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PubMedDate not supplied

Concurrent use of intranasal and orally inhaled fluticasone propionate does not affect hypothalamic-pituitary-adrenal-axis function.

Two double-blind, randomized, placebo-controlled, parallel group safety and efficacy studies included evaluation of the hypothalamic-pituitary-adrenal (HPA)-axis effects of concurrent treatment with intranasal and orally inhaled fluticasone propionate (FP). In the first study, patients with asthma who were > or =12 years of age were assigned randomly to receive twice-daily doses (either 88 or 220 microg) of orally inhaled FP delivered from a metered-dose inhaler (MDI). In the second study, patients were assigned randomly to receive either orally inhaled FP 250 microg or orally inhaled FP 250 microg/salmeterol 50 microg delivered via the Diskus device. In both studies, patients with rhinitis were allowed to continue the use of intranasal FP at their usual dosing. Treatment periods were 26 weeks and 12 weeks for the MDI and Diskus studies, respectively. HPA-axis effects were assessed using response to short cosyntropin stimulation testing. The number and percentage of patients with an abnormal cortisol response, defined as a morning plasma cortisol of <5 microg/dL, a poststimulation peak of <18 microg/dL, or a poststimulation rise of <7 microg/dL, were summarized in two subgroups: patients who used intranasal FP and those who did not. The concurrent administration of intranasal FP and orally inhaled FP via an MDI or Diskus or via Diskus with salmeterol was not associated with HPA-axis effects compared with orally inhaled FP alone. The results of these two studies suggest that concurrent use of intranasal FP with orally inhaled FP administered via MDI or Diskus for treatment of comorbid rhinitis and asthma does not increase the risk of HPA-axis abnormalities.

Administration, Inhalation↗
PubMed1997

Time-action profile of inhaled insulin.

We compared the pharmacodynamics of insulin after inhalation of 99 U microcrystalline solid insulin and subcutaneous injection of 10 U regular insulin and intravenous injection of 5 U regular insulin. The time-action profiles of the three insulin administrations were studied in 11 healthy volunteers using the euglycaemic glucose clamp technique. The insulins were administered to each volunteer on three separate occasions in random order. Onset of action, assessed as glucose infusion rate, after insulin inhalation was substantially more rapid than after subcutaneous injection and half-maximal action was reached earlier (31 +/- 17 vs 54 +/- 12 min; p < 0.001). Maximal metabolic response was reached earlier after insulin inhalation in comparison to subcutaneous injection (108 +/- 49 vs 147 +/- 53 min; p < 0.001). The maximal glucose infusion rate after inhalation of insulin was lower than after subcutaneous insulin injection (6.2 +/2- 2.4 vs 9.1 +/- 2.5 mg kg-1 min-1; p < 0.001). The glucose infusion rates in the first 60 min after inhalation were significantly greater than after insulin injection (area under the glucose infusion rate curve: 0.23 +/- 0.12 vs 0.13 +/- 0.08 g kg-1 60 min-1; p < 0.001). However, the total metabolic effect after inhalation was significantly lower than after insulin injection (1.44 +/- 0.68 vs 1.90 +/- 0.47 g kg-1 360 min-1; p < 0.001). Relative effectiveness of inhaled insulin calculated with regard to the data from the intravenous insulin application was 9.5 +/- 4.1% and of the subcutaneous insulin application was 7.6 +/- 2.9%. With its rapid onset of action, inhaled insulin might have potential for clinical use.

Administration, Inhalation↗
PubMed1999

Impact of constant and breath-synchronized nebulization on inhaled mass of nebulized budesonide in infants and children.

