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PubMed2004

Subjective benefit of inhaled therapies in patients with bronchiectasis: a questionnaire study.

The objectives of this study were to obtain information about the use and subjective benefits of inhaled therapies in patients with bronchiectasis and to determine if these benefits were related to the presence of airflow obstruction. One hundred and twenty patients completed a questionnaire on inhaled therapies and performed spirometry. Inhalers were used daily by 85/120 patients with bronchiectasis and 42/120 patients had a nebuliser. Inhaled therapies were used extensively in patients with (FEV1 < 80%) and without (FEV1 > 80%) evidence of airflow obstruction. The majority of patients reported subjective benefits from their inhaled therapies. Chi2 analysis showed that there was no association between perceived benefits of short acting bronchodilators (SAB), long acting bronchodilators (LAB), corticosteroids or nebulisers and degree of airflow obstruction. This study provides information about the subjective benefits of inhaled therapies which could facilitate a more comprehensive assessment of the net benefit of inhaled therapies in patients with bronchiectasis with and without airflow obstruction.

Administration, Inhalation↗
PubMed2005

Do patients think that dry powder inhalers can be used interchangeably?

As recognised in management guidelines, patients are the most important group of people in any prescribing decision. Despite their importance, few studies have asked what patients think about being switched between different inhalers. This paper reports two such studies, one involving interviews of a sample of patients and the other consisting of a quantitative survey of patients across five countries. In the qualitative study, four of the five patients interviewed reported that they would be confused, worried and unhappy about a switch in their dry powder inhaler and would revisit their physician to be shown how to use the inhaler or to ask for a new prescription for their old inhaler. In the quantitative survey of 499 patients with asthma, more than half (51%) were opposed to their current dry powder inhaler being replaced by a substitute device, with 83% reporting concerns. There was considerable concern about training in use of the new device and confusion about the need for change. Almost a quarter of patients (23%) would want training, and 23% of patients thought they would need information about the new inhaler. From limited information, it appears that patients would be concerned about switching of their existing dry powder inhaler for another, with the potential for confusion, need for additional consultations and need for training in the new device.

Administration, Inhalation↗
PubMed2005

Effects of allergen inhalation and oral glucocorticoid on serum soluble CTLA-4 in allergic asthmatics.

BACKGROUND: The serum soluble cytotoxic T lymphocyte associated antigen-4 (sCTLA-4) concentration is significantly elevated in patients with asthma, and sCTLA-4 concentration correlate with the severity of asthma. The aim of the present study was to investigate effects of allergen inhalation and oral glucocorticoid on concentration of serum sCTLA-4 in patients with allergic asthma. METHODS: Allergen inhalation challenge was conducted in allergic asthmatics with isolated early asthma response and those with dual asthma response. In a randomized, double-blind, placebo-controlled, parallel group fashion, prednisolone or placebo was give orally once a day for 2 weeks. Venous blood samples were collected before and after allergen inhalation or prednisolone administration for obtaining sera. The serum sCTLA-4 concentrations were determined using enzyme-linked immunosorbent assay. RESULTS: The serum sCTLA-4 concentrations in the dual responder group increased from 29.0 (14.5-43.7) microg/l [median (25-75 percentiles)] before allergen inhalation to 44.0 (24.3-61.3) microg/l 24 h after allergen inhalation. In the isolated early responders, there were no significant increase in serum sCTLA-4 concentrations after allergen inhalation compared with baseline levels. There was a significant decrease in serum sCTLA-4 concentrations after 2 weeks of glucocorticoid therapy [22.0 (15.5-31.0) microg/l] compared with baseline values [37.0 (19.5-53.0) microg/l], whereas there was no significant difference in the placebo group. CONCLUSION: This study has demonstrated that serum sCTLA-4 concentrations increased after allergen inhalation in sensitized asthmatic subjects, and that serum sCTLA-4 concentrations were downregulated by prednisolone therapy.

Administration, Inhalation↗
PubMed1996

Effect of inhaled nitric oxide on venous admixture depends on cardiac output in patients with acute lung injury and acute respiratory distress syndrome.

