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PubMed1985

The effect of corticosteroids on monocyte and neutrophil activation in bronchial asthma.

The expression of IgG (Fc) receptor (FcR) and complement receptor (CR) on peripheral blood monocytes and neutrophils was determined by the rosette technique in patients with asthma receiving different forms of treatment. In 31 patients taking inhaled therapy (i.e., bronchodilators alone or in combination with inhaled corticosteroids), monocyte FcR (48.19 +/- 1.24%, mean +/- SEM) and complement (66.54 +/- 1.09%) rosettes were significantly higher (FcR p less than 0.001, CR p less than 0.001) than in the 17 healthy, normal control subjects (FcR 37.94 +/- 0.82%, CR 59.7 +/- 0.98%). These increases in the percent rosettes between the two groups were observed even when a wide concentration range of IgG or complement was used to coat the red cells. No significant differences in monocyte receptor expression were observed between those patients being treated with bronchodilators alone or patients being treated in combination with inhaled corticosteroids. In 19 patients with asthma receiving oral corticosteroids, the mean monocyte FcR (38.21 +/- 1.73%) and CR (52.78 +/- 2.09%) were significantly reduced when these patients were compared with those patients receiving inhaled therapy alone (FcR p less than 0.001, CR p less than 0.001), and there was a significant inverse correlation between the percent rosettes and the dose of prednisolone. Neutrophil CR (51.32 +/- 1.30%, p less than 0.05) but not FcR expression (24.7 +/- 0.80%) was significantly increased when these were compared with those of control subjects (FcR 24.7 +/- 0.60%, CR 47.11 +/- 0.86%), and both neutrophil FcR and CR expression was significantly reduced (FcR p less than 0.01, CR p less than 0.001) in those patients with asthma receiving oral corticosteroids. (ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Oxygen desaturation in adults following inhaled metaproterenol therapy.

Following bronchodilator therapy in asthmatic patients, a fall in arterial oxygen tension (PaO2) has been attributed to increased perfusion of persistently underventilated alveoli. We used continuous noninvasive pulse oximetry to evaluate the extent and timing of oxygen saturation (SaO2) decrease in adults following metaproterenol inhalation for acute bronchospasm. We also examined the effect of supplemental oxygen upon these factors. Baseline and peak drop in SaO2 after completion of the first bronchodilator therapy were measured and the percent change in SaO2 was calculated. A total of 47 patient visits were studied; 10 patients received supplemental oxygen. Mean age was 38 +/- 17.9 years. Baseline was SaO2 = 94.6 +/- 2.9%, peak drop SaO2 = 91.4 +/- 3.4%, and percent change in SaO2 = -3.4 +/- 2.5%. The mean time to peak drop was 24.4 +/- 15.4 minutes in the 40 patients, with an observed drop after initial treatment. The absolute change in SaO2 from baseline was significant both with and without oxygen (P less than .05 and less than .01, respectively). The group receiving oxygen had a significantly smaller percent drop and a larger proportion of patients showing no drop in SaO2 (P less than 0.01 and less than 0.03, respectively). Clinically significant oxygen desaturation can occur within 30 minutes of inhaled bronchodilator therapy. Supplemental oxygen (2-3 L/min) helps blunt the metaproterenol-induced drop in SaO2.

Acute Disease↗
PubMedDate not supplied

Is serum ECP level helpful in determining discontinuation of inhaled corticosteroid therapy in asthmatic children?

BACKGROUND: Serum eosinophil cationic protein (ECP) has been promoted as a direct marker of eosinophilic inflammation of the airways in patients with asthma. However, its role in monitoring disease activity and management of inhaled corticosteroid (ICS) therapy is not well defined. METHODS: We determined serum ECP (s-ECP) levels in 95 children (mean +/- SD age, 6.2 +/- 3.9 years) with asthma. At the time of measurements, 34 out of 95 children were symptomatic whereas 61 were in stable condition; and 56 of 95 patients were on maintenance ICS therapy. ICS prophylaxis was withdrawn in 16 of those 56 patients who remained asymptomatic with a dose of 100 micrograms/day of budesonide for 8 weeks. Eight out of these 16 children had to restart ICS therapy within the following 12 weeks, while the remaining 8 children continued to be asymptomatic within the same period. RESULTS: ECP values and number of patients with a high ECP level (> or = 15 micrograms/L) were significantly higher in the symptomatic group (p = 0.01 and p = 0.006, respectively). Also, ECP levels were significantly lower in the group who achieved clinical remission (n = 16) in which ICS therapy was withdrawn when compared with those who needed to continue ICS prophylaxis. On the other hand, no difference was observed in the comparison of the ECP levels of children who had to restart ICS therapy and those who did not. CONCLUSION: Our results suggest that, although the determination of s-ECP levels are in accordance with clinical evaluation of disease activity, it is not useful in determining discontinuation of ICS therapy.