The aim of the present study was to compare the output of a breath-synchronized jet nebulizer to a conventional constant output nebulizer over a fixed period of time in terms of inhaled mass of budesonide, i.e., the amount of budesonide deposited on a filter interposed between the nebulizer and the face mask. One hundred and sixty-five asthmatic children (103 boys) were enrolled in this open, randomized, crossover trial. Their age ranged from 6 months to 7.9 years, height from 69 to 132 cm, and weight from 8.2 to 31.3 kg. Their duration of asthma ranged from less than 1 to 7 years. Budesonide suspension, 0.5 mg mL-1, 2 mL, was used. With 5 min of constant output nebulization, the mean inhaled mass of budesonide in percent of the nominal dose was 11.4% in the youngest children and 14.9% in the 7-year-old children. Expressed in percent of the total output of budesonide, i.e., the amount that left the nebulizer as an aerosol, the inhaled mass ranged from 34.6-48.6%. Thus, 51.4-65.4% of the total output was deposited on the expiratory filter. With 5 min of breath-synchronized nebulization, the mean inhaled mass ranged from 10.5-14.9% of the nominal dose. For the youngest patients less than 3-4 years of age, it was approximately 80-90% of the total output. For the older patients the inhaled mass was approximately 95% of the total output, i.e., only small amounts of budesonide were deposited on the expiratory filter. For both modes of nebulization the between-subject variation in inhaled mass was large: up to 6-fold in the young children and 3-4-fold in the older ones. The results of the present study showed that the inhaled mass of budesonide was significantly age-dependent with both modes of nebulization, i.e., the inhaled mass was less in younger children. Breath-synchronized nebulization resulted in reduced waste of drug during expiration.

Administration, Inhalation↗
PubMed2006

Inhaled nitric oxide for respiratory failure in preterm infants.

BACKGROUND: Inhaled nitric oxide has been proven effective in term infants with hypoxic respiratory failure. The pathophysiology of respiratory failure, and the potential risks, differ substantially in preterm infants. Analysis of the efficacy and toxicities of inhaled nitric oxide in infants born before 35 weeks is therefore necessary. OBJECTIVES: To determine whether, in preterm newborn infants (< 35 weeks gestation) who have hypoxic respiratory failure, treatment with inhaled nitric oxide improves oxygenation within 2 hours and reduces the rates of death, bronchopulmonary dysplasia, intraventricular haemorrhage, or neurodevelopmental disability SEARCH STRATEGY: Standard methods of the Cochrane Neonatal Review Group were used. We searched MEDLINE, EMBASE, Healthstar and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), using the following keywords: nitric oxide, clinical trial, newborn, and covering years from 1985 to 2005. In addition, we searched the abstracts of the Pediatric Academic Societies. SELECTION CRITERIA: Randomised and quasi randomised studies in preterm infants with hypoxic respiratory failure. Administration of inhaled nitric oxide compared to control with or without placebo. Clinically relevant outcomes that were analysed included death, bronchopulmonary dysplasia (defined as oxygen dependence at 36 weeks postconceptional age), intraventricular haemorrhage, long term neurodevelopmental outcome and short term effects on oxygenation. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Neonatal Review Group were used. Two investigators extracted, assessed and coded separately all data for each study. Any disagreement was resolved by discussion. MAIN RESULTS: Seven randomised controlled trials of inhaled nitric oxide therapy in preterm infants were found. One study consisted of infants determined to have a high risk of developing bronchopulmonary dysplasia (Subhedar 1997). One study studied routine use of inhaled NO in all ventilated preterm infants (Schreiber 2003). The remaining studies consisted of infants with high predicted mortality based on poor oxygenation (Kinsella 1999; Hascoet 2005; INNOVO 2005; Van Meurs 2005; Mercier 1999). No significant effect of inhaled nitric oxide on mortality or bronchopulmonary dysplasia was demonstrated. There was no evidence of effect on the risk of intraventricular haemorrhage. There may be short term improvements in oxygenation. Two studies (Schreiber 2003; INNOVO 2005) have so far presented data on long term neurodevelopmental outcome, one of which demonstrated improved outcome at two years corrected age. AUTHORS' CONCLUSIONS: The currently published evidence from randomised trials does not support the use of inhaled nitric oxide in preterm infants with hypoxic respiratory failure. Further studies may need to be performed to evaluate the potential benefit of routine use of this therapy in infants with milder forms of respiratory failure, and these trials will need to be designed to evaluate not only neonatal survival, and the occurrence of neonatal morbidities, but should be powered to evaluate neurodevelopmental outcome at a minimum of two years of age.

Administration, Inhalation↗
PubMed2000

Inhaled corticosteroids for cystic fibrosis.

