Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Inhalation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 595 records · Page 33Linked to original sources
PubMed2005

Key issues in inhalation therapy in children.

In order to achieve asthma control it is essential that children receive the appropriate education and training pertaining to the management of their disease, are prescribed the correct medication according to severity, and most importantly, are prescribed the correct inhaler to ensure medication is deposited in their lungs. There are three major misconceptions which physicians and patients have regarding the use of inhalers in children. Firstly, that the nebulizer is more effective than a pressurised metered dose inhaler (pMDI) plus spacer in treating acute asthma in children. Secondly that using an inhaler correctly is easy, and lastly that correct use of the inhaler, once taught, persists over time. However, recent studies have shown that these conceptions are false. Firstly, comparable efficacy is achieved by treatment with inhaled corticosteroids or bronchodilators delivered through a nebulizer and a pMDI plus spacer, both when used to treat acute asthma and for maintenance therapy. Secondly, contrary to general opinion, using an inhaler correctly is difficult for children. Many children with asthma use their inhaler devices incorrectly, even after instruction for correct use of the inhaler. Thirdly, correct inhalation technique deteriorates over time; and inhalation instructions, therefore, should be given repeatedly to achieve and maintain correct inhalation technique in asthmatic children. The profile of the ideal inhaler comprises good drug deposition in the lower airways, deliverance of a consistent dose, being easy to teach and to use correctly, and being small in size and convenient to handle. It should also be multidose, require a low inspiratory airflow for activation, provide feedback to patients on correct use of the inhaler, be re-usable, have an appealing design and feel, and have a reliable dose counter which may help to monitor the patient's compliance. The Novolizer device, a new multidose dry powder inhaler (DPI), shows many of these characteristics making it potentially very suitable for children with asthma.

Administration, Inhalation↗
PubMed2005

Status of inhalation therapy in bronchial asthma in adults above twelve years of age in armed forces.

OBJECTIVE: The aim of this study was to evaluate the status of inhalation therapy in bronchial asthma in terms of frequency of its use, role of general physicians and general practitioners in prescribing inhalation therapy, role of inhaled steroids and B2 agonists, concurrent use of oral drugs, technique of using inhaler devices, use of spacer devices and peak flow monitoring. MATERIAL AND METHODS: 150 patients (76 males, 74 females) of bronchial asthma over 12 years of age referred to chest clinic of a tertiary care hospital for inadequate control were interviewed on the basis of a questionnaire and screening of prescription and case records wherever available. RESULTS: 127 (84.6%) patients were on inhalation therapy and maximum number of prescriptions was by general physicians (81%). The dosages of inhaled steroids were less than 400 mg in 60 (83.3%) cases and 26 (36%) patients discontinued it after some time. All patients were on beta-2 agonist inhalers and 74 (58.3%) patients were using these on regular basis. The concurrent use of oral short acting B2 agonist and oral steroids was seen in 107 (84%) and 41 (32.2%) patients respectively. Metered dose inhalers (MDIs) were most frequently used inhaler devices in 100 (78.7%) cases followed by rotahalers in 27 (21%) cases. The technique of using MDI and rotahalers was incorrect in 64 (64%) and 7 (25.9%) cases respectively. Spacer devices were used rarely and none of the patients were monitored by peak flow rates. CONCLUSIONS: Although inhalation therapy was being prescribed in large number of patients, more so by general physicians, yet the therapy was not being effective considering the fact that the referral to chest clinic in all the cases was for uncontrolled asthma. The main reasons for ineffective inhalation therapy were, underuse of inhaled steroids, overuse of B2 agonists and incorrect use of inhaler devices. There is an urgent need to educate general physicians especially in regards to usefulness of inhaled steroids, as on demand use of B2 agonists, demonstration of correct inhalation technique to patients, use of spaces devices and peak flow monitoring.

Adolescent↗
PubMed2000

The protective effect of salbutamol inhaled using different devices on methacholine bronchoconstriction.

