Point-of-care biomarkers or laboratory-based tests to reduce antibiotic prescribing for COPD exacerbations: a literature review and meta-analysis in primary care

Mathieu Frénois; Roxane Fovet; David Wyts; Claire Collins; Matthieu Calafiore; Christophe Berkhout

doi:10.3399/BJGP.2025.0593

Abstract

Background Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are frequently treated with antibiotics in primary care, leading to antibiotic resistance and adverse effects. Assessing biomarkers might assist in reducing unnecessary antibiotic prescribing when used alongside clinical assessment.

Aim To evaluate the benefit of reviewing biomarkers in point-of-care testing (POCT) within practices and through laboratory blood tests in efforts to decrease antibiotic prescribing for AECOPD.

Design and setting Systematic review of randomised controlled trials (RCTs) and non-randomised studies conducted in primary care from January 2022 to November 2025 assessing POCTs for chronic obstructive pulmonary disease (COPD).

Method The primary outcome was the rate of antibiotic prescribing or use, and secondary outcomes were biomarker thresholds for prescribing antibiotics and patient harm. Searches were conducted in four medical databases, six registers, and COPD academic societies. Data were extracted and assessed for quality and bias. A meta-analysis was performed whenever possible.

Results A total of seven studies were included: one RCT and four non-randomised studies for C-reactive protein (CRP) POCT; and two RCTs on procalcitonin (PCT) in laboratories. The meta-analysis of CRP POCT indicated a statistically significant reduction in antibiotic prescribing (odds ratio 0.41, 95% confidence interval = 0.32 to 0.53; I² = 36%; low certainty of evidence). No meta-analysis for PCT was feasible.

Conclusion CRP POCT reduced antibiotic prescribing for AECOPD in primary care settings when used alongside clinical assessment. There were insufficient data to draw conclusions about the PCT biomarker.

How it fits in

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) represent a common primary care situation in which the choice of whether to prescribe an antibiotic is difficult. In addition to clinical examination, the use of biomarkers such as C-reactive protein (CRP) in point-of-care testing (POCT) or procalcitonin (PCT) in laboratories could help in the decision making on whether to prescribe an antibiotic. Rapid CRP POCTs reduced antibiotic prescribing without increasing respiratory risk for AECOPD in primary care, but the level of certainty was low. There are insufficient data to conclude on the usefulness of PCT in laboratories in reducing antibiotic prescribing for AECOPD in primary care.

Introduction

GPs diagnose about 80% of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in primary care settings.¹ GPs usually manage them with bronchodilators, corticosteroids, or antibiotics.² Limiting unnecessary antibiotic prescribing in primary care is vital in reducing bacterial resistance to antibiotics at both societal^3,4 and individual levels.⁵ Antibiotic resistance leads to ineffective treatments, increased risk of serious complications, such as bacterial infections and death, and increased healthcare costs.^6,7 Antibiotics have side effects and drug interactions that may harm patients. However, patient safety must also be carefully considered by the GP to reduce the risk of undertreatment of serious bacterial infections.

The decision on whether to prescribe antibiotics for an AECOPD is challenging. On one hand, it reassures both GPs and patients but, on the other hand, only bacterial AECOPD may benefit from antibiotics and the majority of AECOPD are not caused by bacteria (bacterial AECOPD account for 20%–50% in clinical samples)^8,9 but rather by virus or environmental factors, such as air pollution. Clinical signs of bacterial AECOPD may not be easily identified by the GP and are controversial. Since 1987,¹⁰ Anthonisen criteria are often used with increased dyspnoea, increased sputum volume, and increased sputum purulence, even though they are not specific to bacterial infection as they may be caused by local inflammation.¹¹ These signs are subjective and remain vague in identifying whether a patient could be treated without antibiotics.

In 2018, Vollenweider et al updated a Cochrane systematic review from 2012 with 19 randomised trials (n = 2663 participants) about the value of antibiotics for inpatients and outpatients with AECOPD.¹² It reported inconsistent effects of antibiotics and called for measuring biomarkers through blood tests to identify who would benefit from antibiotics, while avoiding antibiotics for patients who are unlikely to experience benefits and for those who may experience antibiotic drawbacks. The US Food and Drug Administration and National Institutes of Health define a biomarker as a biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease.¹³ Another systematic literature review¹⁴ and a trial¹⁵ have already explored many biomarkers but mainly in secondary care settings. Such biomarkers were either very specialised and not relevant to primary care, or participant recruitment spanned undifferentiable primary and secondary care, making them unusable for primary care patients.¹⁴ In 2022, Smedemark et al, in another Cochrane systematic review, explored the use of point-of-care tests (POCTs) in primary care for upper and lower respiratory tract infections alongside clinical examination and concluded a likely reduction of antibiotic prescribing due to C-reactive protein (CRP) POCTs, with moderate to high certainty of evidence.¹⁶ It emphasised the need for further analysis on specific subgroups such as immunocompromised patients, children, and older people. Studies show that, for the ranges useful in general practice, rapid CRP POCTs are sufficiently concordant with laboratory measures to guide management.¹⁷

To date, to the authors’ knowledge, no systematic review has considered biomarkers specifically for the AECOPD population in primary care settings to help reduce antibiotic prescribing.

The aim of this systematic review and meta-analysis was to assess the benefit of POCTs in GPs’ practices or blood tests in laboratories to reduce unnecessary antibiotic prescribing for AECOPD in primary care settings.

Method

This systematic review of literature applied the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement¹⁸ and the Cochrane Handbook for Systematic Reviews and Interventions.¹⁹ A Cornell University diagram was used to ensure this work met systematic literature review criteria.²⁰ The protocol of this review was registered on PROSPERO, an international prospective register of systemic reviews (registration number: CRD42024575414).

Eligibility criteria

The primary outcome was the rate of antibiotic prescribing or use, and secondary outcomes were biomarker thresholds for prescribing antibiotics and patient harm.

To be eligible, studies had to have a primary outcome related to a POCT or a laboratory blood test to reduce unnecessary antibiotic prescribing for AECOPD in primary care settings. Included studies had to report the following criteria:

proven diagnosis of COPD with spirometry (any GOLD stage) and/or diagnosis of COPD in primary care clinical records;²
only primary care patients or separate analysis of primary care patients;
patients presenting with an AECOPD with at least one of the Anthonisen criteria (increased dyspnoea, increased sputum volume, increased sputum purulence, and lasting a minimum of 24 hours and a maximum of 21 days);¹⁰ and
blood test as POCT, or in a laboratory, to help decision making about antibiotic prescribing or use.

The authors excluded studies that reported:

hospital patients (emergency or medical wards or intensive care unit); or
patients requiring urgent hospital admission.

Randomised controlled trials (RCTs), cohort studies, retrospective, cross-sectional, before-after, and case–control studies were included. Systematic literature reviews, meta-analyses, qualitative studies, editorial letters, or comments were excluded.

Information sources

A first review of literature was conducted from 1 January 2022 to 31 August 2023, with an updated search carried out from 1 September 2023 to 30 November 2025 in four medical databases: MEDLINE (1977–2023 then 2023–2025); the Cochrane Central Register of Controlled Trials (CENTRAL) (1948–2023 then 2023–2025); Embase (1975–2023 then 2023–2025); and the Web of Science (1900–2023 then 2023–2025), in the same months, respectively. The following registers were explored: ClinicalTrials.gov; Australia New Zealand Trauma Registry; EU Clinical Trials Register; Dutch Trial Register; UK International Standard Randomised Controlled Trial Number registry; and US Clinical Trials Transformation Initiative. The authors also explored COPD academic societies’ websites.

Search strategy

A research equation by database was built in several steps:

Breaking down the research aim: ‘Assessment of the benefit of POCT in GPs’ practice or blood test in laboratories to reduce unnecessary antibiotic prescribing for AECOPD in primary care settings’ into three blocks. Each block resulted in one research equation with semantic specificities related to each database.
Breakdown resulted in Block 1: ‘COPD’; Block 2: ‘Antibiotics’; and Block 3: ‘Biomarkers’.
One final research equation per database merged the three blocks.

The export feature in the four databases was used by generating a .ris or .nbib file enabling an import in the ZOTERO tool (version 5.0.96.4 in February 2022 to version 7.0.30 in November 2025). Then, a ZOTERO group library was created to remove duplicates. The search was not restricted to any language.

