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PubMed1997

Halothane inhalation inhibits the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits.

We demonstrated the inhibitory effect of halothane (HAL) inhalation on the metabolism of chlorzoxazone (CZZ), a substrate for CYP2E1, in a bolus and a continuous injection study in rabbits receiving artificial ventilation. In a bolus injection study, the inhalation of 1.0% HAL significantly increased the half-life and the area under the curve and decreased the clearance of CZZ compared with those variables in midazolam administration. In a continuous injection study, the effect of various concentrations of inhaled HAL on plasma CZZ concentration at steady state was compared. Systolic and diastolic arterial blood pressure were decreased dose-dependently after 0.5%, 1.0%, or 2.0% HAL was inhaled. Although the plasma concentration of CZZ was increased 2.5-fold after 3 h of HAL inhalation, there was no significant difference in mean plasma concentrations among the groups treated with 0.5%, 1.0%, or 2.0% HAL. In contrast, the plasma concentration of lidocaine, a substrate for CYP3A, remained unchanged after 1.0% HAL was inhaled. These results suggest that general anesthesia obtained with HAL inhalation will affect the metabolism of drugs administered concomitantly when the drug is a substrate for CYP2E1.

Anesthesia, Inhalation↗

PubMed2006

Comparison of minimum alveolar concentration between intravenous isoflurane lipid emulsion and inhaled isoflurane in dogs.

BACKGROUND: As in inhaled isoflurane anesthesia, when isoflurane lipid emulsion (ILE; 8%, vol/vol) is intravenously administered, the primary elimination route is through the lungs. This study was designed to determine the minimum alveolar concentration (MAC) and the time course of washout of isoflurane for intravenously infused ILE by monitoring end-tidal isoflurane concentration. METHODS: Twelve healthy adult mongrel dogs were assigned randomly to an intravenous anesthesia group with 8% ILE or to an inhalation anesthesia group with isoflurane vapor. An up-and-down method and stimulation of tail clamping were used to determine MAC of 8% ILE by intravenous injection in the intravenous anesthesia group and MAC by the inhaled approach in the inhalation anesthesia group, respectively. Isoflurane concentration and partial pressure in end-tidal gas, femoral arterial blood, and jugular venous blood were measured simultaneously just before each tail clamping and during washout. RESULTS: The induction time in the intravenous anesthesia group (105 +/- 24 s) was shorter than that in the inhalation anesthesia group (378 +/- 102 s; P < 0.01). MAC of 8% ILE by intravenous injection (1.12 +/- 0.18%) was significantly less than MAC by the inhaled approach (1.38 +/- 0.16%; P < 0.05). No significant difference was found between the two groups in the time course of washout of isoflurane. CONCLUSION: The MAC of intravenous anesthesia with 8% ILE was less than that of inhalation anesthesia with isoflurane vapor in dogs.

Administration, Inhalation↗

PubMed2000

Inhaled nitric oxide reduces the need for extracorporeal membrane oxygenation in infants with persistent pulmonary hypertension of the newborn.

OBJECTIVE: We previously reported improved oxygenation, but no change, in rates of extracorporeal membrane oxygenation (ECMO) use or death among infants with persistent pulmonary hypertension of the newborn who received inhaled nitric oxide (NO) with conventional ventilation, irrespective of lung disease. The goal of our study was to determine whether treatment with inhaled NO improves oxygenation and clinical outcomes in infants with persistent pulmonary hypertension of the newborn and associated lung disease who are ventilated with high-frequency oscillatory ventilation (HFOV). DESIGN: Single-center, prospective, randomized, controlled trial. SETTING: Newborn intensive care unit of a tertiary care teaching hospital. PATIENTS: We studied infants with a gestational age of > or =34 wks who were receiving mechanical ventilatory support and had echocardiographic and clinical evidence of pulmonary hypertension and hypoxemia (PaO2 < or =100 mm Hg on FIO2 = 1.0), despite optimal medical management Infants with congenital heart disease, diaphragmatic hernia, or other major anomalies were excluded. INTERVENTIONS: The treatment group received inhaled NO, whereas the control group did not. Adjunct therapies and ECMO criteria were the same in the two groups of patients. Investigators and clinicians were not masked as to treatment assignment, and no crossover of patients was permitted. MEASUREMENTS AND MAIN RESULTS: Primary outcome variables were mortality and use of ECMO. Secondary outcomes included change in oxygenation and duration of mechanical ventilatory support and supplemental oxygen therapy. Forty-two patients were enrolled. Baseline oxygenation and clinical characteristics were similar in the two groups of patients. Infants in the inhaled NO group (n = 21) had improved measures of oxygenation at 15 mins and 1 hr after enrollment compared with infants in the control group (n = 20). Fewer infants in the inhaled NO group compared with the control group were treated with ECMO (14% vs. 55%, respectively; p = .007). Mortality did not differ with treatment assignment. CONCLUSIONS: Among infants ventilated by HFOV, those receiving inhaled NO had a reduced need for ECMO. We speculate that HFOV enhances the effectiveness of inhaled NO treatment in infants with persistent pulmonary hypertension of the newborn and associated lung disease.