BACKGROUND: Maintenance of optimal lung function is an important therapeutic goal in cystic fibrosis as it is lung damage that, in the long term, is responsible for most premature death among affected people. Inhaled corticosteroids are being increasingly used to treat children and adults with cystic fibrosis. The rationale for their use is that they have the potential to reduce lung damage arising from inflammation. However chronic use of inhaled steroids may also have adverse effects. It is thus important to establish the current level of evidence about the potential benefits and harms of this practice. OBJECTIVES: The objective of this review is to assess the effectiveness of regular use of inhaled corticosteroids when compared to no inhaled corticosteroids, in the management of patients with cystic fibrosis. SEARCH STRATEGY: Trials were ascertained from the Cochrane Cystic Fibrosis and Genetic Disorders Specialised Register of Controlled Trials which includes published and unpublished trials identified through electronic databases such as Medline and Embase as well as those identified from handsearching of journals and conference proceedings. Pharmaceutical companies manufacturing inhaled corticosteroids were also contacted to identify any trials of inhaled corticosteroids in cystic fibrosis. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: All trials, both published and unpublished, in which inhaled corticosteroids were compared to either placebo or standard treatment in patients with cystic fibrosis. Trials employing random treatment allocation and those using quasi-random allocation methods such as alternate allocation to treatment and control group were included. DATA COLLECTION AND ANALYSIS: The following outcomes were assessed: objective measures of lung function, respiratory exacerbations, use of intravenous antibiotics, hospital admissions, nutritional status, symptoms, quality of life, survival and frequency of adverse effects. Methodological quality of trials was assessed independently using established criteria by two reviewers, who also extracted relevant data independently using standard proformas. Differences were resolved by discussion. MAIN RESULTS: Nine trials were identified reporting the use of inhaled steroids in 266 subjects aged between seven and 45 years with cystic fibrosis. Methodological quality was difficult to assess from published information, specifically with respect to concealment of allocation and method used to generate random sequence. Trials were heterogeneous with respect to inclusion criteria, specifically age, severity of pulmonary involvement, clinical diagnosis of asthma and pulmonary colonisation with Pseudomonas aeruginosa. Trials also differed in type and duration of treatment. Beclomethasone was given for periods of between four and 22 weeks in four trials, budesonide for six weeks and six months respectively in two, and fluticasone for periods of between six weeks and two years in the remaining three. Measures of the volume of air breathed out on a forcible expiration (forced expiratory volumes) were reported in most trials but these data could not be combined for this review partly because reports differed in the way data were summarised and partly because some data were not included in published reports. Outcomes of potentially greater relevance to affected individuals such as nutritional status or quality of life were not reported in any trial. Survival was not reported in any trial, but this may reflect the fact that maximum duration of follow up was too short to allow this outcome to be meaningfully assessed. Adverse effects were systematically documented in only two trials. Although one trial was halted prematurely because a proportion of all those taking part had acquired chronic lung infections with Pseudomonas aeruginosa, no conclusions can be reached from this one small trial as to whether this risk is increased as

Administration, Inhalation↗
PubMed2003

Inhaled versus systemic corticosteroids for the treatment of chronic lung disease in ventilated very low birth weight preterm infants.

