Table 2

Crude and adjusted hazard ratio (HR) of a subsequent exacerbation and of death associated with each successive exacerbation, as a function of the time since the first exacerbation, estimated by Cox proportional hazards model with time-dependent covariate defining the exacerbation number and its timing

Exacerbation sequence numberMedian time to subsequent exacerbation (years)Number with a subsequent exacerbationCrude HRAdjusted* HR (95% CI)Number of deathsCrude HRAdjusted* HR (95% CI)
First (reference)5.433 1661.01.0 (reference)25 9531.01.0 (reference)
Second1.619 3593.02.9 (2.8 to 2.9)98281.81.9 (1.8 to 1.9)
Third0.912 4135.14.9 (4.8 to 5.0)52032.42.4 (2.3 to 2.5)
Fourth0.783747.36.9 (6.8 to 7.1)30782.82.9 (2.8 to 3.0)
Fifth0.559039.89.2 (8.9 to 9.4)18793.03.2 (3.0 to 3.4)
Sixth0.4431611.911.2 (10.8 to 11.5)12073.13.3 (3.1 to 3.5)
Seventh0.3319013.913.0 (12.5 to 13.5)8723.43.6 (3.4 to 3.9)
Eighth0.3240416.615.2 (14.6 to 15.9)6453.94.2 (3.9 to 4.5)
Ninth0.3182318.116.6 (15.8 to 17.4)4703.84.3 (3.9 to 4.7)
Tenth or greater0.2140325.823.5 (22.8 to 24.2)14454.55.2 (4.9 to 5.5)
  • * Adjusted for age, sex, calendar time (cohort entry prior to 2000), and the modified Chronic Disease Score divided in quartiles with a fifth category to account for subjects with no or partial medication information in the year prior to cohort entry.