Lung function in relation to preterm birth and asthma in early childhood

The prevalence of preterm birth (ie., before 37 weeks of gestation) is increasing and estimated to be around 11 % worldwide. In high-income countries, survival is the most probable outcome even after extreme preterm deliveries. Children born preterm exhibit different stages of lung immaturity at birth and follow-up studies have shown lung function impairment and respiratory morbidity, including asthma-like disease, during infancy and into adulthood. Asthma or asthma-like disease is common in the general pediatric population. Differentiation of early childhood asthma phenotypes demonstrates different underlying pathophysiologic mechanisms and trajectories with age. The general aims of the present thesis were: To investigate lung function from infancy to adolescence in relation to preterm birth and asthma in early childhood. To investigate if similarities and differences in measured lung function after preterm birth and among childhood asthma phenotypes may give information on mechanisms for the obstructive patterns seen in these different conditions. Longitudinal follow-up during the first 18 months of life of infants with bronchopulmonary dysplasia (BPD) showed significant reductions of lung function in the cohort. Maximal expiratory flows were on average below the 2.5 th percentile for both mild and moderate/severe BPD at both 6 and 18 months, with the exception VmaxFRC at 6 months and no improvement was seen between the two time-points. Compliance of the respiratory system (COso) was the only lung function variable that differed statistically between mild and moderate/severe BPD, with lower values for the more severe disease. Significant lower values were consistently seen for Cso and all maximal expiratory variables in infants with respiratory symptoms compared to infants without. In a follow-up of children born extremely preterm (before gestational week 27), a subset of the population based cohort EXPRESS, performed lung function at age 61⁄2 years. The extreme preterm children had lower forced expiratory volume in 1 sec (FEV1, z-score: -1.1, 95% CI: -1.4; -0.8) than the control group born at term. Impulse oscillometry (IOS) measurements showed significantly higher peripheral airway resistance and reactance in children born extremely preterm than in controls. In children born at 22-24 weeks of gestation, 44% had FEV1 below the <5 th percentile. Using the BAMSE cohort study, lung function after moderate-to-late preterm birth was investigated at 8 and 16 years of age. At age 16 years, both genders in the preterm group demonstrated lower FEV1 (female subjects: –116 mL [95 % CI: –212 to –20]; male subjects: –177 mL [95 % CI: –329 to –25]) compared with the term group. IOS demonstrated higher frequency dependence of resistance (R5-20) for male subjects (20.9 Pa・L–1・s−1 [95 % CI: 9.8 to 31.9]) compared with the term group. No catch up of lung function between ages 8 and 16 years was observed in either gender. In the last study, children taking part in the BAMSE cohort study were categorized into ̳never asthma‘, ̳early transient asthma‘, ̳early persistent asthma‘, and ̳late onset asthma‘ and lung function data from the 8 and 16 year follow-ups was used to compare groups. Compared with the never asthma group, all asthma groups were associated with lower FEV1 at 16 years of age (early transient—119 ml, 95% confidence interval 204 to 34; early persistent—410 ml, 95 %CI 533; 287; and late onset—148 ml, 95%CI 237; 58). R5-20 was significantly associated with active asthma at 16 years, but not transient asthma. In conclusion: A significant proportion of children born very and extreme preterm have lung function values below the normal range in infancy and at at early scool-age. Lung function in adololescense is lower after moderate-to-late preterm birth than after term. Staging BPD severity did not predict lung function. Early measured lung function is associated with respiratory morbidity in children with BPD. IOS identifies children with low lung function after preterm birth and those with active pediatric asthma. Clinical remark: Measurements of lung function may identify children at risk for respiratory morbidity and provide insights into long-term sequel of preterm birth. Regular assessments of lung function from infancy, during childhood and possibly throughout life, are therefore suggested to be an important tool when monitoring individuals born preterm. LIST OF SCIENTIFIC PAPERS I. Thunqvist Per, Gustafsson Per M, Norman Mikael, Wickman Magnus, Hallberg Jenny. Lung function at 6 and 18 months after preterm birth in relation to severity of bronchopulmonary dysplasia. Pediatr Pulmonol. 2015 Oct;50(10):978-86. II. Thunqvist Per, Tufvesson Ellen, Bjermer Leif, Fellman Vineta, Domellöf Magnus, Melén Erik, Norman Mikael, Hallberg Jenny. Lung function in 6-year-old children born extremely preterm a population-based cohort study (EXPRESS). Submitted. III. Thunqvist Per, Gustafsson Per, Schultz Erica, Bellander Tom, BerggrenBrostrom Eva, Norman Mikael, Wickman Magnus, Melén Erik, Hallberg Jenny. Lung Function at 8 and 16 years after Moderate-to-Late Preterm birth: A Prospective Cohort Study. Pediatrics. 2016 Mar 23. pii: peds.2015-2056. IV. Hallberg Jenny, Thunqvist Per, Schultz Erica S, Kull Inger, Bottai Matteo, Merritt AS, Chiesa Flaminia, Gustafsson Per M, Melén Erik. Asthma phenotypes and lung function up to 16 years of age-the BAMSE cohort. Allergy. 2015 Jun;70(6):667-73.