Association of symptom dynamic phenotypes, reference phenotypes and risk factors with outcomes during childhood
| Outcome | Univariable association | Multivariable association# | ||||
| OR | 95% CI | p-value | OR | 95% CI | p-value | |
| Any wheezing between one and 6 years¶ (n=105/322) | ||||||
| Reference phenotypes | ||||||
| Phenotype 1 (baseline; n=147) | 1 | Reference | 1 | Reference | ||
| Phenotype 2 (n=128) | 2.14 | 1.26–3.62 | 0.005 | 1.93 | 1.11–3.35 | 0.019 |
| Phenotype 3 (n=47) | 3.61 | 1.81–7.19 | <0.001 | 2.84 | 1.32–6.11 | 0.008 |
| Symptom dynamic phenotypes | ||||||
| Phenotype 1 (baseline; n=145) | 1 | Reference | 1 | Reference | ||
| Phenotype 2 (n=135) | 1.07 | 0.63–1.79 | 0.809 | 1.06 | 0.61–1.84 | 0.830 |
| Phenotype 3 (n=42) | 4.72 | 2.27–9.72 | <0.001 | 4.31 | 1.95–9.48 | <0.001 |
| Risk factors | ||||||
| Male sex | 3.05 | 1.86–5.01 | <0.001 | 2.90 | 1.75–4.81 | <0.001 |
| Siblings | 1.22 | 0.77–1.95 | 0.386 | 1.27 | 0.78–2.09 | 0.328 |
| Maternal asthma | 2.23 | 1.09–4.58 | 0.028 | 2.16 | 1.03–4.55 | 0.041 |
| Childcare | 1.49 | 0.84–2.64 | 0.169 | 1.40 | 0.75–2.59 | 0.284 |
| Parental smoking during infancy | 1.08 | 0.61–1.89 | 0.783 | 0.99 | 0.55–1.81 | 0.995 |
| Low maternal education | 1.23 | 0.76–2.01 | 0.391 | 1.13 | 0.66–1.93 | 0.644 |
| Current wheezing at 6 years+ (n=38/322) | ||||||
| Reference phenotypes | ||||||
| Phenotype 1 (baseline; n=147) | 1 | Reference | 1 | Reference | ||
| Phenotype 2 (n=128) | 1.36 | 0.62–2.99 | 0.433 | 1.22 | 0.54–2.75 | 0.618 |
| Phenotype 3 (n=47) | 2.78 | 1.13–6.86 | 0.026 | 2.25 | 0.83–6.11 | 0.110 |
| Symptom dynamic phenotypes | ||||||
| Phenotype 1 (baseline; n=145) | 1 | Reference | 1 | Reference | ||
| Phenotype 2 (n=135) | 0.99 | 0.45–2.21 | 0.994 | 1.01 | 0.44–2.31 | 0.968 |
| Phenotype 3 (n=42) | 3.32 | 1.37–8.01 | 0.008 | 3.01 | 1.15–7.88 | 0.025 |
| Risk factors | ||||||
| Male sex | 2.52 | 1.21–5.28 | 0.014 | 2.26 | 1.06–4.81 | 0.033 |
| Siblings | 1.15 | 0.58–2.28 | 0.670 | 1.19 | 0.61–2.42 | 0.616 |
| Maternal asthma | 1.71 | 0.65–4.45 | 0.141 | 1.66 | 0.62–4.41 | 0.306 |
| Childcare | 1.35 | 0.61–3.02 | 0.462 | 1.38 | 0.58–3.27 | 0.457 |
| Parental smoking during infancy | 1.33 | 0.61–2.89 | 0.468 | 1.15 | 0.51–2.59 | 0.723 |
| Low maternal education | 1.77 | 0.82–3.78 | 0.141 | 1.63 | 0.73–3.66 | 0.229 |
| Atopic disease at 6 years§ (n=120/320) | ||||||
| Reference phenotypes | ||||||
| Phenotype 1 (baseline; n=146) | 1 | Reference | 1 | Reference | ||
| Phenotype 2 (n=127) | 1.13 | 0.69–1.86 | 0.602 | 1.06 | 0.63–1.78 | 0.824 |
| Phenotype 3 (n=47) | 0.99 | 0.51–1.97 | 0.987 | 0.89 | 0.41–1.91 | 0.772 |
| Symptom dynamic phenotypes | ||||||
| Phenotype 1 (baseline; n=144) | 1 | Reference | 1 | Reference | ||
| Phenotype 2 (n=135) | 1.07 | 0.65–1.74 | 0.778 | 1.12 | 0.66–1.88 | 0.667 |
| Phenotype 3 (n=41) | 1.57 | 0.78–3.17 | 0.205 | 1.74 | 0.81–3.77 | 0.159 |
| Risk factors | ||||||
| Male sex | 2.15 | 1.35–3.42 | 0.001 | 2.10 | 1.29–3.40 | 0.003 |
| Siblings | 1.09 | 0.69–1.72 | 0.686 | 1.01 | 0.63–1.63 | 0.944 |
| Maternal asthma | 1.55 | 0.76–3.18 | 0.226 | 1.51 | 0.72–3.17 | 0.274 |
| Childcare | 0.62 | 0.34–1.14 | 0.127 | 0.63 | 0.33–1.21 | 0.168 |
| Parental smoking during infancy | 1.09 | 0.63–1.88 | 0.752 | 0.92 | 0.55–1.64 | 0.786 |
| Low maternal education | 2.30 | 1.40–3.77 | 0.001 | 2.03 | 1.20–3.41 | 0.008 |
Logistic regression analysis was carried out for the outcomes any wheezing, current wheezing and atopic disease. Symptom dynamic phenotypes were defined by average entropy of transition states and reference phenotypes by weeks with any respiratory symptom. When considering phenotypes as exposure, phenotype 1 from the reference phenotype or symptom dynamic phenotype, respectively, served as baseline. OR: odds ratio. #: adjusted for the binary variables male gender, low maternal education, maternal asthma, maternal smoking during pregnancy, childcare attendance during infancy and presence of siblings; ¶: defined as any wheezing episode between one and 6 years of age; +: defined as wheezing over the past 12 months before follow-up; §: defined as allergic rhinitis, allergic asthma, or atopic dermatitis before follow-up.