Early inhaled glucocorticoid therapy to prevent bronchopulmonary dysplasia.
(9/2342)
BACKGROUND: The safety and efficacy of inhaled glucocorticoid therapy for asthma stimulated its use in infants to prevent bronchopulmonary dysplasia. We tested the hypothesis that early therapy with inhaled glucocorticoids would decrease the frequency of bronchopulmonary dysplasia in premature infants. METHODS: We conducted a randomized, multicenter trial of inhaled beclomethasone or placebo in 253 infants, 3 to 14 days old, born before 33 weeks of gestation and weighing 1250 g or less at birth, who required ventilation therapy. Beclomethasone was delivered in a decreasing dosage, from 40 to 5 microg per kilogram of body weight per day, for four weeks. The primary outcome measure was bronchopulmonary dysplasia at 28 days of age. Secondary outcomes included bronchopulmonary dysplasia at 36 weeks of postmenstrual age, the need for systemic glucocorticoid therapy, the need for bronchodilator therapy, the duration of respiratory support, and death. RESULTS: One hundred twenty-three infants received beclomethasone, and 130 received placebo. The frequency of bronchopulmonary dysplasia was similar in the two groups: 43 percent in the beclomethasone group and 45 percent in the placebo group at 28 days of age, and 18 percent in the beclomethasone group and 20 percent in the placebo group at 36 weeks of postmenstrual age. At 28 days of age, fewer infants in the beclomethasone group than in the placebo group were receiving systemic glucocorticoid therapy (relative risk, 0.6; 95 percent confidence interval, 0.4 to 1.0) and mechanical ventilation (relative risk, 0.8; 95 percent confidence interval, 0.6 to 1.0). CONCLUSIONS: Early beclomethasone therapy did not prevent bronchopulmonary dysplasia but was associated with lower rates of use of systemic glucocorticoid therapy and mechanical ventilation. (+info)
The diagnosis, classification, and management of asthma according to severity.
(10/2342)
This activity is designed for primary care and specialist physicians. GOAL: To provide prompt and appropriate treatment for asthma of all levels of severity resulting in improved level of activity and decreased need for urgent care and hospitalization with a possible reduction in the annual decline of lung function, degree of permanent airway damage, and mortality. OBJECTIVES: 1. To provide a framework on the basis of history, physical findings, and laboratory results for the diagnosis of asthma. 2. To improve the ability to classify asthma by degree of severity. 3. To describe an incremental therapeutic approach to asthma by degree of severity. 4. To provide a systematic approach with regard to periodic reevaluation of asthma severity and modification of the treatment plan. (+info)
Randomised controlled trial of aminophylline for severe acute asthma.
(11/2342)
OBJECTIVES: To determine whether children with severe acute asthma treated with large doses of inhaled salbutamol, inhaled ipratropium, and intravenous steroids are conferred any further benefits by the addition of aminophylline given intravenously. STUDY DESIGN: Randomised, double blind, placebo controlled trial of 163 children admitted to hospital with asthma who were unresponsive to nebulised salbutamol. RESULTS: The placebo and treatment groups of children were similar at baseline. The 48 children in the aminophylline group had a greater improvement in spirometry at six hours and a higher oxygen saturation in the first 30 hours. Five subjects in the placebo group were intubated and ventilated after enrollment compared with none in the aminophylline group. CONCLUSIONS: Aminophylline continues to have a place in the management of severe acute asthma in children unresponsive to initial treatment. (+info)
Randomised trial of three doses of inhaled nitric oxide in acute respiratory distress syndrome.
