Use of inhaled corticosteroids in patients with mild asthma.

A double blind, parallel group study was carried out to investigate the effect of inhaled budesonide in a moderate (200 micrograms) and a low (100 micrograms) twice daily dosage compared with the effect of placebo in 103 adults with mild symptomatic asthma. Subjects recorded peak expiratory flow (PEF), asthma symptoms, and beta 2 agonist consumption at home for a period of seven weeks (a one week run in and six weeks' treatment). Morning baseline PEF (around 80% of predicted normal) increased non-significantly to 88% with 200 micrograms budesonide daily and to 90% (p less than 0.05) with 400 micrograms, compared with 81% with placebo. Evening PEF (around 94% of predicted normal) did not change significantly with active or placebo treatment. By comparison with placebo, there was a significant decrease in nocturnal asthma symptoms and beta 2 agonist consumption. The changes during the day were less pronounced and significant only for 400 micrograms budesonide daily. No significant differences between the two active treatments were detected. It is concluded that low doses of inhaled budesonide are effective in patients with mild symptomatic asthma, particularly for night time symptoms and early morning lung function. The early introduction of inhaled corticosteroids for patients with mild asthma and night time symptoms may improve their quality of life during the night and early morning.     

Effects of high doses of inhaled corticosteroids on adrenal function in children with severe persistent asthma.

BACKGROUND--Childhood asthma generally responds well to inhaled corticosteroids within the dosage range recommended by the manufacturers, but it is sometimes necessary to use higher doses--that is, above 400 micrograms/day--a practice which has become more widespread recently. Whereas the lack of adrenal suppression in children given inhaled corticosteroids in normal doses is well documented, little is known about the effects of higher doses. METHODS--The effects on adrenal function of high dose (above 400 micrograms/day) inhaled corticosteroids were evaluated by measuring cortisol concentration in the morning and performing a short tetracosactrin test in 49 children taking budesonide (mean age 9.2 years (range 4 to 16 years) and 28 children taking beclomethasone dipropionate (10.2 years (5 to 13 years)). Twenty three non-asthmatic children (8.9 years (4.9 to 13 years)) who were under investigation for short stature served as controls for the study. RESULTS--Compared with controls mean basal cortisol concentration was lower in children taking budesonide and beclomethasone dipropionate (control 401 (26.8) nmol/l, budesonide 284 (22) nmol/l, beclomethasone dipropionate 279 (23.2) nmol/l). Sixteen of the 49 children taking budesonide had subnormal basal cortisol concentrations compared with seven of the 28 taking beclomethasone dipropionate. Mean stimulated cortisol concentrations were lower in children taking inhaled corticosteroids than in controls, with no difference between those taking budesonide or beclomethasone dipropionate. CONCLUSIONS--Adrenal suppression occurs in some children who are given inhaled corticosteroids in doses greater than 400 micrograms/day. It may therefore be advisable to try alternative treatments before such doses are used.     

Exhaled nitric oxide rather than lung function distinguishes preschool children with probable asthma

BACKGROUND: Respiratory function and airway inflammation can be evaluated in preschool children with special techniques, but their relative power in identifying young children with asthma has not been studied. This study was undertaken to compare the value of exhaled nitric oxide (FE(NO)), baseline lung function, and bronchodilator responsiveness in identifying children with newly detected probable asthma. METHODS: Ninety six preschool children (age 3.8-7.5 years) with asthmatic symptoms or history and 62 age matched healthy non-atopic controls were studied. FE(NO) was measured with the standard online single exhalation technique, and baseline lung function and bronchodilator responsiveness were measured using impulse oscillometry (IOS). RESULTS: Children with probable asthma (n=21), characterised by recent recurrent wheeze, had a significantly higher mean (SE) concentration of FE(NO) than controls (22.1 (3.4) ppb v 5.3 (0.4) ppb; mean difference 16.8 ppb, 95% CI 12.0 to 21.5) and also had higher baseline respiratory resistance, lower reactance, and larger bronchodilator responses expressed as the change in resistance after inhalation of salbutamol. Children with chronic cough only (n=46) also had significantly raised mean FE(NO) (9.2 (1.5) ppb; mean difference 3.9 ppb, 95% CI 0.8 to 7.0) but their lung function was not significantly reduced. Children on inhaled steroids due to previously diagnosed asthma (n=29) differed from the controls only in their baseline lung function. The analysis of receiver operating characteristics (ROC) showed that FE(NO) provided the best power for discriminating between children with probable asthma and healthy controls, with a sensitivity of 86% and specificity of 92% at the cut off level of 1.5 SD above predicted. CONCLUSIONS: FE(NO) is superior to baseline respiratory function and bronchodilator responsiveness in identifying preschool children with probable asthma. The results emphasise the presence of airway inflammation in the early stages of asthma, even in young children.     

