Skip to main content

Methodological Implications and Repeatability of Nasal Nitric Oxide: Relevance for Challenge Studies

  • Chapter
  • First Online:
Respiratory Ailments in Context

Abstract

There is an interest in assessing changes in nasal NO (nNO) levels as an effect marker of upper airways. In this study, we examined methodologic influences on short and long term repeatability of nNO levels assessed by a portable electrochemical analyzer. Nine atopic and eighteen healthy subjects were exposed for 4 h to ethyl acrylate concentration of 0.05 ppm (sham) and mean concentrations of 5 ppm (either constant 5 ppm or variable 0 to 10 ppm). Sampling of nNO was performed by using passive aspiration during both breath-holding (634 ppb) or calm tidal breathing (364 ppb, p < 0.0001). The intra-session (between-session) repeatability in terms of coefficient of variation was 16.4% (18.5%) using the tidal-breathing and 8.6% (13.0%) using the breath-holding method, respectively. Atopic subjects demonstrated a significant increase in nNO (breath-holding mean 16%, tidal-breathing mean 32%) after applying a constant ethyl acrylate concentration (5 ppm). Our findings suggest that the less elaborate tidal-breathing method might be sufficient to detect significant changes at a group level. Given a lower coefficient of variation of breath-holding we assume there is an advantage of that approach at an individual level. Further research is needed to validate the usefulness of nNO in the evaluation of irritative, non-allergic responses.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Antosova M, Mokra D, Tonhajzerova I, Mikolka P, Kosutova P, Mestanik M, Pepucha L, Plevkova J, Buday T, Calkovsky V, Bencova A (2017) Nasal nitric oxide in healthy adults - reference values and affecting factors. Physiol Res 66(Suppl 2):247–255

    Google Scholar 

  • Arts JH, de Heer C, Woutersen RA (2006) Local effects in the respiratory tract: relevance of subjectively measured irritation for setting occupational exposure limits. Int Arch Occup Environ Health 79:283–298

    Article  Google Scholar 

  • ATS/ERS (2005) American Thoracic Society; European Respiratory Society recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide. Am J Respir Crit Care Med 71:912–930

    Google Scholar 

  • Bartley J, Fergusson W, Moody A, Wells AU, Kolbe J (1999) Normal adult values, diurnal variation, and repeatability of nasal nitric oxide measurement. Am J Rhinol 13:401–405

    Article  CAS  Google Scholar 

  • Boot JD, de Kam ML, Mascelli MA, Miller B, van Wijk RG, de Groot H, Cohen AF, Diamant Z (2007) Nasal nitric oxide: longitudinal reproducibility and the effects of a nasal allergen challenge in patients with allergic rhinitis. Allergy 62:378–384

    Article  CAS  Google Scholar 

  • Brüning T, Bartsch R, Bolt HM, Desel H, Drexler H, Gundert-Remy U, Hartwig A, Jäckh R, Leibold E, Pallapies D, Rettenmeier AW, Schlüter G, Stropp G, Sucker K, Triebig G, Westphal G, van Thriel C (2014) Sensory irritation as a basis for setting occupational exposure limits. Arch Toxicol 88:1855–1879

    Article  Google Scholar 

  • Colantonio D, Brouillette L, Parikh A, Scadding GK (2002) Paradoxical low nasal nitric oxide in nasal polyposis. Clin Exp Allergy 32:698–701

    Article  CAS  Google Scholar 

  • Dalton P (2003) Upper airway irritation, odor perception and health risk due to airborne chemicals. Toxicol Lett 140-141:239–248

    Article  CAS  Google Scholar 

  • De Winter-de Groot KM, van der Ent CK (2009) Measurement of nasal nitric oxide: evaluation of six different sampling methods. Eur J Clin Investig 39:72–77

    Article  Google Scholar 

  • Dressel H, Bihler A, Jund F, de la Motte D, Nowak D, Jörres RA, Kramer MF (2008) Diurnal variation of nasal nitric oxide levels in healthy subjects. J Investig Allergol Clin Immunol 18:316–317

