Inhaled corticosteroids for sub-acute cough in children (Protocol)

This is the protocol for a review and there is no abstract. The objectives are as follows: To evaluate the efficacy of inhaled corticosteroids in reducing the severity of cough in children with sub-acute cough (defined as cough duration of two to four weeks).

Combination inhaled corticosteroids and long-acting beta2-agonists for children and adults with bronchiectasis

BACKGROUND Bronchiectasis is a major contributor to chronic respiratory morbidity and mortality worldwide. Wheeze and other asthma-like symptoms and bronchial hyperreactivity may occur in people with bronchiectasis. Physicians often use asthma treatments in patients with bronchiectasis. OBJECTIVES To assess the effects of inhaled long-acting beta2-agonists (LABA) combined with inhaled corticosteroids (ICS) in children and adults with bronchiectasis during (1) acute exacerbations and (2) stable state. SEARCH METHODS The Cochrane Airways Group searched the the Cochrane Airways Group Specialised Register of Trials, which includes records identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and other databases. The Cochrane Airways Group performed the latest searches in October 2013. SELECTION CRITERIA All randomised controlled trials (RCTs) of combined ICS and LABA compared with a control (placebo, no treatment, ICS as monotherapy) in children and adults with bronchiectasis not related to cystic fibrosis (CF). DATA COLLECTION AND ANALYSIS Two review authors extracted data independently using standard methodological procedures as expected by The Cochrane Collaboration. MAIN RESULTS We found no RCTs comparing ICS and LABA combination with either placebo or usual care. We included one RCT that compared combined ICS and LABA with high-dose ICS in 40 adults with non-CF bronchiectasis without co-existent asthma. All participants received three months of high-dose budesonide dipropionate treatment (1600 micrograms). After three months, participants were randomly assigned to receive either high-dose budesonide dipropionate (1600 micrograms per day) or a combination of budesonide with formoterol (640 micrograms of budesonide and 18 micrograms of formoterol) for three months. The study was not blinded. We assessed it to be an RCT with overall high risk of bias. Data analysed in this review showed that those who received combined ICS-LABA (in stable state) had a significantly better transition dyspnoea index (mean difference (MD) 1.29, 95% confidence interval (CI) 0.40 to 2.18) and cough-free days (MD 12.30, 95% CI 2.38 to 22.2) compared with those receiving ICS after three months of treatment. No significant difference was noted between groups in quality of life (MD -4.57, 95% CI -12.38 to 3.24), number of hospitalisations (odds ratio (OR) 0.26, 95% CI 0.02 to 2.79) or lung function (forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)). Investigators reported 37 adverse events in the ICS group versus 12 events in the ICS-LABA group but did not mention the number of individuals experiencing adverse events. Hence differences between groups were not included in the analyses. We assessed the overall evidence to be low quality. AUTHORS' CONCLUSIONS In adults with bronchiectasis without co-existent asthma, during stable state, a small single trial with a high risk of bias suggests that combined ICS-LABA may improve dyspnoea and increase cough-free days in comparison with high-dose ICS. No data are provided for or against, the use of combined ICS-LABA in adults with bronchiectasis during an acute exacerbation, or in children with bronchiectasis in a stable or acute state. The absence of high quality evidence means that decisions to use or discontinue combined ICS-LABA in people with bronchiectasis may need to take account of the presence or absence of co-existing airway hyper-responsiveness and consideration of adverse events associated with combined ICS-LABA.

Multicenter Randomized Controlled Trial of Withdrawal of Inhaled Corticosteroids in Cystic Fibrosis

Rationale: Lung inflammation and injury is critical in cystic fibrosis. An ideal antiinflammatory agent has not been identified but inhaled corticosteroids are widely used despite lack of evidence.

Objectives: To test the safety of withdrawal of inhaled corticosteroids with the hypothesis this would not be associated with an earlier onset of acute chest exacerbations.

Methods: Multicenter randomized double-blind placebo-controlled trial in 18 pediatric and adult UK centers. Eligibility criteria included age > 6.0 yr, FEV1 ? 40% predicted, and corticosteroid use > 3 mo. During the 2-mo run-in period, all patients received fluticasone; they then took either fluticasone or placebo for 6 mo.

