Iolo Doull

Effect of inhaled corticosteroids on episodes of wheezing associated with viral infection in school age children: randomised double blind placebo controlled trial

Abstract Objectives: To determine the effect of regular prophylactic inhaled corticosteroids on wheezing episodes associated with viral infection in school age children. Design: Randomised, double blind, placebo controlled trial. Setting: Community based study in Southampton. Subjects: 104 children aged 7 to 9 years who had had wheezing in association with symptoms of upper and lower respiratory tract infection in the preceding 12 months. Interventions: After a run in period of 2–6 weeks children were randomly allocated twice daily inhaled beclomethasone dipropionate 200 μg or placebo through a Diskhaler for 6 months with a wash out period of 2 months. Children were assessed monthly. Main outcome measures: Forced expiratory volume in 1 second (FEV1); bronchial responsiveness to methacholine (PD20); percentage of days with symptoms of upper and lower respiratory tract infection with frequency, severity, and duration of episodes of upper and lower respiratory symptoms and of reduced peak expiratory flow rate. Results: During the treatment period there was a significant increase in mean FEV1 (1.63 v 1.53 l; adjusted difference 0.09 l (95% confidence interval 0.04 to 0.14); P=0.001) and methacholine PD20 (12.8 v 7.2 μmol/l; adjusted ratio of means 1.7 (1.2 to 2.4); P=0.007) in children receiving beclomethasone dipropionate compared with placebo. There were, however, no significant differences in the percentage of days with symptoms or in the frequency, severity, or duration of episodes of upper or lower respiratory symptoms or of reduced peak expiratory flow rate during the treatment period between the two groups. Conclusions: Although lung function is improved with regular beclomethasone dipropionate 400 μg/day, this treatment offers no clinically significant benefit in school age children with wheezing episodes associated with viral infection. Key messages Increasing evidence suggests that episodic wheezing in children in association with viral infections is a separate entity from atopic asthma Although inhaled corticosteroids are beneficial in asthma, their role in treating wheezing associated with viral infections is unclear In this study regular inhaled corticosteroids resulted in improved lung function and decreased bronchial responsiveness but did not have any effect on episodes of wheezing Inhaled corticosteroids are of little benefit in children with episodic wheezing associated with viral infection

Differential inhibitory effect of regular inhaled corticosteroid on airway responsiveness to adenosine 5′ monophosphate, methacholine, and bradykinin in symptomatic children with recurrent wheeze

Indirect tests of bronchial responsiveness to agents such as adenosine 5′‐monophosphate (AMP) or bradykinin might be more specific markers of a therapeutic responses to anti‐inflammatory treatment than a test of direct responsiveness to agents such as methacholine. In children selected from the community on the basis of mildly symptomatic wheeze, we compared in a randomized, double‐blind study design the effect of 400 μg/day of beclomethasone dipropionate (BDP) or placebo on three separate ways of provoking bronchial responsiveness, using methacholine, bradykinin, and AMP as the provoking agents. Following pre‐treatment bronchial challenges, 29 children received paired monthly methacholine and AMP challenges for 3 months, while for the same period another 33 children received paired monthly methacholine and bradykinin challenges.

Bronchoscopic appearances of congenital lobar emphysema

Although decreased bronchial cartilage is found in 50% of cases of congenital lobar emphysema (CLE), it can only be surmised that this defect produces a ball valve effect with consequent overinflation. We describe the flexible bronchoscopic features of CLE in a 3‐year‐old child. The observed airway patency during inspiration, and dynamic airway collapse on expiration suggests that bronchomalacia contributes to lung overinflation in these cases. Pediatr Pulmonol. 1996; 21:195–197.

Burkholderia cepacia complex infection in patients with cystic fibrosis: laboratory investigations, epidemiology and clinical management

Burkholderia cepacia complex is a collection of related species/genomovars of which nine members have so far been characterized. Each member of the complex has been isolated as a lung pathogen from patients with cystic fibrosis (CF) but the vast majority of such isolates are Burkholderia multivorans or genomovar III (GIII). Although the incidence of B. cepacia complex infection is rarely above 10% in a CF population, such acquisition may have a profound effect on clinical management and resources within the clinic or hospital attended by the infected individual. This is because some strains are highly transmissible and can lead rapidly to acute pulmonary infection and death. In addition, there are only a limited number of antibiotics to which the bacteria are sensitive and B. cepacia complex infection is rarely completely eradicated once acquired. Although some epidemic markers have been proposed, they have not been identified consistently in all outbreak strains and thus there is currently no way of predicting if a new strain will prove to be highly virulent. Although definitive evidence is still needed, it is generally accepted that clinical management of B. cepacia complex in the context of CF requires segregation of infected patients from those who are not infected. In recent years polymerase chain reaction methods have been developed for the identification, speciation and strain typing of isolates resulting in a more rapid and reliable feedback from the laboratory to the CF clinic/ward. Such advances in diagnostics have made management of B. cepacia by segregation more effective.

A risk-benefit assessment of corticosteroids in the management of croup.

