To compare the efficacy and safety of procalcitonin-guided versus standard protocols to decide on the initiation or early termination of antibiotics in patients admitted with an acute exacerbation of chronic obstructive pulmonary disease.
Our search strategy will aim to yield studies that assess procalcitonin in patients with COPD. We will use controlled vocabulary and free searches to find studies regarding procalcitonin AND COPD.
We will search the following electronic databases to find reports of relevant randomised controlled trials:
• The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2016, latest issue);
• MEDLINE OVID (1946 to date);
• EMBASE (from 1980 to date).
We will also search trial registries via the World Health Organization International Clinical Trials Platform Search Portal (ICTRP).
Furthermore, we will search the abstract proceeding registries of European Respiratory Society and American Thoracic Society. Only abstracts available online will be searched.
Finally, we will check the reference lists of all trials identified by the above mentioned searches.
Types of study to be included
Randomised or quasi-randomised controlled trials.
Condition or domain being studied
Acute Exacerbations of COPD (AECOPD), defined as acute deterioration of patients’ symptoms that is beyond normal day-to-day variations, comprise critical events in the natural history of the disease, as they account for the majority of disease morbidity, mortality, health care utilization and costs.
Successful identification of infective versus non-infective exacerbations would lead to the limitation of unneeded antibiotic prescription and administration.
Patients with a diagnosis of COPD, presenting with an acute exacerbation, defined as an acute event characterized by a deterioration of patients respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medication.
Patients with immunodeficiencies or receiving immune-suppressants (apart from steroids) or patients with chronic infections requiring chronic antibiotic therapy to be excluded.
Randomised or quasi-randomised controlled trials compared procalcitonin-based protocols to guide the decision on the initiation (or not) or early discontinuation of antibiotics in patients presenting with acute exacerbations of COPD, versus standard protocols, not using procalcitonin.
Standard protocols are usually based on clinical characteristics such as sputum purulence, inflammatory markers such as the white cell count or CRP, or generally based on the decision of the healthcare professional.
Setting: Primary care or Hospital Emergency, General Medicine or Respiratory Departments.
1. Treatment failure for the index exacerbation, defined as symptoms deterioration, non-improvement, ICU admission or death (short term, within one to three weeks)
2. Length of hospitalisation for the index exacerbation
1. Antibiotic exposure for the index exacerbation (including proportion of patients who were prescribed on antibiotics and mean duration of the course of antibiotics) and at longest follow up.
2. Antibiotic prescription after opposite initial decision.
3. Re-exacerbation rate at longest follow up.
4. Re-admission rate at longest follow up.
5. Mortality at longest follow up
Data extraction, (selection and coding)
Title and abstract screening, study selection and data extraction will be performed by two review authors independently. Data will be extracted to pre-specified standardised forms. Discrepancies in each stage will be resolved through discussion.
Risk of bias (quality) assessment
Risk of bias and quality assessment will be performed by two review authors, following the guidance from Cochrane and GRADE Working Group. Discrepancies will be resolved through discussion and adjudication by a third author if necessary.
Strategy for data synthesis
If sufficient studies are available, we will pool the data to perform meta-analysis. We will use the fixed or random effects model, in cases where heterogeneity through the I-squared statistic will be found to be less than 50% or between 50-75% respectively. Results will be presented in the form of relative risks (RR) with their 95% confidence intervals (CI), for dichotomous data and in the form of mean differences (MD) with the corresponding 95% CI for continuous data. We will carry out the statistical analyses using the Review Manager software (RevMan 2014)
Analysis of subgroups or subsets
In one sensitivity analysis we will only include studies of low risk of bias. In another subanalysis we will only include studies where the COPD diagnosis of the participants is confirmed by spirometry. We will also perform an additional analysis only including studies with high adherence to the procalcitonin protocols (>75%). If there are significant differences in the follow up periods, we will group the studies with follow up of up to 3 months, up to 6 months or more than 6 months. Finally, for meta-analyses performed using the fixed effects model, we will repeat the analysis using the random effects model.
We intend to publish our systematic review in a peer reviewed journal.
Contact details for further information
Centre for Respiratory Medicine and Allergy
Institute of Inflammation and Repair
University of Manchester
Organisational affiliation of the review
Dr Alexander G. Mathioudakis, Centre for Respiratory Medicine and Allergy, Wythenshawe Hospital, University of Manchester, UK Dr Victoria Chatzimavridou-Grigoriadou, Respiratory Department, General Hospital of Nikaia, Greece Dr Alexandru Corlateanu, Respiratory Department, State University of Medicine and Pharmacy "Nicolae Testemitanu", Chisinau, Moldova Professor Jorgen Vestbo, Centre for Respiratory Medicine and Allergy, Wythenshawe Hospital, University of Manchester, UK
Anticipated or actual start date
09 May 2016
Anticipated completion date
30 June 2016
No funding received
Conflicts of interest
England, Greece, Moldova
Subject index terms status
Subject indexing assigned by CRD
Subject index terms
Anti-Bacterial Agents; Calcitonin; Humans; Protein Precursors; Pulmonary Disease, Chronic Obstructive
Stage of review
Completed and published
Date of registration in PROSPERO
11 May 2016
Date of publication of this revision
07 February 2017
Details of final report/publication(s)
Mathioudakis AG, Chatzimavridou-Grigoriadou V, Corlateanu A, Vestbo J. Procalcitonin to guide antibiotic administration in COPD exacerbations: a meta-analysis. Eur Respir Rev. 2017 Jan 31;26(143). pii: 160073. doi: 10.1183/16000617.0073-2016. http://err.ersjournals.com/content/26/143/160073
Stage of review at time of this submission
Piloting of the study selection process
Formal screening of search results against eligibility criteria
Risk of bias (quality) assessment
PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites.