Josh Stanton and Michael Epton Respiratory Physiology Laboratory, Canterbury Respiratory Research Group Christchurch Hospital

Josh Stanton and Michael Epton Respiratory Physiology Laboratory, Canterbury Respiratory Research Group Christchurch Hospital

Setting Scene Advancements in neonatal care over past 30 years has resulted in an increase in survivability of people born with Very Low Birth Weight (VLBW). Most data available during childhood and adolescence. Little is known about pulmonary function sequelae and exercise capacity in adult survivors of VLBW

FEV 1 Research in VLBW A.-M. Gibson, L.W. Doyle / Seminars in Fetal & Neonatal Medicine 19 (2014) 105-111

FEV 1 Research in VLBW A.-M. Gibson, L.W. Doyle / Seminars in Fetal & Neonatal Medicine 19 (2014) 105-111

Common Themes Spirometry A.-M. Gibson, L.W. Doyle / Seminars in Fetal & Neonatal Medicine 19 (2014) 105-111: Adapted from Tager et al, Am J Epidemiol 1979;110:15e26.

Common Themes Other lung function indices Decreased DLCO (Hakulinen, Vrijlandt) Increased gas trapping Exercise Capacity Mixed literature on maximal oxygen consumption reduced (Kilbride) no change cf age matched controls (Heldt, Vrijlandt) Reduced maximal WR (Vrijlandt) Reduced AT (Vrijlandt)

Aim To investigate the effect of VLBW on lung function and exercise capacity in young adult survivors.

Methods A multi-specialty research project involving New Zealand babies born in 1986 is in progress 250 VLBW (<1500g) 100 age matched term controls 2-day visit to Christchurch including: cardiac echo and ECG, Cranial MRI, psychometric testing, eye exam, dental exam, multiple questionnaires/interviews, blood test and respiratory function This presentation focuses on the respiratory physiology First 69 VLBW and 27 Controls

Methods Testing Regimen: Spirometry Diffusing capacity not corrected for Hb yet Lung volumes via plethysmography Sensormedics V62J autobox Tests conducted to ATS/ERS 2005 specifications

Methods Testing Regime: Spirometry Diffusing capacity not corrected for Hb yet Lung volumes via plethysmography Single breath Nitrogen Washout (SBN 2 ) Sensormedics Vmax 229 Tests conducted to ATS/ERS 2005 specifications

Methods Testing Regime: Spirometry Diffusing capacity not corrected for Hb yet Lung volumes via plethysmography Single breath Nitrogen Washout (SBN 2 ) Sensormedics Vmax 229 25% 75% Tests conducted to ATS/ERS 2005 specifications

Methods Testing Regime: Spirometry Diffusing capacity not corrected for Hb yet Lung volumes via plethysmography Single breath Nitrogen Washout (SBN 2 ) Symptom limited maximal cycle ergometer ramp protocol CPET 15-30 Watt.min -1 ramp Borg Scores 12 lead ECG Tests conducted to ATS/ERS 2005 specifications

Statistical methods Mann-Whitney U test for between group differences Fishers exact for contingency table p value < 0.05 considered significant Group results reported as median values +/- IQR

Results: Demographics 69 VLBW, (39 female) 27 Control (17 female) Age range 26-28 VLBW Control p value Height cm 168.5 (161-175) Weight kg 70.5 (58-89) BMI 24.7 (22-30) 168 (165-178) 77.5 (70-93) 27.1 (24-31) ns 0.04 ns Median (IQR) values reported

Respiratory Function Tests Spirometry (Hankinson 1999) Parameter VLBW Control p value FEV 1 % predicted 95.8 (86-105) 101.9 (94-106) 0.04 FVC % predicted 102.4 (95-110) 102.9 (95-108) ns FEV 1 /FVC % 78.3 (73-84) 83.7 (78-86) 0.01 Median (IQR) values reported

Respiratory Function Tests Spirometry Categorisation Smoking Status VLBW (n=68) Control (n=27) Normal 43 (63%) 23 (85%) Restricted 3 (4%) 1 (4%) Mild Obstruction 18 (26%) 3 (11%) VLBW (n=65) Control (n=27) Never 45 (69%) 18 (67%) Current 16 (25%) 7(26%) Ex 4 (6%) 2 (7%) Moderate Obstruction Moderately Severe Obstruction 3 (4%) 0 1 (1%) 0 Fishers exact test: normal vs abnormal p<0.05 n( %) values reported