Administration, Inhalation↗

PubMed2005

Could interchangeable use of dry powder inhalers affect patients?

The aim of asthma treatment is optimal disease control. Poor asthma control results in considerable patient morbidity, as well as contributing to the considerable burden placed by the disease on healthcare budgets. There is a need for costs to be carefully scrutinised, with the switching of patients to inhaler devices with lower acquisition costs likely to be increasingly considered. However, before such practice becomes widespread, it is important to establish whether or not this could adversely impact on patients and the level of disease control. For approval to have been given, all marketed inhalers must have satisfied current regulatory requirements for devices. Full preclinical and clinical development programmes are not required when application is made for authorisation to market a new inhaler containing an existing chemical entity, although clinical equivalence testing must be used. Both beneficial and adverse effects should be tested, and the limits of equivalence must be clearly defined, based on therapeutic relevance. It should be noted that equivalence studies are invalid when the end point is not responding (i.e. at the top of the dose-response curve) and when equivalence limits approach or are equal to the magnitude of the drug effect. Approval on the basis of regulations designed to safeguard quality of dry powder inhalers does not mean that devices are interchangeable. When using an inhaler, there are many stages between the patient and the therapeutic effect, involving device design, pharmaceutical performance and patient behaviour. Regulations governing new devices cover only a few of the many factors affecting disease control. Furthermore, clinical trials to assess equivalence may not take into account factors in patient behaviour or variations in patient inhaler technique that may affect use of devices in real-life situations. When assessing the consequences of interchangeable use of dry powder inhalers on healthcare costs, it is important to ensure that the acquisition cost of the devices is not the only cost considered. Other costs that should be considered include the cost of time spent demonstrating to the patient how to use the new device, the cost of additional physician visits to address patient concerns and the management costs if disease control is adversely affected.

Administration, Inhalation↗

PubMed2006

Spacer inhalation technique and deposition of extrafine aerosol in asthmatic children.

The aim of the present study was to measure airway, oropharyngeal and gastrointestinal deposition of (99m)Tc-labelled hydrofluoroalkane-beclomethasone dipropionate after inhalation via a pressurised metered-dose inhaler and spacer (Aerochamber Plus) in asthmatic children. A group of 24 children (aged 5-17 yrs) with mild asthma inhaled the labelled drug. A total of 12 children took five tidal breaths after each actuation (tidal group). The other 12 children used a slow maximal inhalation followed by a 5 - 10-s breath-hold (breath-hold group). Simultaneous anterior and posterior planar gamma-scintigraphic scans (120-s acquisition) were recorded. For the tidal group, mean+/-sd lung deposition (% ex-actuator, attenuation corrected) was 35.4+/-18.3, 47.5+/-13.0 and 54.9+/-11.2 in patients aged 5-7 (n = 4), 8-10 (n = 4) and 11-17 yrs (n = 4), respectively. Oropharyngeal and gastrointestinal deposition was 24.0+/-10.5, 10.3+/-4.4 and 10.1+/-6.2. With the breath-hold technique, lung deposition was 58.1+/-6.7, 56.6+/-5.2 and 58.4+/-9.2. Oropharyngeal and gastrointestinal deposition was 12.9+/-3.2, 20.1+/-9.5 and 20.8+/-8.8. Inhalation of the extrafine formulation with the breath-hold technique showed significantly improved lung deposition compared with tidal breathing across all ages. Oropharyngeal and gastrointestinal deposition was markedly decreased, regardless of which inhalation technique was applied, compared with a previous paediatric study using the same formulation delivered via a breath-actuated metered-dose inhaler.

