---
title: "Respiratory syncytial virus in COPD exacerbations: RECODE study protocol (full text blocked)"
id: "bmj-open-11-respiratory-syncytial-virus-infection-in-copd-exacerbations-the-recode-study"
canonical_url: "https://medichelpline.com/clinical-feed/bmj-open-11-respiratory-syncytial-virus-infection-in-copd-exacerbations-the-recode-study"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "BMJ Open"
source_url: "http://bmjopen.bmj.com/cgi/content/short/16/7/e119939?rss=1"
published_at: "2026-07-20T14:00:46.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Respiratory syncytial virus in COPD exacerbations: RECODE study protocol (full text blocked)
## Provenance & Clinical Metadata
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- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** BMJ Open
- **Source URL:** [Original Journal Publication](http://bmjopen.bmj.com/cgi/content/short/16/7/e119939?rss=1)
- **Published At:** 2026-07-20T14:00:46.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
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## Clinical Analysis & Structured Key Points
Skip to main content Intended for healthcare professionals Log In Basket Search for this keyword Advanced search Latest content Archive For authors About Browse by collection You are here Home Archive Volume 16, Issue 7 Email alerts Article Text Article info Citation Tools Share Rapid Responses Article metrics Alerts PDF Respiratory medicine Protocol Respiratory syncytial virus infection in COPD exacerbations: the RECODE study protocol http://orcid.org/0000-0003-3271-3788Alvar Agusti1,2,3,4, http://orcid.org/0000-0002-3592-3839Rosario Menéndez5, Elisa Salamanca6, Elisa Turriani7, http://orcid.org/0000-0002-9023-581XFederico Martinon-Torres4,8,9 Correspondence to Dr Alvar Agusti; AAGUSTI@clinic.cat Abstract Introduction Patients with chronic obstructive pulmonary disease (COPD) often suffer episodes of exacerbation (ECOPD). Respiratory syncytial virus (RSV) is an increasingly recognised cause of illness in adults. Yet the prevalence of RSV during ECOPD and its association with clinically relevant outcomes remain insufficiently defined. The RECODE study sought to determine the prevalence of RSV infection in patients with ECOPD and to assess the association between RSV and hospitalisation, length of stay, acute cardiovascular events and/or death. Methods and analysis Prospective, multicentre, observational, controlled (RSV-positive cases vs RSV-negative controls), longitudinal study (NCT06735612). Adults ≥50 years with ECOPD will be enrolled at urgent-care presentation (V1), contacted by telephone at day 15 (V2) and seen in the clinic at 3 months (V3). RSV status will be determined by Reverse Transcription (RT-PCR) on nasopharyngeal swabs; additional measures include paired serology, routine clinical data, spirometry at V3 and predefined outcomes. Ethics and dissemination The leading Ethics Committee was that of Clinic Barcelona (HCB/2024/0771). All participating centres accepted this approval or requested local approval from their respective Institutional Review Boards (Appendix). Results will be disseminated in international publications and meeting presentations as well as in a plain language summary to be distributed among participating patients. Trial registration number NCT06735612. Data availability statement Data are available upon reasonable request. https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: https://creativecommons.org/licenses/by-nc/4.0/. https://doi.org/10.1136/bmjopen-2026-119939 Request Permissions If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways. Request permissions STRENGTHS AND LIMITATIONS OF THE STUDY Prospective, multicentre design, standardised sampling and follow-up across three predefined time points with molecular confirmation of respiratory syncytial virus (RSV) infection. Provision of up-to-date information on the role of RSV infection in chronic obstructive pulmonary disease (COPD) patients with exacerbation (ECOPD), when there is now an RSV vaccine approved for adults. If the true prevalence of RSV infection in ECOPD differs from the assumed value (based on previous studies), the precision of the estimate will vary accordingly. Follow-up to 3 months captures short-term recovery but may miss longer-term sequelae. The exploratory multi-omics analyses are hypothesis-generating, subject to multiple-testing concerns, and will require appropriate corrections and external validation. Background Respiratory syncytial virus (RSV) is a well-known cause of acute bronchiolitis in children.1 RSV is also an increasingly recognised cause of illness in adults,2 particularly in patients with chronic cardio-respiratory diseases such as chronic obstructive pulmonary disease (COPD).3 In a study performed during four consecutive RSV seasons almost 20 years ago in 540 adults aged 65 years or more with a variety of chronic heart or lung diseases, RSV infection developed annually in 4–10% of them, of whom 15% required intensive care and 8% died.4 Based on the International Classification of Diseases