STUDY OBJECTIVE: To determine the protective effect of salbutamol, 100 microg, inhaled by different devices (pressurized metered-dose inhaler [pMDI; Ventolin; GlaxoWellcome; Greenford, UK], pMDI + spacer [Volumatic; GlaxoWellcome], or breath-activated pMDI [Autohaler; 3M Pharmaceuticals; St. Paul, MN]) on bronchoconstriction induced by methacholine. DESIGN: Randomized, double-blind, cross-over, placebo-controlled study. PATIENTS: Eighteen subjects with stable, moderate asthma, asymptomatic, receiving regular treatment with salmeterol, 50 microg bid, and inhaled beclomethasone dipropionate, 250 microg bid, in the last 6 months, with high hyperreactivity to methacholine (baseline provocative dose of methacholine causing a 20% fall in FEV(1) [PD(20)] geometric mean [GM], 0.071 mg). Subjects were classified into two groups: subjects with incorrect (n = 5) pMDI inhalation technique, and subjects with correct (n = 13) inhalation technique. METHODS AND MEASUREMENTS: After cessation of therapy for 3 days, all subjects underwent four methacholine challenge tests, each test 1 week apart, each time 15 min after inhalation of salbutamol, 100 microg (via pMDI, pMDI + spacer, or Autohaler), or placebo. The protective effect on methacholine challenge test was evaluated as the change in the PD(20), and expressed in terms of doubling doses of methacholine in comparison with placebo treatment. RESULTS: The PD(20) was significantly higher after salbutamol inhalation than after placebo inhalation, but no significant difference was observed among the three different inhalation techniques. Only when salbutamol was inhaled via pMDI + spacer, PD(20) was slightly but not significantly higher (pMDI GM, 0.454 mg; pMDI + spacer GM, 0.559 mg; and Autohaler GM, 0.372 mg; not significant [NS]) than other inhalation techniques. Similar results (mean +/-SEM) were obtained with doubling doses of methacholine (pMDI, 2 +/- 0.47; pMDI + spacer, 3 +/- 0.35; and Autohaler, 2.4 +/- 0.40; NS). No significant difference was found among techniques when subjects with correct or incorrect inhalation technique were separately considered. CONCLUSIONS: Our data show that the protective effect of salbutamol, 100 microg, on methacholine-induced bronchoconstriction is not affected by the different inhalation techniques, although inhalation via pMDI + spacer tends to improve the bronchoprotective ability of salbutamol. These data confirm the clinical efficacy of salbutamol, whatever the device, and the patient's inhalation technique.

Adolescent↗
PubMed1998

Dipyridamole attenuates rebound pulmonary hypertension after inhaled nitric oxide withdrawal in postoperative congenital heart disease.

OBJECTIVE: Inhaled nitric oxide therapy causes selective and sustained pulmonary vasodilation in patients with pulmonary hypertension; however, attempts to discontinue inhaled nitric oxide therapy may be complicated by abrupt life-threatening events. Dipyridamole, a cyclic guanosine monophosphate-specific phosphodiesterase inhibitor, blocks the hydrolysis of cyclic guanosine monophosphate in vascular smooth muscle cells. METHODS: We studied 23 consecutive children who were treated with inhaled nitric oxide because of clinically significant pulmonary hypertension after surgery for congenital heart disease. Inhaled nitric oxide therapy was withdrawn before and after dipyridamole treatment of children in whom sustained elevations of pulmonary artery pressure developed for over 30 minutes. RESULTS: In 7 of 23 children, inhaled nitric oxide withdrawal caused a 40% increase in pulmonary artery pressure, a 17% decrease in systemic venous oxygen saturation, and a 46% increase in the ratio of mean pulmonary artery pressure to aortic pressure. Compared with children who had no significant increase in pulmonary artery pressure, children who experienced the development of prolonged pulmonary hypertension after inhaled nitric oxide therapy withdrawal had higher mean pulmonary artery pressure immediately before inhaled nitric oxide withdrawal (22 +/- 1 mm Hg versus 27 +/- 2 mm Hg; p = 0.04) and received inhaled nitric oxide for a longer duration (2 +/- 1 days versus 4 +/- 1 days; p = 0.01). Dipyridamole therapy attenuated the rise in pulmonary artery pressure and fall in systemic venous oxygen saturation in all six patients studied with rebound pulmonary hypertension after withdrawal of inhaled nitric oxide. CONCLUSION: We conclude that dipyridamole therapy acutely attenuates the adverse hemodynamic effects of rapid withdrawal of inhaled nitric oxide therapy. Children with higher pulmonary artery pressure and who are treated with inhaled nitric oxide for a longer duration may be at increased risk for adverse hemodynamic effects of inhaled nitric oxide therapy withdrawal. We speculate that dipyridamole therapy may sustain elevations of smooth muscle cyclic guanosine monophosphate induced by inhaled nitric oxide and that phosphodiesterase activity contributes to acute pulmonary hypertension after inhaled nitric oxide withdrawal.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1999

Low-dose inhaled nitric oxide improves the oxygenation and ventilation of infants and children with acute, hypoxemic respiratory failure.

