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Ventilation inhomogeneity in infants with recurrent wheezing
  1. Zihang Lu1,2,
  2. Rachel E Foong1,3,
  3. Krzysztof Kowalik1,
  4. Theo J Moraes1,
  5. Ayanna Boyce1,
  6. Aimee Dubeau1,
  7. Susan Balkovec1,
  8. Per Magnus Gustafsson4,
  9. Allan B Becker5,
  10. Piush J Mandhane6,
  11. Stuart E Turvey7,
  12. Wendy Lou2,
  13. Felix Ratjen1,
  14. Malcolm Sears8,
  15. Padmaja Subbarao1
  1. 1 Division of Respiratory Medicine and Translational Medicine, Department of Pediatrics & Physiology, Hospital for Sick Children & University of Toronto, Toronto, Ontario, Canada
  2. 2 Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
  3. 3 School of Physiotherapy and Exercise Science, Curtin University, Bentley, Western Australia, Australia
  4. 4 Department of Pediatrics, Central Hospital, Skövde, Sweden
  5. 5 Department of Pediatrics and Child Health, University of Manitoba, Children’s Hospital Research Institute of Manitoba, Winnipeg, Manitoba, Canada
  6. 6 Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
  7. 7 Department of Pediatrics, BC Children’s Hospital, University of British Columbia, Vancouver, British Columbia, Canada
  8. 8 Department of Medicine, McMaster University, Hamilton, Ontario, Canada
  1. Correspondence to Dr Padmaja Subbarao, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; padmaja.subbarao{at}


Background The care of infants with recurrent wheezing relies largely on clinical assessment. The lung clearance index (LCI), a measure of ventilation inhomogeneity, is a sensitive marker of early airway disease in children with cystic fibrosis, but its utility has not been explored in infants with recurrent wheezing.

Objective To assess ventilation inhomogeneity using LCI among infants with a history of recurrent wheezing compared with healthy controls.

Methods This is a case–control study, including 37 infants with recurrent wheezing recruited from outpatient clinics, and 113 healthy infants from a longitudinal birth cohort, the Canadian Healthy Infant Longitudinal Development study. All infants, at a time of clinical stability, underwent functional assessment including multiple breath washout, forced expiratory flows and body plethysmography.

Results LCI z-score values among infants with recurrent wheeze were 0.84 units (95% CI 0.41 to 1.26) higher than healthy infants (mean (95% CI): 0.26 (−0.11 to 0.63) vs −0.58 (−0.79 to 0.36), p<0.001)). Nineteen percent of recurrently wheezing infants had LCI values that were above the upper limit of normal (>1.64 z-scores). Elevated exhaled nitric oxide, but not symptoms, was associated with abnormal LCI values in infants with recurrent wheeze (p=0.05).

Conclusions Ventilation inhomogeneity is present in clinically stable infants with recurrent wheezing.

  • asthma
  • paediatric asthma
  • lung physiology
  • respiratory measurement

Statistics from


  • Contributors PS, ABB, PJM, SET and MS designed the study. ZL, PS, MS and FR interpreted the data and drafted the manuscript. ZL and WL performed the statistical analyses. ZL, PS, REF and FR interpreted the data and revised the manuscript. KK, TJM, ABB, AD, SB and PMG collected data, interpreted results and revised the manuscript. All authors approved the final version of the manuscript.

  • Funding CIHR, AllerGen NCE, Don & Debbie Morrison and SickKids Foundation.

  • Competing interests None declared.

  • Patient consent Guardian consent obtained.

  • Ethics approval All studies were approved by the Hospital for Sick Children Research Ethics Board (REB #1000011761 for Healthy Infants and REB #1000008533 for Wheezy Infants).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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