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Central and peripheral airway/alveolar sites of exhaled nitric oxide in acute asthma
  1. Arthur F Gelb1,
  2. Steven C George2,
  3. Philip E Silkoff3,
  4. Anita Krishnan4,
  5. Christine Fraser4,
  6. Colleen Flynn Taylor4,
  7. Chris M Shinar5,
  8. Tamara Maginot4
  1. 1Pulmonary Division, Department of Medicine, Lakewood Regional Medical Center, and Geffen School of Medicine, University of California at Los Angeles Medical Center, Lakewood, California, USA
  2. 2Department of Biomedical Engineering and Chemical Engineering and Materials Science, University of California, Irvine, USA
  3. 3Drexel University School of Medicine, Philadelphia, Pennsylvania, USA
  4. 4Lakewood Regional Medical Center, Lakewood, California, USA
  5. 5Department of Performance Improvement and Patient Safety, Orange Coast Memorial Medical Center, Fountain Valley, California, USA
  1. Correspondence to Professor Arthur F Gelb, 3650 E. South St., Suite 308 Lakewood, CA 90712, USA; afgelb{at}


Introduction Central airway nitric oxide flux (J'awNO) and peripheral airway/alveolar nitric oxide concentration (CANO) during asthma exacerbation has not been investigated after correction for axial NO back-diffusion.

Methods After measuring exhaled NO (fraction of exhaled nitric oxide (FENO); ppb) at 50, 100, 150 and 200 ml/s, J'awNO (nl/s) and CANO (ppb) were calculated using the two-compartment model and corrected for axial NO back-diffusion. Fifteen (8 males), non-smoking, patients with moderate-to-severe treated (inhaled corticosteroid (ICS) and inhaled long-acting β2-agonist (LABA)) asthma, age 57±13 years (mean±SD), were studied at baseline, during exacerbation prior to oral corticosteroid, and during recovery after an 8 day tapering prednisone course. Based on earlier asthma studies without correction, it was hypothesised that with correction for NO axial back-diffusion, the incidence of abnormal J'awNO and CANO at baseline and after exacerbation would be ≥30% in 15 patients with asthma with 80% power.

Results At baseline when clinically stable, after 180 μg of albuterol, forced expiratory volume in 1 s (FEV1; litres) was 78±26% predicted (p=0.009) with increased FENO at 50 ml/s (p=0.01) and J'awNO (p=0.02), but CANO was normal compared with the controls. During exacerbation FEV1 (litres) was 57±20% predicted (p=0.02), with increased FENO at 50 ml/s (p=0.01) and J'awNO (p=0.004), but CANO was normal. Recovery results were similar to baseline. Two of 15 patients with asthma always had normal exhaled NO gas exchange.

Conclusions The central airways were the major site of abnormal NO flux in 13 of 15 patients with moderate–severe asthma when stable and during exacerbation and could be easily detected with abnormal FENO at 50 ml/s. CANO was normal.

Clinical trial number NCT00576069.

  • Asthma
  • exhaled nitric oxide
  • lung function
  • exhaled airway markers
  • lung physiology
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  • AK, CF, CFT and TM are independent research contractors.

  • Competing interests PS receives royalties from patents licensed to General Electric Instruments and Aperion, both manufacturers of exhaled NO equipment (range US$2000–US$3000/annum). Consultant to GE Instruments, Aperion and Aperion (range US$10 000–$15 000/annum).

  • Ethics approval This study was conducted with the approval of the Lakewood Regional Medical Center, Lakewood, California, USA; Western IRB, Olympia, Washington, USA and Registered National Clinical Trials: 00576069.

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

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