A suitable protocol for measuring alveolar nitric oxide in asthma with differing severity to assess peripheral airways inflammationCitation formats

  • External authors:
  • Z. Lázár
  • P. Horváth
  • R. Puskás
  • G. Gálffy
  • G. Losonczy
  • I. Horváth

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A suitable protocol for measuring alveolar nitric oxide in asthma with differing severity to assess peripheral airways inflammation. / Lázár, Z.; Horváth, P.; Puskás, R.; Gálffy, G.; Losonczy, G.; Horváth, I.; Bikov, A.

In: Journal of Asthma, 2018.

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Lázár, Z. ; Horváth, P. ; Puskás, R. ; Gálffy, G. ; Losonczy, G. ; Horváth, I. ; Bikov, A. / A suitable protocol for measuring alveolar nitric oxide in asthma with differing severity to assess peripheral airways inflammation. In: Journal of Asthma. 2018.

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@article{3103200ecb9f4a57ab18ecac2b1b49af,
title = "A suitable protocol for measuring alveolar nitric oxide in asthma with differing severity to assess peripheral airways inflammation",
abstract = "Objective: Extended nitric oxide (NO) analysis offers the partitioned monitoring of inflammation in central and peripheral airways. Different mathematical models are used to estimate pulmonary NO dynamics in asthma with variable results and limitations. We aimed to establish a protocol for extended NO analysis in patients with differing asthma severity. Methods: Forty patients with stable asthma and 25 matched control subjects were recruited. Exhaled NO was measured at constant flow rates between 10 and 300 mL/s. Twelve controls performed NO measurements weekly for 4 weeks. Results: The proportions of patients with technically acceptable measurements at 10–30–50–100–150–200–250–300 mL/s exhalation flow rates were 8–58–100–98–98–95–90–80{\%}, respectively. Alveolar NO (CANO) and total flux of NO in the conducting airways (JawNO) were calculated with the linear method from NO values measured at 100–150–200–250 mL/s exhalation flows. The mean intrasubject bias for JawNO and CANO in controls was 0.16 nL/s and 0.85 ppb, respectively. Both JawNO (1.31/0.83–2.97/vs. 0.70/0.54–0.87/nL/s, p < 0.001) and CANO (4.08/2.63–7.16/vs. 2.42/1.83–2.89/ppb, p < 0.001) were increased in patients with asthma compared to controls. In patients, CANO correlated with RV/TLC (r = 0.58, p < 0.001), FEF25-75{\%} (p = 0.02, r = –0.36) and DL,CO (r = –0.46, p = 0.004). JawNO was not related to lung function parameters. Conclusions: Calculation of alveolar NO concentration with the linear method from values obtained at medium flow rates (100–250 mL/s) is feasible even in asthmatic patients with severe airflow limitation and may provide information on small airways dysfunction in asthma. {\circledC} 2018, {\circledC} 2018 Taylor & Francis Group, LLC.",
keywords = "Airway inflammation, disease monitoring, exhaled biomarker, extended nitric oxide analysis, severe asthma",
author = "Z. L{\'a}z{\'a}r and P. Horv{\'a}th and R. Pusk{\'a}s and G. G{\'a}lffy and G. Losonczy and I. Horv{\'a}th and A. Bikov",
note = "Cited By :1 Export Date: 20 February 2019 Article in Press CODEN: JOUAD Correspondence Address: L{\'a}z{\'a}r, Z.; Department of Pulmonology, Semmelweis University, 1/c Di{\'o}s {\'a}rok, Hungary; email: lazar.zsofia@med.semmelweis-univ.hu References: http://www.ginaasthma.org, Available from:, [last accessed 15 Dec 2016]; Hamid, Q., Song, Y., Kotsimbos, T.C., Minshall, E., Bai, T.R., Hegele, R.G., Hogg, J.C., Inflammation of small airways in asthma (1997) J Allergy Clin Immunol, 100, pp. 44-51; Minshall, E.M., Hodd, J.C., Hamid, Q.A., Cytokine mRNA expression in asthma is not restricted to the large airways (1998) J Allergy Clin Immunol, 101, pp. 386-390; Kraft, M., Djukanovic, R., Wilson, S., Holgate, S.T., Martin, R.J., Alveolar tissue inflammation in asthma (1996) Am