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Background: Respiratory syncytial virus (RSV) infection is a common cause of hospital admission. The association between chronic obstructive pulmonary disease (COPD) exacerbation and RSV infection is not well studied., Objective: To analyze the hospitalizations of patients with COPD and RSV infection in Spain between 2018 and 2022., Methods: The data used were obtained from the Spanish Hospital Discharge Database. We selected subjects aged ≥40 years diagnosed with COPD, admitted to the hospital from 1 January 2018 to 31 December 2022. The COPD population that met the selection criteria was subdivided based on the presence of an ICD-10 code for RSV infection. To obtain comparable populations, for each subject with COPD and RSV infection, a subject without an RSV code was selected, with the COPD code in the same diagnostic position (1 to 20), as well as the same year of admission, sex, and age., Results: Among subjects aged ≥40 years, 1,429,288 were identified as having COPD, of whom 5673 also had RSV infection. The number of hospitalizations with COPD and RSV infection increased during the study period. The proportion of RSV infection among patients admitted for COPD increased significantly over time, from 0.32% in 2018 to 0.65% in 2022, p < 0.001. In-hospital mortality (IHM) increased over time, but the differences were not significant (6.23% in 2018 vs. 6.79% in 2022). Patients with COPD and RSV infection had, compared with those without RSV infection, a higher use of mechanical ventilation, both invasive (3.44% vs. 1.34%, p < 0.001) and noninvasive (8.09% vs. 4.51%, p < 0.001) and a higher proportion of intensive care unit (ICU) admission (7.21% vs. 3.9%, p < 0.001). After multivariate adjustment, a significant increase in IHM was found from 2018 to 2022 in subjects with and without RSV infection. The presence of RSV infection was associated with a higher mortality (OR 1.22; 95% CI 1.01-1.46)., Conclusions: The proportion of RSV infection among patients admitted for COPD increased significantly over time. Patients with COPD and RSV infection had, compared with those without RSV infection, a higher severity, a higher use of mechanical ventilation, and a higher proportion of ICU admission. The presence of RSV infection was associated with IHM. These results can help to identify patients at higher risk and make decisions to avoid the increased risk of hospitalization and mortality in this population.

This study aims to develop a protocol for respiratory disease-associated biomarker discovery by combining urine proteome studies with urinary exosome components analysis (i.e., miRNAs). To achieve this, urine was DTT treated to decrease uromodulin, then concentrated and ultracentrifuged. Proteomic analyses of exosome-free urine were performed using LC-MS/MS. Simultaneously, miRNA expression from urine exosomes was measured using either RTqPCR (pre-amplification) or nCounter Nanostring (non-amplication) analyses. We detected 548 different proteins in exosome-free urine samples (N = 5) with high confidence (FDR < 1%), many of them being expressed in different non-renal tissues. Specifically, lung-related proteins were overrepresented (Fold enrichment = 1.31; FDR = 0.0335) compared to whole human proteome, and 10-15% were already described as protein biomarkers for several pulmonary diseases. Urine proteins identified belong to several functional categories important in respiratory pathology. We could confirm the expression of miRNAs previously connected to respiratory diseases (i.e., miR-16-5p, miR-21-5p, miR-146a-5p, and miR-215-5p) in urine exosomes by RTqPCR. Finally, we detected 333 miRNAs using Nanostring, 15 of them up-regulated in T2 high asthma (N = 4) compared to T2 low asthma (N = 4) and healthy subjects (N = 4). Therefore, this protocol combining the urinary proteome (exosome free) with the study of urinary exosome components (i.e., miRNAs) holds great potential for molecular biomarker discovery of non-renal and particularly respiratory pathologies., Competing Interests: The authors declare that they have no competing interests.

Competing Interests: Declaration of competing interest The authors declare no conflict of interest.