BACKGROUND: It has been shown that inhaled nitric oxide (NO) reduces intrapulmonary venous admixture (QVA/QT) and improves oxygenation in patients suffering from acute respiratory distress syndrome (ARDS). The change in QVA/QT during NO inhalation varies individually. Factors known to influence the respiratory response to NO are the NO concentration and the level of shunt before NO administration. Other factors that may modify the effect on gas-exchange during NO breathing are unknown. METHODS: We studied the effect of 40 ppm inhaled NO on pulmonary gas-exchange and haemodynamics in 37 patients with acute lung injury (ALI) and ARDS, respectively, and factors that may influence the respiratory response to NO. RESULTS: Inhalation of 40 ppm NO produced a decrease in mean pulmonary artery pressure (MPAP) from 33.1 +/- 7.2 to 30.2 +/- 6.8 (mean +/- SD) mmHg (P < 0.0001) while pulmonary artery wedge pressure (PAWP), cardiac output and mean arterial pressure remained constant. Change in QVA/QT during NO inhalation depended on the preinhalation cardiac output and had no association with mixed venous oxygen tension, MPAP-PAWP, and QVA/QT before NO delivery. QVA/QT decreased in 26 patients (group 1) and increased in 11 patients (group 2) during NO inhalation. In group 1, cardiac output was lower than in group 2 (8.6 vs 12.2 l.min-1; P < 0.0005). CONCLUSION: We conclude that the change in venous admixture during inhalation of 40 ppm NO depends on cardiac output. If preinhalation cardiac output is high, 40 ppm NO can adversely affect gas exchange in patients with ALI and ARDS.

Acute Disease↗
PubMed1998

The effects of nitric oxide inhalation on respiratory mechanics and gas exchange during endotoxaemia in the pig.

BACKGROUND: In the adult respiratory distress syndrome, nitric oxide (NO) inhalation improves oxygenation through reducing ventilation-perfusion mismatching, but detailed information on the pulmonary effects of NO inhalation in septic shock is scarce. The present study investigated the effects of inhaled NO on alveolar dead space (Vdalv) and venous admixture as well as on respiratory system compliance (Crs) and respiratory system resistance (Rrs) in a porcine model of septic shock. Protective effects of NO are discussed. METHODS: Thirteen anaesthetised and ventilated pigs were given an infusion of endotoxin for an observation time of 220 min to induce acute lung injury (ALI). In the NO-early group (n=6), an inhalation of 60 ppm NO was started simultaneously with the endotoxin infusion and continued for 190 min. In 7 control/NO-late animals, 60 ppm NO was administered for 30 min following 190 min of endotoxin infusion. Haemodynamics, single-breath CO2-, pressure-, and flow signals were recorded. RESULTS: Endotoxin induced haemoconcentration, pulmonary vasoconstriction, and a decrease in Crs, while venous admixture, Vdalv, and Rrs increased. In the NO-early group, the pulmonary vasoconstriction was attenuated, no increase in pulmonary venous admixture or in Vdalv was seen before cessation of NO, and the improvements in oxygenation outlasted the NO inhalation. In the control/NO-late group, the NO inhalation reversed the changes in dead space and venous admixture. NO had no effect on the changes in respiratory mechanics. CONCLUSION: In porcine ALI, 60 ppm NO diminishes pulmonary vasoconstriction and improves gas exchange by reducing pulmonary venous admixture and alveolar dead space, but does not prevent a fall in Crs. NO inhalation may help prevent long-lasting pulmonary failure.

Administration, Inhalation↗
PubMed1998

Increased use of inhaled corticosteroids and reduced hospitalizations in adult asthmatics: 11 years' experience in a Japanese hospital.

Until recently, inhaled corticosteroids have not been recognized as a first-line drug mainly because of the traditional polypharmaceutical approach to asthma in Japan. To examine the trend more precisely following the introduction of inhaled corticosteroids, we retrospectively analysed the relation between the number of prescriptions for anti-asthma drugs including inhaled corticosteroids and the number of hospitalizations due to asthma exacerbation, near fatal episodes and deaths from asthma for a period of 11 years from 1986 to 1996 at Kobe City General Hospital (KCGH). A marked decline in these actual indices in patients attending KCGH, which shows the improvement in asthma control, started coincidentally with the increased use of inhaled corticosteroid, which was followed by both a discontinuation of the trend for increased use of inhaled beta-agonists and the decreased use of oral anti-asthma agents. There was no significant difference in the mean duration of hospital stays between 1988 and 1996. Although the intensification of patient education is likely to play an important role in enhancing the protective effect of inhaled corticosteroids, we highly suspect that the major contributory factor in the great decline in hospitalizations is the increased use of inhaled corticosteroids.

