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RSV in Chronic Respiratory Patients

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Summary

icon-showing-a-cartoon-of-an-inhaler.

Older adults with chronic obstructive pulmonary disease (COPD) and asthma are at increased risk of severe respiratory syncytial virus (RSV) disease.1

icon-showing-a-cartoon-of-a-hospital-building.

COPD and asthma exacerbations are common in older adults hospitalized with RSV.2

icon-showing-a-cartoon-of-lungs.

Persistent RSV infection is associated with decline in lung function and higher airway inflammation in patients with COPD.3

Risk of Severe RSV Disease in Older Adults With COPD and Asthma

In a large prospective study in two regions of New York State, USA (2017–2020; N=1099), hospitalization rates for RSV were higher in older adults (aged 50–64 and ≥65 years) with certain underlying comorbidities*, including COPD and asthma.1

Comorbidity and age Incidence rate ratio
  Rochester New York City
COPD    
50–64 YOA 6.35 6.30
≥65 YOA 13.41 3.51
Asthma    
50–64 YOA 2.34 3.60
≥65 YOA 2.52 2.27

Table independently created for GSK from the original data from Branche AR et al. Clin Infect Dis 2022;74(6):1004–1011

*Comorbidities of interest were COPD, asthma, diabetes, coronary artery disease, congestive heart failure; ratio rate among people with each comorbidity versus those without it; the incidence rate ratio was not statistically significant

Longitudinal assessment over 12 seasons (2004–2016) in Wisconsin, USA, showed that RSV was a common cause of outpatient respiratory illness in adults ≥60 years of age (YOA).4

Patients with certain underlying comorbidities had a higher incidence of medically attended RSV and proportion of moderate to severe lower respiratory tract disease (msLRTD).4

figure-showing-the-average-seasonal-incidence-of-all-medically-attended-r-s-v-among-patients-with-and-without-chronic-cardiopulmonary-disease.-average-seasonal-incidence-of-r-s-v-in-patients-with-and-without-chronic-cardiopulmonary-disease-was-196-cases-per-10,000-and-103-cases-per-10,000,-respectively.-the-incidence-rate-ratio-was-1.89-and-the-95-percent-confidence-interval-was-1.44-to-2.48.

Figure independently created for GSK from the original data from Belongia EA et al. Open Forum Infect Dis 2018;5(12):ofy316

The risk of a serious outcome was approximately double for patients with COPD compared with patients without this condition (relative risk of serious versus nonserious outcome: 2.18 [95% CI: 1.27–3.76]).4

bar-chart-depicting-the-proportion of patients-aged-60-years-and-above-with-medically-attended-r-s-v-and-select-comorbidities-stratified-by-clinical-presentation-and-outcomes.-comorbidities-included-were-c-o-p-d,-congestive-heart-failure,-asthma,-immunocompromised,-and-diabetes.

Graph independently created for GSK from the original data from Belongia EA et al. Open Forum Infect Dis 2018;5(12):ofy316

*Serious outcomes included acute care hospital admission, emergency department visit, and pneumonia occurring within 28 days after enrollment. Moderate outcomes included new antibiotic or antiviral therapy, new/increased bronchodilator therapy, and new/increased systemic corticosteroid therapy during the 28-day window after enrollment. Mild outcomes were those that did not meet criteria for moderate or severe RSV illness outcome; RSV-msLRTD is defined by at least 3 of the following symptoms/signs during the initial clinical encounter: cough, wheezing (or worsening in baseline wheezing), new sputum production (or increase in baseline sputum), new (or worsening) shortness of breath, and observed tachypnea (≥20 breaths/minute)

Exacerbation of COPD and Asthma

Respiratory viral infections are a major factor in COPD and asthma exacerbations, and are linked with poor clinical outcomes.5,6

figure-showing-that-respiratory-viruses-are-detected-in-22-to-64-percent-of-c-o-p-d-exacerbations-and-60-to-80-percent-of-asthma-exacerbations.-the-most-commonly-detected-respiratory-viruses-are-influenza,-human-rhinovirus,-r-s-v-and-coronavirus.

Figure independently created for GSK from the original data from Hewitt R et al. Ther Adv Respir Dis 2016;10(2):158–174

*Presence of viruses in asthma exacerbations in adults

COPD or asthma exacerbations due to viral infections are associated with a more severe clinical course than nonviral-associated exacerbations.5–14

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Longer hospitalization6–8

11.6 ± 0.6 days for infective* exacerbations versus 8.8 ± 0.8, P<0.02 for noninfective exacerbations8

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Accelerated lung function decline6,8

Greater decreases in FEV1 (0.25 ± 0.03 L vs 0.12 ± 0.04 L, P<0.05) in infective* versus noninfective exacerbations8

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Greater hypoxemia7,8

A trend for a greater decrease in PaO2 (15.3 ± 1.35 vs 11.92 ± 1.86 mm Hg, P=0.078) in infective* versus noninfective exacerbations8

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Greater airway inflammation8–10

Higher airway eosinophils and serum IL-6 levels in virus-associated exacerbations than nonviral exacerbations, P=0.0648,9

*Viral and/or bacterial infection

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Hospital admissions11

RSV infection accounted for 7.2% of asthma hospitalizations in adults ≥65 YOA11

icon-showing-a-cartoon-of-lungs-with-viral-particles-above-the-upper-lobes.