Selection and data collection process

Resulting records on ZOTERO after removing duplicates were then imported into the Rayyan platform (version 1.6.0), to select reports by title and abstract.²¹ Two independent reviewers, and occasionally three reviewers on specific points, blind to their allocations proceeded with report selection. The reviewers could choose three allocations: ‘yes’, ‘no’, and ‘maybe’ if researchers were unsure. The ‘maybe’ reports were then allocated either to ‘yes’ or ‘no’ after consensus between reviewers or discussion with the supervisor.

Included reports remained blinded during this process and were then imported back into ZOTERO.

Citations and bibliographical references at the end of included reports and excluded systematic reviews of literature and meta-analysis were also investigated with a tool called ‘citationchaser’ (version 0.0.4), offering two features ‘forward citation chaser’ and ‘backward citation chaser’ to ensure no relevant reports were missed.²²

Data items

All reports referring to inpatients were excluded. Reports referring to patients with lower respiratory tract infection (LRTI) were only included if a relevant AECOPD primary care subgroup was created and analysed. A single researcher extracted the relevant data for analysis purposes. Any primary or secondary outcome was considered, and any limitation or missing information was considered as a bias.

Study risk of bias assessment

The risk of bias of the included reports was assessed by two independent investigators using the Cochrane tool, as explained in the Cochrane Handbook for Systematic Reviews of Interventions. ¹⁹ RobVis (version 0.3.0) was used to generate risk-of-bias assessment figures.²³

The quality of reports was assessed using a standard tool to assess risk of bias according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.²⁴

Effect measures and synthesis method (meta-analysis)

The effect of biomarkers was reported as an odds ratio (OR) with a 95% confidence interval (CI). The adjusted OR within reports, when available, was input in Cochrane Review Manager (RevMan, version 5.3). When the OR was not available in reports, computation through RevMan with four values from reports was performed.

Unpublished measures were not sought. Generic inverse variance was used, adjusting for the direction of the effect (that is, increase or decrease). OR and 95% CI were computed using random effects in the context of an important difference in weight of the studies. Heterogeneity was computed using the I² statistic and the heterogeneity χ². The result was presented as a forest plot.

Reporting bias assessment

A RevMan funnel plot assessed potential missing results for the primary outcome.

Certainty of evidence

Certainty of evidence for the meta-analysis was aggregated from the individual level of evidence (GRADE) for each report included in the meta-analysis. Three sensitivity analyses were conducted to assess the robustness of the synthesised results: one with non-randomised studies only; one with the three best quality reports; and another giving a clear cut-off value for biomarker intervention.

Results

Study selection

The records selection is presented in Figure 1. Searches by keywords in databases and registers returned 4413 and 116 records, respectively, without duplicates. Records identified from other sources, including citation searching, returned 2142 records.

PRISMA flow diagram showing process for identifying included studies. Left: Identification of studies via databases and registers. Right: Identification of studies via other methods.

Figure 1. PRISMA 2020 flow chart diagram.¹⁸ Excluded reports can feature in multiple reasons. ANZTR = Australia New Zealand Trauma Registry. CNGE = Collège National des Généralistes Enseignants. ISRCTN = International Standard Randomised Controlled Trial Number. MG = de Médecine Générale.

The four final search equations returned 422 records in MEDLINE, 3367 records in EMBASE, 420 records in Web of Science, and 828 records in CENTRAL. Records searched were mainly in English and rarely in French, German, or Spanish. At the end of the selection process, seven studies were included in the review:

five quantitative studies related to CRP biomarkers as POCT (one RCT with 653 patients,²⁵ two observational studies totalling 405 patients,^26,27 and two before-and-after studies totalling 1449 patients^28,29); and
two RCTs related to PCT biomarkers as blood tests in laboratories with AECOPD subgroups including 21 and six patients.^30,31

Two included observational studies were conducted by the same first author and were published only 1 year apart (Llor et al 2012 and Llor et al 2013).^27,28 The first study examined a cohort in Spain, whereas the second involved a multinational cohort (Argentina, Denmark, Lithuania, Russia, Spain, and Sweden), though CRP POCT was mainly used in Sweden and Denmark. Therefore, these two studies did not address the same population.

The two PCT studies^30,31 were included because at the abstract review stage it was interpreted that the primary outcome was the antibiotic prescribing rate with a PCT-guided approach. However, it turned out to be a secondary outcome. After discussion between reviewers, the authors decided to include them in the review for information purposes since no PCT study was used in the meta-analysis.

The RCT²⁵ related to CRP biomarkers as POCT included in this study mentioned patient health outcomes as a secondary outcome. It indicated that less antibiotic use and fewer prescriptions from clinicians did not compromise patient-reported disease-specific quality of life.

One of the non-randomised studies, Strykowski et al,²⁹ reported that underprescribing did not significantly increase. However, this may have been due to limitations in sample size. None of the other included studies addressed patient health outcomes.

A qualitative study³² based on the same English and Welsh population as the only RCT included that related to CRP biomarkers as POCT²⁵ was excluded from this systematic review, as it did not provide quantitative data for the defined primary outcome. Interestingly, the study concluded that CRP POCT had high acceptability among primary care staff and patients, though commissioning arrangements and further simplification of the CRP POCT needed attention to facilitate implementation in routine practice.

Two studies reported cost analyses of CRP POCT (Sewell et al and Francis et al).^33,34 Both were based on the RCT²⁵ included in this review. These studies were excluded because the current systematic review aim did not encompass health economic outcomes. However, Sewell et al, ³³ as the most recent and comprehensive cost analysis of CRP POCT, is considered in the Discussion section of this article.

CRP and PCT were the main biomarkers retrieved in the current review — CRP as a POCT and PCT in laboratories. Though leucocyte count appears in some records and considering a white blood count POCT device exists,³⁵ no study assessed it as a biomarker to reduce antibiotic prescribing in AECOPD exacerbation in primary care. Likewise, neutrophil count exists as a POCT device³⁶ and is mainly used for patients at risk of neutropenia following chemotherapy;³⁷ however, no report mentioned its use in AECOPD exacerbation.

Eight records required discussion among the reviewers, and all were ultimately excluded, mainly owing to an incorrect publication type, an ineligible population, or an irrelevant outcome.^38–45

Not peer-reviewed literature

The grey literature was also explored but no records were included since by definition they were not approved through the official peer-review process. Five relevant theses were noticed but with a different population, with a different outcome, or were relatively old research works (from 2010) and without POCT analysis.

Characteristics of the included studies

Table 1 reports the characteristics of the seven included quantitative studies.

View this table:

Table 1. Characteristics of the included studies

Risk of bias within studies

Figure 2 shows the biases within the studies. The RCT by Butler et al was well designed but had two noticeable biases: it was not blinded and the first author had a conflict of interest with Roche Molecular Systems (advisory board fees) and Roche Molecular Diagnostics (grant support) are a provider of POCT devices. However, another company, Abbott, loaned POCT devices for the study and had no role in the design, accrual, analysis, data interpretation, or manuscript preparation.²⁵ This study had a good methodological quality, and a double-blind design may have proved difficult to implement in primary care with a POCT; therefore, a moderate overall bias was decided by both reviewers. Two non-randomised studies for CRP biomarkers had serious biases owing to confounding, selection of participants, or measurement of outcome.^26,28

Risk of bias domains for all included studies in the systematic review. Domains are rated on a traffic-light system. Full domains are listed at bottom of Figure. Overall, 3 studies rated moderate; 4 studies rated serious.

Figure 2. Risk of bias within studies. D = domain.

Results of individual studies and level of evidence

All studies related to the CRP biomarker referred to POCT and found a statistically significant reduction in antibiotic prescribing rate for AECOPD (Table 2). The CRP cut-off for antibiotic prescribing from the best quality study was 40 mg/L, with no evidence of harm for patients.²⁵ Other studies suggest either 50 mg/L,²⁶ or a grey area between 20 mg/L and 100 mg/L where antibiotic prescribing should be discussed on a case-by-case basis (sputum purulence providing more weight to antibiotic prescribing).^27–29 When CRP is ≥100 mg/L, antibiotics must be prescribed.^27–29

View this table:

Table 2. Main results of included studies

The two studies related to PCT biomarker (blood test in laboratories and not POCT) did not allow for a conclusion on the subgroup AECOPD because of an antibiotic prescribing rate evaluated as a secondary outcome and the absence of statistical analysis.^30,31

Quantitative study meta-analysis

Figure 3 shows the meta-analysis of the five quantitative studies for the CRP POCT, computed through the RevMan tool and totalling 2507 patients. It was in favour of an antibiotic prescribing reduction for AECOPD patients in primary care, with moderate homogeneity among studies: OR 0.41 (95% CI = 0.32 to 0.53); I² = 36%.

