Virus-associated pulmonary exacerbations, often associated with rhinoviruses (RVs), contribute to cystic fibrosis (CF) morbidity. Currently, there are only a few therapeutic options to treat virus-induced CF pulmonary exacerbations. The macrolide antibiotic azithromycin has antiviral properties in human bronchial epithelial cells. We investigated the potential of azithromycin to induce antiviral mechanisms in CF bronchial epithelial cells.

Primary bronchial epithelial cells from CF and control children were infected with RV after azithromycin pre-treatment. Viral RNA, interferon (IFN), IFN-stimulated gene and pattern recognition receptor expression were measured by real-time quantitative PCR. Live virus shedding was assessed by assaying the 50% tissue culture infective dose. Pro-inflammatory cytokine and IFN-β production were evaluated by ELISA. Cell death was investigated by flow cytometry.

RV replication was increased in CF compared with control cells. Azithromycin reduced RV replication seven-fold in CF cells without inducing cell death. Furthermore, azithromycin increased RV-induced pattern recognition receptor, IFN and IFN-stimulated gene mRNA levels. While stimulating antiviral responses, azithromycin did not prevent virus-induced pro-inflammatory responses.

Azithromycin pre-treatment reduces RV replication in CF bronchial epithelial cells, possibly through the amplification of the antiviral response mediated by the IFN pathway. Clinical studies are needed to elucidate the potential of azithromycin in the management and prevention of RV-induced CF pulmonary exacerbations.

Pulmonary exacerbation treatment aims to eradicate increased respiratory symptoms and recover acute loss in lung function. Current treatment strategies remain suboptimal, with conventional intravenous antibiotics and intensive physiotherapy failing to achieve this in 25% of patients [1]. Despite this worrying statistic, optimising recovery from acute pulmonary exacerbations has not been a focus of recent cystic fibrosis (CF) research efforts. There is a lack of adjunct evidence-based therapies for use in this setting [2] and strategies to optimise airway clearance with physiotherapy have been largely overlooked, despite common use in the outpatient setting [3, 4]. Inhaled dry-powder mannitol (IDPM), a mucoactive agent, improves mucociliary clearance [5], mucus rheology, and hydration and surface properties of mucus [6]. In the CF outpatient setting, IDPM treatment improves lung function, both in the short (>2 weeks) and long (>12 months) term [3, 7].

Accurate and rapid diagnosis is crucial for tuberculosis control by ensuring a timely start to treatment and reducing transmission. In 2012, almost one third of tuberculosis cases were not diagnosed and/or reported to national tuberculosis programmes (NTPs), and <25% of estimated incident multidrug-resistant (MDR) cases were diagnosed [1]. Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA), a nucleic acid amplification test, was recommended in 2010 by the World Health Organization (WHO) for detection of HIV-associated pulmonary tuberculosis and rifampicin resistance [2]. In 2013, the test was recommended for detection of paediatric tuberculosis and some forms of extrapulmonary tuberculosis (EPTB), as well as an initial test to replace smear microscopy [3].

The relationship between low-dose corticosteroid use and mortality in patients with severe community-acquired pneumonia (CAP) remains unclear.

6925 patients with severe CAP who received mechanical ventilation with or without shock (defined as use of catecholamines) at 983 hospitals were identified using a Japanese nationwide administrative database. The main outcome measure was 28-day mortality.

2524 patients with severe CAP who received catecholamines were divided into corticosteroid (n=631) and control (n=1893) groups. The 28-day mortality was significantly different between corticosteroid and control groups (unmatched: 24.6% versus 36.3%, p<0.001; propensity score-matched: 25.3% versus 32.6%, p=0.01; inverse probability-weighted: 27.5% versus 34.2%, p<0.001). 4401 patients with severe CAP who did not receive catecholamines were also divided into corticosteroid (n=1112) and control (n=3289) groups. The 28-day mortality was not significantly different between corticosteroid and control groups in propensity score-matched analyses (unmatched: 16.0% versus 19.4%, p=0.01; propensity score-matched: 17.7% versus 15.6%, p=0.22; inverse probability-weighted: 18.8% versus 18.2%, p=0.44).

Low-dose corticosteroid use may be associated with reduced 28-day mortality in patients with septic shock complicating CAP.