Prevalence and clinical implications of respiratory viruses in stable chronic obstructive pulmonary disease (COPD) and exacerbations: a systematic review and meta-analysis protocol

Abstract

IntroductionBoth stable chronic obstructive pulmonary disease (COPD) and acute exacerbations represent leading causes of death, disability and healthcare expenditure. They are complex, heterogeneous and their mechanisms are poorly understood. The role of respiratory viruses has been studied extensively but is still not adequately addressed clinically. Through a rigorous evidence update, we aim to define the prevalence and clinical burden of the different respiratory viruses in stable COPD and exacerbations, and to investigate whether viral load of usual respiratory viruses could be used for diagnosis of exacerbations triggered by viruses, which are currently not diagnosed or treated aetiologically.Methods and analysisBased on a prospectively registered protocol, we will systematically review the literature using standard methods recommended by the Cochrane Collaboration and the Grading of Recommendations Assessment, Development and Evaluation working group. We will search Medline/PubMed, Excerpta Medica dataBASE (EMBASE), the Cochrane Library, the WHO’s Clinical Trials Registry and the proceedings of relevant international conferences on 2 March 2020. We will evaluate: (A) the prevalence of respiratory viruses in stable COPD and exacerbations, (B) differences in the viral loads of respiratory viruses in stable COPD vs exacerbations, to explore whether the viral load of prevalent respiratory viruses could be used as a diagnostic biomarker for exacerbations triggered by viruses and (C) the association between the presence of respiratory viruses and clinical outcomes in stable COPD and in exacerbations.Ethics and disseminationEthics approval is not required since no primary data will be collected. Our findings will be presented in national and international scientific conferences and will be published in peer reviewed journals. Respiratory viruses currently represent a lost opportunity to improve the outcomes of both stable COPD and exacerbations. Our work aspires to ‘demystify’ the prevalence and clinical burden of viruses in stable COPD and exacerbations and to promote clinical and translational research.PROSPERO registration numberCRD42019147658.

COVID‐19 Susceptibility in chronic obstructive pulmonary disease

“…Exacerbations arise from several risk factors and triggers, being viral infections one of the most important causes 49 . Hence, viruses are responsible for a half to two‐thirds of COPD exacerbations, 50 while these pathogens are also identified in over 10% of all stable COPD patients, being associated with worse clinical outcomes 51 . Picornaviruses, influenza A, RSV and parainfluenza are among the most detected viruses in COPD exacerbations 52 .…”

Assessing Treatment Success or Failure as an Outcome in Randomised Clinical Trials of COPD Exacerbations. A Meta-Epidemiological Study

“…As previously mentioned, the course and outcomes, but also treatment responses of different COPD exacerbation subtypes, such as those caused by bacterial or viral infections, or those characterised by enhanced eosinophilic inflammation, vary significantly [ 2 , 72 , 80 , 81 ]. Clinical trialists should consider conducting more personalised trials, focusing on specific exacerbation subtypes, as the study populations, treatment effects, and outcomes would be more homogeneous and more easily interpretable.…”

Unmet needs in the management of exacerbations of chronic obstructive pulmonary disease

“…With respect to the respiratory virome, viral infections may increase the risk of exacerbations although their role in exacerbation frequency is less significant [ 40 ]. Nevertheless, the presence of viruses worsens clinical outcomes during both the stable disease and exacerbations [ 81 ]. Possible explanations include the upregulation of bacterial adhesion molecules, damage to epithelial cells, and decreased mucociliary clearance, all of which are triggered by viral infections [ 68 ] and favor the persistence of pathogens.…”

“…Possible explanations include the upregulation of bacterial adhesion molecules, damage to epithelial cells, and decreased mucociliary clearance, all of which are triggered by viral infections [ 68 ] and favor the persistence of pathogens. Commonly identified viruses at acute exacerbations are HRV, respiratory syncytial virus, influenza virus, and coronavirus [ 40 , 53 , 81 ]. Currently, it is still unknown whether viral infections promote the persistence of new infections or rather the outgrowth of pre-existing bacterial strains.…”

“…Currently, it is still unknown whether viral infections promote the persistence of new infections or rather the outgrowth of pre-existing bacterial strains. While awaiting the results of a systemic review focused on the role of respiratory viruses in the stable disease state and during exacerbations in patients with COPD [ 81 ], no specific functional role of the virome has so far been identified other than inducing exacerbations [ 68 ].…”