Administration, Inhalation↗
PubMed1990

The role of prostanoid TP- and DP-receptors in the bronchoconstrictor effect of inhaled PGD2 in anaesthetized guinea-pigs: effect of the DP-antagonist BW A868C.

1. In anaesthetized, pump-ventilated guinea-pigs, bolus intravenous injection of prostaglandin D2 (PGD2 5-160 micrograms kg-1) caused a dose-dependent rise in both heart rate and systemic mean arterial blood pressure with only a small monophasic rise in pulmonary inflation pressure (PIP). 2. In contrast, inhaled PGD2 (0.1-1 mg ml-1, 30s) provoked a substantial concentration-dependent biphasic rise in PIP. The bronchoconstrictor action of inhaled PGD2 was accompanied by minimal cardiovascular effects. 3. The 3-benzyl substituted hydantoin BW A868C (0.1-1 mg kg-1 i.v.) a novel prostanoid DP-receptor antagonist, had no significant effect on the cardiovascular or bronchoconstrictor effects of intravenously administered or inhaled PGD2. 4. However, BW A868C (0.1-1 mg kg-1 i.v.) did inhibit the hypotensive actions of the DP-receptor agonist, BW 245C (1-3 micrograms kg-1 i.v.). 5. The prostanoid TP-receptor antagonist BM 13.177 (2.5 mg kg-1 i.v.) strongly inhibited the bronchoconstrictor effect of inhaled PGD2, abolishing the first phase of this response and reducing the peak increase in PIP provoked by PGD2 (0.1 or 1 mg ml-1 for 30 s), by 67 +/- 16% and 44 +/- 5% respectively. 6. A combination of BW A868C (0.1 or 1 mg kg-1 i.v.) with BM 13.177 (2.5 mg kg-1 i.v.) produced no greater inhibition of the bronchoconstrictor effect of inhaled PGD2 than that seen with BM 13.177 (2.5 mg kg-1 i.v.) alone. 7. Neither bilateral vagotomy, nor selective inhibition of arachidonate cyclo-oxygenase with indomethacin or 5-lipoxygenase with the novel acetohydroxamic acid BW A4C, significantly reduced the bronchoconstrictor effect of inhaled PGD2. 8. These findings indicate that the bronchoconstrictor effect of inhaled PGD2 in guinea-pigs in vivo is mediated primarily through direct TP-receptor activation and not through actions on DP-receptors.

Administration, Inhalation↗
PubMed1994

Inhibition of substance P-induced microvascular leakage by inhaled methoxamine in rat airways.