J Respir Crit Care Med, 154, pp. 1505-1510; Tsoukias, N.M., George, S.C., A two-compartment model of pulmonary nitric oxide exchange dynamics (1998) J Appl Physiol (1985), 85, pp. 653-666; George, S.C., Hogman, M., Permutt, S., Silkoff, P.E., Modeling pulmonary nitric oxide exchange (2004) J Appl Physiol (1985), 96, pp. 831-839; Horvath, I., Barnes, P.J., Loukides, S., Sterk, P.J., Hogman, M., Olin, A.C., Amann, A., A European Respiratory Society technical standard: exhaled biomarkers in lung disease (2017) Eur Respir J, 49, p. 1600965; Nathan, R.A., Sorkness, C.A., Kosinski, M., Schatz, M., Li, J.T., Marcus, P., Murray, J.J., Pendergraft, T.B., Development of the asthma control test: a survey for assessing asthma control (2004) J Allergy Clin Immunol, 113, pp. 59-65; ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005 (2005) Am J Respir Crit Care Med, 171, pp. 912-930; Miller, M.R., Hankinson, J., Brusasco, V., Burgos, F., Casaburi, R., Coates, A., Crapo, R., Standardisation of spirometry (2005) Eur Respir J, 26, pp. 319-338; Wanger, J., Clausen, J.L., Coates, A., Pedersen, O.F., Brusasco, V., Burgos, F., Casaburi, R., Standardisation of the measurement of lung volumes (2005) Eur Respir J, 26, pp. 511-522; Macintyre, N., Crapo, R.O., Viegi, G., Johnson, D.C., van der Grinten, C.P., Brusasco, V., Burgos, F., Standardisation of the single-breath determination of carbon monoxide uptake in the lung (2005) Eur Respir J, 26, pp. 720-735; Bland, J.M., Altman, D.G., Statistical methods for assessing agreement between two methods of clinical measurement (1986) Lancet, 327, pp. 307-310; Zeidler, M.R., Goldin, J.G., Kleerup, E.C., Kim, H.J., Truong, D.A., Gjertson, D.W., Kennedy, N.J., Small airways response to naturalistic cat allergen exposure in subjects with asthma (2006) J Allergy Clin Immunol, 118, pp. 1075-1081; in 't Veen, J.C., Beekman, A.J., Bel, E.H., Sterk, P.J., Recurrent exacerbations in severe asthma are associated with enhanced airway closure during stable episodes (2000) Am J Respir Crit Care Med, 161, pp. 1902-1906; Roos, A.B., Mori, M., Gronneberg, R., Osterlund, C., Claesson, H.E., Wahlstrom, J., Grunewald, J., Elevated exhaled nitric oxide in allergen-provoked asthma is associated with airway epithelial iNOS (2014) PLoS One, 9; Gelb, A.F., Taylor, C.F., Nussbaum, E., Gutierrez, C., Schein, A., Shinar, C.M., Schein, M.J., Alveolar and airway sites of nitric oxide inflammation in treated asthma (2004) Am J Respir Crit Care Med, 170, pp. 737-741; van Veen, I.H., Sterk, P.J., Schot, R., Gauw, S.A., Rabe, K.F., Bel, E.H., Alveolar nitric oxide versus measures of peripheral airway dysfunction in severe asthma (2006) Eur Respir J, 27, pp. 951-956; Brindicci, C., Ito, K., Barnes, P.J., Kharitonov, S.A., Differential flow analysis of exhaled nitric oxide in patients with asthma of differing severity (2007) Chest, 131, pp. 1353-1362; Berry, M., Hargadon, B., Morgan, A., Shelley, M., Richter, J., Shaw, D., Green, R.H., Alveolar nitric oxide in adults with asthma: evidence of distal lung inflammation in refractory asthma (2005) Eur Respir J, 25, pp. 986-991; Lehtimaki, L., Kankaanranta, H., Saarelainen, S., Turjanmaa, V., Moilanen, E., Increased alveolar nitric oxide concentration in asthmatic patients with nocturnal symptoms (2002) Eur Respir J, 20, pp. 841-845; Lehtimaki, L., Kankaanranta, H., Saarelainen, S., Turjanmaa, V., Moilanen, E., Inhaled fluticasone decreases bronchial but not alveolar nitric oxide output in asthma (2001) Eur Respir J, 18, pp. 635-639; Williamson, P.A., Short, P.M., Vaidyanathan, S., Lipworth, B.J., Inhaled and systemic corticosteroid response in severe asthma assessed by alveolar nitric oxide: a randomized crossover pilot study of add-on therapy (2013) Br J Clin Pharmacol, 75, pp. 93-102; Sorkness, R.L., Bleecker, E.R., Busse, W.W., Calhoun, W.J., Castro, M., Chung, K.F., Curran-Everett, D., Lung function