Early childhood lower respiratory tract infection linked to elevated adult mortality risk

Key takeaways:

• Lower respiratory tract infection by age 2 years increased premature death risk from a respiratory cause in adults.
• From 1972 to 2019, 179,188 excess deaths in England and Wales were linked to these infections.

A lower respiratory tract infection before turning 2 years old was related to a 93% higher likelihood for a respiratory-related premature death in adulthood compared with no childhood infection, according to results published in The Lancet.

“Current preventative measures for adult respiratory disease mainly focus on adult lifestyle risk factors such as smoking,” James P. Allinson, PhD, honorary senior clinical lecturer at National Heart & Lung Institute and consultant respiratory physician at the Royal Brompton Hospital, said in a press release from Imperial College London. “Linking one in five adult respiratory deaths to common infections many decades earlier in childhood shows the need to target risk well before adulthood.

“To prevent the perpetuation of existing adult health inequalities we need to optimize childhood health, not least by tackling childhood poverty,” Allinson continued. “Evidence suggesting the early life origins of adult chronic diseases also helps challenge the stigma that all deaths from diseases such as COPD are related to lifestyle factors.”

In a longitudinal observational cohort study, Allinson and colleagues followed and analyzed 3,589 individuals (age, 26 years; 51% men) from The National Survey of Health and Development cohort of babies born in March 1946 in England, Scotland and Wales until 2019 to find how early lower respiratory tract infections in individuals aged younger than 2 years are related to the risk for dying prematurely, defined as at age 73 years or younger, due to respiratory disease as an adult.

Using competing risks Cox proportional hazards models, researchers figured out hazard ratios (HRs) and the population attributable risk linked to lower respiratory tract infections during early childhood. They also adjusted for childhood socioeconomic position, childhood home overcrowding, birthweight, sex and smoking during the ages of 20 to 25 years when determining the risk for premature death in adulthood.

Results

Since 76% of individuals were alive by December 2019, 47.9 years was both the maximum and median follow-up time for this study.

Of the total cohort, 674 (19%) individuals died before turning 73 years old, and 913 individuals (25%) suffered one or more early childhood lower respiratory tract infections.

Researchers observed that 52 individuals died from a respiratory disease, and COPD was the cause of death in the majority (n = 31). Other causes included acute lower respiratory tract infections (n = 7), interstitial lung disease (n = 4), asthma (n = 4), bronchiectasis (n = 3), respiratory disease due to external agents (n = 2) and other respiratory disease (n = 1).

In an adjusted analysis, a heightened risk for respiratory-cause mortality by age 73 years was found in those who experienced a lower respiratory tract infection early on in life compared with those who did not experience this infection (adjusted HR = 1.93; 95% CI, 1.1-3.37).

Researchers found an even higher risk for death due to respiratory disease with three or more early childhood lower respiratory tract infections (aHR = 2.87; 95% CI, 1.18-7.02), when the infection happened before the infant turned 1 year old (aHR = 2.12; 95% CI, 1.16-3.88) or when the infection required inpatient treatment (aHR = 4.35; 95% CI, 1.31-14.5) than in individuals who did not experience an infection.

When looking at lower respiratory tract infections during early childhood in the context of other types of mortality, including circulatory, cancer, external, other-cause and all-cause, researchers found that this infection did not raise the risk for any of these specific cases of death.

Adjusting further for smoking intensity between ages 20 and 25 years and early childhood pollution exposure led to no changes to the main findings, according to researchers.

Population attributable risk, prevention

Comparing study findings with national mortality patterns, researchers found a corresponding 20.4% (95% CI, 3.8-29.8) population attributable risk for premature respiratory-cause mortality from early lower respiratory tract infections. Researchers additionally observed that this corresponded to 179,188 excess deaths between 1972 and 2019 in England and Wales.

“The results of our study suggest that efforts to reduce childhood respiratory infections could have an impact on tackling premature mortality from respiratory disease later in life,” Rebecca Hardy, PhD, MSc, co-author and professor of epidemiology and medical statistics at Loughborough University, said in the release. “We hope that this study will help guide the strategies of international health organizations in tackling this issue.”

This study by Allinson and colleagues contributes to growing literature on how childhood exposures are related to health outcomes in adulthood and signals the importance of efforts that can reduce the occurrence of lower respiratory tract infections in children, according to an accompanying editorial by Heather J. Zar, PhD, professor and head of the department of pediatrics and child health director of the School of Child and Adolescent Health at the University of Cape Town, South Africa, and Andrew Bush, MD, professor of pediatric respirology at the National Heart and Lung Institute and Imperial College London.

“While preventing and minimizing smoking remains crucial to optimizing health, this study indicates that prevention of early childhood lower respiratory tract infections should be a key priority,” Zar and Bush wrote. “Unavailability or unaffordability of current effective childhood immunizations against lower respiratory tract infections, especially pneumococcal conjugate vaccine, remains an important issue in LMICs, with only about 40% global coverage for eligible children. New interventions against respiratory syncytial virus, a major cause of childhood lower respiratory tract infections globally, have been developed, with potential to further reduce the burden of lower respiratory tract infections. With such effective strategies imminent, the overall burden of preventable disease might be substantial.”

References:

• Respiratory disease in early childhood linked to higher risk of death in adulthood. https://www.imperial.ac.uk/news/243593/respiratory-disease-early-childhood-linked-higher/. Published March 7, 2023. Accessed March 7, 2023.
• Zar HJ, et al. Lancet. 2023;doi:10.1016/S0140-6736(23)00341-0.