Figures
- Figure 1–
Concordance of ever asthma, allergic sensitisation (positive skin prick test, SPT+) and current rhinitis (proportional Venn diagram). Data on current rhinitis was missing for four participants without allergic sensitisation and asthma, one participant with asthma and one participant with allergic sensitisation (n=517).
- Figure 2–
Associations between exhaled nitric oxide fraction (FeNO), total NO2−/NO3− and (NO2− + NO3−)/NO ratio levels in exhaled breath condensate with allergic sensitisation, current rhinitis and both. Regression coefficients (beta) and 95% confidence intervals for associations between FeNO, total NO2−/NO3− levels, (NO2− + NO3−)/NO ratio and allergic sensitisation, current rhinitis and both, estimated through generalised estimating equation linear regression methods, and adjusted for covariates: age, sex, smoking, ambient ozone concentration, asthma and centre for NO2−/NO3− level; age, sex, smoking, height, asthma and centre for FeNO level; age, sex, smoking, asthma and centre for (NO2− + NO3−)/NO ratio. SPT+: positive skin prick test, i.e. a mean wheal diameter ≥3 mm than the negative control for at least one of 12 aeroallergens.
Tables
- Table 1– Characteristics of subjects according to asthma status
All subjects Subjects without asthma Subjects with asthma p-value Subjects n 523 268 255 Age years 39.9±16.6 43.2±15.9 36.5±16.8 <0.0001 Sex female % 51.0 57.5 44.3 0.003 Body mass index kg·m−2 23.7±3.9 23.8±3.8 23.5±4.0 0.4 Smoking habits % Never smokers 51.6 49.6 53.7 Ex-smokers 25.3 28.0 22.4 0.3 Current smokers 23.1 22.4 23.9 Asthma % Ever asthma 48.7 100.0 Current asthma 40.5 83.1 Age at asthma onset % 237 0–4 years 36.7 4–16 years 39.7 >16 years 23.6 Symptomatic score# 1.17±1.35 (517) 0.51±0.81 (266) 1.86±1.46 (251) <0.0001 Asthma control (GINA 2006) % Controlled 20.6 42.3 Partly controlled 10.7 22.0 Uncontrolled 8.2 16.9 Eosinophilia (cells >5%) % 12.4 6.7 18.4 <0.0001 Eosinophilic asthma (≥250 cells per mm2) % 36.5 FEV1 % pred 103.4±17.2 108.5±16.6 98.0±17.5 <0.0001 Methacholine test¶ (PD20 ≤4 mg) % 45.4 28.8 65.1 <0.0001 Inhaled corticosteroids past 12 months % 20.6 2.2 40.0 <0.0001 Inhaled corticosteroids past 3 months % 7.3 0.0 14.9 SPT+ and current rhinitis SPT+ % 58.1 38.8 78.4 <0.0001 SPTQ (median number of SPT+) 1 (0–3) 0 (0–1) 2 (1–4) <0.0001 Current rhinitis % 39.2 22.3 56.9 <0.0001 SPT+ and current rhinitis % 32.9 18.0 48.6 <0.0001 Biological phenotypes (geometric means) EBC NO2−/NO3− μmol per mg proteins 2.25 (1.12–4.98) 2.33 (1.15–4.81) 2.16 (1.13–5.11) 0.5 FeNO ppb 15.1 (10.0–23.0) 13.2 (9.00–18.8) 17.5 (11.5–29.6) <0.0001 EBC (NO2− + NO3−)/NO ratio (median) 0.30 (0.04–0.60) 0.34 (0.06–0.61) 0.26 (0.04–0.58) 0.16 Plasma NO2−/NO3− μM 39.1 (28.0–53.7) (510) 38.9 (26.3–56.4) (263) 39.3 (29.1–53.2) (247) 0.8 Eosinophil cells per mm3 170 (100–280) (505) 145 (100–200) (256) 199 (100–300) (249) <0.0001 IgE IU·mL−1 81.7 (28.8–226) 49.8 (19.4–128) 137 (59.0–332) <0.0001 Data are presented as mean±sd, unless otherwise stated. Medians and geometric means are shown with interquartile ranges. Values of n are present in italics when differing from total n. GINA: Global Initiative for Asthma; FEV1: forced expiratory volume in 1 s; PD20: provocative dose causing a 20% fall in FEV1; SPT+: positive skin prick test, i.e. a mean wheal diameter ≥3 mm than the negative control for at least one of 12 aeroallergens; SPTQ: quantitative SPT score; EBC: exhaled breath condensate; FeNO: exhaled nitric oxide fraction; Ig: immunoglobulin. #: symptomatic score is based on the number of asthma symptoms (wheeze and breathlessness, woken with chest tightness, woken by attack of shortness of breath, attack of shortness of breath at rest, attack of shortness of breath after exercise); ¶: methacholine challenge test was not performed if baseline FEV1 <80% pred.