Administration, Inhalation↗

PubMed2004

Inhaled iloprost is a potent acute pulmonary vasodilator in HIV-related severe pulmonary hypertension.

As antiretroviral therapy has improved life expectancy in human immunodeficiency virus (HIV) infection, the life-limiting complication of HIV-related pulmonary hypertension has come into focus. Inhalation of the stable prostacyclin analogue iloprost is an effective treatment for various forms of precapillary pulmonary hypertension. The main objective of the present study was to evaluate the safety and efficacy of inhaled iloprost in HIV-related pulmonary hypertension. In eight patients with severe pulmonary hypertension related to HIV infection, right heart and femoral artery catheterisation were performed. The acute effect of oxygen, inhaled nitric oxide and aerosolised iloprost was investigated. Four patients underwent long-term treatment with inhaled iloprost. The rank order of pulmonary vasodilatory potency was iloprost>NO>O2, with a maximum reduction (mean +/- SEM) in pulmonary vascular resistance of 30.6 +/- 3.1% (p < 0.001), 5.9 +/- 3.9% and -0.6 +/- 3.9%, respectively. Concomitantly, inhaled iloprost significantly increased the cardiac index and central venous oxygen saturation. Chronic treatment with inhaled iloprost tended to improve the 6 min walking distance and decreased pulmonary vascular resistance in all patients (although not significantly). No serious adverse events and no major interactions with the ongoing antiretroviral therapy were noted. In conclusion, inhaled iloprost is a potent pulmonary vasodilator in human immune deficiency virus-related pulmonary hypertension. Future studies are warranted to confirm the encouraging long-term beneficial results observed in the present limited number of patients.

Administration, Inhalation↗

PubMed1997

The effect of low-dose inhalation of nitric oxide in patients with pulmonary fibrosis.

The aim of this study was to determine whether low-dose inhalation of nitric oxide (NO) improves pulmonary haemodynamics and gas exchange in patients with stable idiopathic pulmonary fibrosis (IPF). The investigation included 10 IPF patients breathing spontaneously. Haemodynamic and blood gas parameters were measured under the following conditions: 1) breathing room air; 2) during inhalation of 2 parts per million (ppm) NO with room air; 3) whilst breathing O2 alone (1 L.min-1); and 4) during combined inhalation of 2 ppm NO and O2 (1 L.min-1). During inhalation of 2 ppm NO with room air the mean pulmonary arterial pressure (Ppa 25 +/- 3 vs 30 +/- 4 mmHg) and the pulmonary vascular resistance (PVR 529 +/- 80 vs 699 +/- 110 dyn.s.cm-5) were significantly (p < 0.01) lower than levels measured whilst breathing room air alone. However the arterial oxygen tension (Pa,O2) did not improve. The combined inhalation of NO and O2 produced not only a significant (p < 0.01) decrease of Ppa (23 +/- 2 vs 28 +/- 3 mmHg) but also, a remarkable improvement (p < 0.05) in Pa,O2 (14.2 +/- 1.2 vs 11.7 +/- 1.0 kPa) (107 +/- 9 vs 88 +/- 7 mmHg)) as compared with the values observed during the inhalation of O2 alone. These findings suggest that the combined use of nitric oxide and oxygen might constitute an alternative therapeutic approach for treating idiopathic pulmonary fibrosis patients with pulmonary hypertension. However, further studies must first be carried out to demonstrate the beneficial effect of oxygen therapy on pulmonary haemodynamics and prognosis in patients with idiopathic pulmonary fibrosis and to rule out the potential toxicity of inhaled nitric oxide, particularly when used in combination with oxygen.

Administration, Inhalation↗

PubMed2026

Post-operative pain, nausea, vomiting and optic nerve sheath diameter following total intravenous versus inhalational anesthesia for adults undergoing robotic transabdominal surgery - a systematic review and meta- analysis.