OBJECTIVE: To describe the effects of inhaled nitric oxide on oxygenation and ventilation in patients with acute, hypoxic respiratory failure and to characterize those who respond to low doses with a significant improvement in PaO2. DESIGN: Prospective dose response trial of inhaled nitric oxide. Patients who demonstrated a > or =15% improvement in PaO2 were randomized to receive conventional mechanical ventilation with or without prolonged inhaled nitric oxide. SETTING: Pediatric intensive care unit of a tertiary care children's hospital serving as a regional referral center for respiratory failure. PATIENTS: Pediatric patients with an acute parenchymal lung disease requiring mechanical ventilation, an F(IO2) of > or =0.5, a positive end-expiratory pressure of > or =7 cm H2O, and whose PaO2/FIO2 ratio was < or =160. INTERVENTIONS: PaO2, PaCO2, pH, heart rate, blood pressure, and methemoglobin were recorded at baseline and after inhaling 1, 5, 10, and 20 ppm of nitric oxide. Peak expiratory flow rate and mean airway resistance were measured while subjects received 0 and 20 ppm of inhaled nitric oxide. Patients were followed up until extubation or death. MEASUREMENTS AND MAIN RESULTS: Twenty-six patients (median age, 2.6 yrs [range, 1 mo-18.2 yrs]) were enrolled in the study. PaO2 increased (p< .001) and Pa(CO2) fell (p< .0001) from baseline with the administration of inhaled nitric oxide. There was no statistical difference among 1, 5, 10, and 20 ppm with regard to effects on oxygenation. Sixteen patients (62%) responded to inhaled nitric oxide with a > or =15% improvement in PaO2; 14 of these responses occurred at a dose of 1 or 5 ppm. Response to inhaled nitric oxide was not associated with age, length of intubation, presence of primary lung disease, chest radiograph, or illness severity. Among patients weighing < or =20 kg, responders showed a greater fall in mean airway resistance (p < .05) than nonresponders. Mortality was not influenced by prolonged inhaled nitric oxide when analyzed by intention to treat. Patients receiving prolonged inhaled nitric oxide at doses of < or =20 ppm maintained methemoglobin levels of <3.0% and circuit concentrations of NO2 of <1 ppm. CONCLUSIONS: Inhaled nitric oxide at doses of < or =5 ppm improves the oxygenation and (to a lesser extent) ventilation of most children with acute, hypoxic respiratory failure. The unpredictable response of patients necessitates individualized dosing of inhaled nitric oxide, starting at concentrations of < or =1 ppm. Inhaled nitric oxide at < or =20 ppm may exert a small salutary effect on bronchial tone. The benefits of prolonged inhaled nitric oxide remain unknown.

Acute Disease↗
PubMed2005

Lack of alteration of endogenous nitric oxide pathway during prolonged nitric oxide inhalation in intensive care unit patients.

OBJECTIVE: To compare hemodynamic and gasometric variables and the plasma concentrations of nitric oxide metabolites (cyclic guanosine monophosphate and nitrate and nitrite), endothelin-1, and renin-angiotensin metabolites before and after the start of nitric oxide inhalation, after prolonged nitric oxide inhalation, and before and after nitric oxide withdrawal. DESIGN: Prospective study. SETTING: Surgical intensive care unit, university hospital. SUBJECTS: Patients with acute lung injury and right ventricular failure. INTERVENTIONS: Nitric oxide inhalation (10-12 ppm) during a median of 2.9 days (12 hrs to 6.5 days). MEASUREMENTS AND MAIN RESULTS: The pulmonary vasodilator effects of inhaled nitric oxide improved arterial oxygenation in patients with acute lung injury (p < .05) and reduced right atrial pressure in patients with right ventricular dysfunction (p < .01). These beneficial effects lasted the whole period of prolonged inhaled nitric oxide therapy up to 6.5 days. However, when inhaled nitric oxide was withdrawn, pulmonary vasodilator effects rapidly disappeared, and Pao2/Fio2 ratio markedly deteriorated in all studied patients to return to pre-inhaled nitric oxide levels. Changes in plasma cyclic guanosine monophosphate and nitrate and nitrite paralleled those of pulmonary vasodilatory effects. An immediate increase in plasma cyclic guanosine monophosphate with a slightly delayed increase in plasma nitrate and nitrite was observed at inhaled nitric oxide start with no attenuation during the prolonged inhaled nitric oxide therapy. A marked decrease toward pre-inhaled nitric oxide levels was seen within hours of inhaled nitric oxide withdrawal. In addition, no alteration of plasma endothelin-1 or renin-angiotensin mediators was observed during or after inhaled nitric oxide therapy. CONCLUSIONS: Our study showed a lack of attenuation in the beneficial effects of inhaled nitric oxide and a lack of alteration of endogenous nitric oxide, endothelin-1, and renin-angiotensin pathways during prolonged nitric oxide inhalation.

Administration, Inhalation↗
PubMed1999

Inhaled NO impacts vascular but not extravascular compartments in postischemic peripheral organs.

