Thorax 1998;53:1030-1034 ( December )

Increase in exhaled nitric oxide levels in patients with difficult asthma and correlation with symptoms and disease severity despite treatment with oral and inhaled corticosteroids

R G Stirling, S A Kharitonov, D Campbell, D S Robinson, S R Durham, K F Chung, P J Barnes, for the Asthma and Allergy Group

Royal Brompton Hospital and National Heart and Lung Institute at Imperial College, London, SW3 6LY, UK

Correspondence to: Professor P J Barnes.

Received 29 January 1998; Returned to authors 20 May 1998; Revised version received 2 July 1998; Accepted for publication 2 July 1998

BACKGROUNDPatients with difficult asthma suffer chronic moderate to severe persistent asthma symptoms despite high doses of inhaled and oral corticosteroid therapy. These patients suffer a high level of treatment and disease related morbidity but little is known about the degree of airway inflammation in these patients.
METHODSFifty two patients were examined to assess levels of exhaled nitric oxide (NO) as a surrogate marker of inflammatory activity in this condition. From this group, 26 patients were defined with severe symptoms and current physiological evidence of reversible airway obstruction requiring high dose inhaled (2000 µg beclomethasone dipropionate (BDP) equivalent) or oral steroid therapy to maintain disease control.
RESULTSExhaled NO levels were higher in subjects with difficult asthma (mean 13.9 ppb, 95% CI 9.3 to 18.5) than in normal controls (7.4 ppb, 95% CI 6.9 to 7.8; p<0.002), but lower than levels in steroid naive mild asthmatics (36.9 ppb, 95% CI 34.6 to 39.3; p<0.001). Prednisolone treated patients had higher exhaled NO levels than patients only requiring inhaled corticosteroids (17.5 ppb, 95% CI 11.1 to 24.0 versus 7.2 ppb, 95% CI 4.6 to 9.8; p = 0.016), suggesting greater disease severity in this group. Non-compliance with prednisolone treatment was observed in 20% of patients but this did not explain the difference between the treatment groups. Exhaled NO levels were closely correlated with symptom frequency (p = 0.03) and with rescue  agonist use (p<0.002), but they did not correlate with lung function.
CONCLUSIONSExhaled NO may serve as a useful complement to lung function and symptomatology in the assessment of patients with chronic severe asthma, and in the control and rationalisation of steroid therapy in these patients.

Keywords: exhaled nitric oxide; inflammatory markers; difficult asthma

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© 1998 by Thorax
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