version 9 codes at hospital discharge, in that study, RSV infection accounted for 11.4% of hospitalisations for COPD, 10.6% for pneumonia, 7.2% for asthma and 5.4% for congestive heart failure.4 Data on the current epidemiological situation need update. Patients with COPD often suffer acute episodes of increased respiratory symptoms called exacerbations (ECOPD).5 These episodes are highly relevant clinically because they significantly impact the health-related quality of life of the patient, are often associated with acute cardiovascular (CV) events, increase the rate of decline of lung function and worsen their prognosis.5 ECOPD episodes are most often caused by viral and/or bacterial infection, although some COPD patients may suffer so-called eosinophilic or pauci-inflammatory exacerbations.6 The prevalence and clinical impact of RSV infection during ECOPD are not well known but, since the prevention of ECOPD is a key strategic objective of COPD treatment,7 the recent availability of highly effective and well-tolerated vaccines against RSV in adults in the general population8 9 calls for a careful examination of the prevalence and outcomes of RSV infection in patients with ECOPD as an important population that may benefit most from these new RSV vaccines. In fact, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends vaccination against RSV in adults with COPD.7 Here, we discuss the working hypothesis, goals and design of an ongoing multicentric observational study entitled ‘Respiratory Syncytial Virus Infection in Exacerbations of Chronic Obstructive Pulmonary Disease: the RECODE Study’ (ClinicalTrials.gov NCT06735612) that aims to determine the prevalence of RSV in patients with COPD suffering an exacerbation recruited at the emergency room (ER) or day hospital facilities and to assess the association of RSV in ECOPD patients with relevant clinical outcomes such as hospitalisation, length of hospital stay, acute cardiovascular (CV) events and/or death. Methods Working hypothesis Based on previous reports,2–4 we hypothesise that the prevalence of RSV infection in patients with ECOPD (as defined by the Rome consensus definition5) oscillates between 6 and 10%. We also hypothesise that the clinical outcomes associated with RSV infection in COPD patients will be worse than those in ECOPD patients testing negative for RSV, both at short term (first 15 days after the acute event, as determined by telephone call and electronic medical record review, including hospitalisation, length of stay, acute CV events (ischaemia, arrhythmias) and/or death3) and long term (3 months later). Objectives of the study Primary objective The primary objective of the RECODE study is to determine the prevalence of RSV infection among COPD patients seeking acute medical attention in the emergency room (ER) or day hospital facilities because of ECOPD during the RSV season (October–April). Secondary objectives The secondary objectives of the RECODE study are to (1) compare the RSV immune status of RSV+ versus RSV− patients (based on reverse transcriptase (RT)-PCR of naso-pharyngeal swab samples) by serology, both at recruitment and 3 months’ follow-up; (2) compare the clinical characteristics of RSV+ versus RSV− patients (based on RT-PCR of naso-pharyngeal swab samples) with respect to the severity of airflow limitation (as determined by forced spirometry when clinically stable, 3 months after the acute event), level of circulating eosinophils (determined both at the acute event and at clinical stability 3 months later) and presence/absence of comorbid diseases (CV, metabolic, bronchiectasis (by previous CT scan, others), pulmonary infiltrates (pneumonia)); and (3) compare the associated outcomes, both during the acute event (hospitalisation, non-invasive mechanical ventilation, admission to critical care, invasive mechanical ventilation, CV events, death) and 3 months after it (health status, healthcare utilisation, COPD assessment test (CAT)) between RSV+ and RSV− patients. Exploratory objectives The following are exploratory objectives of the RECODE study: (1) to determine the prevalence of RSV infection among COPD patients seeking acute medical attention in the Emergency Room or Day Hospital facilities because of ECOPD5 outside the RSV season (May to September); (2) to describe the microbiologic ecology by conventional microbiologic cultures as well as other potential causes of ECOPD (eosinophilic and pauci-inflammatory) in a large cohort of patients, since our current understanding is based on previous studies that included a rather small number of ECOPD (182 exacerbations captured from 86 patients);6 (3) to assess inflammatory and cardiac biomarkers in RSV+ versus RSV− patients and its relationship with acute complications and during the follow-up; (4) to explore transcriptomic (based on RNA analysis by RNAseq) in a subset (selection of subset of RSV+ vs RSV− patients for the exploratory analysis will be matched according to age, gender, and timing and place of study inclusion (same week or month, and site)) of RSV+ versus RSV− subjects and