EARLY DETERMINANTS OF LUNG FUNCTION IN AFRICAN INFANTS D Gray 1 , L - PowerPoint PPT Presentation

EARLY DETERMINANTS OF LUNG FUNCTION IN AFRICAN INFANTS D Gray 1 , L Willemse 1 , A Visagie 1 , E Smith 1 , PD Sly 2, GL Hall 3 , HJ Zar 1 1 Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital, University of Cape Town, South Africa, 2 Queensland Children's Medical Research Institute, University of Queensland, Brisbane, Australia 3 Telethon Kids Institute, University of Western Australia, Perth, Australia

Disclosures • None

Background • Low lung function in early life is a risk for respiratory illness • High prevalence of respiratory disease in African children • No data on lung function in African infants

Aim To assess antenatal and early life factors associated with early lung function in infants enrolled in a South African birth cohort study

Methods: Drakenstein Child Health Study • Multidisciplinary birth cohort study • Peri urban area, 60km outside Cape Town • High burden of childhood respiratory disease

Methods: Antenatal recruitment from two primary health care clinics Mbekweni community Newman community (Ethnicity – African) (Ethnicity – Mixed) • Questionnaires at schedules study visits • Maternal smoking confirmed on antenatal urine cotinine

Infant lung function measures • 6-10 weeks • Natural quiet sleep • Lung function tests: • Tidal breathing measures • Exhaled nitric oxide • SF6 Multiple breath • ATS/ERS testing guidelines washout

Results 552 infants tested Specific TBFVL exclusions: Specific eNO exclusions: Specific MBW exclusions: Insufficient sleep: 7 Insufficient sleep:: 7 Insufficient sleep: 18 Technical problem: 2 Technical problem: 10 Technical problem: 11 Poor quality: 1 Poor quality: 2 Poor quality: 11 Technically Technically Technically acceptable MBW acceptable eNO acceptable 512 (93%) 533 (97%) TBFVL 542 (98%)

Demographics of infants by ethnicity/site African ethnicity Mixed ethnicity Total med (IQR) N = 260 N = 292 N = 552 Age at test (weeks) 7.1 (6.4; 8.1) 7.2 (6.6;8.3) 7.3 (6.6; 8.1) Weight (kg) 4.9 (4.4; 5.5) 4.7 (4.2; 5.2) 4.8 (4.3; 5.4) Height (cm) 55 (53; 58) 55 (53; 57) 55 (53; 57) Birth weight (kg) 3.1 (2.8; 3.5) 3.0 (2.6; 3.4) 3.0 (2.7; 3.4) Gestation (weeks) 39 (38; 40) 39 (38; 40) 39 (38; 40) N (%) N (%) N (%) Male 117 (45) 166 (57) 283 (51) Preterm (<37 wk) 37 (14) 41 (14) 78 (14) Active smoker 39 (16) 145 (52) 185 (35) Maternal HIV 91 (35) 8 (3) 99 (18) Mbekweni site 257 (99) 2 (1) 259 (47) bold text : statistically significant p<0.05

Association of lung function at 6 -10 weeks and sex Female Male Total Multivariate linear regression Mean (SD) Mean (SD) Mean (SD) P value* 95% CI Respiratory rate 48.7 (12.3) 48.2 (11.7) 48.4 (12.0) 0.6 -1.4 to 2.6 n.min -1 t PTEF /t E % 40.9 (12.2) 37.9 (12.7) 39.4 (12.5) 0.05 -4.3 to -0.01 FRC mL 78.0 (17) 75.9 (15.8) 77.1 (16.4) 0.03 -6.0 to -0.3 Exhaled NO 9.7 (6.6) 9.6 (6.7) 9.7 (6.6) 0.5 -1.5 to 0.8 *Adjusted for weight, height, age, ethnicity, maternal smoking, maternal HIV status, previous pneumonia and prematurity

Association lung function at 6-10 weeks and maternal smoking during pregnancy Maternal non- Maternal Total Multivariate linear regression smoker smoker P value* 95% CI Mean (SD) Mean (SD) Mean (SD) Respiratory rate .min -1 49.4 (12.1) 49.2 (11.9) 49.3 (12.0) 0.8 -2.8 to 3.4 t PTEF /t E % 42.0 (11.7) 38.0 (12.4) 39.7 (12.2) 0.01 -7.4 to -0.9 FRC mL 79.6 (16.8) 75.0 (14.8) 77.1 (15.8) 0.1 -7.3 to 0.8 Exhaled NO 10.2 (6.7) 9.3 (5.7) 9.7 (6.2) 0.02 -0.25 to -0.02 *Adjusted for weight, height, age, ethnicity, sex, maternal HIV status, previous pneumonia and prematurity

Association of lung function at 6 to 10 weeks and ethnicity/site African ethnicity Mixed ethnicity Total Multivariate linear regression Mean (SD) Mean (SD) Mean (SD) P value* 95% CI 49.8 (12.2) 47.2 (11.6) 48.4 (12.0) Respiratory rate <0.001 2.1 to 6.9 n.min -1 41.7 (11.8) 37.2 (12.8) 39.4 (12.5) t PTEF /t E % 0.02 0.4 to 5.5 78.8 (17.3) 75.6 (15.4) 77.1 (16.4) FRC mL 0.7 -2.6 to 4.0 9.3 (6.9) 10.0 (6.4) 9.7 (6.6) Exhaled NO 0.5 -1.5 to 0.8 *Adjusted for weight, height, age, sex, maternal smoking, maternal HIV status, previous pneumonia and prematurity

Association infant lung function at 6 -10 weeks and maternal HIV infection Mother HIV negative Mother HIV positive Total Multivariate linear regression Mean (SD) Mean (SD) Mean (SD) P value* 95% CI Respiratory rate 50.6 (12.0) 48.6 (12.4) 49.9 (12.2) 0.1 -6.0 to 0.7 n.min -1 t PTEF /t E % 40.9 (10.8) 43.4 (13.2) 41.7 (11.8) 0.06 -0.1 to 6.6 FRC mL 78.0 (17.8) 79.9 (16.4) 78.6 (17.3) 0.1 -1.2 to 8.6 Exhaled NO 9.0 (6.4) 10.0 (7.6) 9.3 (6.7) 0.2 -0.6 to 3.2 *Adjusted for weight, height, age, sex, maternal smoking, maternal HIV status, previous pneumonia and prematurity

Conclusions • Male infants have lower early lung function compared to female infants. • I n utero smoke exposure is an important determinant of decreased early lung function. • The ethnic differences in lung function may be due to gene-environment interactions. • Maternal HIV infection was not associated with early lung function outcomes. • Antenatal and early life factors have a significant impact on lung growth and function in early infancy, which may impact on risk for respiratory disease.

Acknowledgements • Drakenstein study staff: • Lauren Willemse, Ane Alberts, Des Pietersen, Joavine Fourie • Study participants • Paarl Hospital for testing space • Supervisors and collaborators • Prof Heather Zar, Prof Graham Hall, Prof Peter Sly • Funders • The Wellcome Trust • Thrasher Foundation • Bill and Melinda Gates Foundation • Worldwide Universities Network, University of Cape Town

Association lung function and maternal smoking during pregnancy – no exposure, passive exposure and active smoking P=0.06 P=0.04