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• W2055945249 abstract "Measurement of exhaled nitric oxide is widely used in respiratory research and clinical practice, especially in patients with asthma. However, interpretation is often difficult, due to common interfering factors, and little is known about interactions between factors. We assessed the influences and interactions of factors such as smoking, respiratory tract infections and respiratory allergy concerning exhaled nitric oxide values, with the aim to derive a scheme for adjustment. We studied 897 subjects (514 females, 383 males; mean age±standard deviation 34.5±13.0 years) with and without respiratory allergy (allergic rhinitis and/or asthma), smoking and respiratory tract infection. Logarithmic nitric oxide levels were described by an additive model comprising respiratory allergy, smoking, respiratory tract infection, gender and height (p⩽0.001 each), without significant interaction terms. Geometric mean was 17.5ppb in a healthy female non smoker of height 170cm, whereby respiratory allergy corresponded to a change by factor 1.50, smoking 0.63, infection 1.24, male gender 1.17, and each 10cm increase (decrease) in height to 1.11 (0.90). Factors were virtually identical when excluding asthma and using the category allergic rhinitis instead of respiratory allergy (n=863). Within each category formed by combinations of these different predictors, the range of residual variation was approximately constant. We conclude that the factors influencing exhaled nitric oxide, which we analyzed, act independently of each other. Thus, circumstances such as smoking and respiratory tract infection do not appear to affect the usefulness of exhaled nitric oxide, provided that appropriate factors for adjustment are applied. Measurement of exhaled nitric oxide is widely used in respiratory research and clinical practice, especially in patients with asthma. However, interpretation is often difficult, due to common interfering factors, and little is known about interactions between factors. We assessed the influences and interactions of factors such as smoking, respiratory tract infections and respiratory allergy concerning exhaled nitric oxide values, with the aim to derive a scheme for adjustment. We studied 897 subjects (514 females, 383 males; mean age±standard deviation 34.5±13.0 years) with and without respiratory allergy (allergic rhinitis and/or asthma), smoking and respiratory tract infection. Logarithmic nitric oxide levels were described by an additive model comprising respiratory allergy, smoking, respiratory tract infection, gender and height (p⩽0.001 each), without significant interaction terms. Geometric mean was 17.5ppb in a healthy female non smoker of height 170cm, whereby respiratory allergy corresponded to a change by factor 1.50, smoking 0.63, infection 1.24, male gender 1.17, and each 10cm increase (decrease) in height to 1.11 (0.90). Factors were virtually identical when excluding asthma and using the category allergic rhinitis instead of respiratory allergy (n=863). Within each category formed by combinations of these different predictors, the range of residual variation was approximately constant. We conclude that the factors influencing exhaled nitric oxide, which we analyzed, act independently of each other. Thus, circumstances such as smoking and respiratory tract infection do not appear to affect the usefulness of exhaled nitric oxide, provided that appropriate factors for adjustment are applied. A multitude of studies have demonstrated the usefulness of measuring the fraction of exhaled nitric oxide (FENO) in patients with asthma,1Alving K. Weitzberg E. Lundberg J.M. Increased amount of nitric oxide in exhaled air of asthmatics.Eur Respir J. 1993; 6: 1368-1370PubMed Google Scholar allergic rhinitis, or atopy,2Olin A.C. Alving K. Toren K. Exhaled nitric oxide: relation to sensitization and respiratory symptoms.Clin Exp Allergy. 2004; 34: 221-226Crossref PubMed Scopus (72) Google Scholar including the evaluation of treatment effects.3Silkoff P.E. McClean P. Spino M. Erlich L. Slutsky A.S. Zamel N. Dose–response relationship and reproducibility of the fall in exhaled nitric oxide after inhaled beclomethasone dipropionate therapy in asthma patients.Chest. 