in adults with stable but severe asthma: air trapping and incomplete reversal of obstruction with bronchodilation (2008) J Appl Physiol, 104, pp. 394-403; Burgel, P.R., The role of small airways in obstructive airway diseases (2011) Eur Respir Rev, 20, pp. 023-033; Fujisawa, T., Yasui, H., Akamatsu, T., Hashimoto, D., Enomoto, N., Inui, N., Nakamura, Y., Alveolar nitric oxide concentration reflects peripheral airway obstruction in stable asthma (2013) Respirology, 18, pp. 522-527; Lehtimaki, L., Kankaanranta, H., Saarelainen, S., Hahtola, P., Jarvenpaa, R., Koivula, T., Turjanmaa, V., Moilanen, E., Extended exhaled NO measurement differentiates between alveolar and bronchial inflammation (2001) Am J Respir Crit Care Med, 163, pp. 1557-1561; Malinovschi, A., Janson, C., Borres, M., Alving, K., Simultaneously increased fraction of exhaled nitric oxide levels and blood eosinophil counts relate to increased asthma morbidity (2016) J Allergy Clin Immunol, 138, pp. 1301-1308 e2; Matsumoto, H., Niimi, A., Jinnai, M., Nakaji, H., Takeda, T., Oguma, T., Otsuka, K., Association of alveolar nitric oxide levels with pulmonary function and its reversibility in stable asthma (2011) Respiration, 81, pp. 311-317; Gelb, A.F., George, S.C., Camacho, F., Fraser, C., Flynn Taylor, C., Shakkottai, S., Increased nitric oxide concentrations in the small airway of older normal subjects (2011) Increased nitric oxide concentrations in the small airway of older normal subjects. Chest, 139, pp. 368-375; Paraskakis, E., Brindicci, C., Fleming, L., Krol, R., Kharitonov, S.A., Wilson, N.M., Barnes, P.J., Bush, A., Measurement of bronchial and alveolar nitric oxide production in normal children and children with asthma (2006) Am J Respir Crit Care Med, 174, pp. 260-267; Kerckx, Y., Michils, A., Van Muylem, A., Airway contribution to alveolar nitric oxide in healthy subjects and stable asthma patients (2008) J Appl Physiol, 104, pp. 918-924. , 1985; Gelb, A.F., George, S.C., Silkoff, P.E., Krishnan, A., Fraser, C., Taylor, C.F., Shinar, C.M., Maginot, T., Central and peripheral airway/alveolar sites of exhaled nitric oxide in acute asthma (2010) Thorax, 65, pp. 619-625; Heijkenskjold-Rentzhog, C., Nordvall, L., Janson, C., Borres, M.P., Alving, K., Malinovschi, A., Alveolar and exhaled NO in relation to asthma characteristics–effects of correction for axial diffusion (2014) Allergy, 69, pp. 1102-1111; Verbanck, S., Malinovschi, A., George, S., Gelb, A.F., Vincken, W., Van Muylem, A., Bronchial and alveolar components of exhaled nitric oxide and their relationship (2012) Eur Respir J, 39, pp. 1258-1261; Giovannelli, J., Cherot-Kornobis, N., Hulo, S., Ciuchete, A., Clement, G., Amouyel, P., Matran, R., Dauchet, L., Both exhaled nitric oxide and blood eosinophil count were associated with mild allergic asthma only in non-smokers (2016) Clin Exp Allergy, 46, pp. 543-554; Spears, M., Weir, C.J., Smith, A.D., McSharry, C., Chaudhuri, R., Johnson, M., Cameron, E., Thomson, N.C., Bronchial nitric oxide flux (J'aw) is sensitive to oral corticosteroids in smokers with asthma (2011) Respir Med, 105, pp. 1823-1830; Orosz, M., Tam{\'a}si, L., G{\'a}lffy, G., Cigarette smoking and asthma control in Hungarian asthmatic patients (2009) Med Thor, 62, pp. 112-119; Chen, Y., Mai, X.M., Smoking and asthma in men and women with normal weight, overweight, and obesity (2011) J Asthma, 48, pp. 490-494; Polosa, R., Thomson, N.C., Smoking and asthma: dangerous liaisons (2013) Eur Respir J, 41, pp. 716-726; Konno, S., Taniguchi, N., Makita, H., Nakamaru, Y., Shimizu, K., Shijubo, N., Fuke, S., Distinct phenotypes of smokers with fixed airflow limitation identified by cluster analysis of severe asthma (2018) Ann Am Thorac Soc, 15, pp. 33-41",
year = "2018",
doi = "10.1080/02770903.2018.1477957",
language = "English",
journal = "Journal of Asthma",
issn = "0277-0903",
publisher = "Taylor & Francis",