Acoustic rhinometry in preschool children.

OBJECTIVE: The aim of this study was to measure nasal cavity volume (NV) in preschool children with the use of acoustic rhinometry (AR). STUDY DESIGN AND SETTING: Prospective study: 1) Nasal cavity models were used to test the correlations between NV, minimal cross-sectional area (MCA), and nasal resistance; 2) 97 four-year-olds (48 boys, 49 girls) and 137 five-year-olds (68 boys, 69 girls) children were selected to undergo AR. RESULTS: 1. Model tests showed that the resistance correlated better with the changes of the volume than the MCA. 2. The average bilateral NV in preschool children was 2.03 +/- 0.4 mL. There was no significant difference in either gender (P = 0.2) or age (P = 0.197). CONCLUSIONS: Volume measurement appears more sensitive and reliable than the MCA in assessing nasal patency. AR was easily performed on preschool children, and normative NV values were achieved. SIGNIFICANCE: The results and conclusions can be used to establish a standardized technique for AR measurement and interpretation.     

Predicting patient attitudes to asthma medication.

BACKGROUND--Studies of patient attitudes to asthma and its control have focused on crisis action, and little attention has been paid to attitudes to regular preventive medication. It is not clear whether attitudes to regular medication are related to the degree of distress or interference with life perceived by patients as being caused by their asthma. For this reason this study examined how far dislike of medication related to dislike of other aspects of interference of asthma with daily life. METHODS--Three hundred and ninety one patients were surveyed with a questionnaire which assessed their dislike of the interference of asthma with their physical, social, and emotional functioning, together with dislike of regular asthma medication. A response was received from 320 patients (82%). RESULTS--Four attitude clusters were identified. Recorded in descending factor order, these were (1) dislike of asthma medication, (2) dislike of disability, (3) dislike of public life interference, and (4) dislike of social and emotional interference. The attitude clusters were not related: in particular, dislike of asthma medication could not be predicted from other dislikes, or from asthma best function ratio (ratio of best recorded peak expiratory flow rate in the previous year to predicted value), age, or sex. The most significant predictors of the patients' dislike of taking their own inhaled steroid were (1) dislike of using bronchodilator, (2) dislike of steroids generally, and (3) dislike of taking medicine every day. CONCLUSIONS--Patient attitudes to regular asthma medication are not related to general anxieties and dislikes about asthma, nor to the potential for asthma control as judged by the best function ratio. Patients were not always consistent in their attitude to inhaled steroids in general, nor to their own named inhaled steroid in particular. A general cluster of antimedication attitudes existed, independent of whether the medication was for prophylaxis or relief. Attitudes to asthma medication may be helpful in predicting patient behaviour.     

Nebulisers comparison with inhaled tobramycin in young children with cystic fibrosis.

BackgroundThis randomised cross-over pilot study was undertaken in 10 cystic fibrosis children aged 10 to 63 months to describe lung absorption of tobramycin delivered by the PariLC+/PariTurboboyN (Pari GmbH) and the disposable NL9M/AtomisorBoxPlus (Diffusion Technique Française) nebulising systems.MethodsEach child inhaled 300 mg tobramycin delivered with one or the other apparatus via a facemask in two separate and standardised sessions. Urine was collected for 6 h. Tobramycin concentrations determined by immunoprecipitation were expressed in mg per g of creatinine and compared by a Wilcoxon test for matched pairs. The influences of age, weight and Brasfield score on this parameter were evaluated by correlation tests, and those of sex, previous nebulisation treatment, and crying or coughing were evaluated by Student's t-test.ResultsThe amount of tobramycin measured in urines was low and variable. Median values for urinary tobramycin concentration were 47.6 mg/g (14.9–79.6) with the PariLC+ and 42.6 mg/g (6.3–112.8) with the NL9M (p = 0.6). PariLC+ delivered tobramycin in 22 min and NL9M in 12 min (p = 0.005). Crying or coughing dramatically reduced the amount of tobramycin collected.ConclusionThis pilot study shows that evaluation of nebulisers based on tobramycin renal excretion is feasible in young children with cystic fibrosis.     