    CAS  PubMed  Google Scholar 

  • Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO, Olin AC, Plummer AL, Taylor DR, American Thoracic Society Committee on Interpretation of Exhaled Nitric Oxide Levels (FENO) for Clinical Applications (2011) An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med 184:602–615

    Article  CAS  Google Scholar 

  • Ferguson EA, Eccles R (1997) Changes in nasal nitric oxide concentration associated with symptoms of common cold and treatment with a topical nasal decongestant. Acta Otolaryngol 117:614–617

    Article  CAS  Google Scholar 

  • Furukawa K, Harrison DG, Saleh D, Shennib H, Chagnon FP, Giaid A (1996) Expression of nitric oxide synthase in the human nasal mucosa. Am J Respir Crit Care Med 153:847–850

    Article  CAS  Google Scholar 

  • Gehring U, Oldenwening M, Brunekreef B, Wieringa MH, Kerkhof M, Smit HA, van der Ent CK, De Jongste JC (2009) The impact of ambient NO on online measurements of exhaled and nasal NO: the PIAMA study. Pediatr Allergy Immunol 20:665–672

    Article  Google Scholar 

  • Gelardi M, Abbattista G, Quaranta VN, Quaranta N, Seccia V, Buttafava S, Frati F, Ciprandi G (2016) Standardization procedure for the nasal nitric oxide measurement method using Niox MINO® and the tidal-breathing technique with velum-closure. J Biol Regul Homeost Agents 30:853–858

    CAS  PubMed  Google Scholar 

  • Henriksen AH, Sue-Chu M, Holmen TL, Langhammer A, Bjermer L (1999) Exhaled and nasal NO levels in allergic rhinitis: relation to sensitization, pollen season and bronchial hyperresponsiveness. Eur Respir J 13:301–306

    Article  CAS  Google Scholar 

  • Hoffmeyer F, Bünger J, Monsé C, Berresheim H, Jettkant B, Beine A, Brüning T, Sucker K (2016) Clinical effects, exhaled breath condensate pH and exhaled nitric oxide in humans after ethyl acrylate exposure. Adv Exp Med Biol 921:11–20

    Article  CAS  Google Scholar 

  • Hoffmeyer F, Sucker K, Berresheim H, Monsé C, Jettkant B, Beine A, Raulf M, Bünger J, Brüning T (2017) Impact of internal and external factors on EBC-pH and FeNO changes in humans following challenge with ethyl acrylate. Adv Exp Med Biol 1020:7–16

    Article  CAS  Google Scholar 

  • Horváth I, Barnes PJ, Loukides S, Sterk PJ, Högman M, Olin AC, Amann A, Antus B, Baraldi E, Bikov A, Boots AW, Bos LD, Brinkman P, Bucca C, Carpagnano GE, Corradi M, Cristescu S, de Jongste JC, Dinh-Xuan AT, Dompeling E, Fens N, Fowler S, Hohlfeld JM, Holz O, Jöbsis Q, Van De Kant K, Knobel HH, Kostikas K, Lehtimäki L, Lundberg J, Montuschi P, Van Muylem A, Pennazza G, Reinhold P, Ricciardolo FLM, Rosias P, Santonico M, van der Schee MP, van Schooten FJ, Spanevello A, Tonia T, Vink TJ (2017) A European Respiratory Society technical standard: exhaled biomarkers in lung disease. Eur Respir J 49:1600965

    Article  Google Scholar 

  • Kharitonov SA, Rajakulasingam K, O’Connor B, Durham SR, Barnes PJ (1997) Nasal nitric oxide is increased in patients with asthma and allergic rhinitis and may be modulated by nasal glucocorticoids. J Allergy Clin Immunol 99:58–64

    CAS  PubMed  Google Scholar 

  • Kharitonov SA, Walker L, Barnes PJ (2005) Repeatability of standardised nasal nitric oxide measurements in healthy and asthmatic adults and children. Respir Med 99:1105–1114

    Article  Google Scholar 

  • Krantz C, Janson C, Borres MP, Nordvall L, Alving K, Malinovschi A (2014) Nasal nitric oxide is associated with exhaled NO, bronchial responsiveness and poor asthma control. J Breath Res 8(2):026002