Log, standard error, weight, odds ratio, and 95% confidence interval for the five quantitative studies favouring C-reactive protein point-of-care testing.

Figure 3. Meta-analysis of the five quantitative studies (CRP POCT). CRP = C-reactive protein. df = degrees of freedom. IV = inverse variance. OR = odds ratio. POCT = point-of-care test. SE = standard error.

Sensitivity analysis

The authors analysed sensitivity separately: non-randomised studies only,^26–29 best quality studies (very low quality excluded),^25,27,29 and studies with clear CRP cut-off values (CRP at 40 mg/L or 50 mg/L).^25,26

The four non-RCT studies totalling 1854 patients were also in favour of the CRP POCT to reduce antibiotic prescribing with low heterogeneity: OR 0.46 (95% CI = 0.36 to 0.58); I² = 12%.^26–29

The three best quality studies were also in favour of the CRP POCT to reduce antibiotic prescribing, without heterogeneity: OR 0.37 (95% CI = 0.29 to 0.48); I² = 0%.

The two studies with a clear CRP cut-off value at 40 mg/L and 50 mg/L also returned in favour of the CRP POCT to reduce antibiotic prescribing without heterogeneity: OR 0.33 (95% CI = 0.24 to 0.45); I² = 0%.

Reporting biases

Regarding the overall publication bias, Figure 4 illustrates an acceptable risk with a well-balanced distribution of the results around the total OR.

Funnel plot of the five quantitative studies (C-reactive protein point-of-care testing), shows an acceptable risk with a well-balanced distribution of results around the total odds ratio.

Figure 4. Funnel plot of the five quantitative studies (CRP POCT). CRP = C-reactive protein. OR = odds ratio. POCT = point-of-care testing. SE = standard error.

Certainty of evidence (GRADE)

In the CRP POCT studies, two non-randomised studies had a very low level of evidence due to significant biases,^26,28 two had a low level of evidence,^27,29 and the RCT had a moderate level of evidence.²⁵ In the meta-analysis of the CRP biomarker, both reviewers evaluated the aggregated certainty of evidence as low (low to moderate if the sensitivity analysis with the three best quality studies is considered). Both randomised studies for PCT biomarkers had a low level of evidence (Table 2).^30,31

Discussion

Summary

Of the seven quantitative studies: five related to CRP POCT, and two related to PCT as a blood test in laboratories. The CRP POCT studies included one RCT with 653 patients, and four non-randomised studies with a total of 1854 patients. The meta-analysis performed on one RCT and the four non-randomised studies for CRP POCT was in favour of an antibiotic prescribing reduction for patients with AECOPD in primary care.

Regarding secondary outcomes, it was difficult to aggregate different recommendations from the studies about CRP thresholds but in the single RCT, the cut-off value was set at 40 mg/L for antibiotic prescribing with an area under the curve (AUC) of 0.732.^25,46 This threshold intended to support the clinical judgement and not replace it. If increased sputum purulence was observed, AUC for CRP POCT improved at 0.842,¹¹ making it a quite efficient diagnosis tool without compromising patient safety.²⁵

Only two of the five studies on CRP POCT, including the RCT, reported that the reduction in antibiotic prescribing did not result in patient harm or increased underprescribing as secondary outcomes.^25,29

However, the certainty of evidence for the meta-analysis for CRP POCT was low (low to moderate if the sensitivity analysis with the three best quality is considered), mainly due to the lack of RCTs. The single RCT included was of good quality, yet open-labelled. The four remaining studies being non-randomised were at a higher risk of bias.

As the two studies investigating the effect of measuring PCT did not provide exploitable results for the AECOPD subgroup, and because the antibiotic prescribing rate was a secondary outcome, the evidence was very uncertain about the effect of measuring PCT for antibiotic prescribing reduction in primary care patients with AECOPD.

This systematic review and meta-analysis shows evidence to assert CRP POCT in significantly reducing antibiotic prescribing for AECOPD in primary care to support rather than replace clinical assessment. The evaluation of this intervention proves to be cost-effective in the UK.

Strengths and limitations

To the authors’ knowledge, this is the first systematic review and meta-analysis addressing specifically an AECOPD population in primary care and assessing the effect of biomarkers to reduce unnecessary antibiotic prescribing as an adjunct to clinical examination. Data were gathered from broad sources: four databases, six registers, over 2000 citation searches, and six academic societies. Though some systematic reviews and meta-analyses were excluded from the search, citations and bibliographical references from these reviews were retrieved with the tool ‘citationchaser’, ensuring no relevant reports were missed.

In terms of limitations, the meta-analysis included one single RCT and four non-randomised studies. The lack of RCTs in the body of evidence limited the level of certainty. Combining RCTs and non-randomised studies with different designs and methods in a meta-analysis is not ideal, as mentioned in the Cochrane Handbook for Systematic Reviews of Interventions,¹⁹ though the results of the sensitivity analysis with non-randomised studies only remained close to the results of the five quantitative studies.

When the OR was not available within two non-randomised studies^26,28 it was computed through the RevMan tool, but confounding factors may not have been taken into account leading to an unadjusted OR and a higher risk of bias (though these two studies were already considered the most biased in this review).

Regarding limitations related to included studies, the single RCT, the PACE trial, was open-labelled thus at risk of bias due to the lack of blinding. The main author had a conflict of interest with Roche Molecular Systems (advisory board fees) and Roche Molecular Diagnostics (grant support), a provider of POCT.²⁵ For both reasons, this RCT study was downgraded from high to moderate level of evidence, despite the reputation of the journal in which it was published. The included non-randomised studies were of variable quality and did not always address patient harm as a secondary outcome, though antibiotic underprescribing may be an issue for patient safety in the case of serious bacterial infection. The level of evidence was assessed as low or very low for these non-randomised studies. Most included studies enrolled an AECOPD population based on physician-diagnosed COPD even though the official COPD definition is spirometry confirmed, albeit time consuming and not readily available in primary care settings.⁴⁷ Even if the possibility of an alternate diagnosis, such as asthma, created a selection bias, this situation represents the real-word population being treated as patients with COPD in primary care.

Comparison with existing literature

Sewell et al,³³ in a cost analysis based on the PACE trial originally reported by Butler et al, ²⁵ the only RCT included in this review, concluded that CRP POCT is a cost-effective intervention for safely reducing antibiotic consumption in patients with AECOPD. The cost of CRP POCT (£11.31 per test) was offset by savings in healthcare resource use related to COPD management.

The qualitative study, excluded from this systematic review, conducted on the PACE trial English and Welsh population concluded that CRP POCT had high acceptability among primary care staff and patients, though commissioning arrangements and further simplification of the CRP POCT need attention to facilitate implementation in routine practice.³²

Implications for research and practice

The authors suggest that more RCTs should be designed in a double-blind setting and without conflict of interest from POCT providers to confirm, on a bigger scale, that CRP POCT significantly reduces antibiotic prescribing for AECOPD. The academic society GOLD also suggested, in its latest 2024 report, that additional studies in other settings be conducted before a recommendation to generalise this approach.² A CRP cut-off value for antibiotic prescribing should also be evaluated as a primary outcome to confirm a CRP cut-off value around 40 mg/L.

Evidence is very scarce about PCT measurement effect on antibiotic prescribing for AECOPD in primary care as no studies specifically focused on this population, particularly for PCT POCT. The cost of measuring PCT (about 10 times more expensive than CRP)⁴⁸ also raises questions about its future viability in primary care at a time when healthcare spending is being carefully monitored.⁴⁹

Other POCT biomarkers exist (mainly leucocytes and neutrophils),^35,36 but, to the authors’ knowledge, no study has assessed them for reducing antibiotic prescribing for AECOPD in primary care. Some studies in secondary care suggest combining CRP with other biomarkers might enhance performance diagnosis in case of bacterial AECOPD.^50–52 A dual or triple biomarker (CRP/neutrophils or CRP/leucocytes/neutrophils) might then identify AECOPD requiring antibiotic prescribing more accurately.