2001; 119: 1322-1328Crossref PubMed Scopus (144) Google Scholar Besides disease and therapy,4Taylor D.R. Pijnenburg M.W. Smith A.D. De Jongste J.C. Exhaled nitric oxide measurements: clinical application and interpretation.Thorax. 2006; 61: 817-827Crossref PubMed Scopus (394) Google Scholar there are further factors influencing FENO.5ATS/ERS recommendations for standardized procedures for online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide. Am J Respir Crit Care Med 2005;171:912–30.Google Scholar Some of these, such as performing spirometry prior to FENO measurement,6Gabriele C. Pijnenburg M.W.H. Monti F. Hop W. Bakker M.E. de Jongste J.C. The effect of spirometry and exercise on exhaled nitric oxide in asthmatic children.Pediatr Allergy Immunol. 2005; 16: 247Google Scholar can be easily taken into account in clinical practice, while this is more difficult for others, such as current smoking or respiratory tract infections, which are difficult to exclude in patients visiting a physician. Smoking leads to a decrease in FENO,7Kharitonov S.A. Robbins R.A. Yates D. Keatings V. Barnes P.J. Acute and chronic effects of cigarette smoking on exhaled nitric oxide.Am J Respir Crit Care Med. 1995; 152: 609-612Crossref PubMed Scopus (395) Google Scholar though values are still higher in smokers with asthma than in those without.8Horvath I. Donnelly L.E. Kiss A. Balint B. Kharitonov S.A. Barnes P.J. Exhaled nitric oxide and hydrogen peroxide concentrations in asthmatic smokers.Respiration. 2004; 71: 463-468Crossref PubMed Scopus (68) Google Scholar The effects of smoking have been further specified by revealing that the logarithm of FENO showed additive contributions from smoking history and the hours since the last cigarette.9McSharry C.P. McKay I.C. Chaudhuri R. Livingston E. Fraser I. Thomson N.C. Short and long-term effects of cigarette smoking independently influence exhaled nitric oxide concentration in asthma.J Allergy Clin Immunol. 2005; 116: 88-93Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar FENO is also known to be elevated in upper respiratory tract infections,10Kharitonov S.A. Yates D. Barnes P.J. Increased nitric oxide in exhaled air of normal human subjects with upper respiratory tract infections.Eur Respir J. 1995; 8: 295-297Crossref PubMed Scopus (329) Google Scholar and correspondingly in exacerbations of patients with chronic obstructive pulmonary disease (COPD)11Bhowmik A. Seemungal T.A. Donaldson G.C. Wedzicha J.A. Effects of exacerbations and seasonality on exhaled nitric oxide in COPD.Eur Respir J. 2005; 26: 1009-1015Crossref PubMed Scopus (55) Google Scholar or in pulmonary infections of lung transplant patients.12Antus B. Csiszer E. Czebe K. Horvath I. Pulmonary infections increase exhaled nitric oxide in lung transplant recipients: a longitudinal study.Clin Transplant. 2005; 19: 377-382Crossref PubMed Scopus (27) Google Scholar Studies furthermore demonstrated an association with height13Olin A.C. Rosengren A. Thelle D.S. Lissner L. Bake B. Toren K. Height, age, and atopy are associated with fraction of exhaled nitric oxide in a large adult general population sample.Chest. 2006; 130: 1319-1325Crossref PubMed Scopus (242) Google Scholar and gender14Olivieri M. Talamini G. Corradi M. et al.Reference values for exhaled nitric oxide (reveno) study.Resprir Res. 2006; 7: 94Crossref PubMed Scopus (119) Google Scholar; the latter, however, might be attributable to differences in height.13Olin A.C. Rosengren A. Thelle D.S. Lissner L. Bake B. Toren K. Height, age, and atopy are associated with fraction of exhaled nitric oxide in a large adult general population sample.Chest. 2006; 130: 1319-1325Crossref PubMed Scopus (242) Google Scholar In addition, age might be associated with FENO,13Olin A.C. Rosengren A. Thelle D.S. Lissner L. Bake B. Toren K. Height, age, and atopy are associated with fraction of exhaled nitric oxide in a large adult general population sample.Chest. 2006; 130: 1319-1325Crossref PubMed Scopus (242) Google Scholar especially in children15Buchvald F. Baraldi E. Carraro S. et al.Measurements of exhaled nitric oxide in healthy subjects age 4–17 years.J Allergy Clin Immunol. 