eventually find predictive biomarkers in RSV+ versus RSV− patients; (5) to explore cytokine profile in nasal epithelium of RSV+ subjects as compared with RSV− to better understand the host immune response in a subset of patients; and (6) to explore methylation pattern (epigenetic changes) in RSV+ versus RSV− patients and its influence in disease course in a subset of patients. Study design The RECODE study is a prospective, ongoing, multicentre, observational, controlled (RSV+ considered as cases and RSV− considered as controls) assessing the prevalence of RSV infection in ECOPD at the emergency room or day hospital facilities. Recruitment will last for 2 years (two RSV seasons and one summer season in between). Patients will be seen during the acute event (V1), 15 days after their visit to the ER (V2, by telephone call) and 3 months later (V3, face to face in a pulmonary clinic). Table 1 presents the variables collected at each visit following standardised procedures and international recommendations. VIEW INLINE VIEW POPUP Table 1 Chronogram and study variables. For further explanations, see text Ethics, legal, safety and dissemination aspects The study is being conducted in full accordance with the Ethical Principles for Medical Research Involving Human Subjects as described in the Declaration of Helsinki (2013) and the most recent amendment by the World Medical Assembly (http⁄www.wma.net⁄en⁄30publications⁄10policies⁄b3⁄17c.pdf), the Guidelines for Good Epidemiology Practices, Good Clinical Practice, Law 14/2007 of 3 July, on biomedical investigation and local regulatory requirements. The leading Ethics Committee was that of Clinic Barcelona (HCB/2024/0771). All participating centres accepted this approval or requested local approval to their respective Institutional Review Boards (online supplemental appendix). Results will be disseminated in international publications and meeting presentations. Informed consent will be obtained prior to any study-related activities. Patients did not participate in the design of this observational, non-interventional study, but a plain language summary of results will be distributed among participating patients. There are minimal safety risks associated with the study procedures, which are often used in routine clinical practice (nasal swabs, blood sampling by venipuncture). The general public was not involved in the design of the study. Supplemental material [bmjopen-2026-119939supp001.pdf] Patient selection Patients (both males and females, older than 50 years of age) seeking urgent medical attention in the ER or hospital day care facilities of participating institutions because of ECOPD according to the Rome definition (ie, a COPD patient that complains of dyspnoea and/or cough and sputum that worsen over <14 days, which may be accompanied by tachypnoea and/or tachycardia and is often associated with increased local and systemic inflammation caused by airway infection, pollution, or other insult to the airways5) will be recruited at their admission at the emergency ward of participant sites. Patients with previous RSV vaccination (other vaccines will be allowed and recorded), active cancer (or any other disease) that may alter the immune status of the patient and neurologic disorders that incapacitate the participation of the patient and/or not signing of the informed consent will be excluded. Likewise, other immunocompromised populations are also excluded, including those with a previous history of hematopoietic stem cell transplant and solid organ transplants, patients receiving immunosuppressive therapies or those with primary/secondary immunodeficiencies. Study variables Table 1 summarises the chronogram and study variables, which are presented in more detail in the online supplemental. Supplemental material [bmjopen-2026-119939supp002.pdf] Statistical analysis plan Sample size estimation Because the primary objective of the study is to estimate a population prevalence (not to compare groups), the sample size calculation is driven by the statistical variability of the expected proportion. Based on previous reports,2–4 we hypothesised that the prevalence of RSV infection in patients with ECOPD will oscillate around 8±2%. If this assumption is finally the case, the inclusion of 786 subjects will suffice to estimate with 95% confidence and a precision of ±2%, anticipating a replacement rate of 10%. However, if the true prevalence of RSV infection in ECOPD differs from this assumed value, the precision of the estimate will vary accordingly. For example, a lower prevalence, such as 2–3%, would result in narrower confidence intervals (approximately ±1%), and a lower sample size would be required without compromising the statistical significance of the primary objective. Conversely, higher prevalence values (eg, close to 10%) would lead to slightly wider intervals but will still remain within an acceptable range for descriptive epidemiological purposes. Besides, to get a more complete picture of the role of RSV infection in the episodes of ECOPD around all seasons, an exploratory objective of