Inhaled nitric oxide (NO) reduces pulmonary hypertension and dampens various aspects of lung inflammation; however, its effects are thought to be restricted to the lung because of its short half-life in biological systems. More recently, however, NO was shown to nitrosylate hemoglobin, albumin, and other plasma molecules to form stable nitrosothiol derivatives and could have an impact on the periphery. We examined whether inhaled NO could have an impact on the two compartments of distal organs, namely, the intravascular and extravascular spaces. The feline intestine was exposed to 1 h of ischemia and 1 h of reperfusion, and intestinal blood flow and mucosal dysfunction were measured in animals ventilated with room air and inhaling 0 or 80 ppm NO. A decrease in intestinal blood flow and an increase in mucosal barrier leakiness were noted in animals not exposed to inhaled NO. The intestinal blood flow impairment was entirely reversed in animals breathing 80 ppm NO, but the mucosal dysfunction was not affected. We further examined whether inhaled NO could reach the extravascular space by simply inhibiting NO in the intestine with the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) that causes an increase in mucosal permeability that is rapidly reversed with NO donors. However, inhaled NO had no effect on the rise in mucosal permeability. L-NAME reduced lymph nitrosothiol concentrations, but inhaled NO could not replenish these levels. To further explore the intravascular impact of inhaled NO, we used intravital microscopy to visualize the microvasculature and demonstrated that inhaled NO could be initiated after reperfusion and still reduced microvascular disturbances, including reversing the impairment in blood flow and increasing leukocyte adhesion. The effects of inhaled NO persisted for an additional hour after termination of NO inhalation, consistent with a dramatic increase in nitrate within 1 h of NO inhalation, which persisted for 1 h after the termination of NO inhalation. These data suggest that inhaled NO can reach distal organs to dramatically improve reperfusion-induced microvascular but not extravascular dysfunction.

Administration, Inhalation↗
PubMed2005

How to achieve good compliance and adherence with inhalation therapy.

The correct use of inhaler devices is an inclusion criterion for all studies comparing inhaled treatments. However, in real life patients make many errors when inhaling their medication which may negate the benefits observed in clinical trials. A recently published observational study evaluated inhaler handling in 3811 patients for at least 1 month using the Aerolizer, Autohaler, Diskus, pressurised metered dose inhaler (pMDI) or Turbuhaler devices. Inhalation errors were considered critical if they could have substantially affected drug delivery to the lung. The two most common errors made by patients were device-independent errors and included not breathing out before actuation of the device (28.9%) and failure to breath-hold for a few seconds after inhalation (28.3%). These errors were observed in 40%-47% of patients. The number of patients making at least one error with breath-actuated inhalers was high; with less than 50% of patients inhaling correctly. Seventy-six per cent of patients made at least one error with pMDI compared to 49%-55% with breath-actuated inhalers. With respect to device-dependent errors, the pMDI fared worst with 69% of patients exhibiting at least one error, closely followed by the Turbuhaler (32%) and Autohaler (41%). Critical errors were made by only 11%-12% of patients treated with Aerolizer, Autohaler or Diskus compared to 28% and 32% of patients treated with pMDI and Turbuhaler, respectively. Over-estimation of good inhalation by GPs was maximal for Turbuhaler (24%) and lowest for Autohaler and pMDI (6%). Ninety per cent of GPs felt that participation in the study would improve error detection. Compliance may be improved by educating patients and physicians in the correct use of inhaler devices. Inhalers should be easy to use correctly, and have multiple feedback and control mechanisms which would reduce physician over-estimation of a correct inhalation, allow compliance to be monitored, facilitate patient self-education and give reassurance to patients in the real life setting.

Administration, Inhalation↗
PubMed1999

Inhalation technique of 166 adult asthmatics prior to and following a self-management program.

Self-management of asthma and self-treatment of exacerbations are considered important in the treatment of asthma. For successful self-treatment, medication has to be inhaled correctly, but the percentage of patients inhaling effectively varies widely. As part of a self-management program we checked and corrected inhalation technique. This paper addresses differences among inhalers in relation to patient characteristics and the effect of instruction, 1 year after enrollment. Maneuvers that are essential for adequate inhalation were identified. When errors in inhalation technique were observed, patients were instructed in the correct use of their devices. One year later, inhalation technique was checked again. Only patients who used the same inhaler throughout the entire study period were analyzed. Of the 245 adult asthmatic patients who were enrolled in the self-management program, 166 used the same inhaler throughout the study period. One hundred twenty patients (72%) performed all key items correctly at baseline and this increased to 80% after 1 year. At follow-up, older patients were less likely to demonstrate a perfect inhalation. Patients with a Diskhaler made fewest errors. Adjustment for differences in patient characteristics did not significantly change the results. Because many patients with asthma use their inhaler ineffectively, there is a need to know which inhaler leads to fewest errors. Diskhaler was nominated by this study. When patients are not able to demonstrate adequate inhalation technique in a "tranquil" setting, it is doubtful that they can do so when they experience an exacerbation. Therefore, inhalation instruction should be considered an essential ingredient, not only of self-management programs, but also of asthma patient care in general.

