Does respiratory syncytial virus lower respiratory illness in early life cause recurrent wheeze of early childhood and asthma? Critical review of the evidence and guidance for future studies from a World Health Organization-sponsored meeting

Driscoll, Amanda J.; Arshad, Syed Hasan; Bont, Louis; Brunwasser, Steven M.; Cherian, Thomas; Englund, Janet A.; Fell, Deshayne B.; Hammitt, Laura L.; Hartert, Tina V.; Innis, Bruce L.; Karron, Ruth A.; Langley, Gayle; Mulholland, E. Kim; Munywoki, Patrick K.; Nair, Harish; Ortiz, Justin R.; Savitz, David A.; Scheltema, Nienke M.; Simões, Eric A F; Smith, P. G.; Were, Fred; Zar, Heather J.; Feikin, Daniel R.

doi:10.1016/j.vaccine.2020.01.020

Cited by 71 publications

(76 citation statements)

References 110 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A key unresolved question is whether the association of RSV LRTI with recurrent wheezing reflects an underlying genetic or physiological susceptibility to wheezing, with RSV being the initial manifestation of such susceptibility, or whether RSV is part of a causal pathway leading to recurrent wheezing. 4 , 23 The former possibility is supported by data from twin registry studies. 4 , 24 , 25 Several lines of evidence from our study suggest that the link between RSV and recurrent wheezing might not simply reflect underlying susceptibility.…”

Section: Discussionmentioning

confidence: 84%

“… 4 , 23 The former possibility is supported by data from twin registry studies. 4 , 24 , 25 Several lines of evidence from our study suggest that the link between RSV and recurrent wheezing might not simply reflect underlying susceptibility. First, evidence for a genetic predisposition to recurrent wheezing, as assessed by maternal or family history of asthma or allergy, was uncommon, although this measurement of genetic susceptibility is limited.…”

Section: Discussionmentioning

confidence: 84%

“…An alternative explanation is that RSV might lead to changes in immunological pathways or lung function that subsequently predispose to LRTI or recurrent wheezing. 4 , 23 However, although LRTI in early life was associated with impairments in lung function at 2 years, this association was a general effect of LRTI not of RSV. Importantly, recurrent LRTI, which was more common after an initial RSV LRTI, was associated with further reductions in lung function.…”

Section: Discussionmentioning

confidence: 94%

“…RSV LRTI has been associated with an increased risk of recurrent wheezing or asthma in childhood, but whether this is causal, a marker of underlying susceptibility, or both is unclear. 4 Systematic reviews and meta-analyses report an association between early-life RSV LRTI and recurrent wheezing or asthma, particularly for RSV hospitalisation. 4 , 5 , 6 However, in some studies the association was transient or reduced with age.…”

Section: Introductionmentioning

confidence: 99%

“… 4 Systematic reviews and meta-analyses report an association between early-life RSV LRTI and recurrent wheezing or asthma, particularly for RSV hospitalisation. 4 , 5 , 6 However, in some studies the association was transient or reduced with age. Two randomised controlled trials of monoclonal antibodies to prevent RSV LRTI in infants did not find long-term differences in wheezing or asthma prevalence.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Early-life respiratory syncytial virus lower respiratory tract infection in a South African birth cohort: epidemiology and effect on lung health

