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PubMed2006

Inhaled Glucocorticosteroid and Long-Acting beta(2)-Adrenoceptor Agonist Single-Inhaler Combination for Both Maintenance and Rescue Therapy : A Paradigm Shift in Asthma Management.

Despite aggressive fixed-dose (FD) combination therapy with inhaled glucocorticosteroids (ICS) and long acting beta(2)-adrenoceptor agonists (LABA), many patients with asthma remain suboptimally controlled, based on the need for rescue therapy and rates of severe exacerbations. The strategy of adjustable maintenance dosing (AMD) involves adjustment of the maintenance dose, (using a single combination [budesonide/formoterol] inhaler, Symbicort((R))) in response to variability of asthma control over time. The AMD strategy, like the FD approach, involves the use of a short-acting beta(2)-adrenoceptor agonist (SABA) for rapid relief of bronchospasm. The dose-response characteristics of budesonide/formoterol make the AMD strategy a feasible option that cannot be exploited with the combination of salmeterol/fluticasone propionate (Advair((R))). Several studies suggest that the AMD strategy is superior to a FD approach in terms of overall asthma control.Budesonide/formoterol in a single inhaler is as effective as albuterol (salbutamol) for relief of acute asthma episodes, a feature that makes it possible to use this combination for both maintenance and reliever therapy without the need for the use of a SABA. The single-inhaler strategy has been shown to be safe and more efficacious than FD therapy. In particular, the COSMOS study has demonstrated that exacerbation burden is reduced more effectively when the combination (budesonide/formoterol) single inhaler is used for both maintenance and relief compared with FD therapy with salmeterol/fluticasone and albuterol for rescue in patients with moderate-to-severe asthma. These findings suggest that we will have to reconsider our definition of reliever therapy for patients that require long-term therapy with combination ICS and LABA.The concept of single-inhaler therapy represents a paradigm shift in asthma management that has been validated in several large studies involving thousands of patients. The single-inhaler strategy represents one of the most significant advances in asthma management in many years, and one that appears ideal for adoption in primary care.

Albuterol↗

PubMed1990

[A new inhalation system for bronchodilatation. Study of the acceptance of the Ingelheim M inhaler in chronic obstructive respiratory tract diseases].

The aim of this study was to investigate the acceptance and convenience of a new inhalation system for the treatment of chronic obstructive pulmonary disease. The Ingelheim M inhalator, an inhalation system with a supply magazine for six powder-filled capsules represents a further development of the Ingelheim inhalator in which only a single capsule can be utilized. The study was designed as an open, randomized, crossover trial involving 60 ambulatory adult patients. Each treatment period lasted two weeks. The medication tested was Berodual Inhaletten. The success of treatment was checked on the basis of peak flow metering each morning prior to and after initial inhalation. The results of the study show a highly significant preference on the part of the patients for the new inhalation system. The advantage most emphasized by the patients was the fact that they were able to carry with them their entire daily dose. Differences in the symptomatology of chronic obstructive pulmonary disease were not observed with these inhalation systems.

Adolescent↗

PubMed1989

Effects of chelating on organ distribution and excretion of manganese after inhalation exposure to 54MnCl2. II: Inhalation of chelating agents.

The effect of 1, 2-cyclohexylene-aminetetraacetic acid (CDTA) and diethylenetriaminepentaacetic acid (DTPA) on Min distribution and excretion in rats was examined after 1 hr exposure to 54MnCl2 (0.3 micrograms Mn/m3). Both chelating agents were inhaled independently, by nose only, for 30 min for the four following days, starting immediately after cessation of Mn exposure. During the experiment, the mean concentrations of CDTA and DTPA aerosols were 508 mg/cm3 and 517 mg/cm3, respectively. The activity of 54Mn was determined in lung, liver, kidney and brain 24 hrs after the last treatment, and in urine and faeces collected for 24 hrs on days 1-4 after Mn exposure. The CDTA inhalation appeared to be more effective than DTPA in mobilizing the inhaled manganese: about a twofold decrease of 54Mn was observed in all excised organs: lung, liver, kidney and brain, as compared to the controls. The DTPA inhalation resulted in about a twofold decrease of 54Mn in the lung, but was not effective in removing the metal from the liver, kidney and brain. As it can be seen from the comparison of these results with our previous data (6), the CDTA inhalations were more effective than its i.p. injections mobilizing manganese additionally also from the lung; but generally less effective in the case of DTPA, which decreased 54Mn levels in the lung only. On the first day after 54Mn exposure, manganese levels in the urine of rats inhaling CDTA and DTPA were respectively more than 200 and 30 times higher than in the control group. Excretion of Mn in faeces was not affected significantly in this experiment. Our data show that the effectiveness of removing inhaled Mn depends not only on the chelating agent, the time of its administration (see Part I) but also on the method of its administration.