Besides antibiotics, GPs often prescribe oral glucocorticoids to treat AECOPD in primary care and this treatment may be guided by an eosinophil POCT. In a 2024 multicentre, double-blind, randomised controlled trial in 14 primary care settings in the UK with 308 patients, treating eosinophilic AECOPD only with corticosteroids did not make a significant difference to re-treatment, hospitalisations, or deaths compared with treating all AECOPD with corticosteroids.⁵³ Thus, such biomarkers could identify COPD exacerbation phenotype to guide not only antibiotic use, but also oral glucocorticoid therapy in primary care. This could be a promising path to a more personalised treatment plan, respectful to the ecosystem and alleviating unnecessary costs to primary healthcare systems.

Regarding the practical feasibility, POCT devices in primary care are well implemented and regularly used in many European countries (Denmark, Netherlands, Norway, and Switzerland).^54,55 However, in France, medical biology outsourcing in GP practices is poorly developed and has no legal basis since blood tests must be executed and validated in laboratories only.⁵⁶ Reluctance among some healthcare professionals to change to outsourcing biology has been reported.⁵⁷

Notes

Funding

The authors did not receive any financial or non-financial support from sponsors or funders for this study.

Ethical approval

In France, systematic reviews that do not require any original research are not subject to ethical approval.

Provenance

Freely submitted; externally peer reviewed.

Data

All data are available on request from the first author (mathieu.frenois{at}gmail.com).

Acknowledgements

The research team would like to thank the services of the University of Lille Health Library for its methodological support and for finding documents that were difficult to locate.

Competing interests

The authors have declared no competing interests.

Received September 13, 2025.
Revision received November 26, 2025.
Accepted April 6, 2026.

http://creativecommons.org/licenses/by/4.0/

This article is Open Access: CC BY 4.0 licence (http://creativecommons.org/licenses/by/4.0/).

