Respiratory syncytial virus-Host interaction in the pathogenesis of bronchiolitis and its impact on respiratory morbidity in later life

All newborn infants have limited pulmonary reserve compared with older children. This puts them at increased risk of respiratory complications, such as those associated with infection by the respiratory syncytial virus. Young children with congenital cardiac disease are particularly likely to suffer severe disease related to infection by the virus. In these children, the extreme vulnerability of the lung to pulmonary oedema is compounded by the additional burden caused by the respiratory syncytial virus.In addition to the well-documented acute pulmonary effects of infection with the respiratory syncytial virus, there may also be consequent long-term respiratory morbidity. Clinical studies have shown that infection by the virus in infancy is associated with a higher risk of developing subsequent bronchial obstructive disease. Much debate surrounds the mechanisms underlying this association. It is thought that a combined immunological and neurogenic response mechanism is likely. Prevention of severe respiratory disease in infants and young children with congenital heart disease due to infection by the virus may, therefore, offer both immediate and long-term benefits. Indeed, an increasing body of evidence supports this hypothesis, indicating a clinical rationale for prophylaxis against the virus in infancy, in order to reduce the chance of developing reactive airways disease and asthma in later life.

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Respiratory Morbidity in Adulthood After Respiratory Syncytial Virus Hospitalization in Infancy

The Pediatric Infectious Disease Journal ◽

10.1097/inf.0b013e3181dea5de ◽

2010 ◽

Vol 29 (9) ◽

pp. 872-874 ◽

Cited By ~ 23

Author(s):

Marja Ruotsalainen ◽

Eija Piippo-Savolainen ◽

Mari K. Hyvärinen ◽

Matti Korppi

Keyword(s):

Respiratory Syncytial Virus ◽

Respiratory Morbidity ◽

Syncytial Virus

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Reduced long-term respiratory morbidity after treatment of respiratory syncytial virus bronchiolitis with ribavirin in previously healthy infants: A preliminary report

Pediatric Pulmonology ◽

10.1002/(sici)1099-0496(199803)25:3<154::aid-ppul4>3.0.co;2-m ◽

1998 ◽

Vol 25 (3) ◽

pp. 154-158 ◽

Cited By ~ 32

Author(s):

Dean Edell ◽

Erik Bruce ◽

Kathe Hale ◽

Debra Edell ◽

Vikram Khoshoo

Keyword(s):

Respiratory Syncytial Virus ◽

Preliminary Report ◽

Respiratory Morbidity ◽

Respiratory Syncytial Virus Bronchiolitis ◽

Healthy Infants ◽

Syncytial Virus

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Respiratory Syncytial Virus Prophylaxis in Infants With Congenital Diaphragmatic Hernia in the Canadian Respiratory Syncytial Virus Evaluation Study of Palivizumab, 2005–2017

Clinical Infectious Diseases ◽

10.1093/cid/ciy1010 ◽

2018 ◽

Vol 69 (6) ◽

pp. 980-986 ◽

Cited By ~ 3

Author(s):

Doyoung Kim ◽

Mahwesh Saleem ◽

Bosco Paes ◽

Ian Mitchell ◽

Krista L Lanctôt

Keyword(s):

Respiratory Syncytial Virus ◽

Congenital Diaphragmatic Hernia ◽

Diaphragmatic Hernia ◽

Respiratory Illness ◽

Evaluation Study ◽

Cox Proportional Hazards ◽

Respiratory Morbidity ◽

Increased Risk ◽

Syncytial Virus ◽

Tract Infections

Abstract Background Infants with congenital diaphragmatic hernia (CDH) are at an increased risk of respiratory morbidity from recurrent respiratory tract infections including those from respiratory syncytial virus (RSV). Prospective studies on RSV prophylaxis in CDH infants are limited. We determined the risk of respiratory illness– and RSV-related hospitalizations (RIH and RSVH, respectively) among infants prophylaxed for CDH, standard indications (SIs) and those without increased risk (NR). Methods The prospective Canadian Respiratory Syncytial Virus Evaluation Study of Palivizumab (CARESS) registry was searched for infants who received palivizumab during 12 RSV seasons (2005–2017) in Canada. Cox proportional hazards analyses were conducted to compare RIH and RSVH risks across the groups adjusted for potential confounders. Results In total, 21 107 infants (201 CDH, 389 NR, and 20 517 SI) were included. RIH incidences were 10.0% (CDH), 2.1% (NR), and 6.2% (SI). CDH patients had a significantly higher RIH hazard compared with NR (hazard ratio [HR], 3.6 [95% confidence interval {CI}, 1.5–8.8]; P = .005) but not SI (HR, 1.2 [95% CI, .8–2.0]; P = .379). RSVH incidences were 0.6%, 0.3%, and 1.5% for CDH, NR, and SI, respectively. RSVH risk was similar across groups (SI: HR, 0.0, P = .922; NR: HR, 0.0, P = .934). Conclusions CDH infants had a 3-fold increased risk of RIH compared to NR but not SI infants. RSVH risk was similar with low RSVH incidences across all groups, implying that CDH infants may benefit from palivizumab during the RSV season, similar to other high-risk groups. Clinical Trials Registration NCT00420966.