}

RIS

TY - JOUR

T1 - A suitable protocol for measuring alveolar nitric oxide in asthma with differing severity to assess peripheral airways inflammation

AU - Lázár, Z.

AU - Horváth, P.

AU - Puskás, R.

AU - Gálffy, G.

AU - Losonczy, G.

AU - Horváth, I.

AU - Bikov, A.

N1 - Cited By :1 Export Date: 20 February 2019 Article in Press CODEN: JOUAD Correspondence Address: Lázár, Z.; Department of Pulmonology, Semmelweis University, 1/c Diós árok, Hungary; email: lazar.zsofia@med.semmelweis-univ.hu References: http://www.ginaasthma.org, Available from:, [last accessed 15 Dec 2016]; Hamid, Q., Song, Y., Kotsimbos, T.C., Minshall, E., Bai, T.R., Hegele, R.G., Hogg, J.C., Inflammation of small airways in asthma (1997) J Allergy Clin Immunol, 100, pp. 44-51; Minshall, E.M., Hodd, J.C., Hamid, Q.A., Cytokine mRNA expression in asthma is not restricted to the large airways (1998) J Allergy Clin Immunol, 101, pp. 386-390; Kraft, M., Djukanovic, R., Wilson, S., Holgate, S.T., Martin, R.J., Alveolar tissue inflammation in asthma (1996) Am J Respir Crit Care Med, 154, pp. 1505-1510; Tsoukias, N.M., George, S.C., A two-compartment model of pulmonary nitric oxide exchange dynamics (1998) J Appl Physiol (1985), 85, pp. 653-666; George, S.C., Hogman, M., Permutt, S., Silkoff, P.E., Modeling pulmonary nitric oxide exchange (2004) J Appl Physiol (1985), 96, pp. 831-839; Horvath, I., Barnes, P.J., Loukides, S., Sterk, P.J., Hogman, M., Olin, A.C., Amann, A., A European Respiratory Society technical standard: exhaled biomarkers in lung disease (2017) Eur Respir J, 49, p. 1600965; Nathan, R.A., Sorkness, C.A., Kosinski, M., Schatz, M., Li, J.T., Marcus, P., Murray, J.J., Pendergraft, T.B., Development of the asthma control test: a survey for assessing asthma control (2004) J Allergy Clin Immunol, 113, pp. 59-65; ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005 (2005) Am J Respir Crit Care Med, 171, pp. 912-930; Miller, M.R., Hankinson, J., Brusasco, V., Burgos, F., Casaburi, R., Coates, A., Crapo, R., Standardisation of spirometry (2005) Eur Respir J, 26, pp. 319-338; Wanger, J., Clausen, J.L., Coates, A., Pedersen, O.F., Brusasco, V., Burgos, F., Casaburi, R., Standardisation of the measurement of lung volumes (2005) Eur Respir J, 26, pp. 511-522; Macintyre, N., Crapo, R.O., Viegi, G., Johnson, D.C., van der Grinten, C.P., Brusasco, V., Burgos, F., Standardisation of the single-breath determination of carbon monoxide uptake in the lung (2005) Eur Respir J, 26, pp. 720-735; Bland, J.M., Altman, D.G., Statistical methods for assessing agreement between two methods of clinical measurement (1986) Lancet, 327, pp. 307-310; Zeidler, M.R., Goldin, J.G., Kleerup, E.C., Kim, H.J., Truong, D.A., Gjertson, D.W., Kennedy, N.J., Small airways response to naturalistic cat allergen exposure in subjects with asthma (2006) J Allergy Clin Immunol, 118, pp. 1075-1081; in 't