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Higher exhaled nitric oxide at 6 weeks of age is associated with less bronchiolitis and wheeze in the first 12 months of age
  1. Carla Rebeca Da Silva Sena1,
  2. Ediane de Queiroz Andrade1,
  3. Patricia de Gouveia Belinelo1,
  4. Elizabeth Percival1,
  5. Benjamin Prangemeier2,
  6. Christopher O'Donoghue2,
  7. Sandrine Terry2,
  8. Tanya Burke2,
  9. William Gunning2,
  10. Vanessa E Murphy1,
  11. Paul D Robinson3,
  12. Peter D Sly4,
  13. Peter G Gibson5,6,
  14. Adam M Collison1,
  15. Joerg Mattes1,7
  1. 1Priority Research Centre GrowUpWell, The University of Newcastle and Hunter Medical Research Institute, Newcastle, New South Wales, Australia
  2. 2School of Medicine and Public Health, The University of Newcastle, Callaghan, New South Wales, Australia
  3. 3Respiratory Medicine, The Children's Hospital at Westmead, Sydney, New South Wales, Australia
  4. 4Queensland Children's Medical Research Institute, University of Queensland, Herston, Queensland, Australia
  5. 5Priority Research Centre Healthy Lungs, The University of Newcastle and Hunter Medical Research Institute, Newcastle, New South Wales, Australia
  6. 6Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, New South Wales, Australia
  7. 7Department of Paediatric Respiratory and Sleep Medicine, John Hunter Children's Hospital, Newcastle, New South Wales, Australia
  1. Correspondence to Professor Joerg Mattes, Paediatrics & Child Health, The University of Newcastle, New Lambton Heights, New South Wales, Australia; joerg.mattes{at}newcastle.edu.au

Abstract

Background Nitric oxide in exhaled air (eNO) is used as a marker of type 2 immune response-induced airway inflammation. We aimed to investigate the association between eNO and bronchiolitis incidence and respiratory symptoms in infancy, and its correlation with eosinophil protein X (EPX).

Methods We followed up infants at 6 weeks of age born to mothers with asthma in pregnancy and measured eNO during natural sleep using a rapid response chemiluminescense analyser (CLD88; EcoMedics), collecting at least 100 breaths, interpolated for an expiratory flow of 50 mL/s. EPX normalised to creatinine was measured in urine samples (uEPX/c). A standardised questionnaire was used to measure symptoms in first year of life. Associations were investigated using multiple linear regression and robust Poisson regression models.

Results eNO levels were obtained in 184 infants, of whom 125/184 (68%) had 12 months questionnaire data available and 51/184 (28%) had uEPX/c measured. Higher eNO was associated with less respiratory symptoms during the first 6 weeks of life (n=184, ß-coefficient: –0.49, 95% CI –0.95 to –0.04, p=0.035). eNO was negatively associated with uEPX/c (ß-coefficient: –0.004, 95% CI –0.008 to –0.001, p=0.021). Risk incidence of bronchiolitis, wheeze, cold or influenza illness and short-acting beta-agonist use significantly decreased by 18%–24% for every unit increase in eNO ppb.

Conclusion Higher eNO levels at 6 weeks of age may be a surrogate for an altered immune response that is associated with less respiratory symptoms in the first year of life.

  • exhaled airway markers
  • viral infection
  • paediatric lung disaese
  • respiratory infection
  • respiratory measurement

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

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Footnotes

  • Twitter @DrPLungResearch

  • Contributors PGG, VEM, PDR, PDS and JM conducted the Breathing for Life Trial (BLT) pregnancy study; PGG, VEM, AMC and JM conducted BLT infant follow-up; PdGB and EdQA performed infant lung function; JM supervised the BLT infant follow-up; CRDSS and EP conducted analysis of eNO data; BP, CO'D, ST, TB and WG conducted uEPX/c measurements; AMC and JM supervised uEPX/c measurements; CRDSS statistical analyses; CRDSS and JM wrote a draft manuscript; all authors edited the final version of the manuscript. JM is the guarantor of this work.

  • Funding This research project was supported by National Health and Medical Research Council Grant number 1081667.

  • Competing interests None declared.

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