Early use of inhaled nedocromil sodium in children following an acute episode of asthma

BACKGROUND: Current guidelines on the treatment of childhood asthma recommend the introduction of an anti-inflammatory drug in children who have persistent symptoms and require regular treatment with a bronchodilator. The efficacy and safety of inhaled nedocromil sodium (Tilade Mint aerosol) administered using a Fisonair spacer at a dose of 4 mg three times daily was compared with placebo in the treatment of asthmatic children aged 6-12 years who are symptomatic and recovering from an acute exacerbation of asthma. METHODS: A group comparative, double blind, placebo controlled trial was performed in children who were recovering from an acute episode of asthma following treatment in the emergency department of the hospital or in children referred from their general practitioner following a wheezing episode and documented evidence of at least two previous episodes of wheezing. A two week baseline period on existing bronchodilator treatment was followed by a 12 week treatment period on either nedocromil sodium (2 mg/puff) or placebo. Both treatments were administered using a Fisonair spacer at a dose of two puffs three times daily. Changes from baseline values in daytime asthma and night time asthma symptom scores, usage of rescue bronchodilators, mean peak expiratory flow (PEF) recorded twice daily on diary cards, patients' opinion of treatment, and withdrawals due to treatment failure were measured during the primary treatment period (last six weeks of treatment). RESULTS: One hundred and forty two children aged 6-12 years entered the baseline period. Sixty three were withdrawn due to failure to meet the entry criteria (18) or the criteria for asthma symptom severity (15) or reversibility (9), because they developed uncontrolled asthma (2), because they took disallowed treatment (2), or for other non-trial related reasons (17). Seventy nine patients (46 boys) of mean age 8. 8 years entered the treatment period. There were significant differences in the changes from baseline values during the last six weeks of treatment in favour of nedocromil sodium compared with placebo in the primary variables of daytime asthma and night time asthma, morning and evening PEF, and the usage of rescue inhaled bronchodilators; 53% of patients reported nedocromil sodium to be very or moderately effective compared with 44% placebo. Improvement in asthma symptoms, PEF, and reduction in use of rescue bronchodilators did not reach statistical significance until after six weeks of treatment. Twenty two patients were withdrawn or dropped out during the treatment phase, 12 due to uncontrolled asthma or persistence of asthma symptoms, four due to suspected adverse drug reactions (nedocromil sodium 3 (headaches 2, angio-oedema/urticaria 1), placebo 1(persistent cough)), and six due to non-treatment related reasons. Seventy one adverse events were reported by 27 patients in the nedocromil group and 75 by 30 patients in the placebo group. CONCLUSIONS: Asthma symptoms, use of bronchodilators, and lung function can be improved significantly in children recovering from an acute exacerbation of asthma or wheeze and currently receiving treatment with bronchodilators alone by the addition of inhaled nedocromil sodium at a dose of 4 mg three times daily administered using a Fisonair holding chamber.     

Effect of an inhaled antihistamine on exercise-induced asthma.

The ability of the H1 receptor antagonist clemastine to prevent exercise-induced asthma (EIA) has been studied in 10 adult asthmatic subjects. Exercise was performed for eight minutes on a cycle ergometer on two occasions on each of two days. The first test each day was without premedication and the second was preceded by inhalation of 0.05% clemastine or saline placebo given single blind in random order. Ventilatory function was assessed by serial measurements of peak expiratory flow rate (PEFR) and forced expiratory volume in one second (FEV1). All four tests for each patient were closely matched in terms of oxygen uptake and total ventilation which were monitored throughout exercise. The response to exercise after clemastine or placebo has been compared both directly and in terms of the degree of protection afforded against EIA compared with the initial test on the same day. Clemastine was significantly better than placebo for both PEFR and FEV1. All 10 subjects had less EIA after clemastine, which suggests an important role for histamine in its production. Other mechanisms may also be involved to a variable degree in different individuals.     

Oral ketamine preanesthetic medication in children.

