Table 2

Outcomes by allocation

Vitamin D3 (n=125)Placebo (n=125)Adjusted HR/incidence rate ratio/odds ratio/mean difference/ratio of geometric means (95% CI)*p Value
Severe asthma exacerbation
 Median time to first severe exacerbation, days (IQR)– (192 to –)– (136 to –)1.02 (0.69 to 1.53)0.91
 Rate of severe exacerbations per participant-year136/117.4=1.16145/116.7=1.240.93 (0.57 to 1.51)0.77
 Proportion of participants with ≥1 severe exacerbation (%)†50/108 (46%)47/114 (41%)1.20 (0.70 to 2.05)0.52
 Mean peak asthma symptom score per severe exacerbation‡1.60 (1.22)1.67 (1.13)−0.13 (−0.52 to 0.26)0.51
 Mean area under the curve per severe exacerbation, asthma symptom score§26.2 (23.7)24.5 (18.2)−0.44 (−8.65 to 7.76)0.92
 Proportion of exacerbations associated with URI (%)45/136 (34%)44/145 (30%)1.04 (0.40 to 2.70)0.96
URI
 Median time to first URI, days (IQR)128 (42 to –)112 (40 to 309)0.87 (0.64 to 1.16)0.34
 Proportion of participants with ≥1 URI (%)†85/115 (74%)93/117 (79%)0.71 (0.38 to 1.32)0.28
 Rate of URI per participant-year234/117.4=1.99250/116.7=2.140.89 (0.70 to 1.14)0.35
 Mean peak Jackson symptom score per URI¶11.5 (5.1)10.5 (4.7)0.76 (−0.47 to 1.99)0.23
 Mean area under the curve per URI, Jackson symptom score**105.0 (67.0)90.6 (69.9)5.1 (−13.5 to 23.8)0.59
Days in which asthma is poorly controlled††
 Rate per participant-year4486/117.4=38.24049/116.7=34.71.07 (0.75 to 1.51)0.72
Nights with awakenings due to asthma symptoms
 Rate per participant-year3166/117.4=27.02702/116.7=23.21.14 (0.69 to 1.86)0.61
ACT score
 Mean (SD)
  2 months20.1 (3.9)19.5 (4.4)0.52 (−0.27 to 1.31)0.56‡‡
  6 months20.6 (3.5)20.6 (3.8)0.00 (−0.81 to 0.81)
  12 months20.4 (4.0)20.4 (4.2)0.00 (−0.82 to 0.82)
FEV1 (% predicted)
 Mean (SD)
  2 months81.5 (18.7)81.6 (20.4)−0.95 (−3.71 to 1.81)0.53‡‡
  6 months80.6 (21.0)81.0 (20.8)−1.56 (−4.37 to 1.26)
  12 months81.6 (18.5)80.1 (22.8)0.44 (−2.42 to 3.30)
Morning PEFR (mean over period since preceding study visit)
 Mean (SD)
  2 months380.6 (108.6)375.2 (121.2)−0.2 (−8.1 to 7.7)0.38‡‡
  6 months385.0 (118.6)382.9 (122.4)−5.3 (−13.4 to 2.8)
  12 months388.1 (116.8)387.7 (122.9)−5.4 (−13.6 to 2.8)
Fractional exhaled nitric oxide, ppb
 Mean (SD)
  2 months36.1 (25.7)36.5 (31.7)−1.3 (−6.4 to 3.8)0.71‡‡
  6 months36.7 (28.8)34.6 (32.4)1.6 (−3.7 to 6.8)
  12 months37.5 (26.9)38.5 (36.9)−1.4 (−6.8 to 3.9)
SGRQ total score§§
 Median (IQR)
  2 months16.0 (8.5 to 26.2)17.3 (8.9 to 30.1)0.87 (0.79 to 0.96)¶¶0.005***
  6 months2114.7 (7.5 to 24.4)14.6 (7.1 to 29.7)0.90 (0.82 to 0.99)†††0.038***
  12 months2313.6 (7.1 to 24.7)13.9 (7.2 to 25.0)0.91 (0.82 to 1.00)‡‡‡0.060***
Serum 25(OH)D, nmol/L
 Mean (SD)
  2 months61.2 (22.1)48.5 (25.0)12.5 (7.6 to 17.3)<0.001§§§
  12 months69.4 (21.0)46.5 (24.6)23.0 (17.9 to 28.0)<0.001§§§
Participants with 25(OH)D ≥50 nmol/L
 n (%)
  2 months88/121 (73%)52/119 (44%)1.83 (1.04 to 2.62)<0.001§§§
  12 months86/107 (80%)43/110 (39%)2.72 (1.83 to 3.61)<0.001§§§
  • *Adjusted for stratification factors, that is, British Thoracic Society treatment step (2/3 vs 4/5) and inclusion in vs exclusion from sputum induction substudy.

  • †This analysis excludes participants who withdrew from the trial without experiencing this event prior to withdrawal.

  • ‡Asthma symptoms scored from 0 (no symptoms) to 3 (severe symptoms).

  • §Area under the curve calculated for asthma symptom score from 7 days preonset of exacerbation to 20 days postonset.

  • ¶Jackson symptoms (sneezing, sore throat, headache, subjective sensation of fever or chilliness, malaise, nasal discharge, nasal obstruction, cough) each scored from 0 (no symptoms) to 3 (severe symptoms) and summed for each day of the URI.

  • **Area under the curve calculated for total Jackson symptom score from 7 days preonset of URI to 20 days postonset.

  • ††Poorly controlled asthma day defined as a 24-h period in which diary recorded wakening at night due to asthma symptoms, morning PEFR ≥20% below mean run-in value or ≥2 uses of reliever medication above median run-in value; days included in a severe exacerbation are excluded from the count of poorly controlled asthma days.

  • ‡‡p Value for allocation-time interaction presented; p values for effect of allocation at individual time points are not reported where p for allocation-time interaction ≥0.05.

  • §§A small constant (1.0) was added to each value prior to log transforming for the regression analysis, to avoid taking logs of zero.

  • ¶¶Ratio of geometric means is presented; adjusted mean difference=3.9 points.

  • ***p For allocation-time interaction=0.026.

  • †††Ratio of geometric means is presented; adjusted mean difference=3.7 points.

  • ‡‡‡Ratio of geometric means is presented; adjusted mean difference=3.3 points.

  • §§§p For allocation-time interaction <0.001.

  • 25(OH)D, 25-hydroxyvitamin D; ACT, asthma control test; PEFR, peak expiratory flow rate; ppb, parts per billion; SGRQ, St George's Respiratory Questionnaire; URI, upper respiratory infection.