Article Text


Improving delivery of care in cystic fibrosis
P234 The importance of appropriate reference equations for spirometry: lessons learned from the Cystic Fibrosis Gene Therapy “Run-In” study
  1. G Davies1,
  2. A J Simpson1,
  3. K J Bayfield1,
  4. M J McGovern2,
  5. M A Embley2,
  6. H S Sheridan2,
  7. C Saunders1,
  8. M H Dewar2,
  9. S Cunningham2,
  10. E W F W Alton3,
  11. J A Innes2,
  12. J C Davies1
  1. 1Imperial College, London, UK
  2. 2University of Edinburgh, Edinburgh, UK
  3. 3UK Cystic Fibrosis Gene Therapy Consortium, London, UK


Introduction and Objectives The “Run-In” study is an on-going longitudinal, observational study of CF patients assessing outcome measures for a future gene therapy trial. Spirometry is performed at each visit and volumes are converted to % predicted values according to published reference equations; historically these were separate for adults and children. Here, we describe the issues arising from this approach, and highlight the benefit of using a reference source which bridges the transition from child to adulthood.

Methods CF subjects (=10 years; FEV1=40% predicted) were recruited from three sites in London and Edinburgh. Visits were undertaken during periods of stability every 3–6 months; data presented here are from the first four visits. Spirometry was performed on an Easyone spirometer. Volumes were converted to % predicted values according to Rosenthal (<18 years) and Quanjer (=18 years) reference equations. The FEV1 raw data were subsequently re-analysed using Stanojevic reference equations, which span all age ranges. Comparisons were made using paired t-tests.

Results 191 patients attended visit 1 (mean age 22.7 years, 55% male; 91 patients <18 years). Rosenthal and Quanjer FEV1% predicted values were significantly higher than the Stanojevic values: mean differences 2.8 (95% CI 1.9 to 3.7) for children with Rosenthal equations (p<0.0001), and 2.4 (95% CI 2.1 to 2.8) for adults using Quanjer equations (p<0.0001). 10 patients transitioned between paediatric and adult reference ranges during the study period; the slope of change in their FEV1% over visits 1–4 was significantly greater with Rosenthal/Quanjer references than with Stanojevic (p=0.001) largely due to an artefactual drop when switching from Rosenthal to Quanjer values. As an example, a female patient aged 17.8 years at visit 1 had a drop in absolute FEV1% predicted between visits 1 and 2 of 11% when Rosenthal/Quanjer were used but only 3% with Stanojevic reference values.

Conclusions Our results highlight issues raised when separate adult and paediatric spirometry reference ranges are used in longitudinal study. The UK CF Gene Therapy Consortium has adopted the Stanojevic reference source for all spirometry analysis in its ongoing Clinical Programme.

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  • Funding UK CF Trust.

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