Measurements and Main Results: Fluticasone group: n = 84, median age 14.6 yr, mean (SD) FEV1 76% (18); placebo group: n = 87, median age 15.8 yr, mean (SD) FEV1 76% (18). There was no difference in time to first exacerbation (primary outcome) with hazard ratio (95% confidence interval) of 1.07 (0.68 to 1.70) for fluticasone versus placebo. There was no effect of age, atopy, corticosteroid dose, FEV1, or Pseudomonas aeruginosa status. There was no change in lung function or differences in antibiotic or rescue bronchodilator use. Fewer patients in the fluticasone group withdrew from the study due to lung-related adverse events (9 vs. 15%); with a relative risk (95% confidence interval) of 0.59 (0.23–1.48) fluticasone versus placebo.

Conclusions: In this study population (applicable to 40% of patients with cystic fibrosis in the UK), it appears safe to consider stopping inhaled corticosteroids. Potential advantages will be to reduce the drug burden on patients, reduce adverse effects, and make financial savings.

Exhaled breath temperature measurement and asthma control in children prescribed inhaled corticosteroids: A cross sectional study

BACKGROUND: Exhaled breath temperature (EBT) reflects airways (both eosinophilic and neutrophilic) inflammation in asthma and thus may aid the management of children with asthma that are treated with anti-inflammatory drugs. A new EBT monitor has become available that is cheap and easy to use and may be a suitable monitoring device for airways inflammation. Little is known about how EBT relates to asthma treatment decisions, disease control, lung function, or other non-invasive measures of airways inflammation, such as exhaled nitric oxide (ENO).

OBJECTIVE: To determine the relationships between EBT and asthma treatment decision, current control, pulmonary function, and ENO.

METHODS: Cross-sectional prospective study on 159 children aged 5-16 years attending a pediatric respiratory clinic. EBT was compared with the clinician's decision regarding treatment (decrease, no change, increase), asthma control assessment (controlled, partial, uncontrolled), level of current treatment (according to British Thoracic Society guideline, BTS step), ENO, and spirometry.

RESULTS: EBT measurement was feasible in the majority of children (25 of 159 could not perform the test) and correlated weakly with age (R = 0.33, P = <0.01). EBT did not differ significantly between the three clinician decision groups (P = 0.42), the three asthma control assessment groups (P = 0.9), or the current asthma treatment BTS step (P = 0.57).

CONCLUSIONS & CLINICAL IMPLICATIONS: EBT measurement was not related to measures of asthma control determined at the clinic. The routine intermittent monitoring of EBT in children prescribed inhaled corticosteroids who attend asthma clinics cannot be recommended for adjusting anti-inflammatory asthma therapy.

Suboptimal use of inhaled corticosteroids in children with persistent asthma : inadequate physician prescription, poor patient adherence or both ?

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Prevalence of yeasts in the oral cavity of children treated with inhaled corticosteroids

The aim of this study was to observe the prevalence of Candida spp. in the oral cavity of children undergoing treatment with inhaled corticosteroids. Thirty children treated with inhaled corticosteroids and thirty control children were studied. Saliva samples were collected through oral rinses with phosphate buffered saline (PBS). The samples were plated on Sabouraud's dextrose agar and incubated at 37 degrees C for 48 h. After this period, the number of colony-forming units per ml (cfu/ml) of saliva was calculated. The isolates were identified by phenotypic characterization. Candida spp. was isolated from 43.33% of the samples of children treated with corticosteroids, with a mean of 780 cfu/ml of saliva, and from 30% of the samples of the control group, with a mean of 560 cfu/ml of saliva. No significant statistical difference was observed between the groups. C. albicans was the prevalent species in both groups, followed by C. guilliermondii, C. parapsilosis and C. stellatoidea. Furthermore, Rhodotorula rubra and C. lusitaniae were also isolated from the treated group. We concluded that there was no significant increase in the prevalence and number of Candida spp. in the oral cavity of children treated with inhaled corticosteroids.