1. The effect of the inhaled alpha-adrenoceptor agonist, methoxamine (MTX), was studied on experimental airway oedema induced by injection of substance P (SP) in the rat. Sprague-Dawley rats (300-350 g) were anaesthetized with sodium thiopentone, tracheotomized and artificially ventilated. 2. MTX or its vehicle was administered by inhalation. Airway resistance and blood pressure were monitored continuously. Evans Blue dye (EB, 20 mg kg-1) was injected through a jugular catheter 1 min before SP (14.8 nmol kg-1). Airways were dissected out, weighed and placed in formamide for EB extraction and determination by spectrophotometry. 3. EB extravasation induced by SP was significantly reduced in distal intraparenchymal bronchi by inhaled MTX at doses of 50 micrograms kg-1 (58 +/- 9 vs 96 +/- 9 ng EB mg-1 tissue after vehicle, P < 0.001) and 100 micrograms kg-1 (69 +/- 11 vs 137 +/- 26 ng EB mg-1 tissue after vehicle, P < 0.01). Inhaled MTX by itself (100 micrograms kg-1) increased blood pressure: 172 +/- 6 vs 132 +/- 10 mmHg baseline (P < 0.02), but neither induced extravasation nor increased airway resistance. 4. In another set of experiments without SP, MTX was administered intravenously 1 min after EB. At 100 micrograms kg-1, i.v. MTX increased blood pressure to a similar extent as inhaled MTX (180 vs 147 mmHg baseline, P < 0.01), increased airway resistance and caused leakage of plasma proteins in distal intraparenchymal bronchi (79 +/- 7 vs 47 +/- 1 ng EB mg-1 tissue, P < 0.02). 5 Similarly, after sequential i.v. injections of doubling doses of MTX (50-800 microg kg-1), a marked EB extravasation was found in the airways. This was abrogated by pretreatment with prazosin (100 microg kg-1)but not with propranolol (2 mg kg-1).6 These results suggest that microvascular leakage and airway oedema induced by i.v. MTX may be linked to an increase in pressure in the pulmonary circulation, resulting from vasoconstriction of the pulmonary vasculature and acute cardiac dysfunction due to systemic hypertension.7 Our results with inhaled MTX show that direct deposition of MTX at the bronchial vasculature induces a reduction in SP-induced microvascular leakage in rat airways and that inhaled MTX does not share the untoward effect of i.v. MTX inducing airway oedema.

Administration, Inhalation↗
PubMed2006

Effect of inhaled glucocorticoid treatment on placental 11beta-hydroxysteroid dehydrogenase type 2 activity and neonatal birthweight in pregnancies complicated by asthma.

BACKGROUND: Asthma is a common disease affecting 12% of Australian women with 55% of women experiencing at least one exacerbation during pregnancy. Exacerbations during pregnancy are associated with low birthweight neonates and stillbirth. One of the main reasons for maternal exacerbations during pregnancy is non-compliance with inhaled glucocorticoid treatment due to the misconception that inhaled glucocorticoids are harmful to the fetus. AIMS AND METHODS: We have therefore assessed whether the commonly used inhaled glucocorticoids reduce placental glucocorticoid metabolising capacity, by measuring 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD-2) activity. As these treatments potentially increase the exposure of the fetus to the growth-inhibiting effects of glucocorticoids, we also examined the question of whether inhaled glucocorticoid use was associated with reduced birthweight. Pregnant women using budesonide (n = 18), fluticasone propionate alone (n = 14) and fluticasone propionate in combination with the long-acting beta2 agonist salmeterol (n = 9) were compared to a non-asthmatic control group (n = 20). RESULTS: The use of inhaled budesonide was associated with significantly increased placental 11beta-HSD-2 activity relative to the control group. Inhaled glucocorticoid use for the treatment of asthma was associated with normal birthweight. In the small number of women using combination therapy (fluticasone and salmeterol), there was reduced birthweight compared to the control group. CONCLUSION: Inhaled glucocorticoids alone do not adversely affect fetal growth and placental function.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2003

Prevalence of esophageal candidiasis among patients treated with inhaled fluticasone propionate.

OBJECTIVES: Development of oropharyngeal candidiasis is a frequently reported adverse effect of inhaled corticosteroid use, but the prevalence of esophageal candidiasis is unknown. The aim of this study was to estimate the prevalence of esophageal candidiasis among patients treated with an inhaled corticosteroid, fluticasone propionate. METHODS: Upper GI endoscopy was performed on 49 patients treated with inhaled fluticasone propionate to examine the prevalence of esophageal candidiasis. Of the patients, 36 had bronchial asthma and 13 had chronic obstructive pulmonary disease. To compare the prevalence with control patients, upper GI endoscopy was performed on 700 consecutive patients without malignancy or immunosuppression. RESULTS: The prevalence of esophageal candidiasis was 37% among patients treated with inhaled fluticasone propionate, whereas only 0.3% of the control patients had the infection. The prevalence was especially high among patients with diabetes mellitus or those who were treated with a high dose of inhaled fluticasone propionate. Moreover, a reduction in the daily dose of inhaled fluticasone propionate eliminated the infection in four of five patients. CONCLUSIONS: Esophageal candidiasis is a common complication of inhaled corticosteroid use.

Administration, Inhalation↗
PubMed1990

Foetal and maternal distribution of inhaled mercury vapour in pregnant mice: influence of selenite and dithiocarbamates.