References

1.↵
1. Global Initiative for Chronic Obstructive Lung Disease
(2024) Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (2024 report), accessed. https://goldcopd.org/wp-content/uploads/2024/02/GOLD-2024_v1.2-11Jan24_WMV.pdf. 6 Jul 2026.
2.↵
1. Sharma M,
2. Joshi S,
3. Banjade P,
4. et al.
(2024) Global initiative for chronic obstructive lung disease (GOLD) 2023 guidelines reviewed. Open Respir Med J 18, pmid:38660684. e18743064279064.
OpenUrl PubMed
3.↵
1. Cassini A,
2. Högberg LD,
3. Plachouras D,
4. et al.
(2019) Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European economic area in 2015: a population-level modelling analysis. Lancet Infect Dis 19(1):56–66, pmid:30409683.
OpenUrl CrossRef PubMed
4.↵
1. van de Sande-Bruinsma N,
2. Grundmann H,
3. Verloo D,
4. et al.
(2008) Antimicrobial drug use and resistance in Europe. Emerg Infect Dis 14(11):1722–1730, pmid:18976555.
OpenUrl CrossRef PubMed
5.↵
1. Costelloe C,
2. Metcalfe C,
3. Lovering A,
4. et al.
(2010) Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis. BMJ 340, pmid:20483949. c2096.
OpenUrl Abstract/FREE Full Text
6.↵
1. Carlet J,
2. Collignon P,
3. Goldmann D,
4. et al.
(2011) Society’s failure to protect a precious resource: antibiotics. Lancet 378(9788):369–371, pmid:21477855.
OpenUrl CrossRef PubMed
7.↵
1. Smith R,
2. Coast J
(2013) The true cost of antimicrobial resistance. BMJ 346, pmid:23479660. f1493.
OpenUrl FREE Full Text
8.↵
1. Celli BR,
2. Barnes PJ
(2007) Exacerbations of chronic obstructive pulmonary disease. Eur Respir J 29(6):1224–1238, pmid:17540785.
OpenUrl Abstract/FREE Full Text
9.↵
1. Ritchie AI,
2. Wedzicha JA
(2020) Definition, causes, pathogenesis, and consequences of chronic obstructive pulmonary disease exacerbations. Clin Chest Med 41(3):421–438, pmid:32800196.
OpenUrl CrossRef PubMed
10.↵
1. Anthonisen NR,
2. Manfreda J,
3. Warren CP,
4. et al.
(1987) Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med 106(2):196–204, pmid:3492164.
OpenUrl CrossRef PubMed
11.↵
1. Miravitlles M,
2. Moragas A,
3. Hernández S,
4. et al.
(2013) Is it possible to identify exacerbations of mild to moderate COPD that do not require antibiotic treatment? Chest 144(5):1571–1577, pmid:23807094.
OpenUrl CrossRef PubMed
12.↵
1. Vollenweider DJ,
2. Frei A,
3. Steurer-Stey CA,
4. et al.
(2018) Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 10(10), pmid:30371937. CD010257.
OpenUrl PubMed
13.↵
1. Cagney DN,
2. Sul J,
3. Huang RY,
4. et al.
(2018) The FDA NIH biomarkers, endpoints, and other tools (BEST) resource in neuro-oncology. Neuro Oncol 20(9):1162–1172.
OpenUrl CrossRef PubMed
14.↵
1. Koutsokera A,
2. Stolz D,
3. Loukides S,
4. Kostikas K
(2012) Systemic biomarkers in exacerbations of COPD: the evolving clinical challenge. Chest 141(2):396–405, pmid:21835899.
OpenUrl CrossRef PubMed
15.↵
1. Koutsokera A,
2. Kiropoulos TS,
3. Nikoulis DJ,
4. et al.
(2009) Clinical, functional and biochemical changes during recovery from COPD exacerbations. Respir Med 103(6):919–926.
OpenUrl CrossRef PubMed
16.↵
1. Smedemark SA,
2. Aabenhus R,
3. Llor C,
4. et al.
(2022) Biomarkers as point-of-care tests to guide prescription of antibiotics in people with acute respiratory infections in primary care. Cochrane Database Syst Rev 10(10), pmid:36250577. CD010130.
OpenUrl CrossRef PubMed
17.↵
1. Pohanka M
(2022) Diagnoses based on c-reactive protein point-of-care tests. Biosensors 12(5), pmid:35624645. 344.
OpenUrl PubMed
18.↵
1. Page MJ,
2. McKenzie JE,
3. Bossuyt PM,
4. et al.
(2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372, pmid:33782057. n71.
OpenUrl FREE Full Text
19.↵
1. Higgins JPT,
2. Thomas J,
3. Chandler J.,
4. et al.
, eds (2019) Cochrane handbook for systematic reviews of interventions (Wiley and Sons, Hoboken, NJ).
20.↵
1. Cornell University Library
What type of review is right for you? accessed. https://www.library.cornell.edu/wp-content/uploads/2024/05/SystematicReview_DecisionTreeAndMethodologies_new.pdf. 26 Jun 2026.
21.↵
1. Ouzzani M,
2. Hammady H,
3. Fedorowicz Z,
4. Elmagarmid A
(2016) Rayyan-a web and mobile app for systematic reviews. Syst Rev 5(1), pmid:27919275. 210.
OpenUrl CrossRef PubMed
22.↵
1. Haddaway NR,
2. Grainger MJ,
3. Gray CT
(2022) Citationchaser: a tool for transparent and efficient forward and backward citation chasing in systematic searching. Res Synth Methods 13(4):533–545, pmid:35472127.
OpenUrl CrossRef PubMed
23.↵
1. McGuinness LA,
2. Higgins JPT
(2021) Risk-of-bias visualization (robvis): an R package and shiny web app for visualizing risk-of-bias assessments. Res Synth Methods 12(1):55–61, pmid:32336025.
OpenUrl CrossRef PubMed
24.↵
1. Schünemann HJ,
2. Brennan S,
3. Akl EA,
4. et al.
(2023) The development methods of official GRADE articles and requirements for claiming the use of GRADE – a statement by the GRADE guidance group. J Clin Epidemiol 159:79–84, pmid:37211327.
OpenUrl CrossRef PubMed
25.↵
1. Butler CC,
2. Gillespie D,
3. White P,
4. et al.
(2019) C-reactive protein testing to guide antibiotic prescribing for COPD exacerbations. N Engl J Med 381(2):111–120, pmid:31291514.
OpenUrl CrossRef PubMed
26.↵
1. Barber D,
2. Pilsworth S,
3. Wat D
(2022) Does availability of point of care C-reactive protein measurement affect provision of antibiotics in a community respiratory service? Br J Community Nurs 27(5):218–224, pmid:35522449.
OpenUrl PubMed
27.↵
1. Llor C,
2. Bjerrum L,
3. Munck A,
4. et al.
(2013) Predictors for antibiotic prescribing in patients with exacerbations of COPD in general practice. Ther Adv Respir Dis 7(3):131–137, pmid:23325784.
OpenUrl CrossRef PubMed
28.↵
1. Llor C,
2. Cots JM,
3. López-Valcárcel BG,
4. et al.
(2012) Interventions to reduce antibiotic prescription for lower respiratory tract infections: Happy Audit study. Eur Respir J 40(2):436–441, pmid:22183489.
OpenUrl Abstract/FREE Full Text
29.↵
1. Strykowski DF,
2. Nielsen ABS,
3. Llor C,
4. et al.
(2015) An intervention with access to C-reactive protein rapid test reduces antibiotic overprescribing in acute exacerbations of chronic bronchitis and COPD. Fam Pract 32(4):395–400, pmid:25902912.
OpenUrl CrossRef PubMed
30.↵
1. Briel M,
2. Schuetz P,
3. Mueller B,
4. et al.
(2008) Procalcitonin-guided antibiotic use vs a standard approach for acute respiratory tract infections in primary care. Arch Intern Med 168(18):2000–2007, pmid:18852401.
OpenUrl CrossRef PubMed
31.↵
1. Burkhardt O,
2. Ewig S,
3. Haagen U,
4. et al.
(2010) Procalcitonin guidance and reduction of antibiotic use in acute respiratory tract infection. Eur Respir J 36(3):601–607, pmid:20185423.
OpenUrl Abstract/FREE Full Text
32.↵
1. Phillips R,
2. Stanton H,
3. Singh-Mehta A,
4. et al.
(2020) C-reactive protein-guided antibiotic prescribing for COPD exacerbations: a qualitative evaluation. Br J Gen Pract doi:10.3399/bjgp20X709865, pmid:32424045.
OpenUrl Abstract/FREE Full Text
33.↵
1. Sewell B,
2. Francis N,
3. Harris S,
4. et al.
(2024) Cost-effectiveness of C-reactive protein point of care testing for safely reducing antibiotic consumption for acute exacerbations of chronic obstructive pulmonary disease as part of the multicentre, parallel-arm, open, individually randomised, controlled PACE trial. BMJ Open 14(11), pmid:39609022. e084144.
OpenUrl Abstract/FREE Full Text
34.↵
1. Francis NA,
2. Gillespie D,
3. White P,
4. et al.
(2020) C-reactive protein point-of-care testing for safely reducing antibiotics for acute exacerbations of chronic obstructive pulmonary disease: the PACE RCT. Health Technol Assess 24(15):1–108, pmid:32202490.
OpenUrl CrossRef PubMed
35.↵
1. Osei-Bimpong A,
2. Jury C,
3. McLean R,
4. Lewis SM
(2009) Point-of-care method for total white cell count: an evaluation of the hemocue WBC device. Int J Lab Hematol 31(6):657–664, pmid:18759736.
OpenUrl CrossRef PubMed
36.↵
1. Ordóñez-Mena JM,
2. Fanshawe TR,
3. McCartney D,
4. et al.
(2019) C-reactive protein and neutrophil count laboratory test requests from primary care: what is the demand and would substitution by point-of-care technology be viable? J Clin Pathol 72(7):474–481, pmid:30992343.
OpenUrl Abstract/FREE Full Text
37.↵
1. Dale DC,
2. Kelley ML,
3. Navarro-De La Vega M,
4. et al.
(2018) A novel device suitable for home monitoring of white blood cell and neutrophil counts. Blood 132(Suppl 1). 1103.
38.↵
1. Martínez-González NA,
2. Plate A,
3. Jäger L,
4. et al.
(2022) The role of point-of-care C-reactive protein testing in antibiotic prescribing for respiratory tract infections: a survey among Swiss general practitioners. Antibiotics 11(5), pmid:35625187. 543.
OpenUrl CrossRef PubMed
39.
1. Roy K,
2. Marau A,
3. Esmond G,
4. et al.
(2019) S104 Home based respiratory point of care testing (R-POCTc) to improve the diagnosis and management of COPD exacerbations in the community. Thorax 74(Suppl 2). A66.
40.
1. Llor C,
2. Moragas A,
3. Bayona C
(2018) 139 Overdiagnosis of the bacterial aetiology of the acute exacerbations of chronic obstructive pulmonary disease: discrepancies among current guidelines. BMJ Evid-Based Med 23(Suppl 2). A65.
41.
1. Hart J,
2. Edwards AD,
3. Stainthorpe A
(2023) Insights into implementation planning for point-of-care testing to guide treatment of chronic obstructive pulmonary disease exacerbation: a mixed methods feasibility study. Front Health Serv 3, pmid:38235389. 1302653.
OpenUrl PubMed
42.
1. Gillespie D,
2. Butler CC,
3. Bates J,
4. et al.
(2021) Associations with antibiotic prescribing for acute exacerbation of COPD in primary care: secondary analysis of a randomised controlled trial. Br J Gen Pract doi:10.3399/BJGP.2020.0823, pmid:33657007.
OpenUrl Abstract/FREE Full Text
43.
1. Bazylkiewicz J,
2. Sutherland E
(2025) 203 – CRP/viral biomarker testing to improve patient care, outcomes, cost avoidances and antimicrobial stewardship in a community COPD population. Physiotherapy 126(Suppl 1). 101530.
44.
1. Lapi F,
2. Marconi E,
3. Rossi A,
4. et al.
(2024) The use of C‐reactive protein testing and antibiotic prescribing in Italy: a population‐based study in primary care. Brit J Clinical Pharma 90(9):2314–2319.
OpenUrl
45.↵
1. Llor C,
2. Trapero-Bertran M,
3. Sisó-Almirall A,
4. et al.
(2024) Effects of c-reactive protein rapid testing and communication skills training on antibiotic prescribing for acute cough. a cluster factorial randomised controlled trial. NPJ Prim Care Respir Med 34(1), pmid:38724543. 9.
OpenUrl PubMed
46.↵
1. Llor C,
2. Moragas A,
3. Bayona C,
4. et al.
(2013) Efficacy of anti-inflammatory or antibiotic treatment in patients with non-complicated acute bronchitis and discoloured sputum: randomised placebo controlled trial. BMJ 347, pmid:24097128. f5762.
OpenUrl Abstract/FREE Full Text
47.↵
1. White P,
2. Wong W,
3. Fleming T,
4. Gray B
(2007) Primary care spirometry: test quality and the feasibility and usefulness of specialist reporting. Br J Gen Pract 57(542):701–705, pmid:17761057.
OpenUrl Abstract/FREE Full Text
48.↵
1. Heyland DK,
2. Johnson AP,
3. Reynolds SC,
4. Muscedere J
(2011) Procalcitonin for reduced antibiotic exposure in the critical care setting: a systematic review and an economic evaluation. Crit Care Med 39(7):1792–1799.
OpenUrl CrossRef PubMed
49.↵
1. Park S,
2. Dieleman JL,
3. Kim R,
4. Subramanian SV
(2025) Association of health and social spending with health outcomes in OECD countries. Health Serv Res 60(6). e14660.
50.↵
1. Qian W,
2. Huang GZ
(2016) Neutrophil CD64 as a marker of bacterial infection in acute exacerbations of chronic obstructive pulmonary disease. Immunol Invest 45(6):490–503, pmid:27224474.
OpenUrl PubMed
51.
1. van de Geijn G-J,
2. Denker S,
3. Meuleman-van Waning V,
4. et al.
(2016) Evaluation of new laboratory tests to discriminate bacterial from nonbacterial chronic obstructive pulmonary disease exacerbations. Int J Lab Hematol 38(6):616–628, pmid:27459873.
OpenUrl PubMed
52.↵
1. Ellingsen J,
2. Janson C,
3. Bröms K,
4. et al.
(2021) Neutrophil-to-lymphocyte ratio, blood eosinophils and COPD exacerbations: a cohort study. ERJ Open Res 7(4), pmid:34988219. 00471-2021.
OpenUrl Abstract/FREE Full Text
53.↵
1. Ramakrishnan S,
2. Jeffers H,
3. Langford-Wiley B,
4. et al.
(2024) Blood eosinophil-guided oral prednisolone for COPD exacerbations in primary care in the UK (STARR2): a non-inferiority, multicentre, double-blind, placebo-controlled, randomised controlled trial. Lancet Respir Med 12(1):67–77, pmid:37924830.
OpenUrl PubMed
54.↵
1. Llor C,
2. Plate A,
3. Bjerrum L,
4. et al.
(2024) C-reactive protein point-of-care testing in primary care-broader implementation needed to combat antimicrobial resistance. Front Public Health 12, pmid:39100952. 1397096.
OpenUrl PubMed
55.↵
1. van der Velden AW,
2. van de Pol AC,
3. Bongard E,
4. et al.
(2022) Point-of-care testing, antibiotic prescribing, and prescribing confidence for respiratory tract infections in primary care: a prospective audit in 18 European countries. BJGP Open doi:10.3399/BJGPO.2021.0212, pmid:34920989.
OpenUrl CrossRef PubMed
56.↵
(2025) Inspection générale des affaires sociales, inspection générale des finances. pertinence et efficience des dépenses de biologie médicale (IGAS-IGF, Paris) Available from. https://igas.gouv.fr/sites/igas/files/2025-07/Rapport%20Igas%20Pertinence%20et%20efficience%20des%20d%C3%A9penses%20de%20biologie%20m%C3%A9dicale%20%281%29_0.pdf.
57.↵
1. Steigenberger C,
2. Windisch F,
3. Vogler S
(2023) Barriers and facilitators in pricing and funding policies of european countries that impact the use of point-of-care diagnostics for acute respiratory tract infections in outpatient practices. Diagnostics (Basel) 13(23), doi:10.3390/diagnostics13233596. 3596.
OpenUrl CrossRef PubMed
58.
1. Llor C,
2. Moragas A,
3. Hernández S,
4. et al.
(2012) Efficacy of antibiotic therapy for acute exacerbations of mild to moderate chronic obstructive pulmonary disease. Am J Respir Crit Care Med 186(8):716–723, pmid:22923662.
OpenUrl CrossRef PubMed