The authors sought to define a dose of oral ketamine that would facilitate induction of anesthesia without causing significant side effects. Forty-five children (ASA Physical Status 1 and 2; aged 1-7 yr) were assigned randomly in a prospective, double-blind fashion to three separate groups that received either 3 mg/kg, 6 mg/kg, or no ketamine mixed in 0.2 ml/kg cola-flavored soft drink. They also were evaluated preoperatively and postoperatively for acceptance of oral ketamine as a premedicant, reaction to separation from parents, emotional state, and emergence phenomena. The authors detected no episodes of respiratory depression, tachycardia, or arterial hemoglobin desaturation before, during, or after surgery. The 6 mg/kg dose was well accepted; provided uniform, predictable sedation within 20-25 min; and allowed calm separation from parents and good induction conditions. The 3 mg/kg dose did not always cause sedation and calm separation from parents. Neither dose of ketamine increased the incidence of laryngospasm, prolonged recovery times, or caused emergence phenomena. The authors conclude that an oral dose of 6 mg/kg ketamine is easily administered and well accepted in young children and provides predictable, satisfactory premedication without significant side effects.     

Controlled-analysis of the effects of inhaled lignocaine in exercise-induced asthma.

To determine whether anaesthesia of the intrathoracic airways would attenuate the development of exercise-induced asthma, we studied eight symptomless asthmatic patients by cycle ergometry after saline or lignocaine pretreatment while they were breathing air at 24 degrees C with 9.1 mg of H2O/l. Pulmonary mechanics were measured before and after the administration of each agent, and again five minutes after cessation of exercise. Sufficient lignocaine was administered to abolish the gag reflex and the cough response to aerosols of citric acid. Before exercise there were no significant differences for any lung function variable between the saline and lignocaine results. Equally, there were no significant differences between these agents for minute ventilation (VE) during exercise (VE lignocaine = 71.0 +/- 7.4 (SEM) l/min; VE saline 67.2 +/- 8.1 l/min;), or in the severity of the subsequent bronchospastic response (for example, the FEV1 with saline was 22.6 +/- 2.9% decrease, and with lignocaine 23.6 +/- 8.5%). Thus these results do not support the idea that there are thermally sensitive neural receptors in intrathoracic airways that play a role in the pathogenesis of exercise-induced asthma.     

Comparison of inhaled and intravenous terbutaline in acute severe asthma.

In patients with acute severe asthma, 5 mg of terbutaline by inhalation and 500 microgram intravenously in divided doses both produced equally effective but not maximal bronchodilatation. There was no difference in the production of side-effects. These results support the view that inhaled therapy can be as effective in patients with acute severe asthma as injected treatment. In view of the risks of intravenous treatment, especially using high doses, inhaled bronchodilator therapy would seem advisable as initial treatment.     

Cross-sectional study on bone density-related sonographic parameters in children with asthma: correlation to therapy with inhaled corticosteroids and disease severity

The aim of this study was to screen asthmatic children for bone density-related sonographic parameters on the calcaneal bone. Findings were correlated to therapy with inhaled corticosteroids (ICS) as well as with asthma severity (AS), concomitance and severity of atopic dermatitis (AD), and rhinitis (AR). We enrolled 173 children with AS1-3 consecutively; 44% (AS1) had not received any ICS medication; 56% (AS2 and -3) received ICS therapy for > or =6 months (medium daily dose, 286 microg fluticasone-proprionate-equivalent/maximum 500 microg); and in addition 38% (n = 65) presented with AD and 66% (n = 115) with AR. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) results were compared to regional normative values of 3299 children obtained with the identical system. ICS-treated children showed a tendency toward reduced age-, weight-, and height-adjusted standard deviation scores (SDS) for SOS compared to children without ICS treatment, which tendency did not reach statistical significance and was not as consistent for BUA (mean of ICS-treated children compared to our controls: SOS-SDS, -0.29/-0.31/-0.30; BUA-SDS, -0.23/-0.17/-0.05). For ICS-treated children, the proportion of patients with BUA and SOS values below -1 SDS was statistically significant higher for age-adjusted BUA and SOS than for children without ICS medication (BUA 15.00% vs. 5.41%; SOS 32.98% vs. 17.56%). However, we cannot differentiate possible negative effects of ICS from influences of the underlying inflammatory disease because higher asthma severity was associated with greater use of ICS medication. Additionally, the higher physical activity of children with less severe asthma can have influenced quantitative ultrasound (QUS) parameters positively, compared to patients with a higher degree of exercise-induced symptoms. For differentiation of possible negative effect of ICS on ultrasonic bone quality and for evaluation of the potentials of the method, further longitudinal QUS assessment of asthmatics receiving a new ICS treatment is needed.     