BACKGROUND: The introduction of robotic-assisted abdominal surgery is aimed at reducing the primary and secondary adverse outcomes. Anesthesia in robotic surgery varies from anesthesia for open or laparoscopic surgical procedures. The choice of anesthesia influences the perioperative control of pain, nausea, vomiting, and Optic nerve sheath diameter (ONSD). The purpose of this systematic review was to assess outcome variation in patients undergoing transabdominal robot-assisted surgery done under total intravenous anesthesia or inhalational anesthesia. METHODOLOGY: We searched the Cochrane Central Register of Controlled Trials, PubMed, and Google Scholar (January, 2017 to June, 2024). Search terms included "Anesthesia", "Robotics", "prostatectomy", hysterectomy", "nephrectomy", "cholecystectomy" and "cystectomy" with the Boolean operators "AND" and "OR". We searched for randomized controlled trials (RCTs) including adults of both genders aged 18 years and above, who underwent transabdominal robotic-assisted laparoscopic surgery and targeting the consequences related to TIVA or inhalational anesthesia. We reviewed titles and abstracts and proceeded to full-text articles of the eligible studies relevant to inclusion criteria. Mean and standard deviations with 95% CI were calculated. Forest plots were used to present data visually. RESULTS: Six studies (340 patients) were included. We found only one study in which post-operative pain was assessed and results favored intravenous anesthesia in robotic transabdominal surgery. Only two studies reported post-operative nausea and vomiting (PONV). Both studies stated that PONV is reported in few patients in the inhalation anesthesia group. We found evidence suggesting that change in ONSD measurements at 10 min after induction (MD 0.04,95% CI -0.02 to 0.11 p = 0.19) and 40-60 min after Trendelenburg position (MD -0.26, 95% CI -0.34 to 0.17, p = 0.16) are much less in intravenous anesthesia group than in inhalation anesthesia group. Total intravenous anesthesia maintains the ONSD and hence the ICP better than inhalational anesthesia in robotic transabdominal surgery with CO2 pneumoperitoneum in Trendelenburg positioning requirements. It would be a safer choice than inhalational anesthesia due to fewer adverse events. CONCLUSION: This review concludes that TIVA is a better choice than inhalational anesthesia for transabdominal robotic-assisted surgery in urology, gynecology, and gastroenterology in both male and female patients.

Humans↗

PubMed2006

Influence of mouth washing procedures on the removal of drug residues following inhalation of corticosteroids.

Mouth washing after inhalation of corticosteroids is effective for prevention of local adverse effects such as hoarseness and oropharyngeal candidiasis. To establish an optimal procedure for such mouth washing, we investigated the removal rates of drug residues remaining on the oropharyngeal mucosa using various mouth washing methods following inhalation. A beclomethasone dipropionate metered dose inhaler (BDP-MDI) (100 microg) and a fluticasone propionate dry powder inhaler (FP-DPI) (100 microg) were used. The effects of different mouth washing methods were evaluated by quantification of drugs in the expectorated rinse solution using an HPLC method. The amounts of BDP recovered in the rinse after gargling and rinsing for 5 s each were 47.1+/-13.6 microg, while they were 42.9+/-9.4 microg after rinsing alone for 10 s and 38.7+/-9.2 microg after gargling alone for 10 s. Under the same conditions, FP amounts were 32.9+/-7.3 microg, 28.9+/-2.4 microg, and 27.1+/-7.9 microg, respectively. In a comparison of washing time, the amounts of BDP recovered were 49.8+/-9.7 microg after gargling and rinsing for 2 s each, 53.5+/-10.2 microg after those for 3 s each, and 47.1+/-13.6 microg after those for 5 s each, while the amounts of FP under the same conditions were 36.4+/-2.4 microg, 33.3+/-6.4 microg, and 32.9+/-7.4 microg, respectively. As for the effect of time lag before mouth washing, the amount of BDP recovered decreased by 65.7% with a lag time of 1 min and by 5.6% after 10 min, while that of FP decreased by 51.1% with a lag time of 1 min and by 7.7% after 10 min. Our results suggest that the amount of drugs removed by mouth washing is significantly associated with the time lag between inhalation and mouth washing. We concluded that immediate gargling and rinsing after inhalation is most useful for the removal of drugs following inhalation of corticosteroids.

Administration, Inhalation↗

PubMed1996

Inhalation of single vs multiple metered-dose bronchodilator actuations from reservoir devices. An in vitro study.