Respiratory Function Tests DLCO (Cotes, 1993) Parameter VLBW Control p value DLCO % predicted 76.5 (69-85) 87.0 (75-93) 0.01 VA % predicted 92.9 (87-101) 93.0 (89-101) ns DLCO/VA 4.4 (4.1-4.8) 4.9 (4.4-5.2) 0.004 Median (IQR) values reported

Respiratory Function Tests Lung Volumes (Quanjer, 1993) Parameter VLBW Control p value TLC % predicted 98.5 (92-108) 97 (93-104) ns RV % predicted 70.8 (60-85) 61.3 (53-79) ns RV/TLC % 18.8 (16-23) 17.0 (15-21) ns Median (IQR) values reported

Single Breath N 2 Index of ventilation distribution Parameter VLBW Control p value Phase III slope 0.93 (0.72 1.24) 0.64 (0.53 0.85) 0.002 Median (IQR) values reported

Exercise Exercise capacity Parameter VLBW Control p value VO 2 % predicted 89 (80-99) 91 (77-109) ns WR % predicted 88 (78-99) 95 (83-110) ns VO 2 /WR slope 9.8 (9.3-10.6) 10 (9.4-10.5) ns AT (%pred VO 2 ) 49.7 (43-60) 60.8 (43-69) ns Median (IQR) values reported

Exercise Gas exchange Parameter VLBW Control p value VE/VCO 2 at AT 26 (25-28) 26 (25-27) ns VE/VO 2 at AT 27 (25-29) 27 (25-28) ns Delta SpO 2 (%) -1.0 (-2 to 0) 0 (-2 to 1) ns Median (IQR) values reported

Exercise Cardiovascular Parameter VLBW Control p value O 2 Pulse % predicted 101 (88-110) 104 (94-118) ns HRR (bpm) 17 (7-30) 24 (12-28) ns HR/VO 2 slope 3.5 (3.1-4.4) 3.7 (3.2-4.2) ns Ventilatory Parameter VLBW Control p value VE max % predicted 56 (46-65) 54 (44-62) ns Tidal Volume % pred 88.5 (76-97) 89 (78-95) ns RR max 36 (31-40) 37 (29-43) ns Median (IQR) values reported

Exercise Main reason for stopping exercise VLBW (n=65) Control (n=27) Dyspnoea 11 (17%) 2 (7%) Legs 42 (65%) 19 (70%) Both 5 (8%) 4 (15%) Other 7 (11%) 2 (7%) Borg Scores VLBW Control Borg Dyspnoea peak exercise (/10) 4 4 Borg Workload peak exercise (/10) 4 5 n( %) values reported Median values reported

Breathing Reserve (%) Reserves 80 70 60 50 40 30 20 10 0 Cardiac limited control VLBW HHR= Predicted HR (210-0.65 * age) Max HR BR (%) = (MVV-VE Max ) / MVV *100 Median peak RER in both groups 1.29-10 Ventilatory Limited -20-20 0 20 40 60 80 100 Heart Rate Reserve (beats)

Summary Persisting airway obstruction in the VLBW group into adulthood Reduced FEV 1 /FVC (78% vs 84%) Reduced FEV 1 (96% vs 102%predicted) Reduced DLCO (77% vs 87% predicted) in VLBW subjects No difference in exercise outcomes measured between the VLBW and Controls.

What s Next? Complete data collection Differentiate the cohort: with and without BPD/co-morbidities at birth gestational age gender differences DLCO Hb correction Continue with exercise data collection generate exercise reference equations for 27 year olds from our control data

What does lung function in early life predict in this group? A.-M. Gibson, L.W. Doyle / Seminars in Fetal & Neonatal Medicine 19 (2014) 105-111: Adapted from Tager et al, Am J Epidemiol 1979;110:15e26.

Acknowledgements Investigation team Brian Darlow John Horwood Julia Martin Mike Epton Maureen Swanney Josh Stanton Testing and Analysis Jun Yang Emily Ingram Fiona Fulton Lauren Wallace Maureen Swanney Josh Stanton