Animals↗

PubMed1983

Optimal inhalation procedure for the fenoterol powder inhaler.

To assess the optimal inhalation procedure of a fenoterol (Berotec) powder inhaler, the degree of reversibility of lung function impairment was studied in 10 patients with stable asthma after 1) deposition of 0.2 mg fenoterol under the tongue, 2) a rapid inhalation from residual volume (RV) to total lung capacity (TLC), and 3) a slow inhalation from functional residual capacity (FRC) to TLC. There was no effect on FEV1 of depositing fenoterol under the tongue, but both inhalation menoeuvres improved FEV1 significantly (p less than 0.01) and the rapid inspiration manoeuvre even slightly more (p less than 0.05) than the slow. It is concluded that the problem of impaction of large particles in the mouth and pharynx following rapid inhalation from a conventional pressurized cannister is considerably reduced with the fenoterol powder inhaler, due to the resistance it causes which tend to automatically reduce a forced inspiration flow rate to optimal low values.

Adult↗

PubMed2004

The effects of inhaled nitric oxide on cardiac pathology and energy metabolism in a canine model of smoke inhalation injury.

OBJECTIVE: The effects of inhaled nitric oxide (NO) on cardiac pathology and energy metabolism were studied in a canine model of smoke inhalation injury. MATERIAL AND METHOD: Twenty-one dogs were randomly divided into three groups: four dogs constituted the normal control group (group N), eight dogs subjected to smoke inhalation followed by O(2) inhalation (FiO(2)=0.45) constituted the injury control group (group C), and nine dogs inhaling a mixture of O(2) and 45ppm nitric oxide after smoke exposure served as the treatment group (group T). Myocardial zymograms were continuously measured, and ventricular muscles were examined for histopathology in the end of the experiment. RESULTS: Lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (alpha-HBD), creatine kinase (CK) and glutamic oxalacetic transaminase (GOT) in group T were less than those in group C(P<0.05, or P<0.01). ATP content and energy charge (EC) in group T were higher significantly than those in group C(P<0.01). Light microscopy and electron microscopy indicated that the ventricular pathologic changes in group T were milder than in control group. CONCLUSION: Nitric oxide inhalation relieved myocardial damage and improved energy metabolism.

Actin Cytoskeleton↗

PubMed2005

Dose-response to salbutamol via a novel palm sized nebuliser (Aerodose Inhaler), conventional nebuliser (Pari LC Plus) and metered dose inhaler (Ventolin Evohaler) in moderate to severe asthmatics.