Administration, Inhalation↗
PubMed2003

[Esophageal candidiasis as complication of inhaled steroid therapy].

UNLABELLED: Gastrointestinal endoscopy was performed in two bronchial asthma patients using inhaled corticosteroid who complained of odynophagia. The endoscopic finding was high grade with white moss (Grade III) in both patients. Esophageal candidiasis is often recognized in bronchial asthmatic patients receiving long-term fluticasone propionate (FP) dry powder (Diskhaler) inhalation. We therefore examined the complicated context of esophageal candidiasis in patients with long-term FP inhalation. Out of 20 bronchial asthmatic patients who had been using FP inhalation long-term, seven showed signs of esophageal candidiasis. Three patients had mild grade (Grade I), one middle grade (Grade II) and three high grade (Grade III) candidiasis, with a frequency of 35%. This rate is higher than the usual spontaneous occurrence rate of esophageal candidiasis, and it is suggested that inhalation of corticosteroid medication can penetrate into the esophagus after deep inhalation. We tested this hypothesis in two studies. 1) To measure the esophageal concentration of FP, four healthy adults inhaled 200 microg FP once. Right after inhalation, FP concentration in the esophageal washing fluid was 3.3 microg. On another day, 30 minutes after the same dose of inhaled FP, one FP concentration in the esophageal washing fluid was 0.67 microg (immediately laydown), and another was 0.11 microg (remained standing). This indicates that even though FP dissipates quickly, it remains in the esophagus 30 minutes after inhalation. 2) We observed the process in one patient with high grade (Grade III) esophageal candidiasis. The time of inhalation was changed from just after getting up and just before going to bed to before breakfast and before dinner. Under this regimen, the signs of esophageal candidiasis improved from high to middle grade. CONCLUSION: If asthmatic patients do not go to sleep immediately after FP inhalation, the remaining FP in the esophagus decreases rapidly, thereby decreasing the risk of esophageal candidiasis. In addition, by changing the FP inhalation times to before breakfast and dinner, the remaining FP in the esophagus is washed away and does not remain in the esophagus. Therefore, this study, which avoided inhalation before going to bed, provides useful information for the prevention and improvement of esophageal candidiasis.

Administration, Inhalation↗
PubMed1995

Evaluation of the effectiveness of four different inhalers in patients with chronic obstructive pulmonary disease.

BACKGROUND: The percentage of patients inhaling their medication effectively varies widely, according to methods of assessment and inhalers used. This study was carried out to assess differences among four types of inhalers using inhaler-specific checklists. METHODS: Inhalation technique was evaluated in adult patients with chronic obstructive pulmonary disease (COPD). Inhalers investigated were either metered dose inhalers (MDIs) or the dry powder inhalers Turbohaler (Turbuhaler), Diskhaler, and Rotahaler. Errors were recorded against inhaler-specific checklists. From these, scores were derived by dividing the number of items correctly completed by the total number of items on the checklist and the result was expressed as a percentage. For every inhaler "essential actions" were identified and scores on these key manoeuvres were calculated. The percentage of patients performing all these essential actions correctly was also calculated. Scores were also compared with adjustment for differences in relevant patient characteristics. RESULTS: Important differences among inhalers were found. Of 152 patients with COPD (mean (SD) age 55.1 (8.7) years), those with MDIs performed worst, especially when only essential items were considered. Patients with a Diskhaler did best, although after correction for patient characteristics the differences tended to diminish. Only 60% of patients were able to perform all essential inhaler actions satisfactorily. Of those using the Diskhaler, 96% did so correctly, while the corresponding figure for those using the MDI was only 24%. CONCLUSIONS: Many patients with COPD use their inhaler ineffectively. After adjusting for patient characteristics, differences among inhalers, although less pronounced, persist. Patients using a Diskhaler made fewest errors, while most patients using MDIs made crucial mistakes.

Adult↗
PubMed1996

Health beliefs of adults with asthma: toward an understanding of the difference between symptomatic and preventive use of inhaler treatment.

The aim of this study was to examine the potential differences between beliefs relating to symptomatic and preventive inhaler treatment and to analyze the relationship between these beliefs and the use of inhalers by adult patients with asthma in general practice. Unstructured interviews with a stratified sample of 8 patients, taking a combination of salbutamol and beclomethasone inhalers, were used to develop themes for a structured interview, where questions relating to 8 main areas of interest were measured on a 5-point Likert scale. Forty patients prescribed the same combination of inhalers were randomly selected for the structured interview. All agreed to participate (100% response). Correlations between the responses to the 8 themes and measures of inhaler use were analyzed. High use of salbutamol for the relief of symptoms and low use of beclomethasone for the prevention of asthma were common. Perceived benefits of the inhalers, a positive attitude to using the inhalers, and concern about side effects had strong influences on the use of both inhalers. Uncertainty about the inhalers, a negative attitude to using the inhalers, and the involvement of others in asthma management had less influence on inhaler use. Satisfaction with the doctor and the ease of obtaining an inhaler were more important issues for beclomethasone use than for salbutamol use. There are important differences in the beliefs that patients hold in relation to symptomatic and preventive use of inhaler treatment. These findings suggest that focusing on very specific attitudes to treatment may be of benefit in the health education of adults with asthma. Further work is planned to refine the themes so that doctors will be able to explore patients' views about their inhaler treatment by asking a few direct questions.