the study was also to determine the prevalence of RSV infection during ECOPD episodes outside the RSV season (May–September). Assuming that this prevalence will be much lower (1±2%), we estimate that the inclusion of an additional 106 subjects will suffice to estimate with a 95% confidence and a precision of ±2%, also with an anticipated replacement rate of 10%. Accordingly, we plan to recruit 786 patients during the RSV season and 106 patients outside the season (total number of patients to be recruited=892). Data analysis All statistical analyses will be conducted using R and SPSS. Estimates will be provided with 95% CIs and the threshold for statistical significance will be held at α=0.05. Analysis supporting the primary objective Standard descriptive statistics including n, range, absolute frequencies and corresponding proportions, mean±SD or median (IQR) will be used to present the characteristics of RSV+ and RSV− patients. Calculation of the prevalence of RSV+ in the total study population during one RSV season will be computed as the ratio of RSV+ patients divided by all patients included in the study (RSV+ plus RSV−), assuming the asymptotic normal distribution for proportions to obtain 95% CI. Exact Poisson distribution will also be considered. Estimations will be also computed by age and sex. Analysis supporting secondary objectives Risk ratios (RR) will be estimated with 95% CI to assess the association of RSV with ECOPD clinical outcomes and their significance assessed with the corresponding p value. Univariate logistic regression models will also be used for this purpose. To compare the circulating levels of RSV antibodies (serology) between RSV+ versus RSV− patients, both at recruitment and 3 months’ follow-up, paired and unpaired T test or Mann-Whitney test will be used as appropriate. To compare the quantitative clinical characteristics of RSV+ versus RSV− (severity of airflow limitation and level of circulating eosinophils, among others) at recruitment and/or 3 months’ follow-up paired and unpaired T test will be used as appropriate, whereas discrete variables (prevalence of comorbid diseases among others) will be compared using a χ2 or Fisher test as appropriate. Multivariate logistic regression analysis will be used to investigate the associated outcomes, both during the acute event (hospitalisation, non-invasive mechanical ventilation, admission to critical care, invasive mechanical ventilation, CV events, death) and 3 months after it (health status, healthcare utilisation) between RSV+ and RSV− patients. A multivariate logistic regression model will be selected using a backwards stepwise algorithm selecting those variables at a significance level p<0.1, Akaike’s information criteria will also be considered. Analysis of exploratory objective(s) We will use the same approach described above for the analysis within the RSV season (primary goal; see above) to data obtained outside it (May–September). We will also use similar descriptive and comparative statistics to describe the microbiologic ecology in RSV+ and RSV− patients, as described for the secondary objective. Details of the biological methods used here are presented in the online supplemental. In addition to RSV testing, centralised molecular testing for influenza viruses and SARS-CoV-2 will also be performed to improve virological characterisation and identify potential coinfections or alternative viral aetiologies. Where appropriate and statistically feasible, these pathogens may also be included in exploratory comparative analyses to better contextualise the relative clinical impact of major respiratory viral infections in ECOPD. Current status of the study and expected results The RECODE study is currently recruiting patients in 20 participating centres in Spain (see online supplemental appendix). Results are expected by the end of 2026. Discussion RECODE is positioned in a uniquely timely context marked by the recent licensure and guideline endorsement of adult RSV vaccines.10 11 Unlike most prior work based on administrative codes or small single-centre cohorts, this study prospectively ascertains RSV with RT-PCR in a large COPD population during and outside the RSV season, and integrates clinical, functional, immunologic and exploratory multi-omics readouts. By aligning rigorous case definitions with real-world emergency/short-stay pathways and capturing CV events alongside respiratory outcomes, RECODE provides contemporary, practice-relevant evidence on the contribution of RSV to ECOPD in the post-vaccine era. The study goes beyond a single-endpoint epidemiologic survey by addressing the following: (1) RSV prevalence in ECOPD across seasons; (2) comparative clinical profiles and short-term outcomes for RSV-positive versus RSV-negative exacerbations; (3) immune status dynamics via paired serology; (4) COPD severity and inflammatory phenotyping (spirometry, blood eosinophils, comorbidities); and (5) the broader aetiologic ecology (bacterial cultures and non-RSV viral targets). In a subset, REC
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