AIMS: The Aerodose inhaler is a novel, palm-sized, breath actuated device which requires little patient coordination. This study compared the dose-response of salbutamol delivered by the Aerodose Inhaler (Aerogen Inc., Mountain View, USA) vs Pari LC Plus jet nebulizer (Pari LC Plus; Pari GmbH, Starnberg, Germany) and Ventolin Evohaler HFA pMDI (Evohaler; Allen & Hanburys [GlaxoSmithkline], Uxbridge, UK). METHODS: Twenty-two moderate to severe asthmatic patients, mean (s.d.) age: 44.7 (9.4), FEV(1): 58.1 (12.0), received 4 cumulative doubling doses of salbutamol in a randomised, investigator blind, balanced crossover design. Spirometry and systemic safety variables (heart rate, blood pressure, T wave amplitude, QTc interval and potassium) were measured at baseline and after each dose. RESULTS: Parallel regression analysis revealed that microgram relative potency ratios for the Aerodose Inhaler to be five times more efficient for FEV(1) than either the Pari LC Plus (0.202, 90% CI: 0.189-0.216) or the Evohaler (0.202, 90% CI: 0.189-0.216), while there was no difference between Pari LC Plus vs Evohaler. Similarly, Aerodose Inhaler vs. Pari LC Plus showed approximately five-fold greater potency for all systemic parameters, except blood pressure. As compared to the Evohaler, Aerodose Inhaler had equivalent potency for plasma potassium and T wave amplitude, but demonstrated greater potency for heart rate and QT(c) interval. CONCLUSIONS: This study has indicated therefore, that Aerodose Inhaler is approximately five times as efficient as the Pari LC Plus and Evohaler in relative lung delivery of salbutamol in moderate to severe asthmatics.

Administration, Inhalation↗

PubMed2006

Closer to an 'ideal inhaler' with the Easyhaler: an innovative dry powder inhaler.

The characteristics of an ideal inhaler are based around the design and formulation of the device, patient use and the clinical effect, together with concordance and patient preference. To ensure consistent drug delivery to the lungs, with regular adherence to the prescribed dosage regimen, it is essential that all these characteristics simultaneously interact to provide smooth and sustained therapeutic control affected only by the clinical status of the patient. The literature highlights that dose emission from an Easyhaler is fairly consistent irrespective of the inhalation technique used by patients of all age groups. Clinical studies have shown equivalence of this device to those frequently prescribed and that it is preferred by many patients. Although further research is required into the development of inhalation devices, the literature describing the Easyhaler dry powder inhaler indicates how an inhaler can closely meet the criteria for an ideal inhaler.

Administration, Inhalation↗

PubMed1998

Beclomethasone relative availability of oral versus inhaled beclomethasone dipropionate from an HFA-134A metered dose inhaler.

3M has formulated a new chlorofluorocarbon-free (CFC-free) beclomethasone dipropionate (BDP) metered-dose inhaler (MDI) with the use of the propellant HFA-134a (HFA). Lung deposition studies demonstrated that the HFA BDP MDI delivers to the lungs approximately 56% of the BDP dose (ex-adaptor), a substantially higher percentage than the 5-30% delivered by conventional CFC BDP MDIs. As new sensitive bioanalytical methods are becoming available to quantitate systemic levels of inhaled corticosteroids, pharmacokinetic evaluations are emerging as sensitive and reproducible methods that can be used as a complement to the data obtained from lung deposition studies to assess and compare the performance of MDIs. The present study was designed to determine the beclomethasone (BOH) availability of oral BDP relative to inhaled HFA BDP as a first step to alloy MDI product comparisons in the future. Forty mild asthmatic patients completed this open-label, randomized, single-dose, two-period crossover study. Each patient received an oral dose of BDP (0.2, 0.5, 1, 2 or 5 mg) in one period and an inhaled dose of BDP (0.2 or 0.8 mg) in the other period, with four patients allocated to each of ten different treatment sequences. The BOH availability of orally administered BDP was approximately 40% relative to inhaled HFA BDP. In addition, the fraction of an oral dose that reaches the systemic circulation was estimated from the 40% relative availability and previous lung deposition data to be 0.26. These estimated pharmacokinetic parameters will be used in the future to further characterize the pharmacokinetics of inhaled BDP and to compare the performance of different MDI products.

Administration, Inhalation↗

PubMed2002

Relative lung and systemic bioavailability of sodium cromoglycate inhaled products using urinary drug excretion post inhalation.