(12/2342)
BACKGROUND: Inhaled nitric oxide (iNO) is a potential therapeutic agent for the management of acute respiratory distress syndrome (ARDS). Concerns remain, however, regarding the potential toxicity from iNO and/or its oxidative derivatives and methaemoglobinaemia. AIMS: To determine the risk of toxicity from iNO, which includes worsening of lung injury, a prospective study evaluating the acute effects of three concentrations of iNO on gas exchange and haemodynamics in 12 children with ARDS was performed in a tertiary paediatric intensive care unit. INTERVENTION: iNO was administered for one hour at three concentrations (1, 10, and 20 parts per million (ppm)) in a random order of possible dosing schedules to avoid dose accumulation bias. Arterial blood gas, methaemoglobin concentrations, and haemodynamic parameters were obtained at baseline before commencement of iNO, at the end of each study hour, and after iNO was discontinued. Nitric oxide and nitrogen dioxide concentrations were continuously monitored during the study. RESULTS: iNO significantly improved the oxygenation ratio (Pao2/Fio2) from a mean (SEM) baseline of 11.9 (1.7) kPa to 20 (3.9) kPa, 24 (4.5) kPa, and 21.6 (3.9) kPa at 1, 10, and 20 ppm iNO, respectively. There was no significant difference in the improvement in oxygenation achieved between the three concentrations. Correspondingly, there was a significant improvement in oxygenation index (pre-iNO 28.3 (5) v post-iNO 18 (3) (1 ppm), 15 (3) (10 ppm), 16 (3) (20 ppm)). No toxicity from methaemoglobinaemia or nitrogen dioxide was seen during iNO administration. CONCLUSION: The results show that a low concentration of iNO (1 ppm) is as effective as higher concentrations (10 and 20 ppm) in improving oxygenation in children with ARDS and may be important in minimising toxicity during iNO use. (+info)
Airway hyperresponsiveness to ultrasonically nebulized distilled water in subjects with tetraplegia.
(13/2342)
The majority of otherwise healthy subjects with chronic cervical spinal cord injury (SCI) demonstrate airway hyperresponsiveness to aerosolized methacholine or histamine. The present study was performed to determine whether ultrasonically nebulized distilled water (UNDW) induces airway hyperresponsiveness and to further elucidate potential mechanisms in this population. Fifteen subjects with SCI, nine with tetraplegia (C4-7) and six with paraplegia (T9-L1), were initially exposed to UNDW for 30 s; spirometry was performed immediately and again 2 min after exposure. The challenge continued by progressively increasing exposure time until the forced expiratory volume in 1 s decreased 20% or more from baseline (PD20) or the maximal exposure time was reached. Five subjects responding to UNDW returned for a second challenge 30 min after inhalation of aerosolized ipratropium bromide (2.5 ml of a 0.6% solution). Eight of nine subjects with tetraplegia had significant bronchoconstrictor responses to UNDW (geometric mean PD20 = 7.76 +/- 7.67 ml), whereas none with paraplegia demonstrated a response (geometric mean PD20 = 24 ml). Five of the subjects with tetraplegia who initially responded to distilled water (geometric mean PD20 = 5.99 +/- 4.47 ml) were not responsive after pretreatment with ipratropium bromide (geometric mean PD20 = 24 ml). Findings that subjects with tetraplegia are hyperreactive to UNDW, a physicochemical agent, combined with previous observations of hyperreactivity to methacholine and histamine, suggest that overall airway hyperresponsiveness in these individuals is a nonspecific phenomenon similar to that observed in patients with asthma. The ability of ipratropium bromide to completely block UNDW-induced bronchoconstriction suggests that, in part, airway hyperresponsiveness in subjects with tetraplegia represents unopposed parasympathetic activity. (+info)
Effects of formoterol on histamine induced plasma exudation in induced sputum from normal subjects.