Enhanced responsiveness to allergens12,13

8/10 vs 1/10 patients had FEV1 decline after exposure to a combination of allergen and rhinovirus versus allergen alone12

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Altered antiviral immune response in patients with asthma is associated with asthma worsening5,11,12,14

Positive association between rhinovirus load and CD45+, CD68+, CD20+, neutrophils and eosinophils at 4 days post-infection14

In a systematic review of pooled data on prevalence of respiratory viruses in patients with acute exacerbation of COPD from 19 studies (N=1728), RSV was detected in 10% of acute exacerbations of COPD and, similar to other respiratory viruses, more frequently in lower versus upper respiratory tract.15

bar-chart-showing-the-pooled-prevalence-of-respiratory-viruses-detected-in-patients-with-acute-exacerbation-of-c-o-p-d-in-a-systemic-review.-rhino-entereoviruses-were-detected-most-frequently-in-16.39%-of-acute-c-o-p-d-exacerbations,-followed-by-r-s-v-detected-in-9.90%-of-acute-exacerbations-and-influenza-detected-in-7.83%-of-exacerbations.

Graph independently created for GSK from the original data from Zwaans W et al. J Clin Virol 2014;61:181−188

Virus Pooled prevalence (95% CI)
  Upper respiratory airways Lower respiratory airways
Influenza 5.43 (4.25, 6.91) 9.88 (7.71, 12.58)
Rhino-/enterovirus 13.50 (11.67, 15.57) 16.50 (13.74, 19.69)
RSV 9.02 (7.49, 10.83) 11.93 (9.54, 14.81)

Table independently created for GSK from the original data from Zwaans W et al. J Clin Virol 2014;61:181−188

Among older adults hospitalized with RSV, underlying comorbidities are common, and a high proportion of patients with COPD and asthma experience exacerbation during RSV-associated hospitalization.2

figure-showing-a-bar-chart-in-the-top-panel-and-two-figures-in-the-bottom-panel.-the-bar-chart-in-the-top-panel-depicts-the-most-common-comorbidities-among-664-patients-aged-60-years-or-above-who-were-hospitalized-with-r-s-v-in-Kaiser-Permanente-Southern-California-USA-between-2011-and-2015,-reported-from-a-cohort-study- by-Tseng-et-al.-the-most-common-comorbidities-were-congestive-heart-failure-and-diabetes,-both-were-reported-in-38.6-percent-of-patients.-c-o-p-d-was-reported-in-35.4-percent-of-patients,-and-asthma-was-reported-in-28.6-percent-of-patients.-the-two-figures-in-the-bottom-panel-show-the-proportion-of-patients-who-experienced-exacerbation-events-in-the-Tseng-et-al-cohort-study.-of-the-patients-with-c-o-p-d,-80-percent-experienced-c-o-p-d-exacerbation-during-r-s-v-related-hospitalization.-of-the-patients-with-asthma-50-percent-experienced-asthma-exacerbation-during-r-s-v-related-hospitalization.

Figures independently created for GSK from the original data from Tseng HF et al. J Infect Dis 2020;222(8):1298–1310

*Comorbidities were present in the year before hospital admissions; COPD, chronic bronchitis, or emphysema

Persistent RSV Infection and Lung Function

Persistent RSV infection in patients with COPD is associated with accelerated decline in lung function.3

A prospective study evaluated the consequences of RSV persistence in adults with COPD over 2 years (N=74) and showed that repeated positive tests for RSV (chronic infection) were associated with faster FEV1 decline and higher inflammatory parameters in patients with stable COPD.3

line-chart-showing-the-relationship-between-r-s-v-detection-pattern-and-forced-expiratory-volume-in-1-second-over-the-study-period-in-patients-with-c-o-p-d.-patients-in-the-high-r-s-v-group-showed-greater-decline-in-forced-expiratory-volume-in-1-second-compared-with-the-low-r-s-v-group.-the-difference-in-the-rate-of-decline-between-these-groups-was-significant-with-a-p-value-of-0.01.

Graph redrawn from Wilkinson TM et al. Am J Respir Crit Care Med 2006;173(8):871–876

*Orange lines represent decline in FEV1 with standard errors for low RSV (≤50% of sputum samples were RSV polymerase chain reaction [PCR] positive; solid lines) and high RSV (>50% of sputum samples RSV PCR positive; dashed lines)

Learn more about RSV disease and its burden in adults:

Abbreviations

CD, cluster of differentiation; CI, confidence interval; COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 second; IL-6, interleukin 6; msLRTD, moderate to severe lower respiratory tract disease; PaO2, partial pressure of oxygen in arterial blood; PCR, polymerase chain reaction; RSV, respiratory syncytial virus; YOA, years of age.

References

  1. Branche AR et al. Clin Infect Dis 2022;74(6):1004–1011.
  2. Tseng HF et al. J Infect Dis 2020;222(8):1298–1310.
  3. Wilkinson TM et al. Am J Respir Crit Care Med 2006;173(8):871–876.
  4. Belongia EA et al. Open Forum Infect Dis 2018;5(12):ofy316.
  5. Hewitt R et al. Ther Adv Respir Dis 2016;10(2):158–174.
  6. Linden D et al. Eur Respir Rev 2019;28(151).
  7. Mohan A et al. Respirology 2010;15(3):536–542.
  8. Papi A et al. Am J Respir Crit Care Med 2006;173(10):1114–1121.
  9. Seemungal T et al. Am J Respir Crit Care Med 2001;164(9):1618–1623.
  10. Aghapour M et al. Am J Respir Cell Mol Biol 2018;58(2):157–169.
  11. Westerly BD, Peebles RS, Jr. Immunol Allergy Clin North Am 2010;30(4):523–539, vi–vii.
  12. Adeli M et al. J Family Med Prim Care 2019;8(9):2753–2759.
  13. Ojanguren I et al. Arch Bronconeumol 2022;58(9):632–634.
  14. Zhu J et al. Chest 2014;145(6):1219–1229.
  15. Zwaans WA et al. J Clin Virol 2014;61(2):181–188.

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