The relative lung and systemic bioavailability of sodium cromoglycate following inhalation by different methods have been determined using a urinary excretion pharmacokinetic method. On three separate randomised study days, 7 days apart, subjects inhaled (i) 4x5 mg from an Intal metered dose inhaler (MDI), (ii) 4x5 mg from an MDI attached to a large volume spacer (MDI+SP) and (iii) 20 mg from an Intal Spinhaler (DPI). Urine samples were provided at 0, 0.5, 1, 2, 5 and 24 h post dose. The mean (S.D.) amount of sodium cromoglycate excreted in the urine during the first 30 min post inhalation was 38.1 (27.5), 222.3 (120.3) and 133.1 (92.2) microg following MDI, MDI+SP and DPI, respectively. The mean ratio (90% confidence interval) of these amounts excreted in the urine over the first 30 min for MDI+SP vs. MDI, DPI vs. MDI and MDI+SP vs. DPI was 801.0 (358.0, 1244; p<0.002)%, 457.0 (244.0, 670.0; p<0.02)% and 262.4 (110.2, 414.5)%, respectively. Similarly for the 24 h cumulative amount of sodium cromoglycate excreted over the 24 h post inhalation the ratios were 375.4 (232.9, 517.9; p<0.005)%, 287.5 (183.4, 391.6; p<0.02)% and 211.4 (88.3, 334.5)%, respectively. The results highlight better lung deposition of sodium cromoglycate from a metered dose inhaler attached to a large volume spacer.

Administration, Inhalation↗

PubMed2002

Budesonide/formoterol in a single inhaler versus inhaled corticosteroids alone in the treatment of asthma.

The aim of this study was to evaluate the efficacy (expressed as effect on lung function) and tolerability of Symbicort (budesonide/formoterol in a single inhaler) in children with asthma. This was a double-blind, double-dummy, randomized, parallel-group, multicenter trial. After a 2-4-week run-in period, 286 asthmatic children (177 boys, 109 girls; mean age, 11 years; mean forced expiratory volume in 1 sec (FEV(1)), 75% predicted normal), previously treated with inhaled corticosteroids (average dose 548 microg/day), were randomized to 12 weeks' treatment with either budesonide/formoterol 80/4.5 microg, two inhalations twice daily (n = 148), or an equivalent dose of budesonide 100 microg, two inhalations twice daily (n = 138). Efficacy variables included morning and evening peak expiratory flow (PEF), spirometery, asthma symptoms, and use of rescue medication (beta(2)-agonists). Serial FEV(1) assessments were carried out on a subgroup of children (budesonide/formoterol, n = 41; budesonide, n = 40) at randomization and at week 12. Relative to baseline, morning PEF (primary variable) increased to a significantly greater extent with budesonide/formoterol than with budesonide alone (7.22% predicted normal vs 3.45% predicted normal; P < 0.001). Evening PEF also increased significantly with budesonide/formoterol (6.13% predicted normal vs. 2.73% predicted normal; P < 0.001), as did mean FEV(1) and serial FEV(1) measured over 12 hr (both P < 0.05). Similar improvements in asthma symptoms and rescue medication use were observed in both groups. The two treatment groups were similar in terms of their adverse-event profile and rates of discontinuation. Budesonide/formoterol in a single inhaler provided rapid improvements in PEF and FEV(1) compared to inhaled budesonide alone. These improvements were sustained throughout the study period. Budesonide/formoterol was well-tolerated in children with moderate persistent asthma.

Administration, Inhalation↗

PubMed2002

Dry powder inhalation of antibiotics in cystic fibrosis therapy, part 1: development of a powder formulation with colistin sulfate for a special test inhaler with an air classifier as de-agglomeration principle.

The aim of this study was to investigate the pulmonary administration of antibiotics as dry powder to patients with cystic fibrosis (CF), as an alternative for nebulization. This part of the study describes the development of a powder formulation with colistin sulfate as model substance. The aim of the new dosage form was to increase pulmonary deposition, therapeutic efficiency and, by that, compliance by the CF patients. A physical powder mixture of colistin and a size fraction of lactose (106-150 microm) was prepared and the mixture was optimized with respect to colistin content (83.3%) for use in a special test inhaler. A laser diffraction apparatus with special inhaler adapter was applied for analysis of the size distribution of the aerosol cloud from the inhaler. The size distributions of the aerosol clouds from the test inhaler at flow rates between 30 and 60 l/min for the optimized formulation showed nearly the same median diameter as that for the primary drug particles. But the X(100)-value was much lower, because of an effective large particle separation from the inspiratory air by an air classifier in the test inhaler. The results suggest that dry powder inhalation might be a suitable and highly efficient alternative for nebulization of antibiotic drugs in CF therapy.