(14/2342)
BACKGROUND: A number of studies have shown that beta 2 agonists, including formoterol, inhibit plasma exudation induced by the inflammatory stimulus in animal airways. Whether clinical doses of beta 2 agonists inhibit plasma exudation in human bronchial airways is unknown. METHODS: In order to explore the microvascular permeability and its potential inhibition by beta 2 agonists in human bronchial airways a dual induction method was developed: plasma exudation induced by histamine inhalation followed by sputum induction by hypertonic saline (4.5%) inhalation. Sixteen healthy subjects received formoterol (18 micrograms) in a placebo controlled, double blind, crossover study. Sputum was induced on five occasions: once at baseline and four times after histamine challenge (30 minutes and eight hours after both formoterol and placebo treatments). Sputum levels of alpha 2-macroglobulin were determined to indicate microvascular-epithelial exudation of bulk plasma. RESULTS: Histamine induced plasma exudation 30 minutes after placebo was considerably greater than at baseline (median difference 11.3 micrograms/ml (95% confidence interval 0.9 to 90.0)). At 30 minutes after formoterol the effect of histamine was reduced by 5.1 (0.9 to 61.9) micrograms/ml compared with placebo. At eight hours histamine produced less exudation and inhibition by formoterol was not demonstrated. CONCLUSION: This study shows for the first time an anti-exudative effect of a beta 2 agonist in healthy human bronchial airways. Through its physical and biological effects, plasma exudation is of multipotential pathogenic importance in asthma. If the present findings translate to disease conditions, it suggests that an anti-exudative effect may contribute to the anti-asthmatic activity of formoterol. (+info)
First treatment with inhaled corticosteroids and the prevention of admissions to hospital for asthma.
(15/2342)
BACKGROUND: Early treatment with inhaled corticosteroids appears to improve clinical symptoms in asthma. Whether a first treatment initiated in the year following the recognition of asthma can prevent major outcomes such as admission to hospital has yet to be studied. METHODS: A case-control study nested within a cohort of 13,563 newly treated asthmatic subjects selected from the databases of Saskatchewan Health (1977-1993) was undertaken to investigate the effectiveness of a first treatment with inhaled corticosteroids in preventing admissions to hospital for asthma. Study subjects were aged between five and 44 years at cohort entry. First time users of inhaled corticosteroids were compared with first time users of theophylline for a maximum of 12 months of treatment. The two treatments under study were further classified into initial and subsequent therapy to minimize selection bias and confounding by indication. Odds ratios associated with hospital admissions for asthma were estimated using conditional logistic regression. Markers of asthma severity, as well as age and sex, were considered as potential confounders. RESULTS: Three hundred and three patients admitted to hospital with asthma were identified and 2636 matched controls were selected. subjects initially treated with regular inhaled corticosteroids were 40% less likely to be admitted to hospital for asthma than regular users of theophylline (odds ratio 0.6; 95% CI 0.4 to 1.0). The odds ratio decreased to 0.2 (95% CI 0.1 to 0.5) when inhaled corticosteroids and theophylline were given subsequently. CONCLUSION: The first regular treatment with inhaled corticosteroids initiated in the year following the recognition of asthma can reduce the risk of admission to hospital for asthma by up to 80% compared with regular treatment with theophylline. This is probably due, at least in part, to reducing the likelihood of a worsening in the severity of asthma. (+info)
Comparison of the bronchodilator effects of salbutamol delivered via a metered-dose inhaler with spacer, a dry-powder inhaler, and a jet nebulizer in patients with chronic obstructive pulmonary disease.
(16/2342)
The aim of this study was to compare the bronchodilator effects of salbutamol delivered via three different devices: a dry-powder inhaler (DPI), a metered-dose inhaler (MDI) with a large-volume spacer and a jet nebulizer (NEB) in patients with stable chronic obstructive pulmonary disease (COPD). Ten male patients with stable COPD [age: 67.2 +/- 3.8 years, forced expiratory volume in 1 s (FEV1): 1.56 +/- 0.32 liters] were studied in a randomized, double-blind and crossover manner. Each patient received 200 or 1, 000 microg salbutamol via an MDI with an InspirEaseTM spacer, a RotahalerTM, or a DeVilbiss 646(TM) nebulizer (NEB), or matching placebo on 7 separate days. Spirometry was performed before and 15, 30, 60, 90, 120, and 240 min after inhalation. With the 200- microg dose, only DPI produced a small but greater response in maximum FEV1 and in area under the time-response curve (AUC-FEV1) compared with placebo. With the 1,000- microg dose, DPI and MDI produced equally greater improvements in both maximum FEV1 and AUC-FEV1 than NEB. An equal bronchodilating effect can be obtained using either DPI or MDI with a spacer device, whereas the NEB was less effective when the same dose was administered. (+info)