Randomised controlled trial of montelukast plus inhaled budesonide versus double dose inhaled budesonide in adult patients with asthma

BACKGROUND: Inhaled corticosteroids (ICS) affect many inflammatory pathways in asthma but have little impact on cysteinyl leukotrienes. This may partly explain persistent airway inflammation during chronic ICS treatment and failure to achieve adequate asthma control in some patients. This double blind, randomised, parallel group, non-inferiority, multicentre 16 week study compared the clinical benefits of adding montelukast to budesonide with doubling the budesonide dose in adults with asthma. METHODS: After a 1 month single blind run in period, patients inadequately controlled on inhaled budesonide (800 microg/day) were randomised to receive montelukast 10 mg + inhaled budesonide 800 microg/day (n=448) or budesonide 1600 microg/day (n=441) for 12 weeks. RESULTS: Both groups showed progressive improvement in several measures of asthma control compared with baseline. Mean morning peak expiratory flow (AM PEF) improved similarly in the last 10 weeks of treatment compared with baseline in both the montelukast + budesonide group and in the double dose budesonide group (33.5 v 30.1 l/min). During days 1-3 after start of treatment, the change in AM PEF from baseline was significantly greater in the montelukast + budesonide group than in the double dose budesonide group (20.1 v 9.6 l/min, p<0.001), indicating faster onset of action in the montelukast group. Both groups showed similar improvements with respect to "as needed" beta agonist use, mean daytime symptom score, nocturnal awakenings, exacerbations, asthma free days, peripheral eosinophil counts, and asthma specific quality of life. Both montelukast + budesonide and double dose budesonide were generally well tolerated. CONCLUSION: The addition of montelukast to inhaled budesonide is an effective and well tolerated alternative to doubling the dose of inhaled budesonide in adult asthma patients experiencing symptoms and inadequate control on budesonide alone.     

Inhaled frusemide and exercise-induced bronchoconstriction in children with asthma.

BACKGROUND--Nebulised frusemide has been shown to be protective against bronchoconstricting stimuli in adult asthmatic subjects and against cold air challenge in children. Animal studies suggest that inhaled frusemide may be more effective in the young. METHODS--A double blind placebo, controlled, crossover study on the effect on exercise of pretreatment with frusemide (20 mg) from a metered dose inhaler via a large volume spacer (Volumatic) was performed in 12 asthmatic children. Exercise testing consisted of eight minutes of running on a treadmill in an environmentally controlled laboratory. RESULTS--Deterioration in lung function was less after frusemide than after the placebo exercise tests. The mean (95% CI) maximum percentage falls in forced expiratory volume in one second (FEV1) were 14.4% (7.7 to 21.0) for placebo and 5.7% (2.3 to 9.0) for frusemide. CONCLUSIONS--Inhaled frusemide via a metered dose inhaler reduces exercise-induced bronchoconstriction in children.     

Cuboid fractures in preschool children

The purpose of this study is to describe the clinical and radiographic presentation of cuboid fractures in children and to produce a guide for appropriate evaluation and treatment.Twenty-eight consecutive patients with cuboid fracture treated at the same institution between 1998 and 2004 were retrospectively analyzed.The mean age at presentation was 38.7 months (range, 14-74 months). All patients presented with an avoidance gait pattern, refusing to bear weight on the lateral side of the foot. There was no history of trauma in 8 patients, and the others had minor trauma such as a fall down a few steps on their feet or ankle sprain. Plain radiographs were the method of diagnosis in all but one of the patients. The feet of 21 patients were immobilized at initial presentation. The other 7 patients were observed clinically until symptoms resolved. All fractures healed completely with no complications, and patients were symptom free in 4.9 weeks (range, 2-13 weeks). Twenty-one patients, immobilized immediately after the first presentation, were symptom free in 4 weeks (range, 2-7 weeks). The remaining 7 patients, who were observed and followed up clinically with no immobilization, were symptom free in 7.9 weeks (range, 5-13 weeks). Six patients had associated ipsilateral fractures, and 8 patients had an associated genetic or systemic abnormality.An awareness of cuboid fractures in children can lead to an early diagnosis, treatment, and recovery without the use of a bone scan, and a focus on the possibility of an underlying genetic or medical disorder must be initiated.     

Occult fractures in preschool children

Five hundred consecutive radiographic examinations of acutely limping infants and toddlers were analyzed retrospectively. One hundred of the 500 (20%) had a fracture as the underlying etiology. Although the most common sites of involvement were the tibia/fibula (56 cases) and femur (30 cases), fractures in the pelvis and feet, notably the metatarsals (11 cases), also were seen. We therefore recommend obtaining radiographs of the pelvis and both lower extremities including the feet, when occult trauma is suspected and the exact area of injury cannot be pinpointed clinically.