Administration, Topical↗
PubMed1999

Inhaled antibiotic therapy in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa.

The aim of this study was to investigate the long-term effectiveness and safety of inhaled antibiotic treatment in non-cystic fibrosis patients with bronchiectasis and chronic infection by Pseudomonas aeruginosa, after standard endovenous and oral therapy for long-term control of the infection had failed. After completing a 2-week endovenous antibiotic treatment to stabilize respiratory status, 17 patients were randomly allocated to a 12-month treatment either with inhaled ceftazidime and tobramycin (group A) or a symptomatic treatment (group B). One patient from group A abandoned inhaled treatment because of bronchospasm and another from group B died before the end of the study. The remaining 15 patients, seven from group A and eight from group B, completed the study. Both groups had similar previous characteristics. The number of admissions and days of admission (mean +/- SEM) of group A [0.6 (1.5) and 13.1 (34.8)] were lower than those of group B [2.5 (2.1) and 57.9 (41.8)] (P < 0.05). Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), PAO2 and PACO2 were similar in the two groups at the end of follow-up, showing a comparable decline in these parameters. There were no significant differences either in the use of oral antibiotics or in the frequency of emergence of antibiotic-resistant bacteria between groups. Microbiological studies suggested that several patients had different Pseudomonas aeruginosa strains. None of the patients presented impaired renal or auditory function at the end of the study. This study suggests that long-term inhaled antibiotic therapy may be safe and lessen disease severity in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa which do not respond satisfactorily to antibiotics administered via other routes.

Administration, Inhalation↗
PubMed1992

Lung function and immunopathological changes after inhaled corticosteroid therapy in asthma.

Six patients with asthma (American Thoracic Society (ATS) criteria), maintained on inhaled beta 2-agonists alone, were treated with inhaled corticosteroid (budesonide 400 micrograms b.d.) for a period of three months. Prior to steroid therapy, baseline spirometry, bronchodilator response and bronchial hyperresponsiveness were documented and endobronchial biopsies were obtained for immunopathological analysis. Frozen sections of the biopsies were investigated using immunoperoxidase methods, with a panel of monoclonal antibodies selected to reveal the presence and distribution of lymphocyte and macrophage subsets and HLA-DR expression. After three months the studies were repeated. Studies before steroid therapy revealed a T-cell-dominated inflammation in the bronchial wall of all subjects. Baseline airway obstruction, median (range) forced expiratory volume in one second (FEV1) 78.5 (61-109)% of predicted, with a significant bronchodilator response 20.8 (14-33)% and bronchial hyperresponsiveness to histamine geometric mean (SD) PC20FEV1 0.69 (2.5) mg was documented. Steroid therapy caused a significant reduction in bronchial hyperresponsiveness to histamine, with an increase in geometric mean PC20FEV1 to 2.22 (3.2) mg post steroid (p less than 0.03). Concurrent with a reduction in bronchodilator response and an increase in spirometric variables (improved forced midexpiratory flow (FEF25-75) p less than 0.03), there were marked reductions observed in the overall numbers of T-lymphocytes (CD 2, 5, 8), the numbers of CD45RO+ T-cells, and the numbers of macrophages (RFD1+) with the phenotype of antigen presenting cells. In all six subjects, reductions in the quantitative expression of HLA-DR molecules were also seen.(ABSTRACT TRUNCATED AT 250 WORDS)

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↗
PubMed1998

[New drug delivery systems for the therapy of bronchial asthma].

Inhalation therapy gives us ideal topical therapy for the airway diseases without significant major side-effects. As new century approaches, a major goal for asthma therapy will be to provide more effective therapeutic drugs to prevent airway inflammation and its spasmus. It is also important to produce excellent inhalant devices that are easy to use and do not contain substances that are harmful to the environment. Future inhalers should target the drug to the correct sites in the airways and thus enable optimal therapeutic effects to be achieved. There are many exciting new developments available in this field. And we should finally obtain special therapeutic drugs to prevent the process to the sudden-onset of asthmatic death.

Administration, Inhalation↗
PubMed2006

Aerosol therapy by pressured metered-dose inhaler-spacer in sleeping young children: to do or not to do?

