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[Inhalational antibiotic therapy in patients with cystic fibrosis and Pseudomonas infection].

Treating chronic Pseudomonas infection of the bronchial tree is a very important part of the treatment strategy in patients with cystic fibrosis. There are only a few antibiotics which are effective against pseudomonas. Many of them soon lead to bacterial resistance (e.g. fluoro-quinolones). Inhaling antibiotics produces high sputum concentrations and low systemic toxicity. Tolerance is good and resistance rare. Several clinical studies, some of them doubleblind placebo controlled, have shown a positive effect of inhaled antibiotics on symptoms, on frequency of necessary i.v. therapies and also on pulmonary function. Most commonly aminoglycosides (tobramycin) and colistin, which is not yet registered in Switzerland, are used. The main indication is chronic therapy of Pseudomonas infection.

Administration, Inhalation↗

Persistence, adherence, and effectiveness of combination therapy among adult patients with asthma.

BACKGROUND: Limited evidence exists on adherence and effectiveness of combination therapy (inhaled corticosteroids and long-acting beta(2)-agonists in the same inhaler) in asthma. OBJECTIVE: To compare persistence, adherence, and effectiveness between patients with asthma 16 to 44 years old starting combination or concurrent therapies (inhaled corticosteroids and long-acting beta(2)-agonists in 2 different inhalers). METHODS: This retrospective 1-to-1 matched cohort included newly treated asthmatics with either a combination or concurrent therapy selected from the Régie de l'assurance maladie du Québec database between 1999 and 2002. Persistence was determined by Kaplan-Meier and Cox regression analyses. Adherence was estimated by the number of prescriptions filled during the first year and compared between the 2 drug regimens using a linear regression model. Treatment effectiveness to reduce the rate of moderate to severe asthma exacerbations was estimated with Poisson regression models. RESULTS: Persistence fell to 10% and 5% after 12 months for combination and concurrent users, respectively. Combination users were found to be 17% less likely to stop their treatment (adjusted hazard ratio, 0.83; 95% CI, 0.78, 0.88) and filled on average 0.9 more prescription per year than concurrent users (P = .0001). Combination users were also found to be 17% less likely to have a moderate to severe asthma exacerbation (adjusted rate ratio, 0.83; 95% CI, 0.75, 0.91). CONCLUSION: The observed differences in treatment persistence and adherence were found to be associated with a reduction in the rate of moderate to severe asthma exacerbations among combination users. CLINICAL IMPLICATIONS: Combination therapy might be preferred to concurrent therapy for patients with asthma with low adherence to controller therapies.

Administration, Inhalation↗

Gas-phase oxidation of nitric oxide: chemical kinetics and rate constant.

Inhaled nitric oxide (NO) is gaining popularity as a selective pulmonary vasodilator. Because of the potential toxicity of NO and its oxidizing product nitrogen dioxide (NO2), any system for the delivery of inhaled NO must aim at predictable and reproducible levels of NO and at as low concentrations of NO2 as possible. This review describes the chemical kinetics and rate constant values k for the reaction 2NO + O2 = 2NO2. This reaction has been well established as a third-order homogeneous reaction. Published data support two equally plausible two-step mechanisms for the reaction between NO and O2 over a wide range of temperature and pressure. The Arrhenius equation k (L2 x mol(-2) x s(-1)) = 1.2 x 10(3) e(530/T) (=1.2 x 10(3) x 10(230/T)) gives the best fit to the experimental values of the rate constant thus far reported in a temperature range of 273 to 600 K. Using the reaction mechanism and the rate constant k, one can make reliable predictions about NO2 formation in any set of NO inhalation therapy conditions. It is also pointed out that NO3, the intermediate of one of the two mechanisms, deserves serious attention in NO inhalation therapy.

Administration, Inhalation↗

Initiation, dose reduction, and duration of inhaled corticosteroid therapy.

Asthma is characterized by persistent airway inflammation, which is associated with airway hyperresponsiveness and variable airflow obstruction, which accounts for the majority of symptoms experienced by asthmatic patients. Allergen sensitization and inhalation causes airway inflammation, and is likely important in the initiation and persistence of asthma in more than 50% of patients, and while allergen avoidance (or avoidance of other initiating factors, such as occupational sensitizers) can help some patients, it is often difficult to achieve. For this reason, pharmacologic treatment to reduce airway inflammation is currently the cornerstone of therapy for most individuals who have asthma.

Administration, Inhalation↗

[A pregnant woman with severe asthma effectively treated by inhalational lidocaine therapy].