Albuterol↗
PubMed1995

Particle clearance and histopathology in lungs of F344/N rats and B6C3F1 mice inhaling nickel oxide or nickel sulfate.

The goals of this study were to (1) determine the effects of repeated inhalation of relatively insoluble nickel oxide (NiO) and highly soluble nickel sulfate hexahydrate (NiSO4.6H2O) on lung particle clearance, (2) investigate the effects of repeated inhalation of NiO or NiSO4 on the pulmonary clearance of subsequently inhaled 85Sr-labeled microspheres, (3) correlate the observed effects on clearance with accumulated Ni lung burden and associated pathological changes in the lung, and (4) compare responses in F344 rats and B6C3F1 mice. Male F344/N rats and B6C3F1 mice were exposed whole-body to either NiO or NiSO4.6H2O 6 hr/day, 5 days/week for up to 6 months. NiO exposure concentrations were 0, 0.62, and 2.5 mg NiO/m3 for rats and 0, 1.25, and 5.0 mg NiO/m3 for mice. NiSO4.6H2O exposure concentrations were 0, 0.12, and 0.5 mg NiSO4.6H2O/m3 for rats and 0, 0.25, and 1.0 mg NiSO4.6H2O/m3 for mice. After 2 and 6 months of whole-body exposure, groups of rats and mice were acutely exposed nose-only to 63NiO (NiO-exposed animals only), 63NiSO4.6H2O (NiSO4.6H2O-exposed animals only), or to 85Sr-labeled polystyrene latex (PSL) microspheres (both NiO- and NiSO4.6H2O-exposed animals) to evaluate lung clearance. In addition, groups of rats and mice were euthanized after 2 and 6 months of exposure and at 2 and 4 months after the whole-body exposures were completed to evaluate histopathological changes in the left lung and to quantitate Ni in the right lung. Repeated inhalation of NiO results in accumulation of Ni in lungs of both rats and mice, but to a greater extent in lungs of rats. During the 4 months after the end of the whole-body exposures, some clearance of the accumulated Ni burden occurred from the lungs of rats and mice exposed to the lower, but not the higher NiO exposure concentrations. Clearance of acutely inhaled 63NiO was also impaired in both rats and mice, with the extent of impairment related to both exposure concentration and duration. However, the clearance of acutely inhaled 85Sr PSL microspheres was not impaired. The repeated inhalation of NiO resulted in alveolar macrophage (AM) hyperplasia with accumulation of NiO particles in both rats and mice, chronic alveolitis in rats, and interstitial pneumonia in mice. These lesions persisted throughout the 4-month recovery period after the NiO whole-body exposures were terminated. In contrast, repeated inhalation of NiSO4.6H2O did not result in accumulation of Ni in lungs of either rats or mice and did not affect the clearance of 63NiSO4.6H2O inhaled after either 2 or 6 months of NiSO4.6H2O exposure. Clearance of the 85Sr-labeled microspheres was significantly impaired only in rats exposed to the microspheres after 2 months of exposure to NiSO4.6H2O. Histopathological changes in rats were qualitatively similar to those seen in NiO-exposed rats. Only minimal histopathological changes were observed in NiSO4.6H2O-exposed mice. These results suggest that repeated inhalation of NiO at levels resulting in AM hyperplasia and alveolitis may impair clearance of subsequently inhaled NiO. The potential effects of repeated inhalation of soluble NiSO4.6H2O on the clearance of subsequently inhaled poorly soluble particles are less clear.

Administration, Inhalation↗
PubMed2004

Three 20-minute interspaced salbutamol inhalations as a test for the diagnosis of reversible airflow limitation in adult asthmatics.

