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Antibiotics are commonly used in the management of respiratory disorders such as cystic fibrosis (CF), non-CF bronchiectasis, asthma and COPD. In those conditions long-term antibiotics can be delivered as nebulised aerosols or administered orally. In CF, nebulised colomycin or tobramycin improve lung function, reduce number of exacerbations and improve quality of life (QoL). Oral antibiotics, such as macrolides, have acquired wide use not only as anti-microbial agents but also due to their anti-inflammatory and pro-kinetic properties. In CF, macrolides such as azithromycin have been shown to improve the lung function and reduce frequency of infective exacerbations. Similarly macrolides have been shown to have some benefits in COPD including reduction in a number of exacerbations. In asthma, macrolides have been reported to improve some subjective parameters, bronchial hyperresponsiveness and airway inflammation; however have no benefits on lung function or overall asthma control. Macrolides have also been used with beneficial effects in less common disorders such as diffuse panbronchiolitis or post-transplant bronchiolitis obliterans syndrome. In this review we describe our current knowledge the use of long-term antibiotics in conditions such as CF, non-CF bronchiectasis, asthma and COPD together with up-to-date clinical and scientific evidence to support our understanding of the use of antibiotics in those conditions.

BackgroundGiven that many patients with chronic obstructive pulmonary disease (COPD) smoke despite their symptoms, it is important to understand the long term health impact of cigarette substitution with heated tobacco products (HTPs). We monitored health parameters for 3-years in COPD patients who substantially attenuated or ceased cigarette consumption after switching to HTPs.MethodsChanges in daily cigarette smoking, annualized disease exacerbations, lung function indices, patients reported outcomes (CAT scores) and 6-minute walk distance (6MWD) from baseline were measured in COPD patients using HTPs at 12, 24 and 36 months. These were compared to a group of age- and sex-matched COPD patients who continued smoking.ResultsComplete data sets were available for 38 patients (19 in each group). Subjects using HTPs had a substantial decrease in annualized COPD exacerbations within the group mean (±SD) from 2.1 (±0.9) at baseline to 1.4 (±0.8), 1.2 (±0.8) and 1.3 (±0.8) at 12-, 24- and 36-month follow-up (p<0.05 for all visits). In addition, substantial and clinically significant improvements in CAT scores and 6MWD were identified at all 3 time points in the HTP cohort. No significant changes were observed in COPD patients who continued smoking.ConclusionsThis study is the first to describe the long-term health effects of HTP use in COPD patients. Consistent improvements in respiratory symptoms, exercise tolerance, quality of life, and rate of disease exacerbations were observed in patients with COPD who abstained from smoking or substantially reduced their cigarette consumption by switching to HTP use.

Rationale:The diagnosis of systemic bacterial sepsis is complex and at times challenging. Procalcitonin (PCT) is a 116 amino acid peptide released in response to bacterial endotoxins. PCT levels of <0.5ng/ml suggest possibility of local bacterial infections, between >0.5−<2ng/ml suggest possibility of systemic sepsis, between >2−10ng/ml indicates likelihood of systemic sepsis and levels >10ng/ml indicates severe sepsis/shock. We audited PCT levels in patients admitted with sepsis and compared the results with other markers viz. total white cells (WCC), neutrophil counts and C−reactive protein (CRP) levels. Methods:PCT assays were analysed using BRAHMS PCT ® −Q, a semi−quantitative assay, over 12 months. PCT concentrations were read as <0.5ng/ml, 0.5−2ng/ml, >2−10ng/ml and >10ng/ml as per manufacturer instructions. The results were compared with blood cultures (BC), WCC, neutrophils and CRP. Correlations were also obtained. Results: Patient Demographics, PCT levels &Markers of Sepsis PCT Levels (ng/ml) Number (n=70) Male:Female Age (Mean ±SD) WCC (Median ±SEM) Neutrophils (Median ±SEM) CRP (Median ±SEM) BC +ve(%) <0.5 27 14:13 52.9 ±21.9 10.2 ±1.1 7.5 ±0.9 95 ±17.5 0 0.5−2.0 18 9:9 64.9 ±18.8 13.8 ±1.2 10.7 ±1.2 109 ±22 18.2 >2.0−10.0 10 4:6 63.8 ±20.5 12.6 ±2.5 8.4 ±2.4 187 ±49 50 >10.0 15 6:9 61.8 ±17.4 14.1 ±2.5 9.9 ±2.0 170 ±28 46.2There was a positive correlation between PCT levels and CRP (r=0.31, p=0.007). Of the positive BCs, 84.6 % (11/13) were gram positive organisms. Conclusion:PCT is useful in the diagnosis of systemic bacterial sepsis and correlates well with culture results and CRP. Semi−quantitative assays can be less expensive, easy to use and PCT levels of >2 could suggest systemic sepsis more likely due to gram positive bacteremia and aid in the early initiation of appropriate antibiotic therapy in adults.This abstract is funded by: None.