In this issue

Download PDF

Download PowerPoint

Email Article

Citation Tools

Keywords

More in this TOC Section

Show more Research

Cited By...

Intended for Healthcare Professionals

[1] 1.↵
Global Initiative for Chronic Obstructive Lung Disease
(2024) Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (2024 report), accessed. https://goldcopd.org/wp-content/uploads/2024/02/GOLD-2024_v1.2-11Jan24_WMV.pdf. 6 Jul 2026.

[2] Global Initiative for Chronic Obstructive Lung Disease

[3] 2.↵
Sharma M,
Joshi S,
Banjade P,
et al.
(2024) Global initiative for chronic obstructive lung disease (GOLD) 2023 guidelines reviewed. Open Respir Med J 18, pmid:38660684. e18743064279064.
OpenUrl PubMed

[4] Sharma M,

[5] Joshi S,

[6] Banjade P,

[7] et al.

[8] 3.↵
Cassini A,
Högberg LD,
Plachouras D,
et al.
(2019) Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European economic area in 2015: a population-level modelling analysis. Lancet Infect Dis 19(1):56–66, pmid:30409683.
OpenUrl CrossRef PubMed

[9] Cassini A,

[10] Högberg LD,

[11] Plachouras D,

[12] et al.

[13] 4.↵
van de Sande-Bruinsma N,
Grundmann H,
Verloo D,
et al.
(2008) Antimicrobial drug use and resistance in Europe. Emerg Infect Dis 14(11):1722–1730, pmid:18976555.
OpenUrl CrossRef PubMed

[14] van de Sande-Bruinsma N,

[15] Grundmann H,

[16] Verloo D,

[17] et al.

[18] 5.↵
Costelloe C,
Metcalfe C,
Lovering A,
et al.
(2010) Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis. BMJ 340, pmid:20483949. c2096.
OpenUrl Abstract/FREE Full Text

[19] Costelloe C,

[20] Metcalfe C,

[21] Lovering A,

[22] et al.

[23] 6.↵
Carlet J,
Collignon P,
Goldmann D,
et al.
(2011) Society’s failure to protect a precious resource: antibiotics. Lancet 378(9788):369–371, pmid:21477855.
OpenUrl CrossRef PubMed

[24] Carlet J,

[25] Collignon P,

[26] Goldmann D,

[27] et al.

[28] 7.↵
Smith R,
Coast J
(2013) The true cost of antimicrobial resistance. BMJ 346, pmid:23479660. f1493.
OpenUrl FREE Full Text

[29] Smith R,

[30] Coast J

[31] 8.↵
Celli BR,
Barnes PJ
(2007) Exacerbations of chronic obstructive pulmonary disease. Eur Respir J 29(6):1224–1238, pmid:17540785.
OpenUrl Abstract/FREE Full Text

[32] Celli BR,

[33] Barnes PJ

[34] 9.↵
Ritchie AI,
Wedzicha JA
(2020) Definition, causes, pathogenesis, and consequences of chronic obstructive pulmonary disease exacerbations. Clin Chest Med 41(3):421–438, pmid:32800196.
OpenUrl CrossRef PubMed

[35] Ritchie AI,

[36] Wedzicha JA

[37] 10.↵
Anthonisen NR,
Manfreda J,
Warren CP,
et al.
(1987) Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med 106(2):196–204, pmid:3492164.
OpenUrl CrossRef PubMed

[38] Anthonisen NR,

[39] Manfreda J,

[40] Warren CP,

[41] et al.

[42] 11.↵
Miravitlles M,
Moragas A,
Hernández S,
et al.
(2013) Is it possible to identify exacerbations of mild to moderate COPD that do not require antibiotic treatment? Chest 144(5):1571–1577, pmid:23807094.
OpenUrl CrossRef PubMed

[43] Miravitlles M,

[44] Moragas A,

[45] Hernández S,

[46] et al.

[47] 12.↵
Vollenweider DJ,
Frei A,
Steurer-Stey CA,
et al.
(2018) Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 10(10), pmid:30371937. CD010257.
OpenUrl PubMed

[48] Vollenweider DJ,

[49] Frei A,

[50] Steurer-Stey CA,

[51] et al.

[52] 13.↵
Cagney DN,
Sul J,
Huang RY,
et al.
(2018) The FDA NIH biomarkers, endpoints, and other tools (BEST) resource in neuro-oncology. Neuro Oncol 20(9):1162–1172.
OpenUrl CrossRef PubMed

[53] Cagney DN,

[54] Sul J,

[55] Huang RY,

[56] et al.

[57] 14.↵
Koutsokera A,
Stolz D,
Loukides S,
Kostikas K
(2012) Systemic biomarkers in exacerbations of COPD: the evolving clinical challenge. Chest 141(2):396–405, pmid:21835899.
OpenUrl CrossRef PubMed

[58] Koutsokera A,

[59] Stolz D,

[60] Loukides S,

[61] Kostikas K

[62] 15.↵
Koutsokera A,
Kiropoulos TS,
Nikoulis DJ,
et al.
(2009) Clinical, functional and biochemical changes during recovery from COPD exacerbations. Respir Med 103(6):919–926.
OpenUrl CrossRef PubMed

[63] Koutsokera A,

[64] Kiropoulos TS,

[65] Nikoulis DJ,

[66] et al.

[67] 16.↵
Smedemark SA,
Aabenhus R,
Llor C,
et al.
(2022) Biomarkers as point-of-care tests to guide prescription of antibiotics in people with acute respiratory infections in primary care. Cochrane Database Syst Rev 10(10), pmid:36250577. CD010130.
OpenUrl CrossRef PubMed

[68] Smedemark SA,

[69] Aabenhus R,

[70] Llor C,

[71] et al.

[72] 17.↵
Pohanka M
(2022) Diagnoses based on c-reactive protein point-of-care tests. Biosensors 12(5), pmid:35624645. 344.
OpenUrl PubMed

[73] Pohanka M

[74] 18.↵
Page MJ,
McKenzie JE,
Bossuyt PM,
et al.
(2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372, pmid:33782057. n71.
OpenUrl FREE Full Text

[75] Page MJ,

[76] McKenzie JE,

[77] Bossuyt PM,

[78] et al.

[79] 19.↵
Higgins JPT,
Thomas J,
Chandler J.,
et al.
, eds (2019) Cochrane handbook for systematic reviews of interventions (Wiley and Sons, Hoboken, NJ).