Administration, Inhalation↗

PubMed1995

Effects of inhaled prostacyclin as compared with inhaled nitric oxide in a canine model of pulmonary microembolism and oleic acid edema.

OBJECTIVE: Recently, it has been shown that the inhalation of nitric oxide (NO) and of prostacyclin (PGI2) elicits selective pulmonary vasodilation in a canine model of pulmonary hypertension induced by hypoxic pulmonary vasoconstriction. The present study was designed to investigate whether inhaled NO or PGI2-aerosol, respectively, is also effective in decreasing pulmonary artery pressure in a canine model of acute pulmonary microembolism and oleic acid edema. DESIGN: Prospective, randomized, cross-over design. SETTING: University animal research laboratory. PARTICIPANTS: Eight anesthetized, mechanically ventilated dogs (28 +/- 1 kg). INTERVENTIONS: Acute pulmonary microembolization (PME) was induced using glass microbeads (mean diameter: 100 microns) and 0.01 mL/kg of oleic acid. Subsequently, inhaled PGI2 (concentration: 10 micrograms/mL) or NO (50 ppm), respectively, was randomly administered for 15 minutes each and then withdrawn. MEASUREMENTS AND MAIN RESULTS: Central hemodynamics (heart rate [HR], cardiac output [CO], stroke volume [SV], mean arterial pressure [MAP], systemic vascular resistance [SVR], mean pulmonary artery pressure [PAP], pulmonary vascular resistance [PVR]) and gas exchange (PaO2/FIO2 ratio, intrapulmonary shunt [Qs/Qt], alveolar-arterial oxygen difference, [AaDO2]) were assessed. Measurements were performed at control, after PME, and during administration of PGI2 and NO, respectively. PME induced a significant increase (p < 0.001) of MAP (+9%), PAP (+68%), and PVR (+163%), whereas HR, CO, and SV remained unchanged and lung function deteriorated. Inhalation of NO slightly decreased PAP (-10%; p < 0.05) and PVR (-26%; p < 0.01) and improved AaDO2 and PaO2/FIO2. In contrast, inhalation of PGI2 had no consistent effect on pulmonary vascular tone or gas exchange. CONCLUSION: The data demonstrate that inhaled NO may elicit selective pulmonary vasodilation and improve gas exchange in a canine model of pulmonary microembolism and respiratory insufficiency. However, the degree of these effects was relatively small. The aerosolization of PGI2 under conditions of positive-pressure ventilation did not exert a significant vasodilatory effect on pulmonary vessels and did not improve pulmonary gas exchange in this model.

Administration, Inhalation↗

PubMed2000

Effect of inhaled indomethacin in asthmatic patients taking high doses of inhaled corticosteroids.

BACKGROUND: Cyclooxygenase products of arachidonic acid may play a part in bronchoconstriction and airway inflammation in asthma. OBJECTIVE: We sought to determine the effect of inhaled indomethacin on asthma control and asthma exacerbations during reduction of inhaled corticosteroids in patients with moderate-to-severe steroid-dependent asthma. METHODS: We conducted a double-blind, randomized, parallel-group, multicenter study in 38 patients with asthma taking high doses (> or =1500 microg/d) of beclomethasone dipropionate (BDP). After a run-in period, patients were assigned inhaled indomethacin (50 mg/d) or placebo for 6 weeks, during which the daily doses of BDP were reduced to half at week 2 and then to one third of the baseline dose at week 4. RESULTS: Data were available from 34 patients. After the reduction of BDP doses, FEV(1), peak expiratory flow, asthma symptoms, and exhaled nitric oxide concentrations deteriorated in both treatment groups, but these effects were less pronounced in the indomethacin group compared with the placebo group. During the 6-week treatment period, 89% of the patients receiving placebo had relapse of asthma, whereas only 38% of those receiving inhaled indomethacin did so (P =.003). CONCLUSION: Inhalation of indomethacin can reduce asthma exacerbations induced by reduction of high-dose inhaled corticosteroid in steroid-dependent asthma.

