The heterogeneity of systemic inflammation in bronchiectasis

Saleh, Aarash; Chalmers, James D.; Soyza, Anthony De; Fardon, Thomas C.; Koustas, S.; Scott, Jonathan; Simpson, A. John; Brown, Jeremy S.; Hurst, John R.

doi:10.1016/j.rmed.2017.04.009

Cited by 64 publications

(45 citation statements)

References 24 publications

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“…As fibrinogen concentration was strongly correlated with CRP concentration, the missing 23 fibrinogen values were imputed by regression against CRP. Results for CRP and fibrinogen have been reported previously [27].…”

Section: Reference Ranges For Pwv Have Been Published By the Referencsupporting

confidence: 60%

“…Our data also suggest that anti-inflammatory therapies may have the additional benefit of reducing cardiovascular risk, which should be considered as an exploratory end-point in future clinical trials. Although there are currently no licensed anti-inflammatory interventions available in bronchiectasis, we have recently demonstrated that specific components of systemic inflammation in bronchiectasis are related to disease severity and aetiology, and elucidating the underlying pathways may identify novel therapeutic approaches [27].…”

Section: Discussionmentioning

confidence: 99%

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Correlates and assessment of excess cardiovascular risk in bronchiectasis

et al. 2017

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Patients with bronchiectasis are at increased risk of cardiovascular disease. We aimed to identify factors associated with elevated cardiovascular risk in bronchiectasis, measured using aortic stiffness and cardiac biomarkers. In addition, we sought to compare these direct measures against calculated QRISK2 scores.Aortic stiffness, cardiac biomarkers and systemic inflammation were measured in 101 adults with stable bronchiectasis. In addition, clinical and demographic data were collected to allow calculation of QRISK2 score and the bronchiectasis severity index (BSI) for each patient.The BSI score correlated with measured cardiovascular risk assessments, partly due to greater exacerbation frequency and lower forced expiratory volume in 1 s. Pulse-wave velocity was significantly higher in frequent exacerbators (≥3 events·year) than infrequent exacerbators (<3 events·year; 10.5 9.2 m·s, p=0.01). In addition, frequent exacerbators had elevated serum C-reactive protein concentration, suggesting increased systemic inflammation (4.8 2.2 mg·L, p=0.005). QRISK2 systematically underestimated cardiovascular risk in this population (median change in relative risk 1.29). Underestimation was associated with frequent exacerbations and male sex.Patients with bronchiectasis have greater cardiovascular risk than published reference populations. Excess cardiovascular risk is associated with exacerbation frequency and impaired lung function. Cardiovascular risk assessment in bronchiectasis should be individualised, as calculation tools are likely to underestimate the risk in this population.

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Section: Reference Ranges For Pwv Have Been Published By the Referencsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Correlates and assessment of excess cardiovascular risk in bronchiectasis

et al. 2017

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“…35 Systematic inflammation is a risk factor for exacerbation in patients with bronchiectasis and the anti-inflammatory effects of macrolides have been shown to reduce systemic inflammation including C-reactive protein. 36 The association between increased age, increased systemic inflammation and increased efficacy of macrolides is therefore biologically plausible. It is clear, however, that further studies would be required to provide sufficient statistical power to confidently identify these patients groups as more responsive to macrolide treatment.…”

Section: Discussionmentioning

confidence: 99%

Long-term macrolide antibiotics for the treatment of bronchiectasis in adults: an individual participant data meta-analysis

Chalmers

Boersma

Lonergan

et al. 2019

The Lancet Respiratory Medicine

115

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Evidence before this study: Data sources and searches © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ Two investigators searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials andWeb of Science using the search strategy described in the online supplement. Searches were conducted from 2000 to 30 th September 2018. No language restrictions were applied. Searches were supplemented with review of reference lists and by reviewing previous meta-analyses and guidelines. Clearly ineligible studies were excluded based on abstract review alone.We identified 266 references and after exclusion of non-relevant studies we identified 3 randomized controlled trials comparing long term treatment with macrolide antibiotics (>3 months duration) compared with placebo where the primary outcome was the reduction of exacerbations. We identified several existing aggregate meta-analyses that suggested that macrolides reduce the frequency of exacerbations of bronchiectasis. Neither the individual trials nor the existing meta-analyses reported on the effectiveness of macrolides in different subpopulations. Identifying which patients benefit from macrolides was identified as a key research priority in bronchiectasis. The current European Respiratory Society guidelines suggest consideration of macrolides for patients without Pseudomonas aeruginosa infection with a history of at least 3 exacerbations in the previous year. Added value of this study:We report the first individual patient data meta-analysis of long term macrolide therapy in bronchiectasis. Our data from 341 patients enrolled in randomized clinical trials in the Netherlands, NewZealand and Australia suggests that macrolide treatment compared to placebo for 6-12 months results in a 50% reduction in the frequency of exacerbations. Additional benefits included prolongation of the time to first exacerbation and statistically significant improvements in quality of life measured by the St Georges Respiratory Questionnaire. Lung function was not significantly improved. Analyses in prespecified subgroups including age, sex, disease severity and baseline microbiology suggested that macrolides effectively reduced exacerbations across all subgroups of patients. Importantly, macrolides had a significant and clinically meaningful impact in patients where macrolide are not currently considered as first line treatment, including patients with P. aeruginosa infection and patients with less than 3 exacerbations per year. Implications of all the available evidence:Our data suggests that macrolide therapy is highly effective in reducing the frequency of exacerbations in bronchiectasis. Given the strong evidence that exacerbations contribute to long term morbidity and mortality in bronchiectasis macrolides should be considered in patients with frequent or severe exacerbations. Current bronchiectasis guidelines recommend inhaled antibiotics as first line treatment for patients with P. aeruginosa...

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“…Additionally, the different populations in RESPIRE 1 and 2 yielded similar trends toward benefit from ciprofloxacin DPI therapy but probably with different mechanisms at work, including anti-microbial, anti-inflammatory and/or immunomodulatory effects. A clear challenge emerging from RESPIRE and other clinical therapeutic trials in bronchiectasis is the vast ethnic, geographic and endophenotypic heterogeneity of disease [8][9][10][11]. This makes trials in bronchiectasis challenging to perform, analyse and report accurately.…”

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confidence: 99%