2005; 115: 1130-1136Abstract Full Text Full Text PDF PubMed Scopus (303) Google Scholar and very old subjects showing elevated values.16Haight R.R.G.R. Brooks S.M. The effects of age on exhaled breath nitric oxide levels.Lung. 2006; 184: 119Google Scholar While clearly establishing the influences on FENO, the available results are not easily applicable for the evaluation of individual values in clinical practice. Some studies were restricted to healthy subjects with and without atopy,14Olivieri M. Talamini G. Corradi M. et al.Reference values for exhaled nitric oxide (reveno) study.Resprir Res. 2006; 7: 94Crossref PubMed Scopus (119) Google Scholar, 15Buchvald F. Baraldi E. Carraro S. et al.Measurements of exhaled nitric oxide in healthy subjects age 4–17 years.J Allergy Clin Immunol. 2005; 115: 1130-1136Abstract Full Text Full Text PDF PubMed Scopus (303) Google Scholar, 17Olin A.C. Bake B. Toren K. Fraction of exhaled nitric oxide at 50mL/s.Chest. 2007; 131: 1852-1856Crossref PubMed Scopus (141) Google Scholar and others2Olin A.C. Alving K. Toren K. Exhaled nitric oxide: relation to sensitization and respiratory symptoms.Clin Exp Allergy. 2004; 34: 221-226Crossref PubMed Scopus (72) Google Scholar, 13Olin A.C. Rosengren A. Thelle D.S. Lissner L. Bake B. Toren K. Height, age, and atopy are associated with fraction of exhaled nitric oxide in a large adult general population sample.Chest. 2006; 130: 1319-1325Crossref PubMed Scopus (242) Google Scholar described the multiple effects with great scrutiny in large populations but the complex results did not translate into easily applicable schemes. Only one study18Travers 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 Med. 2007; 176: 238-242Crossref PubMed Scopus (172) Google Scholar based on a large random sample reported reference ranges for combinations of factors as derived by multivariate analysis. In addition, most studies did not include respiratory tract infections into the set of multiple potential influence factors and the issue of interactions with this factor remains unresolved. Correspondingly, a common conclusion seems to be, e.g., that FENO is difficult to interpret in smokers or subjects suffering from respiratory tract infections, and FENO is often not assessed in these. Therefore, an analysis of factors affecting FENO that aims to meet the practical need for simple, transparent, broadly-to-apply reference values could be a step forward. On the statistical side this involves as a major question, whether the various factors show multiple interactions, including different ranges of variation in different strata, or whether they act independently of each other, with similar variation. The latter would offer the potential to derive a reference state with easily applicable factors for adjustment and variability. It would thus probably facilitate a sensible use of FENO measurements across populations. Consequently, the aim of the present study was to quantify the single and combined effects and interactions of factors such as respiratory allergy, smoking, respiratory tract infection, height, lung function, age and gender on FENO, with special focus on the attempt to express the results in a form that favored their application in clinical practice. Measurements were performed during pre-employment examinations and occupational preventive medical checkups in the Outpatient Clinic for Occupational and Environmental Medicine of the Ludwig-Maximilians-University, Munich. Consecutive examinations (n=1037) between April 2005 and March 2007 were examined for analysis. Subjects using oral or inhaled corticosteroids, or showing airways diseases other than asthma and rhinitis or with incomplete data were excluded from the analysis. In case of repeated measurements the first one was taken. After applying these criteria 897 subjects were included (Table 1). This population comprised 34 subjects with mild allergic asthma, having either no or only bronchodilator therapy. Analyses were performed either with or without these subjects.Table 1Characteristics of the study populationn897Female, n (%)514 (57.3)Age, yr34.5±13.0Height, cm172.0±8.8Weight, kg71.4±15.7BMI, m/kg224.0±4.3FENO, ppb*Due to the data distribution geometric mean and SD are given, the latter being expressed as a factor indicated by ÷. The geometric mean has to be multiplied with and divided by this SD factor.19.6÷1.92FEV1, %predicted106.6±13.4FVC, %predicted110.3±13.3FEV1/VC, %predicted98.3±7.9Respiratory allergies (rhinitis and/or asthma), n (%)206 (23.0)Allergic rhinitis, n (%)193 (21.5)Allergic asthma, n (%)34 (3.8)Current smoking, n (%)218 (24.3)Respiratory tract infection, n (%)190 (21.2)Data are presented either as the number of subjects (% in parentheses) or as mean±SD. BMI=body mass index, FENO=fractional concentration of exhaled nitric oxide, FEV1=forced expiratory volume in 1s, FVC=forced vital capacity.