Administration, Inhalation↗

PubMed2003

Adrenal function as assessed by low-dose adrenocorticotropin hormone test before and after switching from inhaled beclomethasone dipropionate to inhaled fluticasone propionate.

Low-dose adrenocorticotropin hormone (ACTH) tests (0.5 microg/L 73 m2) were done before and after switching from inhaled beclomethasone dipropionate to inhaled fluticasone propionate in 12 patients 33-77 years old who had mild-to-severe asthma to compare the effects of these drugs on adrenal function. Low-dose ACTH tests were performed after the subjects had received inhaled beclomethasone dipropionate (200-900 microg/day) for at least 12 wk. Treatment was then switched to inhaled fluticasone propionate (200-600 microg/day) for at least 12 wk, and a second low-dose ACTH test was done. Pulmonary function was assessed on the basis of peak expiratory flow rate (PEFR, % of predicted value). After switching treatment, the daily dose of inhaled corticosteroid decreased by about 40%. Basal serum cortisol and ACTH levels were similar with both treatments. The adrenal response, as assessed by incremental rise in the serum cortisol level (peak minus basal) after ACTH challenge, improved significantly (5.6-7.9 microg/dL, p < 0.01) after switching to fluticasone. All three patients who had lower serum cortisol levels during beclomethasone treatment than during fluticasone treatment showed improvement in both the peak cortisol level and the incremental rise in cortisol. Mean morning and evening PEFRs significantly increased after switching from beclomethasone to fluticasone (morning: 71.2 to 76.0%, p < 0.01; evening: 67.3 to 72.1%, both p < 0.05). The diurnal variation of PEFR significantly decreased from 10.9% to 8.3% after switching treatment (p < 0.01). We conclude that switching from beclomethasone to fluticasone reduces the risk of adrenal dysfunction associated with inhaled steroids and improves pulmonary function.

Administration, Inhalation↗

PubMed2005

No evidence of a mild form of inhalational Bacillus anthracis infection during a bioterrorism-related inhalational anthrax outbreak in Washington, D.C., in 2001.

BACKGROUND: The mail-related dispersal of Bacillus anthracis spores in the Washington, D.C., area during October 2001 resulted in 5 confirmed cases of inhalational anthrax. We identified an additional 144 ill persons who were potentially exposed to aerosolized spores and whose symptoms were compatible with early inhalational anthrax but whose clinical course and nonserologic laboratory evaluation revealed no evidence for B. anthracis infection. We hypothesized that early antibiotic use could have decreased the sensitivity of diagnostic tests or that bioterrorism-related inhalational anthrax may include mild disease. METHODS: Eligible patients included those with illness compatible with early inhalational anthrax who had potential exposure to B. anthracis. Patient serum samples were tested for immunoglobulin G (IgG) antibody against B. anthracis protective antigen (PA) using a sensitive enzyme-linked immunosorbant assay (sensitivity, 97.6%). RESULTS: Of the 144 eligible patients, 66 (46%) had convalescent-phase serum samples available for testing; 29 (44%) worked in an area considered to pose a high risk of exposure to B. anthracis spores. Of the 37 patients who worked in areas that did not meet the definition of high-risk exposure, 23 (62%) worked in United States postal or other government facilities in which exposure was plausible but not documented. None of the 66 patients with convalescent-phase serum samples showed evidence of an anti-PA IgG serologic response to B. anthracis. CONCLUSIONS: These data suggest that a mild form of inhalational anthrax did not occur and that surveillance for moderate or severe illness was adequate to identify all inhalational anthrax cases resulting from the Washington, D.C., bioterrorism-related anthrax exposures.

Adult↗

PubMed1995

Influence of inhaler systems on systemic availability, with focus on inhaled corticosteroids.