[80] Higgins JPT,

[81] Thomas J,

[82] Chandler J.,

[83] et al.

[84] 20.↵
Cornell University Library
What type of review is right for you? accessed. https://www.library.cornell.edu/wp-content/uploads/2024/05/SystematicReview_DecisionTreeAndMethodologies_new.pdf. 26 Jun 2026.

[85] Cornell University Library

[86] 21.↵
Ouzzani M,
Hammady H,
Fedorowicz Z,
Elmagarmid A
(2016) Rayyan-a web and mobile app for systematic reviews. Syst Rev 5(1), pmid:27919275. 210.
OpenUrl CrossRef PubMed

[87] Ouzzani M,

[88] Hammady H,

[89] Fedorowicz Z,

[90] Elmagarmid A

[91] 22.↵
Haddaway NR,
Grainger MJ,
Gray CT
(2022) Citationchaser: a tool for transparent and efficient forward and backward citation chasing in systematic searching. Res Synth Methods 13(4):533–545, pmid:35472127.
OpenUrl CrossRef PubMed

[92] Haddaway NR,

[93] Grainger MJ,

[94] Gray CT

[95] 23.↵
McGuinness LA,
Higgins JPT
(2021) Risk-of-bias visualization (robvis): an R package and shiny web app for visualizing risk-of-bias assessments. Res Synth Methods 12(1):55–61, pmid:32336025.
OpenUrl CrossRef PubMed

[96] McGuinness LA,

[97] Higgins JPT

[98] 24.↵
Schünemann HJ,
Brennan S,
Akl EA,
et al.
(2023) The development methods of official GRADE articles and requirements for claiming the use of GRADE – a statement by the GRADE guidance group. J Clin Epidemiol 159:79–84, pmid:37211327.
OpenUrl CrossRef PubMed

[99] Schünemann HJ,

[100] Brennan S,

[101] Akl EA,

[102] et al.

[103] 25.↵
Butler CC,
Gillespie D,
White P,
et al.
(2019) C-reactive protein testing to guide antibiotic prescribing for COPD exacerbations. N Engl J Med 381(2):111–120, pmid:31291514.
OpenUrl CrossRef PubMed

[104] Butler CC,

[105] Gillespie D,

[106] White P,

[107] et al.

[108] 26.↵
Barber D,
Pilsworth S,
Wat D
(2022) Does availability of point of care C-reactive protein measurement affect provision of antibiotics in a community respiratory service? Br J Community Nurs 27(5):218–224, pmid:35522449.
OpenUrl PubMed

[109] Barber D,

[110] Pilsworth S,

[111] Wat D

[112] 27.↵
Llor C,
Bjerrum L,
Munck A,
et al.
(2013) Predictors for antibiotic prescribing in patients with exacerbations of COPD in general practice. Ther Adv Respir Dis 7(3):131–137, pmid:23325784.
OpenUrl CrossRef PubMed

[113] Llor C,

[114] Bjerrum L,

[115] Munck A,

[116] et al.

[117] 28.↵
Llor C,
Cots JM,
López-Valcárcel BG,
et al.
(2012) Interventions to reduce antibiotic prescription for lower respiratory tract infections: Happy Audit study. Eur Respir J 40(2):436–441, pmid:22183489.
OpenUrl Abstract/FREE Full Text

[118] Llor C,

[119] Cots JM,

[120] López-Valcárcel BG,

[121] et al.

[122] 29.↵
Strykowski DF,
Nielsen ABS,
Llor C,
et al.
(2015) An intervention with access to C-reactive protein rapid test reduces antibiotic overprescribing in acute exacerbations of chronic bronchitis and COPD. Fam Pract 32(4):395–400, pmid:25902912.
OpenUrl CrossRef PubMed

[123] Strykowski DF,

[124] Nielsen ABS,

[125] Llor C,

[126] et al.

[127] 30.↵
Briel M,
Schuetz P,
Mueller B,
et al.
(2008) Procalcitonin-guided antibiotic use vs a standard approach for acute respiratory tract infections in primary care. Arch Intern Med 168(18):2000–2007, pmid:18852401.
OpenUrl CrossRef PubMed

[128] Briel M,

[129] Schuetz P,

[130] Mueller B,

[131] et al.

[132] 31.↵
Burkhardt O,
Ewig S,
Haagen U,
et al.
(2010) Procalcitonin guidance and reduction of antibiotic use in acute respiratory tract infection. Eur Respir J 36(3):601–607, pmid:20185423.
OpenUrl Abstract/FREE Full Text

[133] Burkhardt O,

[134] Ewig S,

[135] Haagen U,

[136] et al.

[137] 32.↵
Phillips R,
Stanton H,
Singh-Mehta A,
et al.
(2020) C-reactive protein-guided antibiotic prescribing for COPD exacerbations: a qualitative evaluation. Br J Gen Pract doi:10.3399/bjgp20X709865, pmid:32424045.
OpenUrl Abstract/FREE Full Text

[138] Phillips R,

[139] Stanton H,

[140] Singh-Mehta A,

[141] et al.

[142] 33.↵
Sewell B,
Francis N,
Harris S,
et al.
(2024) Cost-effectiveness of C-reactive protein point of care testing for safely reducing antibiotic consumption for acute exacerbations of chronic obstructive pulmonary disease as part of the multicentre, parallel-arm, open, individually randomised, controlled PACE trial. BMJ Open 14(11), pmid:39609022. e084144.
OpenUrl Abstract/FREE Full Text

[143] Sewell B,

[144] Francis N,

[145] Harris S,

[146] et al.

[147] 34.↵
Francis NA,
Gillespie D,
White P,
et al.
(2020) C-reactive protein point-of-care testing for safely reducing antibiotics for acute exacerbations of chronic obstructive pulmonary disease: the PACE RCT. Health Technol Assess 24(15):1–108, pmid:32202490.
OpenUrl CrossRef PubMed

[148] Francis NA,

[149] Gillespie D,

[150] White P,

[151] et al.

[152] 35.↵
Osei-Bimpong A,
Jury C,
McLean R,
Lewis SM
(2009) Point-of-care method for total white cell count: an evaluation of the hemocue WBC device. Int J Lab Hematol 31(6):657–664, pmid:18759736.
OpenUrl CrossRef PubMed

[153] Osei-Bimpong A,

[154] Jury C,

[155] McLean R,

[156] Lewis SM

[157] 36.↵
Ordóñez-Mena JM,
Fanshawe TR,
McCartney D,
et al.
(2019) C-reactive protein and neutrophil count laboratory test requests from primary care: what is the demand and would substitution by point-of-care technology be viable? J Clin Pathol 72(7):474–481, pmid:30992343.
OpenUrl Abstract/FREE Full Text

[158] Ordóñez-Mena JM,

[159] Fanshawe TR,

[160] McCartney D,

[161] et al.

[162] 37.↵
Dale DC,
Kelley ML,
Navarro-De La Vega M,
et al.
(2018) A novel device suitable for home monitoring of white blood cell and neutrophil counts. Blood 132(Suppl 1). 1103.

[163] Dale DC,

[164] Kelley ML,

[165] Navarro-De La Vega M,

[166] et al.

[167] 38.↵
Martínez-González NA,
Plate A,
Jäger L,
et al.
(2022) The role of point-of-care C-reactive protein testing in antibiotic prescribing for respiratory tract infections: a survey among Swiss general practitioners. Antibiotics 11(5), pmid:35625187. 543.
OpenUrl CrossRef PubMed

[168] Martínez-González NA,

[169] Plate A,

[170] Jäger L,

[171] et al.

[172] 39.
Roy K,
Marau A,
Esmond G,
et al.
(2019) S104 Home based respiratory point of care testing (R-POCTc) to improve the diagnosis and management of COPD exacerbations in the community. Thorax 74(Suppl 2). A66.

[173] Roy K,

[174] Marau A,

[175] Esmond G,

[176] et al.

[177] 40.
Llor C,
Moragas A,
Bayona C
(2018) 139 Overdiagnosis of the bacterial aetiology of the acute exacerbations of chronic obstructive pulmonary disease: discrepancies among current guidelines. BMJ Evid-Based Med 23(Suppl 2). A65.