BACKGROUND: Chronic lung disease (CLD) remains a serious and common problem among very low birth weight infants despite the use of antenatal steroids and postnatal surfactant therapy to decrease the incidence and severity of respiratory distress syndrome. Corticosteroids have been widely used to treat or prevent CLD due to their anti-inflammatory properties. However, the use of systemic steroids has been associated with serious short and long term adverse effects. Administration of corticosteroids topically through the respiratory tract might result in beneficial effects on the pulmonary system with fewer undesirable systemic side effects. OBJECTIVES: To compare the effectiveness of inhaled versus systemic corticosteroids administered to ventilator dependent preterm neonates with birth weight </= 1500 grams or gestational age </= 32 weeks after two weeks of life for the treatment of evolving CLD. SEARCH STRATEGY: Randomized and quasi-randomized trials were identified by searching the Cochrane Controlled Trials Register (The Cochrane Library, Issue 3, 2002), MEDLINE (1966 - September 2002), EMBASE (1980 - September 2002), CINAHL (1982 - September 2002), reference lists of published trials and abstracts published in Pediatric Research (1990 - April 2002) from the Society for Pediatric Research/Pediatric Academic Societies' Annual Meetings. SELECTION CRITERIA: Randomized or quasi-randomized trials comparing inhaled versus systemic corticosteroid therapy (irrespective of the dose and duration of therapy) starting after the first two weeks of life in ventilator dependent very low birth weight preterm neonates. DATA COLLECTION AND ANALYSIS: Data were extracted regarding clinical outcomes including CLD at 28 days or 36 weeks corrected gestational age (CGA), mortality, combined outcome of death or CLD at 28 days or 36 weeks CGA, other pulmonary outcomes and adverse effects. All data were analyzed using RevMan 4.1. When appropriate, meta-analysis was performed using relative risk (RR), risk difference (RD), and weighted mean difference (WMD) along with their 95% confidence intervals (CI). If RD was statistically significant, number needed to treat (NNT) was calculated. MAIN RESULTS: Five trials comparing inhaled versus systemic corticosteroids in the treatment of CLD were identified. Two trials were excluded as both included non ventilator dependent patients. One trial is awaiting assessment and clarification of published data. Two trials qualified for inclusion in this review. Halliday et al (Halliday 2001a) randomized infants < 72 hours, while Suchomski et al (Suchomski 2002) randomized at 12-21 days. Although the steroids were commenced after the first 2 weeks of life in both the trials, the outcomes were measured over different time periods, from the age at randomization in each trial, making it inappropriate to combine results. In neither trial was there a statistically significant difference between the groups in the incidence of CLD at 36 weeks CGA amongst all randomized infants. The estimates for the trial by Halliday et al (Halliday 2001a) were RR 1.10 (95% CI 0.82, 1.47), RD 0.03 (95% CI -0.08, 0.15); number of infants (n) = 292 and for the trial by Suchomski et al (Suchomski 2002) RR 0.90 (95% CI 0.79, 1.02), RD -0.10 (95% CI -0.22, 0.02; n = 78 ). There were no statistically significant differences between the groups in either trial for oxygen dependency at 28 days, death by 28 days or 36 weeks, the combined outcome of death or CLD by 28 days or 36 weeks CGA, duration of intubation, duration of oxygen dependence, or adverse effects. Information on the long term neurodevelopmental outcomes was not available. REVIEWER'S CONCLUSIONS: This review found no evidence that inhaled corticosteroids confer net advantages over systemic corticosteroids in the management of ventilator dependent preterm infants. Neither inhaled steroids, nor systemic steroids, can be recommended as standard treatment for ventilated preterm infants. There was no evidence of difference in effectiveness or side-effect profiles for inhaled versus systemic steroids. A better delivery system guaranteeing selective delivery of inhaled steroids to the alveoli might result in beneficial clinical effects without increasing side-effects. To resolve this issue, studies are needed to identify the risk/benefit ratio of different delivery techniques and dosing schedules for the administration of these medications. The long term effects of inhaled steroids, with particular attention to neurodevelopmental outcome, should be addressed in future studies.

Administration, Inhalation↗
PubMed2002

Inhaled corticosteroid effects on bone metabolism in asthma and mild chronic obstructive pulmonary disease.

BACKGROUND: Inhaled corticosteroids form the main therapy for asthma, but there is increasing concern about the potential systematic effects of long-term inhaled corticosteroids including their effect on bone metabolism and bone loss. OBJECTIVES: To determine the effect of inhaled corticosteroids use on biochemical markers of bone turnover, bone mineral density and the development of fractures. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register, electronic reference databases, UK National Research Register, bibliographies of included studies, and contacted pharmaceutical companies. SELECTION CRITERIA: Randomised trials of the effect of inhaled steroid versus placebo on markers of bone function and metabolism, in adults with asthma or mild COPD. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data extracted from the papers included (2 reviewers per paper) and from additional data supplied by the authors. MAIN RESULTS: Of 438 references found, seven met the inclusion criteria. Three studies were in healthy subjects asthma or COPD. The patients were generally less than 60 years old and the male:female ratio was 2:1. There was no evidence of increased risk of loss of bone mineral density (BMD) or fractures. There was no significant change in osteocalcin at conventional doses of inhaled corticosteroids (Standardised Mean Difference [SMD] -0.34 (95% Confidence Interval [CI] -0.72, 0.04), although a statistically significant change was seen in those studies using experimental doses of inhaled steroid in excess of the doses recommended by the British Thoracic Society SMD 0.97 (95% CI -1.61, -0.34). A statistically significant change in parathyroid hormone seen in one small short trial (n=10, 6 weeks) may have been due to the trial design and outcome measurements used. REVIEWER'S CONCLUSIONS: In patients with asthma or mild COPD, there is no evidence of an effect of inhaled corticosteroid at conventional doses given for two or three years on BMD or vertebral fracture. Higher doses were associated with biochemical markers of increased bone turnover, but data on BMD and fractures at these doses are not available. There is a need for further, even longer term prospective studies of conventional and high doses of inhaled corticosteroids.

