Early LRTIs Tied to Risk of Premature Adult Death From Respiratory Diseases

Allergies & Asthma

A lower respiratory tract infection (LRTI) in early childhood nearly doubles the risk of premature death from respiratory diseases in adulthood, according to a prospective cohort study that spanned eight decades.

The study of over 3,500 individuals born in the U.K. found that participants diagnosed with an LRTI by age 2 years were 93% more likely to die prematurely in adulthood due to a respiratory disease (adjusted HR 1.93, 95% CI 1.10-3.37, P=0.021), reported James Peter Allinson, MD, PhD, of the National Heart and Lung Institute at Imperial College London, and colleagues.

This increased risk correlated with the number of documented LRTIs as well, such that acquiring three or more infections was associated with a nearly threefold higher risk when compared with participants who never had an LRTI in early childhood (HR 2.87, 95% CI 1.18-7.02).

Furthermore, kids requiring inpatient care for their LRTIs had a more-than fourfold higher risk of premature death in adulthood from a respiratory disease (HR 4.35, 95% CI 1.31-14.5), Allinson’s team detailed in The Lancet.

“Impaired adult lung function is a plausible mediator linking early childhood infection to respiratory-cause adult mortality,” the group suggested. “Infection might disrupt or reflect already disrupted childhood lung development, leading to children reaching lower peak lung function as adults, increasing the risk of respiratory morbidity and mortality.”

Among the 52 premature adult deaths from respiratory diseases identified in the cohort, the leading cause was chronic obstructive pulmonary disease (COPD), in 60%, followed by acute LRTIs in 13%.

On a population level, the researchers estimated that 20.4% (95% CI 3.8-29.8) of premature adult deaths due to respiratory diseases could be attributed to the early childhood LRTIs. Smoking in adulthood was estimated to comprise 57.7% (95% CI 37.3-68.0) of such premature deaths.

“Current preventative measures for adult respiratory disease mainly focus on adult lifestyle risk factors such as smoking. Linking one in five of adult respiratory deaths to common infections many decades earlier in childhood shows the need to target risk well before adulthood,” Allinson said in a press release.

“To prevent the perpetuation of existing adult health inequalities we need to optimize childhood health, not least by tackling childhood poverty,” he added. “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 an accompanying comment, Heather J. Zar, MD, PhD, of the University of Cape Town in South Africa, and Andrew Bush, MD, also of Imperial College London, emphasized the importance of preventing LRTIs in early childhood.

“Unavailability or unaffordability of current effective childhood immunizations against LRTI, especially pneumococcal conjugate vaccine, remains an important issue in LMICs [low- and middle-income countries], with only about 40% global coverage for eligible children,” they wrote. “New interventions against respiratory syncytial virus, a major cause of childhood LRTI globally, have been developed, with potential to further reduce the burden of LRTI.”

“With such effective strategies imminent, the overall burden of preventable disease might be substantial,” Zar and Bush stated. “Furthermore, if the relationship between early childhood LRTI and premature adult mortality is causal, as suggested by this study, these interventions might substantially reduce premature mortality. Ensuring equitable global access to such interventions to prevent early life LRTI, particularly in LMICs, will be crucial to reduce morbidity and mortality through the life course.”

For the study, the U.K. Medical Research Council National Survey of Health and Development prospectively collected data on over 5,000 participants enrolled at birth in March 1946 across England, Scotland, and Wales. A total of 3,589 remained in the study at age 26 and had complete childhood data, smoking history, and mortality information for the current analysis — 1,832 (51%) smoked at age 20 to 25 years (median 10 cigarettes).

A total of 913 individuals (25%) had at least one LRTI before age 2 years, with most occurring in the first year of life and most only having one documented infection.

Over a maximum follow-up of 47.9 years, 674 premature deaths occurred by age 73, with cancer (41%) and circulatory disease (27%) being the leading causes. External causes (10%), respiratory diseases (8%), and other causes (14%) made up the rest.

Aside from COPD and acute LRTIs, premature deaths from respiratory diseases included interstitial lung disease in 8%, asthma in 8%, bronchiectasis in 6%, respiratory disease due to external agents in 4%, and other respiratory diseases in 2%.

The main analysis adjusted for multiple factors, such as birthweight and sex, environmental factors such as childhood home overcrowding, socioeconomic status during childhood, and smoking status as an adult.

Not surprisingly, participants who smoked in the data captured at age 20 to 25 years also saw an increase in the risk of premature death from respiratory diseases (HR 3.73, 95% CI 1.90-7.30).

Study limitations included those inherent to population-based studies, such as unmeasured confounding, along with “unrecorded factors including parental smoking and prematurity,” the authors stated.

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    Elizabeth Short is a staff writer for MedPage Today. She often covers pulmonology and allergy & immunology. Follow

Disclosures

The study was supported by the National Institute for Health and Care Research Imperial Biomedical Research Centre, Royal Brompton and Harefield National Health Service (NHS) Foundation Trust, Royal Brompton and Harefield Hospitals Charity and Imperial College Healthcare NHS Trust, and the U.K. Medical Research Council (MRC).

Allinson disclosed no relationships with industry. Co-authors disclosed relationships with AstraZeneca, Genentech, Novartis, Elsevier, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, 37 Clinical, EpiEndo, Gilead, Pieris, Pulmatrix, Recipharm, the American Journal of Respiratory and Critical Care Medicine, and the Economic and Social Research Council.

Zar disclosed support from, and/or relationships with, the Bill & Melinda Gates Foundation, MRC, NIH, the Wellcome Trust, AstraZeneca, Merck, Pfizer, and Sanofi. Bush disclosed a Wellcome Strategic Award and relationships with the MRC Asthma and Lung Centre in Allergic Mechanisms in Asthma, and the Asthma and Lung Centre for Applied Research.

Primary Source

The Lancet

Source Reference: Allinson JP, et al “Early childhood lower respiratory tract infection and premature adult death from respiratory disease in Great Britain: a national birth cohort study” Lancet 2023; DOI: 10.1016/S0140-6736(23)00131-9.

Secondary Source

The Lancet

Source Reference: Zar HJ, Bush A “Early childhood lower respiratory tract infection: a key determinant of premature adult respiratory mortality” Lancet 2023; DOI: 10.1016/S0140-6736(23)00341-0.

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