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Age at First Viral Infection Determines the Pattern of T Cell–mediated Disease during Reinfection in Adulthood

Journal of Experimental Medicine ◽

10.1084/jem.20020943 ◽

2002 ◽

Vol 196 (10) ◽

pp. 1381-1386 ◽

Cited By ~ 184

Author(s):

Fiona J. Culley ◽

Joanne Pollott ◽

Peter J.M. Openshaw

Keyword(s):

Cytokine Production ◽

Severe Disease ◽

Later Life ◽

Interferon Γ ◽

Respiratory Morbidity ◽

Lung Pathology ◽

Viral Kinetics ◽

Newborn Mice ◽

Rsv Infection ◽

Syncytial Virus

Infants experiencing severe respiratory syncytial virus (RSV) bronchiolitis have an increased frequency of wheeze and asthma in later childhood. Since most severe RSV infections occur between the 8th and 24th postnatal week, we examined whether age at first infection determines the balance of cytokine production and lung pathology during subsequent rechallenge. Primary RSV infection in newborn mice followed the same viral kinetics as in adults but was associated with reduced and delayed IFN-γ responses. To study rechallenge, mice were infected at 1 day or 1, 4, or 8 weeks of age and reinfected at 12 weeks. Neonatal priming produced more severe weight loss and increased inflammatory cell recruitment (including T helper 2 cells and eosinophils) during reinfection, whereas delayed priming led to enhanced interferon γ production and less severe disease during reinfection. These results show the crucial importance of age at first infection in determining the outcome of reinfection and suggest that the environment of the neonatal lung is a major determinant of cytokine production and disease patterns in later life. Thus, simply delaying RSV infection beyond infancy might reduce subsequent respiratory morbidity in later childhood.

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Association Between Respiratory Syncytial Virus-Associated Acute Lower Respiratory Infection in Early Life and Recurrent Wheeze and Asthma in Later Childhood

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz311 ◽

2019 ◽

Vol 222 (Supplement_7) ◽

pp. S628-S633 ◽

Cited By ~ 7

Author(s):

Ting Shi ◽

Yujing Ooi ◽

Ei Mon Zaw ◽

Natasa Utjesanovic ◽

Harry Campbell ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Early Life ◽

Subsequent Development ◽

Respiratory Morbidity ◽

Acute Lower Respiratory Infection ◽

High Risk Population ◽

Rsv Infection ◽

Recurrent Wheeze ◽

Syncytial Virus

Abstract Background Recurrent wheeze and asthma in childhood are commons causes of chronic respiratory morbidity globally. We aimed to explore the association between respiratory syncytial virus (RSV) infection in early life and subsequent respiratory sequelae up to age 12 years. Methods We estimated the strength of association by 3 control groups and 3 follow-up age groups, with data from studies published between January 1995 and May 2018. We also estimated associations by diagnostic criteria, age at infection, and high-risk population. Results Overall, we included 41 studies. A statistically significant association was observed between early life RSV infection and subsequent childhood recurrent wheeze, in comparison to those who were healthy or those without respiratory symptoms: OR 3.05 (95% confidence interval [CI], 2.50–3.71) for 0 to <36 months follow-up age; OR 2.60 (95% CI, 1.67–4.04) for 36–72 months; and OR 2.14 (95% CI, 1.33–3.45) for 73–144 months. For the subsequent development of asthma, a statistically significant association was observed only in relation to those aged 73–144 months at follow-up: OR 2.95 (95% CI, 1.96–4.46). Conclusions Further studies using standardized definitions and from diverse settings are needed to elucidate the role of confounders and provide more robust estimates.

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