Administration, Inhalation↗
PubMed1991

Detection of coronary artery disease by vasodilator thallium imaging of the heart with amyl nitrite inhalation: a pilot study.

Thallium imaging of the heart using dipyridamole-induced coronary arteriolar vasodilation has proven to be an effective means of detecting significant coronary stenosis. However, intravenous dipyridamole has not yet been made available for general use. We therefore examined the feasibility of substituting amyl nitrite inhalation as an arteriolar vasodilator prior to thallium imaging. Seventeen patients, all of whom had catheterization-proven coronary stenosis, inhaled amyl nitrite for 2-5 min. Thallium was injected after 45-60 s of inhalation. Completion of inhalation was followed immediately by planar imaging. Of 6 patients who inhaled amyl nitrite for at least 4 min, 5 had moderate or severe image defects on immediate scans which completely resolved on delayed scans. Only 3 of 11 who inhaled amyl nitrite for 2 min or less prior to scanning had similarly positive tests. Overall sensitivity for significant stenosis was 8 of 17 (47%). Inhalation was well tolerated with only one episode of angina and hypotension. We conclude that amyl nitrite inhalation for at least 4 min may offer an effective and readily available alternative to intravenous dipyridamole for vasodilator imaging of the heart.

Administration, Inhalation↗
PubMed1991

Inhaled epinephrine and oral theophylline-ephedrine in the treatment of asthma.

Inhaled and oral over-the-counter bronchodilators are used for self-therapy by asthmatic patients. To evaluate their safety and efficacy, we compared epinephrine and theophylline combined with ephedrine with inhaled metaproterenol and the placebo. Twelve asthmatic patients were studied in a randomized, double-blind, placebo-controlled, crossover trial comparing forced expiratory volume in 1 second (FEV1) after two inhalations of epinephrine (0.2 mg/inh), 1 minute apart, followed in 15 minutes by theophylline (130 mg) with ephedrine (24 mg) versus two inhalations of metaproterenol (0.65 mg/inh), 1 minute apart, versus placebo inhaler and tablets. Onset of FEV1 greater than 15% above baseline values occurred within 15 seconds after inhalations for 100% of epinephrine-treated patients, 92% of metaproterenol-treated patients, and 33% of placebo-treated patients. FEV1 responses were significantly greater (P less than .05) for epinephrine at 0.66 to 1.66 minutes compared with the responses of metaproterenol, and epinephrine and theophylline that was combined with ephedrine compared with metaproterenol beginning at 2 hours. Mean duration of activity was 5.7 hours for the epinephrine- and theophylline with ephedrine-treated patients, 4.9 hours for metaproterenol-treated patients, and 2 hours for the placebo group. There were statistically significant differences for patients receiving epinephrine and theophylline with ephedrine versus the placebo group (P less than .001), metaproterenol patients versus the placebo group (P = .02), and patients receiving epinephrine and theophylline with ephedrine versus metaproterenol-treated patients (P less than .05). Compared with inhaled metaproterenol, inhaled epinephrine followed in 15 minutes by a theophylline-ephedrine tablet had a significantly earlier onset, longer duration of action, numerically greater peak effect, and patient preference.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed2005

Optimizing inhaled corticosteroid therapy in children with chronic asthma.

Asthma is the most common chronic illness among children, and inhaled corticosteroids (ICS) are the most effective long-term therapy available for suppressing airway inflammation in persistent asthma. While the primary aim of ICS therapy is good efficacy with minimal side effects, early diagnosis and treatment of asthma can also improve asthma control and normalize lung function, and may prevent irreversible airway injury. Poor patient compliance is a major barrier to treatment. Simplified dosing regimens (e.g., once-daily administration), good inhaler technique, and education of the patient/caregiver should improve patient compliance. Concerns over ICS therapy are often based on the potential for systemic effects associated with oral corticosteroids (e.g., effects on bone mineral density, or growth suppression in children). Since adverse events are associated with high doses of ICS, the dose in all patients should be titrated to the minimum effective dose required to maintain control. Optimal distribution of an ICS in the lungs rather than the systemic compartment is affected by several factors, including the drug's pharmacokinetic profile, inhaler type, inhaler technique, and drug particle size. For young patients unable to use a dry-powder inhaler or pressurized metered-dose inhaler, a nebulizer facilitates drug delivery through passive inhalation; ICS therapy in the form of budesonide inhalation suspension can be given to children with persistent asthma from 12 months of age. In conclusion, selecting a drug with good efficacy and minimal side effects, such as budesonide, together with an easy-to-use delivery system and ongoing patient/caregiver education, is important in optimizing ICS therapy for children with persistent asthma.