UNLABELLED: One third of young children are distressed during inhalation therapy. It has been suggested that administration during sleep could be a good alternative for these children. A laboratory study in our department using an infant upper airway model showed significantly higher lung doses from a pressured metered-dose inhaler (pMDI)-spacer for sleep-breathing patterns compared with wake-breathing patterns. OBJECTIVE: We set up a daily life study to investigate the feasibility of aerosol administration by means of pMDI-spacer in sleeping young children. DESIGN: Over a period of 3 weeks, 30 children (age range, 6 to 23 months) with recurrent wheeze daily inhaled 1 puff of budesonide aerosol (200 mug) while awake and 1 puff during sleep. Filters positioned between the chamber and the facemask trapped the budesonide aerosol. Parents scored the child's asthma symptoms, degree of cooperation, and feasibility of administration on diary cards. RESULTS: In 69% of the sleep administrations, the children woke up, and in 75% of these cases the children were distressed. The mean filter dose (expressed as the percentage of the nominal dose) while awake was 47%, and during sleep it was 16% (p = 0.007). The median within-subject dose variability while awake was 50%, and during sleep it was 110% (p = 0.007). CONCLUSION: Aerosol administration by means of pMDI-spacer during sleep offers no advantage and is not a feasible treatment option in most young children.

Administration, Inhalation↗
PubMed2004

Omalizumab as add-on therapy to inhaled steroids for asthma.

In the US, subcutaneous administration of omalizumab is indicated for adults and adolescents (age greater than or equal to 12 years) with allergic asthma that is moderate to severe and inadequately controlled with inhaled corticosteroids. In placebo-controlled trials, omalizumab reduces asthma exacerbations and the need for inhaled steroids in this group. The value of omalizumab to patients with severe asthma (e.g., refractory asthma) has yet to be proven. Data are lacking on the efficacy of omalizumab compared to add-on therapies such as inhaled long-acting beta-2 agonists or anti-leukotriene agents. Further evaluation on omalizumab needs to be done in the pediatric population.

Adolescent↗
PubMed2005

[Inhaled corticosteroid therapy in adults with asthma. Current evidences].

Different international guidelines recommend the early introduction of inhaled corticosteroids (ICS) and their regular use to gain clinical and functional control of persistent asthma. There is now evidence that the starting dose of all ICS is lower than previously regarded. Initial moderate ICS doses appear to be more effective than an initial low ICS dose. The lowest effective dose should always be seeked by a step-down procedure. More than 90% of benefit is achieved by approximately a daily regular dose of 200 microg of fluticasone or 400 microg of beclomethasone or budesonide. The beneficial effects of increasing the dose of ICS alone appear to be modest in most cases. Intermittent ICS therapy has been successfully used in the long term treatment of mild asthma. In general, twice-daily administration of ICS provides greater therapeutic benefit than a once-daily regimen in moderate asthma. When asthma control has been obtained, a once-daily regimen can be tried. In clinical practice, this has the potential advantage of increasing patients' compliance. Chlorofluorocarbon-free formulations of old ICS have also remarkably improved their clinical efficacy mainly through an increased peripheral deposition pattern. Despite some limitations due to poor response in neutrophilic asthma and to potential systemic side effects, ICS will certainly be the cornerstone of asthma therapy even the next future.

Administration, Inhalation↗
PubMed2001

Effect of inhaled budesonide therapy on lung function in schoolchildren born preterm.

We investigated the effect of inhaled glucocorticoid (GC) on bronchial obstruction and on bronchial lability in schoolchildren born preterm. Twenty-one children with bronchial obstruction, increased responsiveness to a beta2-agonist, and/or increased diurnal variation in peak expiratory flow (PEF) were selected for an open longitudinal study of the value of inhaled GC. None of these children had an earlier diagnosis of asthma or current GC treatment. Eighteen children with median (range) birth weight 1025 (640-1600) g and gestational age 28 (24-35) weeks, age at study 10.1 (7.7-13) years, were treated with inhaled budesonide in initially high (0.8 mg m(-2) day(-1) for 1 month) and subsequently lower dose (0.4 mg m(-2) day(-1) for 3 months). Daily symptom scores were recorded. Spirometric values were measured in the clinic at the beginning and end of each treatment period. At home, children used a data storage spirometer. After treatment with budesonide for 4 months, spirometric values in the clinic did not significantly change. The median forced expiratory volume in 1 sec (FEV1) was 74% of predicted both at entry and after budesonide treatment. However, the median number of > or = 20% diurnal change in PEF values at home decreased during treatment. According to the present study, inhaled budesonide for 4 months had no significant effect on basic lung function but may decrease bronchial lability in schoolchildren born preterm.