The distribution of mercury after inhalation of metallic mercury vapour (6-8 mumols 203Hg0/kg b.wt.) was studied in pregnant mice (day 17 of gestation) after pretreatment with selenite (10 mumols Se/kg b.wt. intraperitoneally 1 hr before inhalation), thiram, disulfiram or diethyldithiocarbamate (1 mmol/kg orally 2 hr before inhalation of Hg0). For comparison, the effects of thiram, disulfiram and diethyldithiocarbamate on the distribution of mercury after administration of ionic mercury (7 mumols 203HgCl2/kg b.wt. intravenously) were also studied. Selenite pretreatment caused a longer retention of mercury in maternal tissues but decreased the foetal concentrations after 203Hg0 inhalation, similarly to what has been shown previously after administration of ionic mercury (Hg2+). Pretreatment with the three dithiocarbamates markedly increased the uptake in maternal brain and fat and decreased the foetal concentrations after intravenous injection of 203HgCl2. In contrast, no change in foetal uptake and only slight changes in maternal tissue concentration of mercury were observed after treatment with the dithiocarbamates followed by inhalation of 203Hg0, compared with 203Hg0 inhalation alone. The results are in favour of a firmer binding of mercury after Hg0 inhalation, when oxidation of Hg0 to Hg2+ occurs intracellularly, than after Hg2+ injection. Further studies, using repeatedly low dose administration of selenium, are needed to draw any conclusions concerning the protective effects of selenium after exposure to metallic mercury vapour.

Administration, Inhalation↗
PubMed1997

Growth of asthmatic children is slower during than before treatment with inhaled glucocorticoids.

Reports on the influence of inhaled glucocorticoids on growth have been controversial. We studied the growth of prepubertal asthmatic children prior to and during glucocorticoid therapy. We collected retrospectively the notes of 201 asthmatic children aged 1-11 years receiving inhaled beclomethasone dipropionate or budesonide. We calculated their height and height velocity standard deviation scores (HSDS and HVSDS, respectively) before the treatment and up to 5 years during the treatment and compared those with the growth of healthy peers. The dose of the medication was calculated and the severity of asthma was assessed. The asthmatic children grew similarly to their healthy peers before treatment with inhaled glucocorticoids: the mean HSDS was +0.02 and the mean HVSDS +0.01 for boys and -0.16 and +0.13 for girls, respectively. Growth retardation took place soon after the start of the treatment, the most profound decrease in the growth velocity (the change in the mean HVSDS from +0.05 to -0.88) occurring during the first year of treatment. The growth-retarding effect of inhaled glucocorticoids was not dose dependent. In the covariance analysis the increasing severity of asthma had a significant interaction with repeated measurements, showing more growth retardation along with more severe asthma, especially during long-term treatment. Asthma per se does not impair growth, but inhaled glucocorticoids may do so. Careful monitoring of the growth of all asthmatic children receiving inhaled glucocorticoids is necessary because the growth-retarding effect of the medication is not dose dependent. Individual sensitivity might explain the differences seen in the growth patterns of children receiving inhaled glucocorticoids.

Administration, Inhalation↗
PubMed2005

Population pharmacokinetics of caffeine and its metabolites theobromine, paraxanthine and theophylline after inhalation in combination with diacetylmorphine.

The stimulant effect of caffeine, as an additive in diacetylmorphine preparations for study purposes, may interfere with the pharmacodynamic effects of diacetylmorphine. In order to obtain insight into the pharmacology of caffeine after inhalation in heroin users, the pharmacokinetics of caffeine and its dimethylxanthine metabolites were studied. The objectives were to establish the population pharmacokinetics under these exceptional circumstances and to compare the results to published data regarding intravenous and oral administration in healthy volunteers. Diacetylmorphine preparations containing 100 mg of caffeine were used by 10 persons by inhalation. Plasma concentrations of caffeine, theobromine, paraxanthine and theophylline were measured by high performance liquid chromatography. Non-linear mixed effects modelling was used to estimate population pharmacokinetic parameters. The model was evaluated by the jack-knife procedure. Caffeine was rapidly and effectively absorbed after inhalation. Population pharmacokinetics of caffeine and its dimethylxanthine metabolites could adequately and simultaneously be described by a linear multi-compartment model. The volume of distribution for the central compartment was estimated to be 45.7 l and the apparent elimination rate constant of caffeine at 8 hr after inhalation was 0.150 hr(-1) for a typical individual. The bioavailability was approximately 60%. The presented model adequately describes the population pharmacokinetics of caffeine and its dimethylxanthine metabolites after inhalation of the caffeine sublimate of a 100 mg tablet. Validation proved the stability of the model. Pharmacokinetics of caffeine after inhalation and intravenous administration are to a large extent similar. The bioavailability of inhaled caffeine is approximately 60% in experienced smokers.

