhaled nedocromil sodium had a significant effect on the FEV1 response to NKA inhalation, the geometric mean PD15 value increasing from 16.6 to 32.2 x 10(-9) mol. We conclude that nedocromil sodium attenuates subsequent responsiveness to inhaled NKA in asthmatic subjects.

Adolescent↗
PubMed1995

Ability of inhaled procaterol, a beta 2 adrenoceptor agonist, to attenuate eicosanoid-induced airflow obstruction and airway microvascular leakage.

Beta-2 adrenoceptor agonists are widely used as bronchodilators in the treatment of asthma mainly via inhalation. In the present study, we evaluated the ability of inhaled procaterol, a beta 2 adrenoceptor agonist, to reduce eicosanoid-induced airway microvascular leakage, and compared the ability with its inhibitory effect against bronchoconstriction. Tracheostomized guinea-pigs were given aerosolized procaterol (10 or 100 micrograms/ml) for 10 min under spontaneous breathing. Immediately after the end of inhalation, the animals were mechanically ventilated. Fourteen minutes after the end of inhalation, Evans blue dye (20 mg/kg) was given i.v. One minute later, 2 nmol/kg leukotriene D4 (LTD4), 50 nmol/kg U-46619, a thromboxane A2 mimetic, or vehicle was administered i.v. LTD4- or U-46619-induced increase in lung resistance was measured for 6 min. After removing the lungs, the amount of extravasated Evans Blue due in the lower airways was examined as an index of microvascular leakage. Inhaled procaterol significantly attenuated increases in both lung resistance and Evans Blue dye extravasation caused by these eicosanoids. The degree of inhibition was almost complete for lung resistance (approximately 90%), but it was only partial (range 18.5-61.2%) for the dye extravasation. No significant changes in mean systemic blood pressure and in heart rate was observed after an inhalation of 10 micrograms/ml procaterol. These results suggest that inhaled beta 2 adrenoceptor agonists may reduce airway microvascular leakage caused by inflammatory mediators such as eicosanoids without affecting systemic circulation.

Adrenergic beta-Agonists↗
PubMed1989

Treatment of asthma in pre-school children with inhalation of terbutaline in Turbuhaler compared with Nebuhaler.

The aim of this study was to evaluate the efficacy, safety and preference of pre-school children with regard to two different devices for treatment of bronchial asthma with terbutaline. Turbuhaler, a powder inhaler preloaded with pure terbutaline for inhalation, was compared with a pressurized metered dose inhaler, attached to a Nebuhaler. The study had an open, cross-over randomized design. Each treatment period consisted of 2 weeks. Diary cards were filled in every morning and evening by the parents regarding PEF, asthma symptoms, extra inhalations of terbutaline, and side effects. Twenty-one children (mean age 3.9 years) were included in the study. A highly significant (P less than 0.001) increase in peak expiratory flow (PEF) was obtained after inhalation with both devices. The PEF values in the mornings after inhalation of terbutaline with Turbuhaler were significantly higher (P = 0.046) than those with Nebuhaler. Further, the PEF baseline values in the evenings before inhalation were also significantly higher (P = 0.03) with Turbuhaler. No difference was found in asthma symptoms and extra medication between the two devices. Side effects were mild and few with both devices. The parents found Turbuhaler easier to handle and 19 of 21 preferred this device for future use.

Asthma↗