Administration, Inhalation↗
PubMed2003

The current role of intravenous aminophylline in acute paediatric asthma.

Intravenous aminophylline is effective in children with acute asthma and was the bronchodilator of choice for many years. However, with the advent of inhaled b agonists and anticholinergic agents an alternative, less invasive, therapeutic strategy is currently available. If children with acute asthma fail to respond to inhaled therapy clinicians may consider aminophylline a controversial treatment. The published evidence on whether aminophylline produces further beneficial effect in children already receiving inhaled therapy for acute asthma is reviewed in this paper. The published randomised controlled trials comparing aminophylline with placebo are of good methodological quality, although the numbers of children in many of the studies are small. Trial outcomes included lung function (FEV1 and PEF) and clinical scoring of asthma severity. Aminophylline improved percentage predicted FEV1 by 6 hours, and this effect was maintained for 24 hours. Improvements were also seen in clinical asthma severity scores at 6 hours. Despite improvements in lung function and asthma severity, there was no reduction in hospital stay or the number of nebulisers required. The main side effect of aminophylline therapy was an increased incidence of vomiting. In conclusion, the addition of intravenous aminophylline should be considered early in the treatment of children hospitalised with acute severe asthma with suboptimal response to the initial inhaled bronchodilator therapy. Further research should be carried out to examine whether intravenous aminophylline may have a beneficial effect in other settings such as intensive care to determine if it may reduce intubation and ventilation rates.

Acute Disease↗
PubMed2004

Biochemical markers of bone metabolism and calciuria with inhaled budesonide therapy.

We investigated the changes in renal excretion of calcium, sodium, and potassium in asthmatic children treated with inhaled budesonide, an inhaled glucocorticoid. Twenty-two asthmatic patients (7 female, 15 male, mean age 10.1+/-4.3 years) treated with 400-600 microg/day inhaled budesonide and 23 healthy children (6 female, 17 male, mean age 10.2+/-2.8 years) were enrolled in the study. The parameters recorded were serum sodium, potassium, calcium, phosphorus, alkaline phosphatase (ALP), type I collagen carboxyterminal telopeptide (ICTP), osteocalcin, intact parathyroid hormone (PTH) levels, first spot morning urine calcium/creatinine ratio, sodium/potassium ratio, and daily renal calcium excretion rate (UCa-ER). These parameters were measured in the control group and pre- and post-budesonide treatment in asthmatic children. Serum electrolytes, ALP, PTH, ICTP, and UCa-ER were in the normal ranges and were not significantly different between controls and asthmatic children. Serum levels of ICTP increased, while levels of osteocalcin decreased after budesonide therapy in the asthmatic group ( P=0.001, P=0.005). UCa-ER was decreased after budesonide therapy in asthmatics ( P=0.000). In conclusion, moderate doses of inhaled budesonide cause hypocalciuria and decreased bone turnover. These results may be attributed to a mechanism compensating for decreased absorption of calcium in the gut due to the topical effect of swallowed budesonide rather than the systemic effects of the drug. Increased bone metabolism and decreased turnover may have an important role in this compensatory mechanism.

Administration, Inhalation↗
PubMed2003

The impact of budesonide and other inhaled corticosteroid therapies in the management of asthma in children and adults.

BACKGROUND: Since the recognition that asthma is characterized by extensive inflammation of the airways, the use of inhaled corticosteroids (ICSs) as controller therapy has become central to successful disease management. As the prevalence of asthma increases worldwide, there is concern about increasing numbers of patients with untreated or undertreated asthma, which may lead to deterioration in disease control, with direct effects on morbidity and mortality rates. The costs attributed to asthma translate into a considerable economic burden, from the direct costs of medical treatment to the costs incurred through lost work or school days. International treatment guidelines currently recommend early intervention with ICS therapy to improve lung function and disease control. OBJECTIVE: This article reviews the role of therapy with ICSs, particularly budesonide, in improving the management of asthma in patients of all ages and in reducing the economic and social burdens of this disease. RESULTS: Randomized, controlled clinical studies confirm the efficacy of early intervention with ICSs in patients with mild persistent asthma. Regular use of an ICS can reduce the number of exacerbations and hospitalizations in patients of all ages and with all disease severities. CONCLUSIONS: Budesonide has a well-established efficacy and safety profile. Its once-daily dosing may contribute to improved adherence and cost-effectiveness.

Administration, Inhalation↗