Cytokine responses to two common respiratory pathogens in children are dependent on interleukin-1ß.

Protracted bacterial bronchitis (PBB) in young children is a common cause of prolonged wet cough and may be a precursor to bronchiectasis in some children. Although PBB and bronchiectasis are both characterised by neutrophilic airway inflammation and a prominent interleukin (IL)-1ß signature, the contribution of the IL-1ß pathway to host defence is not clear. This study aimed to compare systemic immune responses against common pathogens in children with PBB, bronchiectasis and control children and to determine the importance of the IL-1ß pathway. Non-typeable Haemophilus influenzae (NTHi) stimulation of peripheral blood mononuclear cells (PBMCs) from control subjects (n=20), those with recurrent PBB (n=20) and bronchiectasis (n=20) induced high concentrations of IL-1ß, IL-6, interferon (IFN)-γ and IL-10. Blocking with an IL-1 receptor antagonist (IL-1Ra) modified the cellular response to pathogens, inhibiting cytokine synthesis by NTHi-stimulated PBMCs and rhinovirus-stimulated PBMCs (in a separate PBB cohort). Inhibition of IFN-γ production by IL-1Ra was observed across multiple cell types, including CD3+ T cells and CD56+ NK cells. Our findings highlight the extent to which IL-1ß regulates the cellular immune response against two common respiratory pathogens. While blocking the IL-1ß pathway has the potential to reduce inflammation, this may come at the cost of protective immunity against NTHi and rhinovirus.

Codeine versus placebo for chronic cough in children.

BACKGROUND: Cough in children is a commonly experienced symptom that is associated with increased health service utilisation and burden to parents. The presence of chronic (equal to or more than four weeks) cough in children may indicate a serious underlying condition such as inhaled foreign body or bronchiectasis. Codeine (and derivative)-based medications are sometimes used to treat cough due to their antitussive properties. However, there are inherent risks associated with the use of these medications such as respiratory drive suppression, anaesthetic-induced anaphylaxis, and addiction. Metabolic response and dosage variability place children at increased risk of experiencing such side effects. A systematic review evaluating the quality of the available literature would be useful to inform management practices. OBJECTIVES: To evaluate the safety and efficacy of codeine (and derivatives) in the treatment of chronic cough in children. SEARCH METHODS: We searched the Cochrane Airways Group Register of Trials, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1946 to 8 June 2016), EMBASE (1974 to 8 June 2016), the online trials registries of the World Health Organization and ClinicalTrials.gov, and the bibliographic references of publications. We imposed no language restrictions. SELECTION CRITERIA: We considered studies eligible for analysis when: the participant population included children aged less than 18 years with chronic cough (duration equal to or more than four weeks at the time of intervention); and the study design evaluated codeine or codeine-based derivatives against placebo through a randomised controlled trial. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results to determine eligibility against a standardised criteria, and we had a pre-planned method for analysis. MAIN RESULTS: We identified a total of 556 records, of which 486 records were excluded on the basis of title and abstract. We retrieved the remaining 70 references in full to determine eligibility. No studies fulfilled the inclusion criteria of this review, and thus we found no evidence to support or oppose the use of codeine or derivatives as antitussive agents for chronic cough in children.While chronic cough is not the same as acute cough, systematic reviews on the use of codeine efficacy for acute cough in children conclude an overall lack of evidence to support or oppose the use of over-the-counter cough and cold medications containing codeine (or derivatives) for treatment of acute cough in children. The lack of sufficient evidence to support the use of these medications has been consistently reaffirmed by medical experts in international chronic cough guidelines and by governing medical and pharmaceutical authorities in the USA, Europe, Canada, New Zealand, and Australia. Due to the lack of sufficient evidence to support efficacy, and the known risks associated with use - in particular the increased risks for children - these medications are now not recommended for children less than 12 years of age and children between 12 to 18 years with respiratory conditions. AUTHORS' CONCLUSIONS: This review has highlighted the absence of any randomised controlled trials evaluating codeine-based medications in the treatment of childhood chronic cough. Given the potential adverse events of respiratory suppression and opioid toxicity, national therapeutic regulatory authorities recommend the contraindication of access to codeine in children less than 12 years of age. We suggest that clinical practice adhere to clinical practice guidelines and thus refrain from using codeine or its derivatives to treat cough in children. Aetiological-based management practices continue to be advocated for children with chronic cough.

Antibiotics for community-acquired lower respiratory tract infections secondary to Mycoplasma pneumoniae in children.

Background. Mycoplasma pneumoniae (M. pneumoniae) is widely recognised as an important cause of community-acquired lower respiratory tract infection (LRTI) in children. Pulmonary manifestations are typically tracheobronchitis or pneumonia but M. pneumoniae is also implicated in wheezing episodes in both asthmatic and non-asthmatic individuals. Although antibiotics are used to treat LRTIs, are view of several major textbooks offers conflicting advice for using antibiotics in the management of M. pneumoniae LRTI in children.Objectives To determine whether antibiotics are effective in the treatment of childhood LRTI secondary to M. pneumoniae infections acquired in the community.Search methods We searched CENTRAL (2014, Issue 3), MEDLINE (1966 to July week 4, 2014), EMBASE (1980 to July, 2014), and both WHOICTRP and ClinicalTrials.gov (13 August 2014).Selection criteria Randomised controlled trials (RCTs) comparing antibiotics commonly used for treating M. pneumoniae (i.e. macrolide, tetracycline or quinolone classes) versus placebo, or antibiotics from any other class in the treatment of children under 18 years of age with community acquired LRTI secondary to M. pneumoniae.Data collection and analysis The review authors independently selected trials for inclusion and assessed methodological quality. We extracted and analysed relevant data separately and resolved disagreements by consensus.Main results A total of 1912 children were enrolled from seven studies. Data interpretation was limited by the inability to extract data that referred to children with M. pneumoniae. In most studies, clinical response did not differ between children randomised to a macrolide antibiotic and children randomised to a non-macrolide antibiotic. In one controlled study (of children with recurrent respiratory infections, whose acute LRTI was associated with Mycoplasma, Chlamydia or both, by polymerase chain reaction and/or paired sera) 100% of children treated with azithromycin had clinical resolution of their illness compared to 77% not treated with azithromycin at one month. Authors' conclusions There is insufficient evidence to draw any specific conclusions about the efficacy of antibiotics for this condition in children (although one trial suggests macrolides may be efficacious in some children with LRTI secondary to Mycoplasma). The use of antibiotics has to be balanced with possible adverse events. There is still a need for high quality, double-blinded RCTs to assess the efficacy and safety of antibiotics for LRTI secondary to M. pneumoniae in children.