UNLABELLED: Differences in inhalation technique with reservoir or spacer devices may affect metered-dose inhaler (MDI) dose availability to a patient. PURPOSE: This study examined the effect of single vs multiple actuations of an MDI into reservoir devices on dose delivery of albuterol, with three clinically available reservoir brands. METHODS: An in vitro lung model simulated inspiration from the MDI reservoir system. Albuterol (Proventil; Schering) was delivered by MDI, with the Monaghan Aerochamber, the Diemolding Healthcare Division (DHD) aerosol cloud enhancer (ACE), and the Schering InspirEase, using standardized volumes and inspiratory flows of 30 L min(-1). The MDI was actuated into each brand of reservoir 1, 2, or 3 times in rapid succession, followed by a single inhalation. Aerosol dose at the reservoir mouthpiece was captured on a cotton filter, dissolved in ethanol, and measured with a spectrophotometer at 278 nm. RESULTS: For all three brands of reservoir, less accumulated dose of drug is delivered with multiple actuations than with multiple single actuations each followed by inhalation. The total dose in milligrams increased significantly with two multiple actuations compared with one actuation in the Aerochamber and ACE (p<0.01), but not in the InspirEase (p>0.05). The Aerochamber, ACE, and InspirEase delivered a mean total dose (SD) of 0.0264 mg (0.012), 0.0271 mg (0.007), and 0.0136 mg (0.006), respectively, with one actuation compared to 0.0485 mg (0.011), 0.0453 mg (0.013), and 0.0218 mg (0.009) with two multiple actuations. The increase in total dose with three multiple actuations was not significant compared to two actuations for any of the brands tested (p>0.05). Although total dose increased with multiple actuations, a decline in efficiency was seen with two and three multiple actuations, compared to single actuation. The dose delivered per actuation decreased for the Aerochamber, ACE, and InspirEase from 0.0264 mg (0.012), 0.0271 mg (0.007), and 0.0136 mg (0.006) with one actuation, to 0.0243 mg (0.006), 0.0226 mg (0.006), and 0.0109 mg (0.005), respectively, with two multiple actuations, for losses of 8.0%, 16.6%, and 19.9% in dose per actuation for each brand. A further decline in delivery per actuation to 0.0164 mg (0.001), 0.0184 mg (0.004), and 0.0097 mg (0.005) for the 3 brands, respectively, was found with 3 multiple actuations before inhalation. This was a loss of 37.9%, 32.1%, and 28.7% of the dose per single actuation in each brand. There was no significant difference between the Aerochamber and the ACE in dose availability with 1, 2, or 3 actuations, but both of these brands provided significantly more drug than the InspirEase. CONCLUSION: Maximal aerosol bronchodilator from an MDI reservoir was given by single actuations each followed by a breath. Two rapid actuations followed by a breath will give a significant accumulation of dose with some loss when compared to two single actuations each followed by inhalation. Three multiple actuations led to a loss of approximately one third of the drug dose obtainable with three single actuations each followed by inhalation, for all three brands.

Administration, Inhalation↗

PubMedDate not supplied

Supraventricular tachycardia after fenoterol inhalation: report of two cases.

Supraventricular tachycardia (SVT) following fenoterol inhalation in metered-dose inhaler (MDI) has never been reported. We report two cases of SVT after fenoterol inhalation in MDI. Case one was a 4-year-old boy who had asthma since early childhood. Paroxysmal supraventricular tachycardia (PSVT) was found after fenoterol inhalation (MDI), which returned to normal sinus rhythm following adenosine injection. The other one was a 9-year-old male who also had asthma since early childhood. He suffered from attacks of PSVT four times after fenoterol inhalation within one year. After verapamil injection and vagal maneuvers, PSVT was converted to normal sinus rhythm. There were no other episodes of SVT after discontinuing usage of fenoterol inhalation for 2 years in the follow-up. We report these two cases to remind pediatricians that cardiac arrhythmias should be evaluated following fenoterol inhalation (MDI).

Administration, Inhalation↗

PubMed2005

[Establishment of a canine model of severe smoke inhalation injury on unilateral lung].

OBJECTIVE: To establish a canine model of severe smoke inhalation injury on unilateral lung, in order to observe the pathomorphological changes in the injured lung within 24 postburn hours (PBHs). METHODS: Twenty five mongrel dogs were employed in the study and randomized into 3 groups. The left lung was injured by inhaling smoke produced by burning sawdust with sparing the right lung with a breathing tube in 10 dogs in group A. A conventional model of smoke inhalation injury to bilateral lungs was reproduced in 8 dogs in group B, and dogs in group C not subjected to smoke inhalation served as controls. Hemodynamic changes, blood gas analysis and the pathophysiologic changes in the lungs were observed within 24 PBHs. RESULTS: All of the dogs in groups A and C survived. Hemodynamic indices in the dogs in groups A and C remained stable without showing signs of systemic hypoxia. The arterial oxygen partial pressure in dogs of group A was 65 +/- 5 mm Hg, and the oxygen saturation in the mixed blood was 0.64 +/- 0.04 at 24 PBHs, and they were much lower than those in group C but higher than those in group B. The pathological changes in the injured side of the lungs in group A were similar to those in group B with high consistency, and the changes, though milder, could also be identified in the contralateral uninjured lung. Five dogs died in the group B within 24 hours after smoke inhalation and the survivors showed signs of multiple organ failure. CONCLUSION: The canine model of acute severe unilateral pulmonary smoke inhalation injury was reproduced reliably, and could be an ideal model for the study on smoke inhalation injury.