* Due to the data distribution geometric mean and SD are given, the latter being expressed as a factor indicated by ÷. The geometric mean has to be multiplied with and divided by this SD factor. Open table in a new tab Data are presented either as the number of subjects (% in parentheses) or as mean±SD. BMI=body mass index, FENO=fractional concentration of exhaled nitric oxide, FEV1=forced expiratory volume in 1s, FVC=forced vital capacity. FENO was determined during a single exhalation using a chemiluminescence analyzer (NOA 280™, Sievers, Boulder, Co, USA) according to international guidelines.5ATS/ERS recommendations for standardized procedures for online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide. Am J Respir Crit Care Med 2005;171:912–30.Google Scholar After inhaling ambient air subjects started to expire through a mouthpiece against a positive pressure, aiming to achieve a flow rate of 50mL/s under visual control on a computer screen. Ambient air levels normally showed NO levels <15ppb and a correlation analysis showed no relationship between FENO and ambient air NO. Measurements were performed at least in triplicate. The mean of three reproducible values was taken for analysis. Acceptable measurements had to show a clearly identifiable plateau (within 10% of each other, typically <5%) and a flow rate within 10% (typically <5%) of the target rate during the plateau measurement. The analyzer was calibrated regularly using a certified calibration gas (Linde AG, Munich, Germany). Afterwards, inspiratory vital capacity (VC) and forced expiratory volume in 1s (FEV1) were determined (MasterLab™, Jaeger, Germany) following the established guidelines.19American thoracic Society documents ATS/ERS standardization of lung function testing: standardization of spirometry.Am J Respir Crit Care Med. 2005; 26: 319-338Google Scholar At least three technical acceptable flow-volume maneuvres were performed and the highest values were taken. The presence of respiratory allergies (allergic rhinitis and/or asthma; yes/no), smoking during the last 4 weeks (yes/no) and respiratory tract infection during the last 4 weeks (yes/no) was assessed by a physician when taking the subjects’ history. The study was approved by the Ethical Review Board of the LMU Munich. In accordance with the usual approach, values of FENO were log10-transformed for all statistical analyses to achieve their normal distribution. The log-transformed values were used to derive geometric mean values and standard deviations (SD) of FENO. Geometric SD was expressed as a dimensionless factor with regard to the geometric mean value, and this specific relation was indicated by the symbol÷. The log10 FENO values were also used as dependent variables in analyses of covariance (ANCOVA), which represents a combination of standard analysis of variance (ANOVA) and multilinear regression analysis. The linear covariates used were age, height, weight, body mass index (BMI), FEV1 and VC. The dichotomous variables were gender, respiratory allergy, smoking and respiratory tract infection. The model was computed either including or excluding subjects with asthma (n=34), corresponding to either the category respiratory allergy (when including asthma) or allergic rhinitis (when excluding asthma). The basic ANCOVA model incorporated not only the linear superposition of all main factors but also all interactions. Based on the p-values regarding the different predictors and interaction terms and by eliminating the term with the greatest p-value in a step-down fashion, a minimal model was derived. In case of correlated covariates the validity of the approach was checked by alternative