- Table 2– Pairwise association of exhaled breath condensate (EBC) NO2−/NO3−, exhaled nitric oxide fraction (FeNO) levels and eosinophil count in all subjects, and according to allergic sensitisation
EBC NO2−/NO3− level μmol per mg proteins# FeNO level ppb¶ n Estimate sd p-value n Estimate sd p-value All subjects Eosinophil cells per mm3 492 0.14 0.09 0.10 505 0.25 0.04 <0.0001 FeNO level ppb 510 0.14 0.08 0.10 Non-sensitised subjects Eosinophil cells per mm3 204 0.15 0.13 0.3 208 0.15 0.05 0.01 FeNO level ppb 215 −0.17 0.15 0.3 Sensitised subjects Eosinophil cells per mm3 288 0.15 0.11 0.2 297 0.31 0.06 <0.0001 FeNO level ppb 295 0.21 0.10 0.04 #: adjusted for age, sex, smoking, ambient ozone concentration, asthma and centre; ¶: adjusted for age, sex, smoking, height, asthma and centre (generalised estimating equation linear regression methods).
- Table 3– Associations between exhaled nitric oxide fraction (FeNO), total NO2−/NO3− and ratio levels in exhaled breath condensate (EBC) with eosinophilic asthma and age at onset
EBC NO2−/NO3− level μmol per mg proteins# FeNO level ppb¶ (NO2−+NO3−)/NO ratio level+ n GM 95% CI p-value n GM 95% CI p-value n Mean 95% CI p-value Eosinophilic asthma No 162 1.97 1.61–2.41 162 15.4 13.7–17.2 162 0.25 0.16–0.34 Yes 93 2.54 1.98–3.26 0.12 93 22.0 19.0–25.5 0.0002 93 0.30 0.22–0.39 0.4 Age at onset 0–4 years 87 2.49 1.93–3.21 87 17.7 15.1–20.6 87 0.33 0.22–0.43 4–16 years 94 2.09 1.60–2.75 0.3§ 94 17.8 15.3–20.7 0.7§ 94 0.25 0.14–0.35 0.4§ >16 years 56 1.99 1.38–2.87 56 16.8 13.6–20.8 56 0.26 0.11–0.41 Model adjusted for all covariates Eosinophilic asthma No 157 1.79 1.35–2.37 162 16.8 14.6–19.4 162 0.20 0.09–0.32 Yes 92 2.30 1.66–3.18 0.13 93 23.9 20.2–28.3 <0.0001 93 0.27 0.14–0.40 0.3 Age at onset 0–4 years 84 2.26 1.60–3.20 87 18.8 15.6–22.6 87 0.30 0.17–0.43 4–16 years 93 1.91 1.37–2.67 0.15§ 94 19.4 16.3–23.1 0.9§ 94 0.21 0.08–0.34 0.15§ >16 years 56 1.59 1.02–2.00 56 18.4 14.6–23.3 56 0.17 0.01–0.34 GM: geometric mean. #: adjusted for age, sex, smoking, ambient ozone concentration, asthma and centre; ¶: adjusted for age, sex, smoking, height, asthma and centre (generalised estimating equation regression methods); +: adjusted for age, sex, smoking, asthma and centre; §: p-value for trend.
