Association between early viral lower respiratory tract infections and subsequent asthma development

Abstract

BACKGROUND The association between hospitalization for human respiratory syncytial virus (HRSV) bronchiolitis in early childhood and subsequent asthma is well established. The long-term prognosis for non-bronchiolitis lower respiratory tract infections (LRTI) caused by viruses different from HRSV and rhinovirus, on the other hand, has received less interest. AIM To investigate the relationship between infant LRTI and later asthma and examine the influence of confounding factors. METHODS The PubMed and Global Index Medicus bibliographic databases were used to search for articles published up to October 2021 for this systematic review. We included cohort studies comparing the incidence of asthma between patients with and without LRTI at ≤ 2 years regardless of the virus responsible. The meta-analysis was performed using the random effects model. Sources of heterogeneity were assessed by stratified analyses. RESULTS This review included 15 articles (18 unique studies) that met the inclusion criteria. LRTIs at ≤ 2 years were associated with an increased risk of subsequent asthma up to 20 years [odds ratio (OR) = 5.0, 95%CI: 3.3-7.5], with doctor-diagnosed asthma (OR = 5.3, 95%CI: 3.3-8.6), current asthma (OR = 5.4, 95%CI: 2.7-10.6), and current medication for asthma (OR = 1.2, 95%CI: 0.7-3.9). Our overall estimates were not affected by publication bias ( P = 0.671), but there was significant heterogeneity [ I 2 = 58.8% (30.6-75.5)]. Compared to studies with hospitalized controls without LRTI, those with ambulatory controls had a significantly higher strength of association between LRTIs and subsequent asthma. The strength of the association between LRTIs and later asthma varied significantly by country and age at the time of the interview. The sensitivity analyses including only studies with similar proportions of confounding factors (gender, age at LRTI development, age at interview, gestational age, birth weight, weight, height, smoking exposure, crowding, family history of atopy, and family history of asthma) between cases and controls did not alter the overall estimates. CONCLUSION Regardless of the causative virus and confounding factors, viral LRTIs in children < 2 years are associated with an increased risk of developing a subsequent asthma. Parents and pediatricians should be informed of this risk.

Expert consensus on the diagnosis, treatment, and prevention of respiratory syncytial virus infections in children

“…The immune response of the body after RSV infections in infants and children, along with the influence of neuromodulatory mechanisms and the persistence of RSV leading to adaptive remodeling of airway ultrastructure, may cause airway hyperresponsiveness, which is strongly associated with the development of recurrent wheezing and asthma later in life [ 155 – 158 ]. A recent review of 906 patients with asthma found that viral LRTIs in infants aged ≤ 2 years were associated with an increased risk of asthma for up to 20 years thereafter (odds ratio = 5.0; 95% confidence interval, 3.3–7.5), with RSV as the predominant pathogen (83.3%) [ 159 ]. Another prospective population-based cohort study showed that the prevalence of asthma at age 5 years was higher in children with RSV infections in infancy than in children without evidence of RSV infections in infancy (21% vs. 16%) [ 150 ].…”

Assessing the Burden of Respiratory Syncytial Virus-related Bronchiolitis in Primary Care and at 15-Day and 6-Month Follow-up Before Prophylaxis in France: A Test-negative Study

“…Several other long-term and/or less frequent aspects need to be assessed after RSV prophylaxis implementation. For example, it is possible that early lower-respiratory-tract infection due to RSV could lead to asthma 35 or RSV infection could trigger invasive pneumococcal diseases. 36 Since March 2020, several nonpharmaceutical interventions have been implemented for the COVID-19 pandemic.…”

A critical analysis of the effect of OM‐85 for the prevention of recurrent respiratory tract infections or wheezing/asthma from systematic reviews with meta‐analysis

“…In addition, RTIs are associated with preschool wheezing affecting up to 30% of children, and nearly 15%–25% of children experience recurrent wheezing before school age 9 . Viral RTIs are associated with a high level of inflammation and may contribute to airway remodeling 10 and to significantly increased risk of preschool recurrent wheezing and asthma later in life, 11–13 which may in turn have irreversible effects on lung function.…”

“…8 In addition, RTIs are associated with preschool wheezing affecting up to 30% of children, and nearly 15%-25% of children experience recurrent wheezing before school age. 9 Viral RTIs are associated with a high level of inflammation and may contribute to airway remodeling 10 and to significantly increased risk of preschool recurrent wheezing and asthma later in life, [11][12][13] which may in turn have irreversible effects on lung function. Some consensus documents and statements recommend the use of immunostimulants to boost the body's natural defenses against infections and reduce the probability of reinfection in susceptible children.…”