choices of covariates to avoid potentially misleading correlations. As all interactions turned out to be non-significant, the final minimal model provided estimates of the four remaining main effects (categories) and one linear regression coefficient (see results). As it could have been possible that the regression coefficient took different values in the subgroups formed by the categories, additional linear regression analyses were performed within these subgroups. The approach described resulted in a standard additive ANCOVA model for log10FENO. As addition of log values corresponds to multiplication of non-log values, this led to a multiplicative model regarding FENO. To obtain the FENO model we retransformed all ANCOVA terms using the antilog. Thus, the additive terms in the model for log10 FENO became multiplicative terms in the model for FENO. These multiplicative terms represent the effects of different factors on FENO relative to a reference value. The result was also given as an explicit formula comprising all factors of influence relative to the geometric mean FENO of a reference state. To facilitate the practical application, we additionally computed tables of FENO stratified according to gender and height. These tables were adjusted for the remaining (categorical) predictors, whose effects can be taken into account by the multiplicative factors reported. The p-values <0.05 were considered statistically significant. Statistical calculations were performed using SPSS 14.0 (SPSS Inc., Chicago, IL). Table 1 shows the characteristics of the study population. Geometric mean (÷SD) FENO was 19.6÷1.92ppb in the whole study population. Univariate analyses (t-test) showed FENO to be lower (p<0.001 each) in females (17.4÷1.91 vs. 23.0÷1.86ppb), subjects without respiratory allergies (17.8÷1.78 vs. 27.3÷2.16ppb), smokers (13.5÷1.98 vs. 22.1÷1.81ppb) and subjects without respiratory tract infection (18.5÷1.88 vs. 24.1÷1.99ppb) as compared to their respective counterparts. Subjects with allergic rhinitis and asthma showed higher values than those with allergic rhinitis without asthma (42.1÷2.2 vs. 26.4÷2.1ppb; p=0.008). The final ANCOVA models did not comprise any interactions, as these were statistically nonsignificant (p⩾0.23 each). Respiratory allergy, smoking, respiratory tract infection and gender remained as categorical factors and height as a covariate (p⩽0.001 each) in the model comprising subjects with asthma; Table 2 provides the coefficients relating the predictors to log10 FENO. The explained variance (R2) was 25.7% of the total variance. Figure 1A illustrates FENO in the eight subgroups formed by the possible combinations of allergy, smoking and infection. Virtually the same picture, though on a lower overall level, emerged when values were adjusted to female gender and normalized to height 170cm (Figure 1B).Table 2Coefficients of log10 FENO with 95% confidence intervals (95%CI) as obtained in 897 subjects in the final ANCOVA model comprising subjects with asthmaVariableCoefficient (95%CI)Intercept0.453 (0.061; 0.846)Male gender0.070 (0.028; 0.111)Respiratory allergy0.175 (0.136; 0.213)Smoking− 0.203 (−0.240; −0.165)Respiratory tract infection0.092 (0.052; 0.131)Height per 10cm (regression coefficient)0.0464 (0.0230; 0.0700) Open table in a new tab To test for the homogeneity of the relation between FENO and height as derived from ANCOVA, we performed additional linear regression analyses within each of the two subgroups formed by each categorical predictor. All regression coefficients regarding height were different from zero (p<0.02 each), and all of their 95% confidence intervals were overlapping. Based on these results, a single additive model that comprised no interactions between the categorical variables and no interaction betweeen the linear covariate height and the categorical variables described log10 FENO adequately. After retransformation of parameter values from the log into the original FENO domain, the corresponding formula for the expected value of FENO wasFENO(ppb)=17.49×{1.496yesallergy}×{0.627yessmoking}×{1.235yesinfection}×{1.174yesmale}×1.113(height(cm)-170)/10. When the ANCOVA analysis was restricted to patients with allergic rhinitis without asthma, the results