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Correspondence |

Reference Values for Exhaled Nitric Oxide in the General Population FREE TO VIEW

Mario Olivieri, MD; Mario Malerba, MD; Giorgio Talamini, MD; Massimo Corradi, MD
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Affiliations: Department of Medicine and Public Health, University of Verona, Verona, Italy,  Department of Internal Medicine, University of Brescia, Brescia, Italy,  Department of Medicine and Public Health, University of Verona, Verona, Italy,  Department of Clinical Medicine, Nephrology and Health Sciences, University of Parma, Parma, Italy

Correspondence to: Mario Malerba, MD, Department of Internal Medicine, University of Brescia, 1° Divisione di Medicina, Spedali Civili, Pzza Spedali Civili 1, 25100 Brescia, Italy; e-mail: malerba@med.unibs.it


Chest. 2008;133(3):831-832. doi:10.1378/chest.07-2087
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To the Editor:

We read with interest the article by Olin et al1 on the influence of age and height on fractional exhaled nitric oxide (Feno) in a sample of lifelong never-smoking adults randomly selected by a postal questionnaire from the general population. According to these authors,,1the upper limits of Feno range from 24.0 to 54.0 parts per billion (ppb), and the geometric mean of Feno for the whole population is 16.6 ppb (95% confidence interval [CI], 5.87 to 47.14 ppb). Age and height would account for 9 to 11% of the variance of reference values. We think that these statements deserve a comment: in fact, such upper Feno values are definitely higher than those reported in healthy subjects, in both adults and children in American Thoracic Society/European Respiratory Society guidelines2 and in our experience.3 The “normal” range for Feno is influenced by constitutional as much as by environmental and pathophysiologic factors.,2 We do agree that only studies in the general population could detect associations between “abnormal” Feno values and known and supposed risk factors. Recently, Rolla et al,,4investigating 108 of 590 consecutive patients referred in 1 year for rhinitis, reported that Feno is significantly higher in patients with allergic rhinitis and chronic rhinosinusitis compared to patients with nonallergic rhinitis (44.3 ppb [95% CI, 34 to 54 ppb] and 53 ppb [95% CI, 42 to 64 ppb] vs 22 ppb [95% CI, 18 to 27 ppb], respectively), reinforcing and extending the Allergic Rhinitis and Its Impact on Asthma guidelines5 of testing for asthma patients with allergic rhinitis. Seasonal variations of Feno values due to fluctuations of exposure to allergens have also been reported in patients with allergic asthma and also seasonal allergic rhinitis. According to this hypothesis, whether the measurements were performed during or outside the pollen season should have been reported,6 with rhinitis and asthma having a similar weight in Feno changes as recently reported by Travers et al7 in a random community survey of adults. The high prevalence of allergic rhinitis and/or nasal symptoms, probably missing in replies to the questionnaire8 or in statistical analysis,1 could represent an important confounder for reference values. Moreover, a positive correlation between Feno and dietary consumption of fats in children with asthma assuming low levels of antioxidants has recently been reported,,9 thus suggesting the need of further studies might aimed at investigating the relationship between Feno levels and dietary habits.

In conclusion, the evaluation of normal values for Feno in the general population must take in account not only smoke, gender, height, weight, age, atopy, current respiratory and nasal symptoms, asthma, and steroid assumption, but probably some other factors such as diet. Establishing reference values is particularly difficult when the prevalence of potential confounders and of the clinical condition to be diagnosed is relatively high in the general population. Unless a valid reason is provided to explain such high values, their use for diagnostic purposes is potentially misleading.

The authors have no conflicts of interest to disclose.

Olin, AC, Rosengren, A, Bake, B, et al (2007) Fraction of exhaled nitric oxide at 50 mL/s: reference values for adult lifelong never-smokers.Chest131,1852-1856
 
ATS/ERS recommendations for standardized procedures for online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide.2005. Am J Respir Crit Care Med2005;171,912-930
 
Olivieri, M, Talamini, G, Corradi, M, et al Reference Values for Exhaled Nitric Oxide (REVENO) study.Respir Res2006;30,94-99
 
Rolla, G, Guida, G, Heffler, E, et al Diagnostic classification of persistent rhinitis and its relationship to exhaled nitric oxide and asthma: a clinical study of a consecutive series of patients.Chest2007;131,1345-1352
 
Bousquet, J, Van Cauwenberge, P, Khaltaev, N Allergic rhinitis and its impact on asthma.J Allergy Clin Immunol2001;108 (5 suppl),S147-S334
 
Vahlkvist, S, Sinding, M, Skamstrup, K, et al Daily home measurements of exhaled nitric oxide in asthmatic children during natural birch pollen exposure.J Allergy Clin Immunol2006;117,1272-1276
 
Travers, J, Marsh, S, Aldington, S, et al Reference ranges for exhaled nitric oxide derived from a random community survey of adults.Am J Respir Crit Care Med2007;176,238-242
 
Olin, AC, Rosengren, A, Thelle, DS, et al Height, age, and atopy are associated with the fraction of exhaled nitric oxide in a large adult general population sample.Chest2006;130,1319-1325
 
Cardinale, F, Tesse, R, Fucilli, C, et al Correlation between exhaled nitric oxide and dietary consumption of fats and antioxidants in children with asthma.J Allergy Clin Immunol2007;119,1268-1270
 

Figures

Tables

References

Olin, AC, Rosengren, A, Bake, B, et al (2007) Fraction of exhaled nitric oxide at 50 mL/s: reference values for adult lifelong never-smokers.Chest131,1852-1856
 
ATS/ERS recommendations for standardized procedures for online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide.2005. Am J Respir Crit Care Med2005;171,912-930
 
Olivieri, M, Talamini, G, Corradi, M, et al Reference Values for Exhaled Nitric Oxide (REVENO) study.Respir Res2006;30,94-99
 
Rolla, G, Guida, G, Heffler, E, et al Diagnostic classification of persistent rhinitis and its relationship to exhaled nitric oxide and asthma: a clinical study of a consecutive series of patients.Chest2007;131,1345-1352
 
Bousquet, J, Van Cauwenberge, P, Khaltaev, N Allergic rhinitis and its impact on asthma.J Allergy Clin Immunol2001;108 (5 suppl),S147-S334
 
Vahlkvist, S, Sinding, M, Skamstrup, K, et al Daily home measurements of exhaled nitric oxide in asthmatic children during natural birch pollen exposure.J Allergy Clin Immunol2006;117,1272-1276
 
Travers, J, Marsh, S, Aldington, S, et al Reference ranges for exhaled nitric oxide derived from a random community survey of adults.Am J Respir Crit Care Med2007;176,238-242
 
Olin, AC, Rosengren, A, Thelle, DS, et al Height, age, and atopy are associated with the fraction of exhaled nitric oxide in a large adult general population sample.Chest2006;130,1319-1325
 
Cardinale, F, Tesse, R, Fucilli, C, et al Correlation between exhaled nitric oxide and dietary consumption of fats and antioxidants in children with asthma.J Allergy Clin Immunol2007;119,1268-1270
 
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