Administration, Inhalation↗
PubMed2006

Assessment of inhalation technique and determinants of incorrect performance among children with asthma.

The objective of our study was to evaluate the pressurized metered dose inhaler (pMDI) with holding chamber technique of asthmatic children attending out patient pediatric chest clinic and determine factors associated with incorrect technique. All patients had previously received instructions regarding inhalation technique. The inhalation technique was assessed on a five-point checklist, four of which were considered essential. Two hundred and thirteen children (mean +/- SD age, 7.3 +/- 3.8 years; 151 boys) completed the study. Children were using their inhaler for a median duration of 6 months (range 1-96 months). One hundred and eighty-eight patients (88.3%) performed all essential steps correctly. The commonest mistake among the essential steps was not shaking the inhaler (n = 21, 9.9%) followed by inability to make a tight seal around the mouthpiece of the holding chamber (n = 12, 5.6%). Correct technique was not affected by gender, asthma severity and socio-economic indices: education level of parents, percapita monthly income, rural or urban background. Our study indicates that a large majority of children from a developing country setting, irrespective of lower education and income levels can be successfully educated to appropriately use inhalation device. Inhalation performance is not affected by socio-economic background of the patients. Comprehensive inhalation instructions and monitoring at each visit are however critical to ensure reliable and consistent performance of correct technique among asthmatic children.

Adolescent↗
PubMed1993

The protective effect of inhaled levomepromazine (Nozinan) on histamine-induced bronchial constriction.

The effect of inhaled levomepromazine (Nozinan, Veractil) on bronchial responsiveness to inhaled histamine was investigated in asthmatics. In a double blind, randomized controlled study, 12 asthmatics (FEV1% pred 52-96%, and PC20 histamine 1.01 mg/ml (geometric mean)) were challenged before and after inhalation of levomepromazine in three different doses. Before and after each inhalation of levomepromazine, PC20, FEV1, the continuous reaction time (CRT) and the subjective sedation score (VAS) were determined. A dose-dependent increase in PC20 was observed after inhalation of levomepromazine. PC20 was increased by up to 4.02 two-fold concentration differences (doubling), i.e. up to a 38-fold increase from the basic values. Inhalation of the two higher doses of levomepromazine had a small sedative effect evaluated from an increase in CRT and the VAS-score and corresponding to the plasma concentrations. We conclude that inhaled levomepromazine has a dose-dependent protective effect on histamine-induced bronchial hyperresponsiveness in asthmatics and that inhalation of levomepromazine was well tolerated. The mechanism by which levomepromazine acts on histamine-induced bronchial hyperresponsiveness is not known but it could be partly explained by the antihistaminic effect. In this respect levomepromazine bears comparison with the most potent second generation antihistamines. The plasma concentrations of levomepromazine measured corresponded to those seen after oral intake of 5-10 mg levomepromazine.

Administration, Inhalation↗
PubMed2002

Effects of inhaled furosemide on CO(2) ventilatory responsiveness in humans.

We previously showed that inhaled furosemide improves experimentally induced dyspnea. In order to test the possibility that inhaled furosemide may alter the CO(2) chemosensitivity and thereby reduce the dyspneic sensation, the effect of inhaled furosemide on CO(2) chemosensitivity was evaluated with a double-blinded, randomized crossover design in 10 healthy subjects. The CO(2) chemosensitivity was measured by the steady-state and rebreathing methods before and after the inhalation of placebo (normal saline) and furosemide aerosols (40 mg). In addition, subjects were asked to rate their sensation of respiratory discomfort using a visual analog scale (dyspneic VAS) during the measurement of CO(2) chemosensitivity with the steady-state method. Our results showed that (1) inhaled furosemide does not affect the breathing patterns of resting breathing, (2) inhaled furosemide does not affect the slope and intercept of the CO(2) response curve, regardless of whether the CO(2) chemosensitivity is measured by the steady-state technique or rebreathing technique and (3) inhaled furosemide improves the dyspneic sensation produced during hypercapnic hyperpnea. These results suggest that the mechanism of the improvement of dyspnea by inhaling furosemide is not associated with the decrease in the ventilatory drive to CO(2).