Animals↗

PubMed1994

Acute inhalation injury.

Toxic inhalants cause injury through a variety of different mechanisms, including direct irritation of the respiratory tract mucosa, asphyxiation, and systemic absorption of the toxin. The nature and extent of the acute injury depends on the inhalant's water solubility, aerodynamic features, pH, and concentration. In addition, a patient's underlying respiratory function may affect the clinical response. Smoke inhalation is a particularly challenging clinical problem because patients often are exposed to a large number of inhaled toxins and may suffer thermal injury to the respiratory tract as well. Several chronic respiratory problems have been identified following acute inhalation injuries. Chronic airflow obstruction has been reported in patients exposed to ammonia, chlorine, nitrogen dioxide, and sulfur dioxide; bronchiolitis obliterans may follow exposure to nitrogen dioxide and sulfur dioxide. Inhalation injuries can be difficult to manage because exposures occur infrequently, and the exact toxic agents involved often are not known immediately. Prevention of occupational exposures remains a cornerstone in the overall management of inhalation injuries.

Burns, Inhalation↗

PubMed1999

Systemic adverse effects of inhaled corticosteroid therapy: A systematic review and meta-analysis.

OBJECTIVE: To appraise the data on systemic adverse effects of inhaled corticosteroids. METHODS: A computerized database search from January 1, 1966, through July 31, 1998, using MEDLINE, EMBASE, and BIDS and using appropriate indexed terms. Reports dealing with the systemic effects of inhaled corticosteroids on adrenal gland, growth, bone, skin, and eye, and reports on pharmacology and pharmacokinetics were reviewed where appropriate. Studies were included that contained evaluable data on systemic effects in healthy volunteers as well as in asthmatic children and adults. A statistical meta-analysis using regression was performed for parameters of adrenal suppression in 27 studies. RESULTS: Marked adrenal suppression occurs with high doses of inhaled corticosteroid above 1.5 mg/d (0.75 mg/d for fluticasone propionate), although there is a considerable degree of interindividual susceptibility. Meta-analysis showed significantly greater potency for dose-related adrenal suppression with fluticasone compared with beclomethasone dipropionate, budesonide, or triamcinolone acetonide, whereas prednisolone and fluticasone propionate were approximately equivalent on a 10:1-mg basis. Inhaled corticosteroids in doses above 1.5 mg/d (0.75 mg/d for fluticasone propionate) may be associated with a significant reduction in bone density, although the risk for osteoporosis may be obviated by post-menopausal estrogen replacement therapy. Although medium-term growth studies showed suppressive effects with 400-microg/d beclomethasone dipropionate, there was no evidence to support any significant effects on final adult height. Long-term, high-dose inhaled corticosteroid exposure increases the risk for posterior subcapsular cataracts, and, to a much lesser degree, the risk for ocular hypertension and glaucoma. Skin bruising is most likely to occur with high-dose exposure, which correlates with the degree of adrenal suppression. CONCLUSIONS: All inhaled corticosteroids exhibit dose-related systemic adverse effects, although these are less than with a comparable dose of oral corticosteroids. Metaanalysis shows that fluticasone propionate exhibits greater dose-related systemic bioactivity compared with other available inhaled corticosteroids, particularly at doses above 0.8 mg/d. The long-term systemic burden will be minimized by always trying to achieve the lowest possible maintenance dose that is associated with optimal asthmatic control and quality of life.

Administration, Inhalation↗

PubMed2001

e-NO peak versus e-NO plateau values in evaluating e-NO production in steroid-naive and in steroid-treated asthmatic children and in detecting response to inhaled steroid treatment.