were virtually the same. To illustrate the application of these formulae, Table 3 provides geometric mean values of FENO for females over a height range from 160 to 185cm in intervals of 5cm, and for males over a height range from 165 to 190cm in the population including subjects with allergic asthma.Table 3Examples of expected geometric mean values of FENO (ppb) in females and males as derived from the formula given in the resultsFemalesSmoking−−−−++++Infection−−++−−++Allergy−+–+−+−+Height (cm) 16015.723.519.429.09.914.712.218.2 16516.624.820.530.610.415.512.819.2 17017.526.221.632.311.016.413.520.2 17518.527.622.834.111.617.314.321.4 18019.529.124.035.912.218.215.122.5 18520.530.725.437.912.919.315.923.8MalesSmoking−−−−++++Infection−−++−−++Allergy−+−+−+−+Height (cm) 16519.529.124.035.912.218.215.122.5 17020.530.725.337.912.919.215.923.8 17521.732.426.740.013.620.316.825.1 18022.834.228.242.214.321.417.726.4 18524.136.129.844.515.122.618.727.9 19025.438.031.447.015.923.819.729.4To estimate the variation within each of the categories, the FENO value has to be multiplied with the 5th or 10th or 90th or 95th percentile factors (0.42, 0.50, 1.97, and 2.44, respectively). Open table in a new tab To estimate the variation within each of the categories, the FENO value has to be multiplied with the 5th or 10th or 90th or 95th percentile factors (0.42, 0.50, 1.97, and 2.44, respectively). As a next step, we compared variances within the subgroups formed by the possible combinations of allergy, smoking and infection. These variances were significantly different from each other (Levene test, p<0.001); however, SD values within the different subgroups (see Figure 1) differed from the adjusted pooled SD by not more than −24% and 22%. For practical purposes we thus considered it justified to take the pooled variance of adjusted values as the variation within each of the subgroups. To describe the range of variation within each of the subgroups defined by combination of the categorical predictors, the corresponding expected value of FENO (see formula or Table 3) can be multiplied either by the factor respresenting the geometric pooled adjusted SD or by factors representing percentiles. Following the arguments given above, these factors can be taken as approximately the same for all subgroups. The respective adjusted SD factor was 1.753, while the 5th and the 95th percentile factors were 0.421 and 2.44, respectively, and the 10th and 90th percentile factors 0.502 and 1.97. The present study addressed the combined effects and potential interactions of factors that are known to affect the level of FENO. The factors studied covered basic anthropometric characteristics as well as circumstances often encountered in patients visiting an outpatient clinic. As a result, the statistically significant predictors which comprised respiratory allergy or allergic rhinitis, smoking, respiratory tract infection, gender and height were found to have quite homogeneous effects on FENO. The homogeneity was reflected in an additive model of log FENO, containing only main factors without signs of statistical interaction. Upon retransformation of the logarithm into the original FENO domain, the model translated into a simple multiplicative scheme to adjust for various effects on FENO. Regarding the kind of influences on FENO, our findings were in accordance with published data. FENO is known to be elevated in subjects with atopy without symptoms,20Horvath I. Barnes P.J. Exhaled monoxides in asymptomatic atopic subjects.Clin Exp Allergy. 1999; 29: 1276-1280Crossref PubMed Scopus (74) Google Scholar or allergic rhinitis,2Olin A.C. Alving K. Toren K. Exhaled nitric oxide: relation to sensitization and respiratory symptoms.Clin Exp Allergy. 