[178] Llor C,

[179] Moragas A,

[180] Bayona C

[181] 41.
Hart J,
Edwards AD,
Stainthorpe A
(2023) Insights into implementation planning for point-of-care testing to guide treatment of chronic obstructive pulmonary disease exacerbation: a mixed methods feasibility study. Front Health Serv 3, pmid:38235389. 1302653.
OpenUrl PubMed

[182] Hart J,

[183] Edwards AD,

[184] Stainthorpe A

[185] 42.
Gillespie D,
Butler CC,
Bates J,
et al.
(2021) Associations with antibiotic prescribing for acute exacerbation of COPD in primary care: secondary analysis of a randomised controlled trial. Br J Gen Pract doi:10.3399/BJGP.2020.0823, pmid:33657007.
OpenUrl Abstract/FREE Full Text

[186] Gillespie D,

[187] Butler CC,

[188] Bates J,

[189] et al.

[190] 43.
Bazylkiewicz J,
Sutherland E
(2025) 203 – CRP/viral biomarker testing to improve patient care, outcomes, cost avoidances and antimicrobial stewardship in a community COPD population. Physiotherapy 126(Suppl 1). 101530.

[191] Bazylkiewicz J,

[192] Sutherland E

[193] 44.
Lapi F,
Marconi E,
Rossi A,
et al.
(2024) The use of C‐reactive protein testing and antibiotic prescribing in Italy: a population‐based study in primary care. Brit J Clinical Pharma 90(9):2314–2319.
OpenUrl

[194] Lapi F,

[195] Marconi E,

[196] Rossi A,

[197] et al.

[198] 45.↵
Llor C,
Trapero-Bertran M,
Sisó-Almirall A,
et al.
(2024) Effects of c-reactive protein rapid testing and communication skills training on antibiotic prescribing for acute cough. a cluster factorial randomised controlled trial. NPJ Prim Care Respir Med 34(1), pmid:38724543. 9.
OpenUrl PubMed

[199] Llor C,

[200] Trapero-Bertran M,

[201] Sisó-Almirall A,

[202] et al.

[203] 46.↵
Llor C,
Moragas A,
Bayona C,
et al.
(2013) Efficacy of anti-inflammatory or antibiotic treatment in patients with non-complicated acute bronchitis and discoloured sputum: randomised placebo controlled trial. BMJ 347, pmid:24097128. f5762.
OpenUrl Abstract/FREE Full Text

[204] Llor C,

[205] Moragas A,

[206] Bayona C,

[207] et al.

[208] 47.↵
White P,
Wong W,
Fleming T,
Gray B
(2007) Primary care spirometry: test quality and the feasibility and usefulness of specialist reporting. Br J Gen Pract 57(542):701–705, pmid:17761057.
OpenUrl Abstract/FREE Full Text

[209] White P,

[210] Wong W,

[211] Fleming T,

[212] Gray B

[213] 48.↵
Heyland DK,
Johnson AP,
Reynolds SC,
Muscedere J
(2011) Procalcitonin for reduced antibiotic exposure in the critical care setting: a systematic review and an economic evaluation. Crit Care Med 39(7):1792–1799.
OpenUrl CrossRef PubMed

[214] Heyland DK,

[215] Johnson AP,

[216] Reynolds SC,

[217] Muscedere J

[218] 49.↵
Park S,
Dieleman JL,
Kim R,
Subramanian SV
(2025) Association of health and social spending with health outcomes in OECD countries. Health Serv Res 60(6). e14660.

[219] Park S,

[220] Dieleman JL,

[221] Kim R,

[222] Subramanian SV

[223] 50.↵
Qian W,
Huang GZ
(2016) Neutrophil CD64 as a marker of bacterial infection in acute exacerbations of chronic obstructive pulmonary disease. Immunol Invest 45(6):490–503, pmid:27224474.
OpenUrl PubMed

[224] Qian W,

[225] Huang GZ

[226] 51.
van de Geijn G-J,
Denker S,
Meuleman-van Waning V,
et al.
(2016) Evaluation of new laboratory tests to discriminate bacterial from nonbacterial chronic obstructive pulmonary disease exacerbations. Int J Lab Hematol 38(6):616–628, pmid:27459873.
OpenUrl PubMed

[227] van de Geijn G-J,

[228] Denker S,

[229] Meuleman-van Waning V,

[230] et al.

[231] 52.↵
Ellingsen J,
Janson C,
Bröms K,
et al.
(2021) Neutrophil-to-lymphocyte ratio, blood eosinophils and COPD exacerbations: a cohort study. ERJ Open Res 7(4), pmid:34988219. 00471-2021.
OpenUrl Abstract/FREE Full Text

[232] Ellingsen J,

[233] Janson C,

[234] Bröms K,

[235] et al.

[236] 53.↵
Ramakrishnan S,
Jeffers H,
Langford-Wiley B,
et al.
(2024) Blood eosinophil-guided oral prednisolone for COPD exacerbations in primary care in the UK (STARR2): a non-inferiority, multicentre, double-blind, placebo-controlled, randomised controlled trial. Lancet Respir Med 12(1):67–77, pmid:37924830.
OpenUrl PubMed

[237] Ramakrishnan S,

[238] Jeffers H,

[239] Langford-Wiley B,

[240] et al.

[241] 54.↵
Llor C,
Plate A,
Bjerrum L,
et al.
(2024) C-reactive protein point-of-care testing in primary care-broader implementation needed to combat antimicrobial resistance. Front Public Health 12, pmid:39100952. 1397096.
OpenUrl PubMed

[242] Llor C,

[243] Plate A,

[244] Bjerrum L,

[245] et al.

[246] 55.↵
van der Velden AW,
van de Pol AC,
Bongard E,
et al.
(2022) Point-of-care testing, antibiotic prescribing, and prescribing confidence for respiratory tract infections in primary care: a prospective audit in 18 European countries. BJGP Open doi:10.3399/BJGPO.2021.0212, pmid:34920989.
OpenUrl CrossRef PubMed

[247] van der Velden AW,

[248] van de Pol AC,

[249] Bongard E,

[250] et al.

[251] 56.↵
(2025) Inspection générale des affaires sociales, inspection générale des finances. pertinence et efficience des dépenses de biologie médicale (IGAS-IGF, Paris) Available from. https://igas.gouv.fr/sites/igas/files/2025-07/Rapport%20Igas%20Pertinence%20et%20efficience%20des%20d%C3%A9penses%20de%20biologie%20m%C3%A9dicale%20%281%29_0.pdf.

[252] 57.↵
Steigenberger C,
Windisch F,
Vogler S
(2023) Barriers and facilitators in pricing and funding policies of european countries that impact the use of point-of-care diagnostics for acute respiratory tract infections in outpatient practices. Diagnostics (Basel) 13(23), doi:10.3390/diagnostics13233596. 3596.
OpenUrl CrossRef PubMed

[253] Steigenberger C,

[254] Windisch F,

[255] Vogler S

[256] 58.
Llor C,
Moragas A,
Hernández S,
et al.
(2012) Efficacy of antibiotic therapy for acute exacerbations of mild to moderate chronic obstructive pulmonary disease. Am J Respir Crit Care Med 186(8):716–723, pmid:22923662.
OpenUrl CrossRef PubMed

[257] Llor C,

[258] Moragas A,

[259] Hernández S,

[260] et al.

Main menu

User menu

Search

Point-of-care biomarkers or laboratory-based tests to reduce antibiotic prescribing for COPD exacerbations: a literature review and meta-analysis in primary care

Abstract

How it fits in

Introduction

Method

Eligibility criteria

Information sources

Search strategy

Selection and data collection process

Data items

Study risk of bias assessment

Effect measures and synthesis method (meta-analysis)

Reporting bias assessment

Certainty of evidence

Results

Study selection

Not peer-reviewed literature

Characteristics of the included studies

Risk of bias within studies

Results of individual studies and level of evidence

Quantitative study meta-analysis

Sensitivity analysis

Reporting biases

Certainty of evidence (GRADE)

Discussion

Summary

Strengths and limitations

Comparison with existing literature

Implications for research and practice

Notes

Funding

Ethical approval

Provenance

Data

Acknowledgements

Competing interests

References

In this issue

Citation Manager Formats

Jump to section

Keywords

More in this TOC Section

Related Articles

Cited By...

NAVIGATE

RCGP

MY ACCOUNT

NEWS AND UPDATES

AUTHORS & REVIEWERS

CUSTOMER SERVICES

CONTRIBUTE

CONTACT US