Administration, Inhalation↗
PubMed1994

Prolonged bleeding time during nitric oxide inhalation in the rabbit.

During a study on the modulatory effect of inhaled nitric oxide (NO) on the airway, we observed an increased bleeding tendency. Therefore, we studied bleeding time and blood rheology in rabbits during inhalation of 3, 30 and 300 parts per million (ppm) NO. The rabbits were intubated during neurolept anaesthesia and were ventilated mechanically. The bleeding time was significantly increased after 15 min of inhalation of 30 ppm NO, from 51 +/- 5 to 72 +/- 7 s (mean +/- SEM, P < 0.001, n = 7). However, there were no changes in haematocrit, whole blood or plasma viscosity, erythrocyte aggregation tendency, or erythrocyte deformability. Inhalation of 3 ppm NO increased bleeding time from 46 +/- 11 to 59 +/- 8 s (n.s., n = 4) and 300 ppm NO from 48 +/- 12 to 78 +/- 17 s (P < 0.05, n = 4). In another group of rabbits mean arterial pressure (MAP) was monitored using NO inhalation. A non-significant decrease was seen with 3 ppm and 30 ppm NO, from 63 +/- 2 to 59 +/- 3 mmHg (n = 6) and from 65 +/- 2 to 61 +/- 1 mmHg (n = 6) respectively. Inhalation with 300 ppm NO decreased MAP from 62 +/- 3 to 55 +/- 2 mmHg (P < 0.05, n = 6). We conclude from these data that inhalation of NO, 30 ppm or more exerts systemic effects.

Administration, Inhalation↗
PubMed2006

Management of 13 cases of canine respiratory disease using inhaled corticosteroids.

OBJECTIVES: To determine the value of inhaled corticosteroids in the management of chronic inflammatory airway disease in dogs. METHODS: Medical records of dogs that were presented for the investigation of respiratory disease were reviewed retrospectively. Criteria for inclusion were knowledge of previous medical treatment including side effects, diagnosis of the underlying disease, use of inhaled corticosteroids and at least two-months follow-up data. RESULTS: Thirteen dogs that fulfilled the criteria were identified. Ten dogs were diagnosed with chronic bronchitis and three with eosinophilic bronchopneumopathy. Four dogs had not previously received corticosteroid treatment for their respiratory disease, and all these showed a reduction or a resolution of clinical signs without obvious side effects after inhaled corticosteroid therapy. Nine dogs had previously received oral or parenteral corticosteroids for treatment of their respiratory disease, and all had exhibited side effects. Five of these dogs were treated with inhaled corticosteroids alone, and all exhibited an improvement in clinical signs without observable side effects. The remaining four dogs were treated with a combination of inhaled and oral corticosteroids, and all showed improvement in clinical signs and reduction in side effects. Inhaled medication was well tolerated in all dogs. CLINICAL SIGNIFICANCE: Inhaled corticosteroids were used for the management of chronic bronchitis and eosinophilic bronchopneumopathy in 13 dogs, and these may have the advantage of reducing side effects associated with oral corticosteroids.

Administration, Inhalation↗
PubMed2005

In situ naphthalene bioactivation and nasal airflow cause region-specific injury patterns in the nasal mucosa of rats exposed to naphthalene by inhalation.

Despite the fact that naphthalene (NA), a volatile, ubiquitous air pollutant, was recently identified as a probable human carcinogen, little is known about nasal cytotoxicity from inhaled NA. To define and compare acute nasal injury from inhalation and systemic NA exposures, male Sprague-Dawley rats were exposed to filtered air; 3.4 or 23.8 ppm NA by inhalation for 4 h; or to 0, 25, 50, 100, or 200 mg/kg NA via intraperitoneal injection. Severe cellular injury occurred exclusively in the olfactory mucosa 24 h postinhalation exposure to 3.4 ppm NA for 4 h. This level is significantly below both the current Occupational Safety and Health Administration standard (10 ppm; 8 h) for NA and the lowest observed adverse effect level (10 ppm; 2 years) for the incidence of rat olfactory neoplasms. Injury within the olfactory mucosa from inhaled NA was confined to the medial meatus, whereas systemic NA generated severe injury throughout the olfactory region. The pattern of nasal injury from inhaled NA in this study is consistent with previous studies of nasal airflow simulation within the olfactory region. The nonolfactory mucosa on the nasal septum, a high airflow region, metabolized naphthalene slowly, whereas the olfactory regions of the nasal septum and ethmoturbinates metabolized this substrate at high rates. This study concludes that 1) the incidence of acute nasal injury from systemic and inhaled NA correlates with the rates of regional microsomal NA metabolism and that 2) the nasal airflow pattern determines the pattern of olfactory mucosal injury from inhaled NA.

Animals↗
PubMed2002

Inhaler devices for asthma: do we follow the guidelines?

BACKGROUND: Despite national guidelines for asthma treatment, many children have troublesome symptoms. AIM: To assess the extent to which the use of inappropriate inhaler devices contributes to this problem. METHODS: Of 14 813 questionnaires distributed to schoolchildren, 6996 (47%) were returned identifying 1444 children using asthma inhalers. Inhalers were categorised as age appropriate or inappropriate according to national guidelines and were compared with those used by 75 patients attending a hospital clinic. RESULTS: A total of 35% of "schools" and 4% of "clinic" children reported using an inappropriate inhaler device. Most were using metered dose inhalers alone. Twenty four per cent of "schools" children < or = 5 years old did not use a spacer. Both children and parents overestimated the child's ability to use their inhaler. CONCLUSIONS: Large numbers of children are given inhalers they cannot use. To improve asthma care we must ensure that prescriptions reflect the age and ability of the child. Recent recommendations by the Department of Health in England and Wales stress the importance of seamless care between primary and secondary services. As the management of childhood asthma is guided primarily by secondary care providers, it is therefore imperative that general paediatricians know the difficulties and issues which are occurring in the community. This will enable them to lead and support necessary change.

Administration, Inhalation↗
PubMed1998

Comparison of potency of inhaled beclomethasone and budesonide in New Zealand: retrospective study of computerised general practice records.

OBJECTIVE: To determine whether inhaled budesonide and beclomethasone are equipotent in the treatment of asthma in primary care. DESIGN: Retrospective study of computerised clinical records from 28 general practices in New Zealand. SUBJECTS: 5930 patients who received 16 725 prescriptions for inhaled budesonide or beclomethasone from 1 July 1994 to 30 June 1995. SETTING: General practices on the database of the Royal New Zealand College of General Practitioners Research Unit. Linked information from secondary care was available for a subset of the practices. MAIN OUTCOME MEASURE: Mean prescribed daily inhaled corticosteroid dose. RESULTS: The daily prescribed dose was higher for patients receiving inhaled budesonide (mean 979 microg) than beclomethasone (mean 635 microg), a difference of 344 microg (95% confidence interval 313 to 376 microg). This difference was consistent in all age bands and with different types of inhalation device. Evidence of systematic prescribing of higher doses of budesonide to patients with more severe asthma was not found. CONCLUSIONS: In primary care in New Zealand evidence suggests that budesonide is less potent than beclomethasone. Consideration of validated, established, and other possible markers of asthma severity did not support confounding by severity as a reason for the higher prescribed doses of budesonide. Pending further epidemiological evaluation, international asthma guidelines may need to be modified on the equivalence of inhaled corticosteroid doses. Furthermore, the comparative potency of newly developed inhaled steroids in clinical trials will need to be confirmed in appropriately designed epidemiological studies based in general practice.

Administration, Inhalation↗