SUMMARY. Airway nitric oxide (NO) production can be measured by chemiluminescence analyzer in children able to perform a single low exhalation. The aim of the present study was to evaluate whether exhaled NO (e-NO) peaks (first part of the exhalation) were as useful as e-NO plateaus (last part of the exhalation) in evaluating e-NO production in asthmatic children and in detecting responses to inhaled steroid treatment. E-NO peak, plateau, and rate of production values were measured in 100 atopic asthmatic children using a chemiluminescence analyser. Thirty-seven patients (mean age, 11.1 +/- 0.7 years) were receiving inhaled steroids (flunisolide, 0.8-1 mg daily) or beclomethasone (0.2-0.4 mg daily), while the remaining 63 (mean age, 12.0 +/- 0.4 yrs) were-steroid naive and treated only with inhaled beta(2)-agonists on an as-needed basis. Fifteen out of the 63 steroid-naive patients were reevaluated after a short course (3 weeks) of inhaled corticosteroid treatment (flunisolide, 0.8-1 mg daily, or beclomethasone, 0.2-0.4 mg daily). Regardless of the type of data analysis (peak, plateau, or rate of production), the e-NO values of the steroid-naive patients were significantly higher than those of inhaled steroid-treated patients (P < 0.01, each comparison). Similarly, in the subgroup of steroid-naive patients, the three methods were able to detect a decrease in e-NO levels by inhaled steroid therapy (P < 0.001, each comparison). Plotting the difference between e-NO peak and e-NO plateau values against their average, the peak e-NO concentrations were higher than e-NO plateau values. This difference was independent of the absolute e-NO concentration. The results of the two types of data analysis seems to agree more closely in steroid-naive patients than in steroid treated patients, or in the subgroup of steroid-naive patients who received a short course treatment with inhaled steroids. In steroid-treated subjects, the differences were up to five times higher for peak than plateau e-NO values. These data suggest that both e-NO plateau and e-NO peak values are useful in detecting airway NO production in atopic asthmatic children, but they cannot be used interchangeably. Because of possible nasal contamination in e-NO peak measurement, we prefer e-NO plateau levels for evaluating lower airway e-NO production.

Administration, Inhalation↗

PubMed2000

Inhaled steroids for neonatal chronic lung disease.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic disorder associated with prematurity. Systemic steroids induce at least a temporary improvement in respiratory function, but are associated with adverse side effects. Inhaled steroids have fewer side effects. OBJECTIVES: To determine if inhaled corticosteroids are effective in alleviating the morbidity of bronchopulmonary dysplasia (BPD) compared to 0-placebo. SEARCH STRATEGY: We identified randomised, controlled trials (RCT) within the Cochrane Database, references from retrieved trials, hand searches of journals and contact with pharmaceutical companies and experts in this field. SELECTION CRITERIA: Only randomised controlled trials involving infants with chronic lung disease of prematurity and treated with inhaled steroids versus placebo were included. Patients receiving systemic corticosteroids were excluded. Co-interventions included antenatal systemic steroids, routine neonatal intensive care, ventilatory support, surfactant replacement therapy, diuretics and bronchodilators. DATA COLLECTION AND ANALYSIS: Four of the seven included trials were of good methodological quality. There were five parallel-group trials in ventilated infants. These were comparable in terms of population, co-interventions and need for increased inspired oxygen concentration. They differed in terms of type, dose and duration (7-28 days) of inhaled steroids. Two cross-over trials were performed in non-ventilated patients. MAIN RESULTS: The inability to extubate during treatment was markedly reduced in infants treated with inhaled steroids; Peto Odds Ratio (OR) 0.12, 95% Confidence Interval (CI) 0.03 to 0.43. There was heterogeneity in this finding, however, with one study that contributed 30% of the total number of patients reporting no successful extubations in either treatment arm over one week. The risk of sepsis appeared similar between the two groups (N=3, OR=0.72, 95%CI: 0.21 to 2.43). The small number of trials precluded analysis to examine the effect of differences in drug, duration of therapy, delivery system, co-interventions, and disease severity. Reduced oxygen requirements were reported in one of the two trials performed in non-ventilated infants, but inadequate data reporting precluded pooling of data. REVIEWER'S CONCLUSIONS: In ventilated infants with BPD, inhaled steroids administered for 1 to 4 weeks improved the rate of extubation with no apparent increase in the risk of sepsis. No firm conclusion could be derived with regard to the efficacy of inhaled steroids in non-ventilated infants.

Administration, Inhalation↗

PubMed2004

Anti-leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma in adults and children.