We report a case of a pregnant woman with severe asthma that was not controlled with ordinary medications but was effectively treated by inhalational lidocaine treatment. The case was a 27-year-old woman who had been repeatedly hospitalized due to acute asthma since her infancy. The patient had an episode of asthma attack caused by the use of aspirin. The daily medication for controlling her asthma included 1.5mg betamethasone. In February, 2004, she was hospitalized because of asthma exacerbation during her 11th week of pregnancy. Despite intensive treatments including repetition of inhaled beta2-agonist and anti-cholinergic drugs, intravenous injection of betamethasone and theophylline, and a leukotriene receptor-antagonist, no obvious improvement in severe cough, wheeze, or hypoxemia was observed for more than 3 weeks. Then inhalational lidocaine was introduced according to the method described by Mayo Clinic, USA. Namely, following inhalation of beta2-agonist, 40 to 100mg lidocaine was given via an ultrasonic nebulizer 5 times a day. Interestingly, symptoms such as wheezing or cough and also her hypoxemia dramatically improved following this treatment and reduction of systemic corticosteroid became possible. Finally, she was delivered of a girl by caesarean section. Nebulized lidocaine treatment may be an useful option as supplementary treatment for refractory asthma especially in pregnant cases.

Administration, Inhalation↗

New frontiers in aerosol delivery during mechanical ventilation.

The scientific basis for inhalation therapy in mechanically-ventilated patients is now firmly established. A variety of new devices that deliver drugs to the lung with high efficiency could be employed for drug delivery during mechanical ventilation. Encapsulation of drugs within liposomes could increase the amount of drug delivered, prolong the effect of a dose, and minimize adverse effects. With improved inhalation devices and surfactant formulations, inhaled surfactant could be employed for several indications in mechanically-ventilated patients. Research is unraveling the causes of some disorders that have been poorly understood, and our improved understanding of the causal mechanisms of various respiratory disorders will provide new applications for inhaled therapies.

Administration, Inhalation↗

[Synergistic effects of combined therapy of inhalational glucocorticosteroids with long-acting beta 2-receptor agonists in treatment of bronchial asthma].

BACKGROUND: Due to the potent anti-inflammatory strength, glucocorticosteroids are the basis of long-term (controller) therapy in asthma. They inhibit transcription of pro-inflammatory cytokines and block humoral as well as cellular derived inflammation in the bronchi. beta 2 sympathomimetics are well known to cause dilatation of the bronchi but also to modulate certain anti-inflammatory responses. SYNERGISM: Just recently it could be demonstrated that beta 2 agonists may also be able to activate glucocorticosteroid receptors, independently of existing glucocorticosteroids. Thus, beta 2 agonists lead to augmentation of glucocorticosteroid receptor concentration, and consequently cause better efficacy of glucocorticosteroids within the cell. Vice versa glucocorticosteroids enhance the transcription rate of beta 2 receptors, causing higher beta 2 receptor number, and thus may contribute to better beta 2 agonist efficacy. These synergies of beta 2 agonists and glucocorticosteroids on molecular level explain additive efficiency in the therapy of asthma--particularly through improving lung function--when using both substances in combination.

Administration, Inhalation↗

[Physical therapy in patients with COPD and tracheobronchial instability--comparison of 2 oscillating PEP systems (RC-Cornet, VRP1 Desitin). Results of a randommized prospective study of 90 patients].

UNLABELLED: In a randomized prospective study in 90 patients with COAD and tracheo-bronchial instability 3 groups were formed. Group 1: Therapy as group 3+ Physiotherapy with VRP1 Desitin, Group 2: Therapy as group 3+ Physiotherapy with RC-Cornet, Group 3: CONTROL GROUP: daily 40 mg prednisolon i.v., 2 x theophylline i.v. in relation to serum levels and 3 x inhalation of beta 2+ parasympathicolytic with a compressor inhaler. Therapy group 1 and 2 received the same drug and inhalation therapy as the controls. Controls of lung function before and after physiotherapy and visual analog scales for dyspnoea, cough, sputum and acceptance of the physiotherapy were performed at days 1, 4 and 7. With RC-Cornet the residual volume decreases statistically significant in comparison to VRP1 Desitin. Hyperventilation is also statistically significant smaller in RC-Cornet compared to VRP1 Desitin. The subjective improvement of sputum, dyspnoea and acceptance of the method of physiotherapy was statistically significant better for RC-Cornet. Regarding cough the significance was just failed by p < 0.055. RC-Cornet is a comfortable, effective, small accepted tool for the long term physiotherapy of patients with COAD and tracheobronchial instability.

Adult↗

Respiratory membrane permeability and bronchial hyperreactivity in patients with stable asthma. Effects of therapy with inhaled steroids.

