RSV lower respiratory tract infection and lung health in the first 2 years of life
Authors: Charl Verwey, Marta C Nunes
Journal: The Lancet Global Health (2020)

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) and hospitalisation in children worldwide. It has been estimated that in 2015 there were 33·1 million RSV-associated LRTI episodes in children under 5 years old, including 3·2 million hospitalisations, and 118 000 deaths; with approximately 45% of all hospitalisations and in-hospital deaths occurring among infants under 6 months of age.1Shi T McAllister DA O'Brien KL et al.Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study.Lancet. 2017; 390: 946-958Google Scholar Although it is estimated that low-income and middle-income countries (LMICs) account for over 90% of the global RSV burden estimates in children, data from these settings is scarce. In The Lancet Global Health, Heather Zar and colleagues2Zar HJ Nduru P Stadler JAM et al.Early-life respiratory syncytial virus lower respiratory tract infection in a South African birth cohort: epidemiology and effect on lung health.Lancet Glob Health. 2020; 8: 1316-1325Google Scholar report on the important ongoing debate of the impact of early-life RSV LRTI on lung health. The authors followed up children born into their unique Drakenstein Child Health Study (DCHS) birth cohort to 2 years of age. This cohort study, investigating multiple facets of child health, was established in a peri-urban area in South Africa, with a high burden of tuberculosis (annual reported incidence 293/100 000) and maternal HIV prevalence (approximately 30%), as well as a high incidence of tobacco smoke exposure. The study includes approximately 1000 mother–infant pairs who were intensively longitudinally investigated for the first year of life and then every 6 months for the next 5 years.3Zar HJ Barnett W Myer L Stein DJ Nicol MP Investigating the early-life determinants of illness in Africa: the Drakenstein Child Health Study.Thorax. 2015; 70: 592-594Google Scholar One of the strengths of this study, besides the great retention of participants, is that 80% of the infants had comprehensive lung function testing done at 6 weeks of age, before the onset of any LRTI or wheezing episodes, thereby providing valuable baseline lung function estimates and allowing for evaluation of determinates for future lung health.4Gray D Willemse L Visagie A et al.Determinants of early-life lung function in African infants.Thorax. 2017; 72: 445-450Google Scholar This approach improves the robustness of data reported regarding lung growth trajectories and the risk factors that affect them, since it does not rely on subjective questionnaire-based information. The authors have previously reported that early LRTI episodes were associated with increased respiratory rate at 1 year of age, and that subsequent LRTIs resulted in further increase in respiratory rate and lung clearance index together with a decrease in tidal volume.5Gray DM Turkovic L Willemse L et al.Lung function in African infants in the Drakenstein Child Health Study. Impact of lower respiratory tract illness.Am J Respir Crit Care Med. 2017; 195: 212-220Google Scholar In the current analysis the influence of RSV LRTI and the severity of these infections on recurrent LRTI and wheeze episodes up to 2 years of age are explored, the effects of all-cause LRTI are also reported. There were 851 LRTIs (0·41 episodes per child-year) with 20% requiring hospitalisation. RSV was detected in 21% of all LRTIs and was more common in hospitalised than ambulatory cases (33% vs 18%), with one third of RSV episodes requiring hospitalisation, a much higher hospitalisation rate than generally reported,2Zar HJ Nduru P Stadler JAM et al.Early-life respiratory syncytial virus lower respiratory tract infection in a South African birth cohort: epidemiology and effect on lung health.Lancet Glob Health. 2020; 8: 1316-1325Google Scholar probably indicating the inherent difficulties of access to health-care facilities in communities with lower socioeconomic status, as well as the possible influence of high HIV exposure and exposure to environmental tobacco smoke. Of note, children with RSV LRTI were at higher risk of developing subsequent new LRTI episodes particularly if the first RSV infection required hospitalisation. Recurrent wheezing was also more likely to develop after RSV LRTI than non-RSV LRTI and was infrequent in children who never had an LRTI. Once again, severity of the initial LRTI had a large influence on subsequent sequelae, with more recurrent wheeze reported after hospitalisation than in ambulatory cases, irrespective of RSV or non-RSV cause. Pulmonary function assessments done accordingly to WHO recommendations for investigating LRTI sequelae6Driscoll AJ Arshad SH Bont L et al.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.Vaccine. 2020; 38: 2435-2448Google Scholar produced results very similar to those reported at 1 year of age, with increased respiratory rate and lower compliance in children with previous LRTI;5Gray DM Turkovic L Willemse L et al.Lung function in African infants in the Drakenstein Child Health Study. Impact of lower respiratory tract illness.Am J Respir Crit Care Med. 2017; 195: 212-220Google Scholar these associations were independent of baseline lung function. Furthermore, recurrent episodes of LRTI were associated with a further increase in respiratory rate and resistance, and a decrease in compliance with each additional event. There were, however, no differences in lung function in children who had RSV LRTI compared with those with non-RSV LRTI. Studies reporting on wheezing and asthma are often limited by the reliance on less objective caregiver questionnaires rather than lung function assessments and even when these are performed, they have reported vastly different outcomes after RSV LRTI.7Verwey C Nunes MC Dangor Z Madhi SA Pulmonary function sequelae after respiratory syncytial virus lower respiratory tract infection in children: a systematic review.Pediatr Pulmonol. 2020; 55: 1567-1583Google Scholar This study used both questionnaires and pulmonary function measurements, thereby improving its validity, but unfortunately, as in many previous studies exploring this association, there are incongruent results between the two reporting methods, highlighting the difficulty investigators experience in describing associations between RSV, and actually LRTI, and its respiratory sequelae. These associations were thoroughly explored by the authors and strong associations between RSV and lung health have come out of this study. We look forward to further data emanating from this cohort especially on recurrent wheeze measured to at least 3 years of age and asthma, measured at 6 years of age or older, as these long-term outcomes of early-life RSV LRTI have been identified as of public health interest.6Driscoll AJ Arshad SH Bont L et al.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.Vaccine. 2020; 38: 2435-2448Google Scholar We hope that their future longitudinal analyses will be able to shed more light on the questions regarding the association between LRTI and pulmonary sequelae, especially in LMICs. We declare no competing interests. Early-life respiratory syncytial virus lower respiratory tract infection in a South African birth cohort: epidemiology and effect on lung healthRSV LRTI was common in young infants and associated with recurrent LRTI, particularly after hospitalised RSV. Hospitalisation for all-cause LRTI, especially for RSV-LRTI, was associated with recurrent wheezing. Impairments in lung function followed LRTI or recurrent episodes, but were not specific to RSV. New preventive strategies for RSV might have an effect on long-term lung health. Full-Text PDF Open Access