SummaryCroup is an acute clinical syndrome of childhood characterised by a barking cough, hoarse voice, stridor and a variable degree of respiratory distress. A metaanalysis and subsequent controlled trials clearly demonstrate that corticosteroids are efficacious in the management of croup, with their benefits conclusively outweighing their risks. In mild to moderate cases of croup either systemic or nebulised corticosteroids decrease symptoms and need for hospitalisation. Most reports use IM dexamethasone 0.6 mg/kg, although it is likely that dexamethasone 0.15 mg/kg has a similar effect. In controlled studies nebulised budesonide 2mg is superior to placebo, and appears to have equivalent efficacy to oral dexamethasone. The risk of a single or short course of systemic corticosteroids are minimal, the only potential significant adverse effect being increased risk of severe varicella infection. Short courses of nebulised budesonide have no major adverse effects, and thus are likely to cause fewer adverse effects than systemic corticosteroids, although this is as yet unproven. On the body of data published to date, either oral dexamethasone 0.15 mg/kg or nebulised budesonide 2mg are effective for mild to moderate croup. In severe croup requiring intubation, oral prednisolone 1 mg/kg every 12 hours decreases the duration of intubation and the need for re intubation. Unless there are clear contraindications, corticosteroids are the treatment of choice in mild, moderate and severe croup.

Full, shared and hybrid paediatric care for cystic fibrosis in South and Mid Wales

Background Although care for children with cystic fibrosis (CF) is increasingly shared between CF centres and local CF clinics, the optimal model is unclear. Objectives The authors compared three models of care within a well established CF network: full centre care; local clinic based care with annual review by the CF centre; and hybrid care, where the child is usually reviewed at least three times a year by the specialist CF centre. Results Of 199 children and young people with CF in South and Mid Wales, 77 were receiving full care, 102 shared care and 20 hybrid care. There were no significant differences in baseline characteristics, nutritional outcomes or use of chronic therapies. There was however a statistically significant difference between full, shared and hybrid care in mean forced expiratory volume in 1 s (FEV1) per cent predicted (89.2% vs 74.5% vs 88.9%; p=0.001). Conclusions These differences in pulmonary function are likely to reflect the model of care received, and may affect long term outcomes.

Hypertonic saline inhalation in cystic fibrosis—salt in the wound, or sweet success?

A large-scale study has put hypertonic saline back in the spotlight Among the greatest challenges facing the cystic fibrosis community at present is the apparently simple task of determining whether a treatment is beneficial or not. Most of the traditional outcome measures may no longer be useful—the outlook for cystic fibrosis has improved so dramatically that using survival is impractical; clinical scoring systems such as the Shwachman-Kulczycki score are too subjective and insensitive,1 and many children have no respiratory symptoms with pulmonary function within the normal range. The vast majority of patients with cystic fibrosis succumb to terminal respiratory failure, and pulmonary function is strongly predictive of survival.2 Consequently attention has concentrated on respiratory outcomes, most notably pulmonary function and pulmonary exacerbations. There is however considerable inherent variability in measurements of pulmonary function in cystic fibrosis. The standard measure of pulmonary function is the forced expiratory volume in one second (FEV1), but a change of 10% can be within normal variation.3 There remains no standard definition of a pulmonary exacerbation, although a number of models have been proposed4–6 The popularity of hypertonic saline in cystic fibrosis increased on the basis of small uncontrolled trials,7–9 and then waned following a large controlled study that reported little effect on pulmonary function.10 However a recent large-scale study has catapulted it back into the limelight,11 with extensive coverage in the lay press. It is in this context that we must try to interpret the evidence for or against the use of hypertonic saline in cystic fibrosis. Cystic fibrosis is a multi-system disorder, caused by mutations in the cystic fibrosis gene. The cystic fibrosis gene encodes for a c-AMP mediated chloride channel known as cystic fibrosis transmembrane conductance regulator (CFTR). In the airway, the defective CFTR …

What and when to collect from infants with cystic fibrosis

Perspective on the papers by Cipolli et al and Hilliard et al (see pages 842 and 898)

Higher dose inhaled steroids in childhood asthma. Conventional doses do have side effects.

Editor—Thomas confirms that intermittent calf compression reduces the rate of pulmonary embolism to 1% after replacement arthroplasty without having the possible side effects of chemoprophylaxis.1 He goes on to state that when the efficacy of foot pumps was compared with that of anticoagulation “the results in terms of preventing deep venous thrombosis were comparable.” The rest of the editorial is aimed at supporting the use of anticoagulation in these patients. I presume that Thomas is neither an orthopaedic surgeon nor a patient who has had a failed joint replacement; if he was he would not regard an incidence of major bleeding with anticoagulation of 1% as being an “acceptable price to pay.” His conclusion that anticoagulation is the single most effective way of preventing these complications is not supported by the rest of his editorial. It seems incongruous that he is suggesting using a method of prophylaxis with a 1% rate of major complications to prevent a complication with the same incidence. If this article is not retracted or a counter-argument published there is a risk that litigation lawyers will use it against the many orthopaedic surgeons who avoid chemoprophylaxis in patients undergoing arthroplasty.