In patients with stable asthma, we assayed plasma proteins in the bronchoalveolar lavage fluid to obtain information on plasma exudation into the airways. Fourteen nonsmoking patients with asthma who were in a stable period of their disease and eight nonsmoking healthy volunteers were studied. The ratios of the concentrations of albumin, ceruloplasmin (CP), and alpha-2-macroglobulin (A2M) between blood and epithelial lining fluid were calculated (cQalb, cQCP, and cQA2M). The cQalb was increased in the patients (Mann-Whitney U test, p less than 0.05). In 10 patients the bronchial hyperreactivity was assessed with histamine provocation tests. Significant relationships between the cQalb, cQCP, and cQA2M on the one hand and PC15 on the other hand were found (Spearman's rank correlation: r = -0.62, p less than 0.05; r = -0.61, p less than 0.05; r = -0.79, p less than 0.01, respectively). Fourteen patients were treated with two inhalations of 200 micrograms glucocorticosteroids per day in a 3-month prospective study. Three of them were excluded from further study because of an intercurrent exacerbation of asthmatic symptoms during therapy. In the 11 patients with stable asthma, the cQalb and cQA2M decreased after treatment with inhaled steroids (Wilcoxon's matched pairs signed rank test, p less than 0.03). Our results show that in patients with stable asthma, there is an increased plasma exudation into the airways, most likely caused by an increased respiratory membrane permeability. The plasma exudation correlated with the bronchial hyperreactivity to histamine, and it decreased after corticosteroid therapy.

Administration, Inhalation↗

Effects of long-term inhaled salbutamol therapy on the provocation of asthma by histamine.

Eight patients with asthma in remission were treated for 4 wk with a regular beta 2 stimulant. (salbutamol, 200 microgram) given 4 times/day by aerosol. Histamine provocation tests were performed at the beginning and at the end of the treatment period, and again 2 wk after cessation of treatment. Throughout the 6-wk period, the patients recorded peak expiratory flow (PEF) at home twice daily before and after inhaling 200 microgram of salbutamol. No significant differences were seen in the average PEF values or in the bronchodilator responses. There were no changes in the bronchial sensitivity to histamine during the study, and the protective effect of inhaled salbutamol against histamine provocation was preserved after the period of regular therapy. The results suggested that the regular use of a selective beta2 stimulant by inhalation in conventional therapeutic amounts in patients with asthma is unlikely to produce clinically important tolerance or increased susceptibility to an asthma-provoking stimulus.

Adult↗

High-performance liquid chromatographic method for the determination of colistin in serum.

Inhalation therapy of colistin is widespread in patients with cystic fibrosis. To date, no pharmacokinetic data of colistin after inhalation are available. To optimize the inhalation therapy, pharmacokinetic data of colistin are necessary. In this study, the authors describe a chromatographic analysis for measurement of colistin concentrations in serum. After protein precipitation, the colistin sample is treated with orthophthalaldehyde for derivatization. The sum of the peak areas of the two main components of colistin (polymyxin E1 and E2) were used for quantitation. The performance of the analytical method was assessed by determining the lower limit of quantitation, the selectivity of the method, the intra-assay variation, the reproducibility, the interassay variation, and the accuracy. The lower limit of quantitation was 28 microg/L. Ceftazidime, aztreonam, piperacilline, or tobramycin showed no interference with the colistin assay. In a pilot study, the authors found a trough value of approximately 10 microg/L and peak values of approximately 100 microg/L after inhalation of 160 mg colistin in serum samples of a representative patient. These values show that the method can be used to design further experiments. The applicability of the method was also tested on urine and sputum samples. Colistin was detectable but further validation experiments are required to confirm the usefulness of the method in these biologic matrices. To the authors' knowledge this is the first study in which serum concentrations are described after inhalation of colistin in patients with cystic fibrosis.

Administration, Inhalation↗

[Inhaled corticosteroid therapy in long-term management of adult asthma].

Bronchial asthma is no longer considered a condition with isolated, acute episodes of bronchoconstriction. Rather, asthma is now understood to be a chronic inflammatory disorder of the airways. Therefore anti-inflammatory agents and, more specifically, inhaled corticosteroids are at present the most effective controllers in long-term treatment and prevention of asthma. Asthma is highly variable, so precise classification of severity is needed for management. Asthma therapy recommended in guidelines follows a stepwise approach in which the level of therapy is increased (step up) as the severity of asthma increased and therapy decreased (step down) once control is achieved and sustained. In this stepwise approach, inhaled corticosteroid is a key drug and establishment of the dosage of inhaled corticosteroid is most important.

Administration, Inhalation↗