Administration, Inhalation↗
PubMed1994

Terbutaline in COPD comparison between Turbuhaler and chlorofluorocarbon (CFC) inhaler.

Patients with chronic obstructive pulmonary disease (COPD) often subjectively benefit from inhaled beta 2-agonists in spite of little or no demonstrable effect in forced expiratory volume in 1 second (FEV1.0). A comparison between the effects of terbutaline administered via a dry powder inhaler (Turbuhaler) and via a chlorofluorocarbon (CFC) inhaler in conjunction with a spacer device (Nebuhaler) was performed in patients with regard to FEV1.0, forced expiratory capacity (FVC), residual volume (RV), and specific conductance (s-Gaw). Fifteen hospitalised patients (11 male) with COPD were studied, each of whom had a diurnal variation in peak expiratory flow (PEF) not exceeding 15% and with a demonstrated volume response to inhaled beta 2-agonists in FVC and/or RV of at least 15%. Patients were administered each of the following five treatments on a single occasion in a randomized order (latin square) in intervals of at least 2 days: placebo, terbutaline via Turbuhaler (1.0 and 2.5 mg) and terbutaline via a CFC inhaler (1.0 mg without and 2.5 mg with Nebuhaler). Inhalation of terbutaline in different doses and from different devices induced a decrease in RV, an increase in FVC, and s-Gaw and a less pronounced increase in FEV1.0. No statistically significant differences between the four terbutaline treatments were seen, but all were significantly different from the placebo. These findings indicate that while patients with COPD may benefit from inhaled terbutaline through decreased hyperinflation, the choice of inhalation device seems to be of little importance for its efficacy.

Administration, Inhalation↗
PubMed1995

Effect of nicotine vapour inhalation on the relief of tobacco withdrawal symptoms.

Fifteen subjects participated in a randomised, placebo-controlled cross-over study to assess the effect of a nicotine vapour inhaler on craving and other withdrawal symptoms during a two-day smoking-free period. Craving and withdrawal symptoms were rated nine times over the two-day period on 10 cm visual analogue scales. Plasma nicotine concentrations in the afternoon of each study day were determined. The results show that active treatment was significantly superior to placebo in decreasing craving and other withdrawal symptom scores. No difference was found between two inhalation techniques, one with shallow, frequent inhalations (buccal technique), and the other with deep inhalations (pulmonary technique). The average number of active nicotine vapour inhalers and placebo inhalers used during the two-day sessions was 12 and 11, respectively. Afternoon plasma nicotine levels of approximately 7 ng/ml were obtained with both inhalation techniques. A strong correlation was found between the afternoon plasma nicotine levels and craving, a high nicotine level being associated with a low craving score. The study has provided information about how to use the nicotine vapour inhaler that could have important implications if it were to be approved for the treatment of tobacco dependence. The use of withdrawal symptom reduction as a surrogate end-point is discussed.

Administration, Inhalation↗
PubMed1996

An international registry for toxic inhalation and pulmonary edema: notes from work in progress.

Acute toxic inhalation by irritant, and particularly oxidant, gases has until recently been considered to be no more complicated conceptually than a chemical burn of the epithelial surface. More recently, however, toxic inhalation has been appreciated to be a complex process involving biochemical, morphological and functional changes which are quantitatively similar, although inducible by different agents. Recent advances in pulmonary pathophysiology, inhalation toxicology, and particularly endothelial biology have clarified the events occurring at the moment of, and immediately following, exposure to oxidant gases. Studies of the pathophysiologic mechanisms associated with toxic inhalation by oxidant gases have been relatively static, however. Implications of recent findings in related fields illuminate the pathophysiology of toxic inhalation. Several principal speakers in this workshop are collaborating in an effort to develop a research facility for the study of toxic inhalation injury. This would be an international registry to serve as a teaching and research facility for documentation of cases of occupational and environmental toxic inhalation, considered as lung injury resulting from the inhalation of a toxic substance in a workplace setting or an uncontrolled release affecting residents of a community. The registry, as proposed, would encourage submissions by clinicians and institutions of a data set on each patient and on each incident; the registry would further encourage long-term follow-up of subjects and documentation of residual effects.