Effectiveness of initiating extrafine-particle versus fine-particle inhaled corticosteroids as asthma therapy in the Netherlands

Acknowledgements Gokul Gopalan (a Senior Global Medical Director [Respiratory], at Teva Pharmaceuticals, Frazer, PA, US, at the time of this study), assisted with study design. Funding Funds to acquire the dataset from the Pharmo Institute for Drug Outcomes Research (Utrecht, the Netherlands) were provided by RiRL. The study received institutional support from Teva Pharmaceuticals Europe B.V. Gokul Gopalan, a Senior Global Medical Director (Respiratory), at Teva Pharmaceuticals, Frazer, PA, US, at the time of this study, assisted with study design, but neither Teva Pharmaceuticals Europe B.V. nor Teva Pharmaceuticals, Frazer, PA, US, contributed, either in part or in whole, to the collection, analysis, or interpretation of study data, manuscript writing, or the decision to submit the manuscript for publication. Erratum The original version of this article unfortunately contained errors that have since been corrected. The word “pharmo” has been fully capitalised to “PHARMO” throughout the article. The reference to Table 2 in the first and second sentence under the Outcomes heading has been replaced with Fig. 3. Under the Abbreviations heading ‘extrafine-particle’ was repeated, this has been corrected to ‘EF-HFA-BDP [Qvar®]: extrafine-particle hydrofluoroalkane beclomethasone dipropionate’. The competing interests of Nicolas Roche and Theresa Guibert have been amended. Academic affiliations for Dirkje S. Postma (2), Richard J. Martin (3), Ron M.C. Herrings (4), Jetty Overbeek (4), and Nicolas Roche (7) have been corrected. Figure 3 in the online and pdf version did not match, this been amended

Long-Acting b-Agonist in Combination or Separate Inhaler as Step-Up Therapy for Children with Uncontrolled Asthma Receiving Inhaled Corticosteroids

Acknowledgments The authors thank Prof. Stanley Szefler for his comments on the paper and Lisa Law for help with editing

The effect of inhaled IFN-β on worsening of asthma symptoms caused by viral infections. a randomized trial

Rationale: Ex vivo, bronchial epithelial cells from people with asthma are more susceptible to rhinovirus infection caused by deficient induction of the antiviral protein, IFN-b. Exogenous IFN-b restores antiviral activity.

Objectives: To compare the efficacy and safety of inhaled IFN-b with placebo administered to people with asthma after onset of cold symptoms to prevent or attenuate asthma symptoms caused by respiratory viruses.

Methods: A total of 147 people with asthma on inhaled corticosteroids (British Thoracic Society Steps 2–5), with a history of virus-associated exacerbations, were randomized to 14-day treatment with inhaled IFN-b (n = 72) or placebo (n = 75) within 24 hours of developing cold symptoms and were assessed clinically, with relevant samples collected to assess virus infection and antiviral responses.

Measurements and Main Results: A total of 91% of randomized patients developed a defined cold. In this modified intention-to-treat population, asthma symptoms did not get clinically significantly worse
(mean change in six-item Asthma Control Questionnaire ,0.5) and IFN-b treatment had no significant effect on this primary endpoint, although it enhanced morning peak expiratory flow recovery (P = 0.033), reduced the need for additional treatment, and boosted innate immunity as assessed by blood and sputum biomarkers. In an exploratory analysis of the subset ofmore difficult-to-treat, Step 4-5 peoplewith asthma (n = 27 IFN-b; n = 31 placebo), Asthma Control Questionnaire-6 increased significantly on placebo; this was prevented by IFN-b (P = 0.004).

Conclusions: Although the trial did not meet its primary endpoint, it suggests that inhaled IFN-b is a potential treatment for virus-induced deteriorations of asthma in difficult-to-treat people with asthma and supports the needforfurther, adequately powered, trialsin this population. Clinical trial registered with www.clinicaltrials.gov (NCT 01126177).

Successful treatment of post-influenza pseudomembranous necrotising bronchial aspergillosis with liposomal amphotericin, inhaled amphotericin B, gamma interferon and GM-CSF

A case of aspergillus tracheobronchitis following influenza A infection in an immunocompetent 35 year old woman is described that required prolonged mechanical ventilation for airways obstruction. Treatment included liposomal amphotericin, inhaled amphotericin, gamma interferon and GM-CSF. Liposomal amphotericin therapy was associated with reversible hepatosplenomegaly. Inhaled corticosteroids with continued antifungal therapy were used for the management of severe recurrent airway obstruction. After a prolonged course of treatment she survived with fixed airways obstruction unresponsive to corticosteroids.