Local treatment of obstructive pulmonary diseases, such as asthma, is achieved by oral inhalation of the active substance. Drug deposited in the lung may then exert its effects locally before it is absorbed into the systemic circulation. The systemic availability of a drug is made up of the fraction deposited in the lung and the fraction deposited in the oropharynx, which is swallowed and absorbed from the gastrointestinal (GI) tract. For many drugs, the fraction absorbed from the GI-tract is subject to hepatic first-pass metabolism before reaching the systemic circulation, and for the corticosteroid budesonide, hepatic first-pass metabolism is substantial. Since metabolic inactivation of inhaled corticosteroids in the lung has not been demonstrated, the systemic absorption of the fraction deposited in the lower respiratory tract can be assumed to be proportional to lung deposition. The local versus total systemic availability (L/T-ratio) can be used to express the effectiveness of the inhaled formulation. For budesonide inhaled via a pMDI and the dry-powder inhaler, Turbuhaler, the L/T-ratio was 0.59 and 0.84, respectively. The ideal L/T-ratio is 1.0. Thus, for inhaled budesonide it is an advantage for patients to change from budesonide pMDI to budesonide Turbuhaler with respect to the balance between desired and undesired effects.

Administration, Inhalation↗

PubMed1992

Treatment with inhaled steroids in asthma and chronic bronchitis: long-term compliance and inhaler technique.

We investigated compliance and inhaler technique in 50 patients with airway obstruction (26 asthma, 24 chronic bronchitis) being treated with inhaled steroid (beclomethasone dipropionate, BDP) via a dry powder inhaler (Rotahaler omega). Patients had already participated for one year in a 2-year trial of BDP in general practice. They were treated daily with two dry powder inhalations of 400 micrograms BDP in combination with a bronchodilator. Compliance with BDP was measured by counting capsules (single-blind) at the end of a 4-month period and through a questionnaire. Counting capsules revealed non-compliance in 46% of the patients. Compliance was not related to age, sex, diagnosis or side-effects of BDP. In chronic bronchitis, but not in asthma, compliance was related to the outcome parameters of steroid treatment (pulmonary symptoms, change in lung function and non-specific bronchial responsiveness). The inhaler technique was judged insufficient in 27% of the patients. This study stresses the importance of regular instruction in inhaler technique and proper information about prophylactic steroid treatment by the general practitioner during the treatment of asthma and chronic bronchitis.

Administration, Inhalation↗

PubMed1999

Unintended inhalation of nitric oxide by contamination of compressed air: physiologic effects and interference with intended nitric oxide inhalation in acute lung injury.

BACKGROUND: Compressed air from a hospital's central gas supply may contain nitric oxide as a result of air pollution. Inhaled nitric oxide may increase arterial oxygen tension and decrease pulmonary vascular resistance in patients with acute lung injury and acute respiratory distress syndrome. Therefore, the authors wanted to determine whether unintentional nitric oxide inhalation by contamination of compressed air influences arterial oxygen tension and pulmonary vascular resistance and interferes with the therapeutic use of nitric oxide. METHODS: Nitric oxide concentrations in the compressed air of a university hospital were measured continuously by chemiluminescence during two periods (4 and 2 weeks). The effects of unintended nitric oxide inhalation on arterial oxygen tension (n = 15) and on pulmonary vascular resistance (n = 9) were measured in patients with acute lung injury and acute respiratory distress syndrome by changing the source of compressed air of the ventilator from the hospital's central gas supply to a nitric oxide-free gas tank containing compressed air. In five of these patients, the effects of an additional inhalation of 5 ppm nitric oxide were evaluated. RESULTS: During working days, compressed air of the hospital's central gas supply contained clinically effective nitric oxide concentrations (> 80 parts per billion) during 40% of the time. Change to gas tank-supplied nitric oxide-free compressed air decreased the arterial oxygen tension by 10% and increased pulmonary vascular resistance by 13%. The addition of 5 ppm nitric oxide had a minimal effect on arterial oxygen tension and pulmonary vascular resistance when added to hospital-supplied compressed air but improved both when added to tank-supplied compressed air. CONCLUSIONS: Unintended inhalation of nitric oxide increases arterial oxygen tension and decreases pulmonary vascular resistance in patients with acute lung injury and acute respiratory distress syndrome. The unintended nitric oxide inhalation interferes with the therapeutic use of nitric oxide.

Administration, Inhalation↗