Reversible airflow limitation represents an important parameter for the diagnosis of bronchial asthma. The aim of this study was to design a simple and useful test for the detection of reversible airflow limitation. The subjects were 29 patients with asthma and forced expiratory volume in 1 second (FEV1) < 80% predicted. Following baseline spirometry, subjects inhaled 1.5 mg of salbutamol by a nebulizer and then spirometry was performed 20 min later. The procedure was repeated three times. Subsequently, 13 patients received 30 mg of predonisolone orally once daily for 1 week. Spirometry was performed before and after the oral predonisolone therapy, and results were compared with those of salbutamol inhalation test. The mean increase in FEV1 over the baseline was 18.3% after the first salbutamol inhalation, 26.4% after the second inhalation, and 30.2% after the third inhalation. The increases in FEV1 were significant after each inhalation. The mean increases in the maximum expiratory flow rate at 50% (V50) and that at 25% (V25), measured from the flow volume loop, were 53.5% and 46.9% after the first inhalation, but there were no significant changes by repeated inhalations. A significant reversal of airflow limitation was demonstrated in 18 subjects after the first inhalation, 22 subjects after the second inhalation, and 27 subjects after the third inhalation. Improvement in FEV1 after oral predonisolone was equivalent to that after the third inhalation of salbutamol. A test composed of three 20-min interspaced salbutamol inhalations is useful for the diagnosis of asthma by demonstrating the presence of reversible airflow limitation.

Administration, Inhalation↗
PubMed2005

Do healthcare professionals think that dry powder inhalers can be used interchangeably?

It is important to assess the attitudes of healthcare professionals to the interchangeable use of dry powder inhalers, as there is the potential for this to occur more frequently in the future. A survey of healthcare professionals in the UK found that 87% were concerned about potential problems arising from prescriptions that do not specify the device to be dispensed, and 46% were aware of actual incidents in which patients received an unfamiliar inhaler, including patient confusion, ineffective inhaler technique and the need to reissue prescriptions. In another survey conducted among 427 primary and secondary care physicians in Germany, Netherlands, UK and USA, one third of the physicians considered the device before considering the chemical entity within a class of treatments and over half the respondents reported problems with the device as one of the main reasons for switching inhaled therapy. In a survey conducted in Australia, Canada, France, Germany and UK, over 90% of the 726 physicians interviewed thought that interchangeable use of dry powder inhalers would have a negative impact on patient compliance and device handling and on willingness to use the inhaler if the patient was not involved in the choice. In total, 79% of physicians thought that substitution of a patient's regular dry powder inhaler with another could have a negative impact on asthma control. The majority of physicians (95%) were opposed to substitution of one dry powder inhaler for another if the pharmacist does not consult the patient or physician. A majority (86%) were concerned that switching between dry powder inhalers would have an adverse impact on workload. Only 9% of physicians thought that dry powder inhalers were interchangeable, with almost eight out of 10 (79%) considering that there should be official recognition that they are not interchangeable. In conclusion, a number of surveys among healthcare professionals have shown that they believe patient involvement in treatment choice to be essential for adherence to therapy. Dry powder inhalers were perceived as different and not interchangeable, with physicians opposed to substitution of one dry powder inhaler by another without consultation with the patient or physician. Consequently, physicians are in favour of official recognition that dry powder inhalers are not interchangeable, with any cost benefits likely to be outweighed by the need for additional consultations and prescriptions.

Administration, Inhalation↗
PubMed2001

Improved asthma control with budesonide/formoterol in a single inhaler, compared with budesonide alone.

Budesonide/formoterol in a single inhaler was compared with budesonide alone, and with concurrent administration of budesonide and formoterol from separate inhalers, in patients with asthma, not controlled with inhaled glucocorticosteroids alone. In this 12-week, double-blind, randomized, double-dummy study, 362 adult asthmatics (forced expiratory volume in one second 73.8% of predicted, inhaled glucocorticosteroid dose 960 microg x day(-1)) received single inhaler budesonide/formoterol (Symbicort Turbuhaler) 160/4.5 microg, two inhalations b.i.d., or corresponding treatment with budesonide, or budesonide plus formoterol via separate inhalers. There was a greater increase in morning peak expiratory flow (PEF) with single-inhaler (35.7 L x min(-1)) and separate-inhaler (32.0 L x min(-1)) budesonide and formoterol, compared with budesonide alone (0.2 L x min(-1); p<0.001, both comparisons); the effect was apparent after 1 day (p<0.001 versus budesonide, both comparisons). Similarly, evening PEF, use of rescue medication, total asthma symptom scores and percentage of symptom-free days improved more with both single inhaler and separate inhaler therapy than with budesonide alone, as did asthma control days (approximately 15% more, p<0.001 versus budesonide, both comparisons, with a marked increase in the first week). All treatments were well tolerated and the adverse event profile was similar in all three treatment groups. It is concluded that single inhaler therapy with budesonide and formoterol is a clinically effective and well-tolerated treatment for patients with asthma that is not fully controlled by inhaled glucocorticosteroids alone.

Administration, Inhalation↗
PubMed2000

Can epinephrine inhalations be substituted for epinephrine injection in children at risk for systemic anaphylaxis?