Veen, J.C., Beekman, A.J., Bel, E.H., Sterk, P.J., Recurrent exacerbations in severe asthma are associated with enhanced airway closure during stable episodes (2000) Am J Respir Crit Care Med, 161, pp. 1902-1906; Roos, A.B., Mori, M., Gronneberg, R., Osterlund, C., Claesson, H.E., Wahlstrom, J., Grunewald, J., Elevated exhaled nitric oxide in allergen-provoked asthma is associated with airway epithelial iNOS (2014) PLoS One, 9; Gelb, A.F., Taylor, C.F., Nussbaum, E., Gutierrez, C., Schein, A., Shinar, C.M., Schein, M.J., Alveolar and airway sites of nitric oxide inflammation in treated asthma (2004) Am J Respir Crit Care Med, 170, pp. 737-741; van Veen, I.H., Sterk, P.J., Schot, R., Gauw, S.A., Rabe, K.F., Bel, E.H., Alveolar nitric oxide versus measures of peripheral airway dysfunction in severe asthma (2006) Eur Respir J, 27, pp. 951-956; Brindicci, C., Ito, K., Barnes, P.J., Kharitonov, S.A., Differential flow analysis of exhaled nitric oxide in patients with asthma of differing severity (2007) Chest, 131, pp. 1353-1362; Berry, M., Hargadon, B., Morgan, A., Shelley, M., Richter, J., Shaw, D., Green, R.H., Alveolar nitric oxide in adults with asthma: evidence of distal lung inflammation in refractory asthma (2005) Eur Respir J, 25, pp. 986-991; Lehtimaki, L., Kankaanranta, H., Saarelainen, S., Turjanmaa, V., Moilanen, E., Increased alveolar nitric oxide concentration in asthmatic patients with nocturnal symptoms (2002) Eur Respir J, 20, pp. 841-845; Lehtimaki, L., Kankaanranta, H., Saarelainen, S., Turjanmaa, V., Moilanen, E., Inhaled fluticasone decreases bronchial but not alveolar nitric oxide output in asthma (2001) Eur Respir J, 18, pp. 635-639; Williamson, P.A., Short, P.M., Vaidyanathan, S., Lipworth, B.J., Inhaled and systemic corticosteroid response in severe asthma assessed by alveolar nitric oxide: a randomized crossover pilot study of add-on therapy (2013) Br J Clin Pharmacol, 75, pp. 93-102; Sorkness, R.L., Bleecker, E.R., Busse, W.W., Calhoun, W.J., Castro, M., Chung, K.F., Curran-Everett, D., Lung function in adults with stable but severe asthma: air trapping and incomplete reversal of obstruction with bronchodilation (2008) J Appl Physiol, 104, pp. 394-403; Burgel, P.R., The role of small airways in obstructive airway diseases (2011) Eur Respir Rev, 20, pp. 023-033; Fujisawa, T., Yasui, H., Akamatsu, T., Hashimoto, D., Enomoto, N., Inui, N., Nakamura, Y., Alveolar nitric oxide concentration reflects peripheral airway obstruction in stable asthma (2013) Respirology, 18, pp. 522-527; Lehtimaki, L., Kankaanranta, H., Saarelainen, S., Hahtola, P., Jarvenpaa, R., Koivula, T., Turjanmaa, V., Moilanen, E., Extended exhaled NO measurement differentiates between alveolar and bronchial inflammation (2001) Am J Respir Crit Care Med, 163, pp. 1557-1561; Malinovschi, A., Janson, C., Borres, M., Alving, K., Simultaneously increased fraction of