BACKGROUND: Anti-leukotrienes agents are currently being studied as alternative first line agents to inhaled corticosteroids in mild to moderate chronic asthma. OBJECTIVES: To compare the safety and efficacy of anti-leukotriene agents with inhaled glucocorticoids (ICS) and to determine the dose-equivalence of anti-leukotrienes to daily dose of ICS. SEARCH STRATEGY: We searched MEDLINE (1966 to Aug 2003), EMBASE (1980 to Aug 2003), CINAHL (1982 to Aug 2003), the Cochrane Airways Group trials register, and the Cochrane Central Register of Controlled Trials (August 2003), abstract books, and reference lists of review articles and trials. We contacted colleagues and international headquarters of anti-leukotrienes producers. SELECTION CRITERIA: Randomised controlled trials that compared anti-leukotrienes with inhaled corticosteroids during a minimal 30-day intervention period in asthmatic patients aged 2 years and older. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the methodological quality or trials and extracted trial data. The primary outcome was the rate of exacerbations requiring systemic corticosteroids. Secondary outcomes included lung function, indices of chronic asthma control, adverse effects and withdrawal rates. MAIN RESULTS: 27 trials (including 1 trial testing two protocols) met the inclusion criteria; 13 were of high methodological quality; 20 are published in full-text. All trials pertained to patients with mild to moderate persistent asthma. Only 3 trials focused on children and adolescents. Trial duration varied from 4 to 37 weeks. In most trials, daily dose of ICS was 400 mcg of beclomethasone or equivalent. Patients treated with anti-leukotrienes were 65% more likely to suffer an exacerbation requiring systemic steroids [Relative Risk 1.65; 95% Confidence Interval (CI) 1.36 to 2.00]. Twenty six (95% CI: 17 to 47) patients must be treated with anti-leukotrienes instead of inhaled corticosteroids to cause one extra exacerbation. Significant differences favouring ICS were noted in secondary outcomes where()the improvement in FEV(1) reached 130 mL [13 trials; 95% CI: 50, 140 mL ]. Other significant benefits of ICS were seen for symptoms, nocturnal awakenings, rescue medication use, symptom-free days, and quality of life. Anti-leukotriene therapy was associated with 160% increased risk of withdrawals due to poor asthma control. Twenty nine (95% CI 20 to 48) patients must be treated with anti-leukotrienes instead of inhaled corticosteroids to cause one extra withdrawal due to poor control. Risk of side effects was not different between groups. REVIEWERS' CONCLUSIONS: Inhaled steroids at a dose of 400 mcg/day of beclomethasone or equivalent are more effective than anti-leukotriene agents given in the usual licensed doses. The exact dose-equivalence of anti-leukotriene agents in mcg of ICS remains to be determined. Inhaled glucocorticoids should remain the first line monotherapy for persistent asthma.

Administration, Inhalation↗

PubMed1993

Surfactant and inhaled particles in the conducting airways: structural, stereological, and biophysical aspects.

We have investigated the displacement into the sol phase of inhaled particles deposited in the intrapulmonary conducting airways. Hamsters inhaled an aerosol of monodisperse polystyrene particles of 6 microns diameter. Their lungs were fixed by intravascular perfusion, and light and electron microscopy was used to study the epithelial coating. The surfactant film at the wall-air interface was investigated by measuring its surface tension. The number of particles retained was determined stereologically. In addition we investigated the displacement of spherical particles in vitro on a DPPC monolayer in a Langmuir-Wilhelmy surface balance and determined the surface tension in vivo in the horse trachea by video bronchoscopy, applying the droplet spreading method. We found that particles deposited onto a surfactant film were pulled into the aqueous subphase, and we concluded that surface forces due to the airway surfactant likely displace deposited particles into the periciliary fluid (sol phase). Comparing lungs fixed immediately after inhalation with lungs fixed 24 hr after inhalation revealed that 86% of the particles retained in the intrapulmonary conducting airways immediately after inhalation had been cleared within 24 hr. One-third of the particles of the lungs fixed immediately after inhalation was phagocytized. The combination of structural and stereological analyses with in vitro and in vivo measurements has led to new insights into the role of airway surfactant with respect to the fate of inhaled particles, which may have important consequences regarding the effects of hazardous particles. These studies may also help to evaluate the deposition pattern and clearance of therapeutic particles, with important implications for their therapeutic use.

Administration, Inhalation↗