BACKGROUND: For out-of-hospital treatment of anaphylaxis, inhalation of epinephrine from a pressurized metered-dose inhaler is sometimes recommended as a noninvasive, user-friendly alternative to an epinephrine injection. OBJECTIVE: To determine the feasibility of administering an adequate epinephrine dose from a metered-dose inhaler in children at risk for anaphylaxis by assessing the rate and extent of epinephrine absorption after inhalation. METHODS: We performed a prospective, randomized, observer-blind, placebo-controlled, parallel-group study in 19 asymptomatic children with a history of anaphylaxis. Based on the child's weight, 10, 15, or 20 carefully supervised epinephrine or placebo inhalations were attempted. Before dosing, and at intervals from 5 to 180 minutes after dosing, we monitored plasma epinephrine concentrations, blood glucose, heart rate, blood pressure, and adverse effects. RESULTS: Eleven children (mean +/- standard error of the mean: 9 +/- 1 years and 33 +/- 3 kg) in the epinephrine group were able to inhale 11 +/- 2 (range: 3-20) puffs, equivalent to 74% +/- 7% of the precalculated dose or 0.078 +/- 0.009 mg/kg. They achieved a mean peak plasma epinephrine concentration of 1822 +/- 413 (range: 230-4518) pg/mL at 32.7 +/- 6.2 minutes. Eight children (10 +/- 1 years of age and 33 +/- 5 kg) in the placebo group were able to inhale 12 +/- 2 (range: 8-20) puffs, 89% +/- 3% of the precalculated dose, and had a peak endogenous plasma epinephrine concentration of 1316 +/- 247 (range: 522-2687) pg/mL at 44.4 +/- 16.7 minutes. In the children receiving epinephrine compared with those receiving placebo, mean plasma epinephrine concentrations were not significantly higher at any time, mean blood glucose concentrations were significantly higher from 10 to 30 minutes, mean heart rate was not significantly different at any time, and mean systolic and diastolic blood pressures were not significantly increased at most times. After the inhalations of epinephrine or placebo, the children complained of bad taste and many experienced cough or dizziness. After inhaling epinephrine, 1 child developed nausea, pallor, and muscle twitching. CONCLUSIONS: Despite expert coaching, because of the number of epinephrine inhalations required and the bad taste of the inhalations, most children were unable to inhale sufficient epinephrine to increase their plasma epinephrine concentrations promptly and significantly. Therefore, we urge caution in recommending epinephrine inhalation as a substitute for epinephrine injection for out-of-hospital treatment of anaphylaxis symptoms in children.

Administration, Inhalation↗
PubMed2005

Inhaled insulins: their potential in the treatment of diabetes mellitus.

The inhalation of insulin was conceptualized by the mid-1920s, but the first successful testing of inhaled insulin occurred in the mid-1990s. The lung has proven to be an organ well capable of absorbing insulin in a reproducible and dose-dependent manner. At present, two concepts of pulmonary insulin delivery at relatively advanced stages of development have been investigated in several published studies. The first involves the Exubera device, a system consisting of a formulation of insulin in a dry and amorphous powder, which is then packaged into blisters. A special delivery system generates a pulse of compressed air, which causes the insulin to form a white fog in a transparent reservoir that can be inhaled by deep breathing. The second approach is the AERx insulin Diabetes Management System, which uses an aqueous formulation of insulin, delivered as an aerosol generated by a special, microprocessor-controlled, inhalation device. This device is capable of monitoring the patient's inspiratory flow and guiding the inhalation by a microelectronic feedback system. The therapeutic efficacy and safety of these inhaled insulins seem comparable to those of subcutaneous insulin regimens; however, inhaled insulins do not appear to achieve significantly better glycemic control. Several other concepts for the pulmonary delivery of insulin are also being developed. With the incidence of diabetes mellitus, especially type 2 diabetes, dramatically increasing worldwide, patients with type 2 diabetes appear to be an important target group for new modalities of insulin delivery. In this group, the onset of insulin treatment is frequently delayed due to the fear of self-injection, preventing effective glycemic control. Patient acceptance of inhaled insulins is excellent and no serious adverse effects have been observed to date. Further advantages of inhaled insulins are the more rapid onset of insulin action and a mitigation of postprandial glucose excursions. However, there are some open questions. The most important concerns the possible long-term effects of insulin inhalation on the lung, as insulin is known to have growth-promoting properties. Thus far, there are no observations of the effects of inhaled insulin on lung structure and function that extend beyond 10 years. In patients with pulmonary disease, the smaller cumulative alveolar surface may cause problems in absorption, and in smokers the action of inhaled insulin has been shown to be stronger and with a faster onset. Furthermore, treatment with inhaled insulin requires larger doses of insulin compared with the subcutaneous route of insulin administration to achieve the same systemic effect, and the costs of this therapy could therefore be significantly higher than the costs of present insulin therapies.

Administration, Inhalation↗