2004; 34: 221-226Crossref PubMed Scopus (72) Google Scholar or asthma.1Alving K. Weitzberg E. Lundberg J.M. Increased amount of nitric oxide in exhaled air of asthmatics.Eur Respir J. 1993; 6: 1368-1370PubMed Google Scholar The variable respiratory allergy used by us included allergic rhinitis and/or asthma as reported by the subjects. We did not additionally validate the answers through objective markers of atopy or assessment of bronchial hyperreactivity; thus, we cannot rule out a bias concerning this variable. The questions we used are standard tools to assess allergic rhinitis and asthma in large international surveys.21The European Community Respiratory Health Survey II Steering Committee The European Community respiratory Health Survey II.Eur Respir J. 2002; 20: 1071-1079Crossref PubMed Scopus (305) Google Scholar If there should have been a bias, it possibly has favored negative answers, as subjects may have symptoms but are not aware of their diagnosis, leading to underestimation of the effects of atopy on FENO. However, the factor which we found was even greater than those reported previously by using objective markers.13Olin A.C. Rosengren A. Thelle D.S. Lissner L. Bake B. Toren K. Height, age, and atopy are associated with fraction of exhaled nitric oxide in a large adult general population sample.Chest. 2006; 130: 1319-1325Crossref PubMed Scopus (242) Google Scholar, 18Travers 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 Med. 2007; 176: 238-242Crossref PubMed Scopus (172) Google Scholar The number of subjects reporting asthma was low (n=34), not allowing for further stratification. We only included subjects without steroid medication, i.e., presumably mild asthma. These subjects accounted for 3.8% of the study population, in accordance with the expected prevalence in the general population. It seemed reasonable to keep these subjects in the analysis as lung function was normal and FENO values were not biased by corticosteroids. The combination of self-reported allergic rhinitis and/or asthma into a single variable could be considered questionable. We would like to note, however, that the statistical model of logFENO remained essentially unchanged, when using the category of allergic rhinitis and restricting the analysis to subjects without asthma. We did not document whether the allergic rhinitis was persistent or seasonal and also did not have reliable information whether subjects with seasonal allergies were examined in their respective season. This might be of interest as FENO values, which are on average lower in allergic rhinitis compared to asthma22Heffler E. Guida G. Marsico P. et al.Exhaled nitric oxide as a diagnostic test for asthma in rhinitic patients with asthmatic symptoms.Respir Med. 2006; 100: 1981-1987Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar can reach similar levels after allergen exposure.23Lopuhaa C.E. Koopmans J.G. Jansen H.M. van der Zee J.S. Similar levels of nitric oxide in exhaled air in non-asthmatic rhinitis and asthma after bronchial allergen challenge.Allergy. 2003; 58: 300-305Crossref PubMed Scopus (26) Google Scholar Since under the conditions of clinical practice acute allergen exposure seems to be difficult to assess with reliability, we focused on the mere presence of a clinically apparent respiratory tract allergy, neglecting the exposure status. Using this approach the multiplicative adjustment of FENO for allergy was found to be about 1.50, being similar in all subgroups. From the average effect size reported by Olin et al.,13Olin A.C. Rosengren A. Thelle D.S. Lissner L. Bake B. Toren K. Height, age, and atopy are associated with fraction of exhaled nitric oxide in a large adult general population sample.Chest. 2006; 130: 1319-1325Crossref PubMed Scopus (242) Google Scholar an average factor of 1.23 across the population studied can be derived, and in another study18Travers 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 Med. 2007; 176: 238-242Crossref PubMed Scopus (172) Google Scholar this value was 1.19. The higher factor found in the present study might be well explained by the fact that subjects were required to report not the presence of elevated IgE or positive skin prick test but the occurrence of clinical symptoms, at present or in the past. Most importantly for practical purposes, our results proved that a single factor of FENO with" @default.
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• W2055945249 title "Exhaled nitric oxide: Independent effects of atopy, smoking, respiratory tract infection, gender and height" @default.
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• W2055945249 doi "https://doi.org/10.1016/j.rmed.2008.02.012" @default.
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