exhaled nitric oxide levels and blood eosinophil counts relate to increased asthma morbidity (2016) J Allergy Clin Immunol, 138, pp. 1301-1308 e2; Matsumoto, H., Niimi, A., Jinnai, M., Nakaji, H., Takeda, T., Oguma, T., Otsuka, K., Association of alveolar nitric oxide levels with pulmonary function and its reversibility in stable asthma (2011) Respiration, 81, pp. 311-317; Gelb, A.F., George, S.C., Camacho, F., Fraser, C., Flynn Taylor, C., Shakkottai, S., Increased nitric oxide concentrations in the small airway of older normal subjects (2011) Increased nitric oxide concentrations in the small airway of older normal subjects. Chest, 139, pp. 368-375; Paraskakis, E., Brindicci, C., Fleming, L., Krol, R., Kharitonov, S.A., Wilson, N.M., Barnes, P.J., Bush, A., Measurement of bronchial and alveolar nitric oxide production in normal children and children with asthma (2006) Am J Respir Crit Care Med, 174, pp. 260-267; Kerckx, Y., Michils, A., Van Muylem, A., Airway contribution to alveolar nitric oxide in healthy subjects and stable asthma patients (2008) J Appl Physiol, 104, pp. 918-924. , 1985; Gelb, A.F., George, S.C., Silkoff, P.E., Krishnan, A., Fraser, C., Taylor, C.F., Shinar, C.M., Maginot, T., Central and peripheral airway/alveolar sites of exhaled nitric oxide in acute asthma (2010) Thorax, 65, pp. 619-625; Heijkenskjold-Rentzhog, C., Nordvall, L., Janson, C., Borres, M.P., Alving, K., Malinovschi, A., Alveolar and exhaled NO in relation to asthma characteristics–effects of correction for axial diffusion (2014) Allergy, 69, pp. 1102-1111; Verbanck, S., Malinovschi, A., George, S., Gelb, A.F., Vincken, W., Van Muylem, A., Bronchial and alveolar components of exhaled nitric oxide and their relationship (2012) Eur Respir J, 39, pp. 1258-1261; Giovannelli, J., Cherot-Kornobis, N., Hulo, S., Ciuchete, A., Clement, G., Amouyel, P., Matran, R., Dauchet, L., Both exhaled nitric oxide and blood eosinophil count were associated with mild allergic asthma only in non-smokers (2016) Clin Exp Allergy, 46, pp. 543-554; Spears, M., Weir, C.J., Smith, A.D., McSharry, C., Chaudhuri, R., Johnson, M., Cameron, E., Thomson, N.C., Bronchial nitric oxide flux (J'aw) is sensitive to oral corticosteroids in smokers with asthma (2011) Respir Med, 105, pp. 1823-1830; Orosz, M., Tamási, L., Gálffy, G., Cigarette smoking and asthma control in Hungarian asthmatic patients (2009) Med Thor, 62, pp. 112-119; Chen, Y., Mai, X.M., Smoking and asthma in men and women with normal weight, overweight, and obesity (2011) J Asthma, 48, pp. 490-494; Polosa, R., Thomson, N.C., Smoking and asthma: dangerous liaisons (2013) Eur Respir J, 41, pp. 716-726; Konno, S., Taniguchi, N., Makita, H., Nakamaru, Y., Shimizu, K., Shijubo, N., Fuke, S., Distinct phenotypes of smokers with fixed airflow limitation identified by cluster analysis of severe asthma (2018) Ann Am Thorac Soc, 15, pp. 33-41

