The Role of Lung Function in Determining Which Children Develop Asthma

Abstract

Longitudinal studies have demonstrated that altered indices of airway function, assessed shortly after birth, are a risk factor for the subsequent development of wheezing illnesses and asthma, and that these indices predict airway size and airway wall thickness in adult life. Pre- and postnatal factors that directly alter early airway function, such as extreme prematurity and cigarette smoke, may continue to affect airway function and, hence, the risks for wheeze and asthma. Early airway function and an associated asthma risk may also be indirectly influenced by immune system responses, respiratory viruses, the airway microbiome, genetics, and epigenetics, especially if they affect airway epithelial dysfunction. Few if any interventions, apart from smoking avoidance, have been proven to alter the risks of developing asthma, but vitamin C supplementation to pregnant smokers may help decrease the effects of in utero smoke on offspring lung function. We conclude that airway size and the factors influencing this play an important role in determining the risk for asthma across the lifetime. Progress in asthma prevention is long overdue and this may benefit from carefully designed interventions in well-phenotyped longitudinal birth cohorts with early airway function assessments monitored through to adulthood.

Keywords: Airway function; Asthma; Lung function; Prenatal determinants; Wheeze.

Figure 1A. Airway Function Test Results Obtained by Spirometry Measurements at Age 5 Years in Children Born to Pregnant Smokers Randomized to Vitamin C Supplementation (500mg/d) vs Placebo Spirometry measurements are shown for offspring of 93 and 99 pregnant smokers in the vitamin C and placebo treatment groups, respectively. P values were adjusted for trial stratification variables of study site and gestational age at randomization, sex, race and ethnicity, and height at testing. All forced expiratory flow (FEF) and forced expiratory volume in 1 second (FEV1) measurements increased significantly in offspring of vitamin C–treated pregnant smokers. FEF25–75 indicates FEF between 25% and 75% expired volume; FEF50 indicates FEF at 50% of expiration; FEF75, FEF at 75% of expiration; and NS, not significant. ^a P < .01; ^b P < .05. Figure 1B. Any Occurrence of Wheeze between the Fourth and Sixth Birthday in Offspring of Pregnant Smokers Randomized to Vitamin C versus Placebo during Pregnancy Multiple logistic regression was used to compare the occurrence of wheeze between the vitamin C and placebo groups adjusting for study trial design factors of study site and gestational age at randomization, and covariates of race, and sex, and significant two-way interactions of all of these variables. 212 children were included (106 vitamin C and 106 placebo treated). The children born to the vitamin C treated pregnant smokers had a significant decrease in current wheeze at 28% versus 47% (estimated OR of 0.41; 95% CI: 0.23–0.74; P= 0.0032). (Reproduced from Jama Pediatr. 2023:177(1):16–24 with permission).

Figure 2.. Changes in Lung Function During the Course of Mild and Moderate Asthma

Schematic representation of airway function trajectories for children without asthma, with asthma and mild or no airflow limitation, and for children with persistent asthma and airflow limitation. As a group, the latter show impaired airways function growth especially during the preschool years. These deficits extend, albeit in a less evident way, to the school age and, as steeper decline in airway function, to adulthood (Reproduced from Lancet 2013 Oct 19;382(9901):1360–72 with permission).