- Table 4– Associations between exhaled nitric oxide fraction (FeNO), total NO2−/NO3− and ratio levels in exhaled breath condensate (EBC) with allergic sensitisation
EBC NO2−/NO3− level μmol per mg proteins# FeNO level ppb¶ (NO2− + NO3−)/NO ratio level+ n GM 95% CI p-value n GM 95% CI p-value n Mean 95% CI p-value Allergic sensitisation No 219 2.03 1.73–2.38 219 12.6 11.6–13.6 219 0.29 11.6–13.6 Yes 304 2.41 2.11–2.76 0.10 304 17.3 15.9–18.8 <0.0001 304 0.31 15.9–18.8 0.7 Current rhinitis No 312 2.20 1.93–2.51 312 13.8 12.8–14.8 312 0.30 0.25–0.36 Yes 205 2.30 1.94–2.72 0.7 205 17.7 16.1–19.6 <0.0001 205 0.29 0.22–0.36 0.8 SPT+ and current rhinitis No 219 2.03 1.73–2.38 219 12.6 11.6–13.6 219 0.29 0.22–0.36 SPT+ 131 2.34 1.90–2.89 0.10§ 131 15.9 14.0–18.0 <0.0001§ 131 0.29 0.21–0.38 0.6§ Both 172 2.47 2.07–2.94 172 18.4 16.5–20.5 172 0.32 0.25–0.39 Model adjusted for centre only Allergic sensitisation No 219 1.87 1.55–2.26 219 14.2 12.8–15.7 219 0.25 0.17–0.33 Yes 304 2.26 1.92–2.66 0.06 304 19.4 17.7–21.1 <0.0001 304 0.27 0.20–0.34 0.6 Current rhinitis No 312 1.97 1.66–2.33 312 15.2 13.9–16.7 312 0.25 0.18–0.32 Yes 205 2.26 1.87–2.72 0.19 205 20.1 18.2–22.2 <0.0001 205 0.27 0.19–0.35 0.7 SPT+ and current rhinitis No 219 1.87 1.55–2.26 219 14.2 12.8–15.7 219 0.25 0.17–0.33 SPT+ 131 2.12 1.70–2.64 0.04§ 131 17.5 15.6–19.8 <0.0001§ 131 0.24 0.15–0.34 0.4§ Both 172 2.37 1.94–2.89 172 20.7 18.6–23.0 172 0.29 0.20–0.37 Model adjusted for all covariates Allergic sensitisation No 215 1.72 1.38–2.14 219 14.8 13.3–16.5 219 0.21 0.13–0.30 Yes 295 2.36 1.96–2.84 0.008 304 18.3 16.7–20.0 0.0006 304 0.29 0.22–0.36 0.10 Current rhinitis No 305 1.90 1.57–2.31 312 15.4 14.0–16.9 312 0.24 0.16–0.31 Yes 199 2.31 1.87–2.84 0.09 205 19.2 17.4–21.2 0.0001 205 0.28 0.20–0.36 0.3 SPT+ and current rhinitis No 215 1.71 1.37–2.13 219 14.8 13.3–16.5 219 0.21 0.12–0.29 SPT+ 128 2.17 1.70–2.76 0.005§ 131 16.4 14.6–18.4 <0.0001§ 131 0.26 0.17–0.36 0.06§ Both 166 2.50 2.01–3.12 172 19.7 17.7–21.9 172 0.32 0.23–0.40 Allergic sensitisation (indoor only) No 215 1.66 1.28–2.16 219 14.2 12.7–15.9 219 0.21 0.10–0.31 Yes 76 2.03 1.47–2.81 0.2 80 17.1 14.8–19.7 0.02 80 0.26 0.13–0.40 0.4 Allergic sensitisation (outdoor only) No 215 1.66 1.28–2.15 219 14.6 13.2–16.3 219 0.20 0.09–0.31 Yes 45 1.78 1.21–2.62 0.7 46 17.2 14.6–20.2 0.06 46 0.20 0.03–0.36 0.9 Allergic sensitisation (moulds only) No 217 1.58 1.20–2.06 219 14.5 13.0–16.2 219 0.18 0.07–0.30 Yes 7 3.96 1.69–9.29 0.04 7 21.2 14.6–30.6 0.06 7 0.49 0.11–0.87 0.12 GM: geometric mean; SPT+: positive skin prick test, i.e. a mean wheal diameter ≥3 mm than the negative control for at least one of 12 aeroallergens. #: adjusted for age, sex, smoking, ambient ozone concentration, asthma and centre; ¶: adjusted for age, sex, smoking, height, asthma and centre (generalised estimating equation regression methods); +: adjusted for age, sex, smoking, asthma and centre; §: p-value for trend.
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