    Article  CAS  Google Scholar 

  • Lundberg JO, Farkas-Szallasi T, Weitzberg E, Rinder J, Lidholm J, Anggåard A, Hökfelt T, Lundberg JM, Alving K (1995) High nitric oxide production in human paranasal sinuses. Nat Med 1:370–373

    Article  CAS  Google Scholar 

  • Maniscalco M, de Laurentiis G, Weitzberg E, Lundberg JO, Sofia M (2008) Validation study of nasal nitric oxide measurements using a hand-held electrochemical analyser. Eur J Clin Investig 38:197–200

    Article  CAS  Google Scholar 

  • Maniscalco M, Bianco A, Mazzarella G, Motta A (2016) Recent advances on nitric oxide in the upper airways. Curr Med Chem 23:2736–2745

    Article  CAS  Google Scholar 

  • Marthin JK, Nielsen KG (2013) Hand-held tidal breathing nasal nitric oxide measurement--a promising targeted case-finding tool for the diagnosis of primary ciliary dyskinesia. PLoS One 8(2):e57262

    Article  CAS  Google Scholar 

  • Montella S, Alving K, Maniscalco M, Sofia M, De Stefano S, Raia V, Santamaria F (2011) Measurement of nasal nitric oxide by hand-held and stationary devices. Eur J Clin Investig 41:1063–1070

    Article  CAS  Google Scholar 

  • Palm JP, Graf P, Lundberg JO, Alving K (2000) Characterization of exhaled nitric oxide: introducing a new reproducible method for nasal nitric oxide measurements. Eur Respir J 16:236–241

    Article  CAS  Google Scholar 

  • Quirce S, Lemière C, de Blay F, del Pozo V, Gerth Van Wijk R, Maestrelli P, Pauli G, Pignatti P, Raulf-Heimsoth M, Sastre J, Storaas T, Moscato G (2010) Noninvasive methods for assessment of airway inflammation in occupational settings. Allergy 65:445–458

    Article  CAS  Google Scholar 

  • Raulf M, van Kampen V, Neumann HD, Liebers V, Deckert A, Brüning T, Bünger J, Hoffmeyer F (2017) Airway and blood inflammatory markers in waste collectors. Adv Exp Med Biol 1021:1–14

    Article  CAS  Google Scholar 

  • Serrano CD, Valero A, Bartra J, Roca-Ferrer J, Muñoz-Cano R, Sánchez-López J, Mullol J, Picado C (2012) Nasal and bronchial inflammation after nasal allergen challenge: assessment using noninvasive methods. J Investig Allergol Clin Immunol 22:351–356

    CAS  PubMed  Google Scholar 

  • Stark HJ, Randell JT, Hirvonen MR, Purokivi MK, Roponen MH, Tukiainen HO (2005) The effects of Aspergillus fumigatus challenge on exhaled and nasal NO levels. Eur Respir J 26:887–893

    Article  CAS  Google Scholar 

  • Stark H, Purokivi M, Kiviranta J, Randell J, Tukiainen H (2007) Short-term and seasonal variations of exhaled and nasal NO in healthy subjects. Respir Med 101:265–271

    Article  Google Scholar 

  • Wodehouse T, Kharitonov SA, Mackay IS, Barnes PJ, Wilson R, Cole PJ (2003) Nasal nitric oxide measurements for the screening of primary ciliary dyskinesia. Eur Respir J 21:43–47

    Article  CAS  Google Scholar 

Download references

Conflicts of Interest

The authors declare no conflicts of interest in relation to this article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Frank Hoffmeyer .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Hoffmeyer, F. et al. (2018). Methodological Implications and Repeatability of Nasal Nitric Oxide: Relevance for Challenge Studies. In: Pokorski, M. (eds) Respiratory Ailments in Context. Advances in Experimental Medicine and Biology(), vol 1113. Springer, Cham. https://doi.org/10.1007/5584_2018_166

Download citation

Publish with us

Policies and ethics