PY - 2018

Y1 - 2018

N2 - Objective: Extended nitric oxide (NO) analysis offers the partitioned monitoring of inflammation in central and peripheral airways. Different mathematical models are used to estimate pulmonary NO dynamics in asthma with variable results and limitations. We aimed to establish a protocol for extended NO analysis in patients with differing asthma severity. Methods: Forty patients with stable asthma and 25 matched control subjects were recruited. Exhaled NO was measured at constant flow rates between 10 and 300 mL/s. Twelve controls performed NO measurements weekly for 4 weeks. Results: The proportions of patients with technically acceptable measurements at 10–30–50–100–150–200–250–300 mL/s exhalation flow rates were 8–58–100–98–98–95–90–80%, respectively. Alveolar NO (CANO) and total flux of NO in the conducting airways (JawNO) were calculated with the linear method from NO values measured at 100–150–200–250 mL/s exhalation flows. The mean intrasubject bias for JawNO and CANO in controls was 0.16 nL/s and 0.85 ppb, respectively. Both JawNO (1.31/0.83–2.97/vs. 0.70/0.54–0.87/nL/s, p < 0.001) and CANO (4.08/2.63–7.16/vs. 2.42/1.83–2.89/ppb, p < 0.001) were increased in patients with asthma compared to controls. In patients, CANO correlated with RV/TLC (r = 0.58, p < 0.001), FEF25-75% (p = 0.02, r = –0.36) and DL,CO (r = –0.46, p = 0.004). JawNO was not related to lung function parameters. Conclusions: Calculation of alveolar NO concentration with the linear method from values obtained at medium flow rates (100–250 mL/s) is feasible even in asthmatic patients with severe airflow limitation and may provide information on small airways dysfunction in asthma. © 2018, © 2018 Taylor & Francis Group, LLC.

AB - Objective: Extended nitric oxide (NO) analysis offers the partitioned monitoring of inflammation in central and peripheral airways. Different mathematical models are used to estimate pulmonary NO dynamics in asthma with variable results and limitations. We aimed to establish a protocol for extended NO analysis in patients with differing asthma severity. Methods: Forty patients with stable asthma and 25 matched control subjects were recruited. Exhaled NO was measured at constant flow rates between 10 and 300 mL/s. Twelve controls performed NO measurements weekly for 4 weeks. Results: The proportions of patients with technically acceptable measurements at 10–30–50–100–150–200–250–300 mL/s exhalation flow rates were 8–58–100–98–98–95–90–80%, respectively. Alveolar NO (CANO) and total flux of NO in the conducting airways (JawNO) were calculated with the linear method from NO values measured at 100–150–200–250 mL/s exhalation flows. The mean intrasubject bias for JawNO and CANO in controls was 0.16 nL/s and 0.85 ppb, respectively. Both JawNO (1.31/0.83–2.97/vs. 0.70/0.54–0.87/nL/s, p < 0.001) and CANO (4.08/2.63–7.16/vs. 2.42/1.83–2.89/ppb, p < 0.001) were increased in patients with asthma compared to controls. In patients, CANO correlated with RV/TLC (r = 0.58, p < 0.001), FEF25-75% (p = 0.02, r = –0.36) and DL,CO (r = –0.46, p = 0.004). JawNO was not related to lung function parameters. Conclusions: Calculation of alveolar NO concentration with the linear method from values obtained at medium flow rates (100–250 mL/s) is feasible even in asthmatic patients with severe airflow limitation and may provide information on small airways dysfunction in asthma. © 2018, © 2018 Taylor & Francis Group, LLC.

KW - Airway inflammation

KW - disease monitoring

KW - exhaled biomarker

KW - extended nitric oxide analysis

KW - severe asthma

U2 - 10.1080/02770903.2018.1477957

DO - 10.1080/02770903.2018.1477957

M3 - Article

JO - Journal of Asthma

JF - Journal of Asthma

SN - 0277-0903

ER -