Zar

Nduru

Stadler

et al. 2020

The Lancet Global Health

View full text Add to dashboard Cite

Summary Background Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection (LRTI) in children. Early-life RSV LRTI might affect long-term health but there are few data from low-income and middle-income countries. We investigated the epidemiology and effect of early-life RSV LRTI on lung health in a South African birth cohort. Methods We conducted the Drakenstein Child Health Study (DCHS), an ongoing birth cohort longitudinal study in the Western Cape province, South Africa. We enrolled pregnant women aged 18 years or older during their second trimester of pregnancy at two public health clinics. We followed up study children from birth to 2 years. The primary outcome of the study was LRTI and RSV LRTI. LRTI and wheezing episodes were identified through active surveillance; respiratory samples were tested for RSV and other pathogens. Wheezing was longitudinally identified by caregiver report and ascertainment at health facilities. Lung function was measured from 6 weeks to 2 years. We analysed the associations between RSV LRTI and subsequent LRTI, wheezing, and lung function using generalised estimating equations and mixed-effects linear regression. Findings We enrolled 1137 mothers between March 5, 2012, and March 31, 2015. Among their 1143 infants, accruing 2093 child-years of follow-up, there were 851 cases of LRTI (incidence 0·41 episodes per child-year, 95% CI 0·38–0·43). Admission to hospital owing to LRTI occurred in 169 (20%) cases (incidence 0·08 episodes per child-year, 0·07–0·09), with a case-fatality ratio of 0·5%. RSV was detected in 164 (21%) of 785 LRTI events with a specimen available for qPCR, an incidence of 0·08 episodes per child-year (0·07–0·09); highest at age 0–6 months (0·15 episodes per child-year, 0·12–0·19). Children with a first RSV LRTI were three times as likely to develop recurrent LRTI compared with those with non-RSV LRTI (0·32 [0·22–0·48] vs 0·10 [0·07– 0·16] episodes per child-year; p<0·0001), particularly following hospitalised RSV LRTI. RSV LRTI and hospitalisation for all-cause LRTI were independently associated with recurrent wheezing (adjusted incident rate ratio 1·41, 95% CI 1·25–1·59, for RSV LRTI and 1·48, 1·30–1·68, for hospitalisation). LRTI or recurrent LRTI was associated with impaired lung function, but a similar outcome was observed following RSV LRTI or non-RSV LRTI. All-cause LRTI was associated with an average 3% higher respiratory rate (95% CI 0·01–0·06; p=0·013) and lower compliance (–0·1, −0·18 to 0·02) at 2 years compared with no LRTI. Recurrent LRTI was associated with further increased respiratory rate (0·01, 0·001–0·02), resistance (0·77 hPa s L −1 , 0·07–1·47), and lower compliance (–0·6 mL hPa −1 , −0·09 to −0·02) with each additional event. Interpretation RSV LRTI was common in young infants and associated with recurrent LRTI, pa...

show abstract

Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Early-life respiratory syncytial virus lower respiratory tract infection in a South African birth cohort: epidemiology and effect on lung health

Zar

Nduru

Stadler

et al. 2020

The Lancet Global Health

View full text Add to dashboard Cite

show abstract

Hosts, microbiomes, and the evolution of critical windows

et al. 2022

View full text Add to dashboard Cite

The absence of microbial exposure early in life leaves individuals vulnerable to immune overreaction later in life, manifesting as immunopathology, autoimmunity, or allergies. A key factor is thought to be a “critical window” during which the host's immune system can “learn” tolerance, and beyond which learning is no longer possible. Animal models indicate that many mechanisms have evolved to enable critical windows, and that their time limits are distinct and consistent. Such a variety of mechanisms, and precision in their manifestation suggest the outcome of strong evolutionary selection. To strengthen our understanding of critical windows, we explore their underlying evolutionary ecology using models encompassing demographic and epidemiological transitions, identifying the length of the critical window that would maximize fitness in different environments. We characterize how direct effects of microbes on host mortality, but also indirect effects via microbial ecology, will drive the optimal length of the critical window. We find that indirect effects such as magnitude of transmission, duration of infection, rates of reinfection, vertical transmission, host demography, and seasonality in transmission all have the effect of redistributing the timing and/or likelihood of encounters with microbial taxa across age, and thus increasing or decreasing the optimal length of the critical window. Declining microbial population abundance and diversity are predicted to result in increases in immune dysfunction later in life. We also make predictions for the length of the critical window across different taxa and environments. Overall, our modeling efforts demonstrate how critical windows will be impacted over evolution as a function of both host‐microbiome/pathogen interactions and dispersal, raising central questions about potential mismatches between these evolved systems and the current loss of microbial diversity and/or increases in infectious disease.

show abstract