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Background We evaluated the effect of once-daily tiotropium Respimat ® 5 mg on lung function, asthma exacerbation and asthma symptom control among patients with symptomatic asthma receiving inhaled corticosteroids (ICS; ≥800 µg/day budesonide or equivalent) + long-acting b 2 -agonist (LABA). Methods Data were pooled from two replicate, double-blind, placebo-controlled, 48-week, parallel-group studies of once-daily tiotropium 5 mg versus placebo, both delivered via the Respimat ® SoftMist™ inhaler (PrimoTinA-asthma ® : NCT00772538, NCT00776984). Eligible patients had: ≥5-year history of asthma diagnosed before the age of 40 years; seven-question Asthma Control Questionnaire (ACQ-7) score of ≥1.5; experienced ≥1 exacerbation during the previous year. Patients were either lifelong non-smokers, or ex-smokers (<10 pack-years) who quit smoking ≥1 year before study enrolment. Exclusion criteria included diagnosis of chronic obstructive pulmonary disease. Coprimary end points in individual trials: peak forced expiratory volume in 1 second (FEV 1 ) within 3 h post-dose (0-3 h) and trough FEV 1 . A co-primary end point in pooled data was time to first severe exacerbation; secondary end points included time to first episode of asthma worsening and ACQ-7 response. Post hoc efficacy analyses were performed. Results 912 patients were randomised to receive tiotropium Respimat ® (n = 456) or placebo Respimat ® (n = 456). At Week 48, tiotropium Respimat ® was associated with statistically significant improvements versus placebo Respimat ® in peak FEV 1(0-3h) (adjusted mean difference 100 mL; 95% confidence interval: 52, 148; p < 0.0001) and trough FEV 1 (adjusted mean difference 62 mL; 95% confidence interval: 18, 106; p = 0.006). Time to first severe asthma exacerbation was significantly longer with tiotropium Respimat ® versus placebo Respimat ® (282 vs 226 days, respectively; hazard ratio 0.79; p = 0.034), as was time to first episode of asthma worsening (315 vs 181 days, respectively; hazard ratio 0.69; p < 0.0001). At Week 24, ACQ-7 responder rate was significantly higher with tiotropium Respimat ® (53.9%) versus placebo Respimat ® (46.9%; odds ratio 1.32; p = 0.0427). Conclusion Once-daily tiotropium Respimat ® add-on to ICS + LABA improves lung function, reduces risk of severe asthma exacerbation and asthma worsening, and significantly improves asthma symptom control compared with placebo Respimat ® in patients with symptomatic asthma.

Background The novel LABA olodaterol has 24-h bronchodilator activity. Objective To evaluate the symptomatic benefit of olodaterol QD in patients with GOLD 2-4 COPD. Methods In replicate, randomised, double-blind, placebo-controlled, parallel-group studies, patients with post-bronchodilator FEV 1 <80% predicted normal and FEV 1 /FVC <70% received olodaterol (5 or 10 mg) QD via Respimat ® , formoterol (12 µg) BID via Aerolizer ® or placebo for 48 weeks (Study A: NCT00793624; Study B: NCT00796653). Patients continued to receive usual care background COPD maintenance therapy, including SAMA, LAMA, ICS and xanthines. In addition to FEV 1 -based primary end points, TDI and SGRQ after 24 weeks were identified as co-primary and key secondary symptomatic end points, respectively. Results 904 (Study A) and 934 (Study B) patients were treated. In the primary analysis using a mixed model for repeated measures (MMRM; combined dataset), there was no significant difference in TDI focal score after 24 weeks for olodaterol or formoterol vs placebo. A post hoc analysis using pattern mixture modelling (PMM) to account for discontinued patients demonstrated statistical significance for olodaterol vs placebo. There were significant improvements in SGRQ total score with olodaterol, but not formoterol, vs placebo after 24 weeks using MMRM and PMM. Conclusions Lung function improvements with olodaterol QD translated into symptomatic benefit in COPD patients receiving usual care background therapy.

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