Administration, Inhalation↗
PubMed1994

Methaemoglobin production in normal adults inhaling low concentrations of nitric oxide.

OBJECTIVE: The study was performed to determine the changes in blood methaemoglobin level during the inhalation of nitric oxide. DESIGN: The study was an unblinded dose-response study. PARTICIPANTS: 5 healthy adult volunteers aged 30-36 (4 male and 1 female) were studied on 4 occasions separated by at least one week. INTERVENTION: Nitric oxide was inhaled at inspired concentrations of 32, 64, 128, and 512 volumes per million (vpm) in air. Venous blood samples were taken every 10 min for methaemoglobin determination. Inhalation continued for 3 h (32, 64 and 128 vpm) or until the methaemoglobin exceeded 5% of the total haemoglobin (512 vpm). The methaemoglobin levels were also recorded for 3 h after 512 vpm nitric oxide had been stopped. MEASUREMENTS AND RESULTS: Both the increase in methaemoglobin fraction during nitric oxide inhalation and the decay after ceasing inhalation fitted well with a first order model describing methaemoglobin elimination. The calculated time constants were between 39-91 min. The predicted mean maximum methaemoglobin levels that would be achieved during inhalation of 32, 64, 128, and 512 vpm nitric oxide were 1.04% (0.92-1.16), 1.75% (1.80-1.90%), 3.75% (3.58-4.05), 6.93% (5.70-8.16) respectively (95% confidence interval of estimate in brackets). CONCLUSIONS: In normal individuals inhalation of up to 128 vpm of nitric oxide, greater than any dose used clinically to date, does not result in clinically significant methaemoglobinaemia. Maximum methaemoglobin levels are likely to be reached in 3-5 h after inhalation begins. However, these figures may not apply to critically ill adults and infants. Nitric oxide may have other toxic effects not examined in this study.

Administration, Inhalation↗
PubMed1994

Inhaled nitric oxide in acute respiratory failure: dose-response curves.

OBJECTIVE: To determine the dose-response curve of inhaled nitric oxide (NO) in terms of pulmonary vasodilation and improvement in PaO2 in adults with severe acute respiratory failure. DESIGN: Prospective randomized study. SETTING: A 14-bed ICU in a teaching hospital. PATIENTS: 6 critically ill patients with severe acute respiratory failure (lung injury severity score > or = 2.5) and pulmonary hypertension. INTERVENTIONS: 8 concentrations of inhaled NO were administered at random: 100, 400, 700, 1000, 1300, 1600, 1900 and 5000 parts per billion (ppb). Control measurements were performed before NO inhalation and after the last concentration administered. After an NO exposure of 15-20 min, hemodynamic parameters obtained from a fiberoptic Swan-Ganz catheter, blood gases, methemoglobin blood concentrations and intratracheal NO and nitrogen dioxide (NO2) concentrations, continuously monitored using a bedside chemiluminescence apparatus, were recorded on a Gould ES 1000 recorder. In 2 patients end-tidal CO2 was also recorded. RESULTS: The administration of 100-2000 ppb of inhaled NO induced: i) a dose-dependent decrease in pulmonary artery pressure and in pulmonary vascular resistance (maximum decrease--25%); ii) a dose-dependent increase in PaO2 via a dose-dependent reduction in pulmonary shunt; iii) a slight but significant decrease in PaCO2 via a reduction in alveolar dead space; iv) a dose-dependent increase in mixed venous oxygen saturation (SVO2). Systemic hemodynamic variables and methemoglobin blood concentrations did not change. Maximum NO2 concentrations never exceeded 165 ppb. In 2 patients, 91% and 74% of the pulmonary vasodilation was obtained for inhaled NO concentrations of 100 ppb. CONCLUSION: In hypoxemic patients with pulmonary hypertension and severe acute respiratory failure, therapeutic inhaled NO concentrations are in the range 100-2000 ppb. The risk of toxicity related to NO inhalation is therefore markedly reduced. Continuous SVO2 monitoring appears useful at the bedside for determining optimum therapeutic inhaled NO concentrations in a given patient.

Acute Disease↗