Table 4.

Analysis of increased doses of promethazine in the entire population.

Primary outcome	No collection of promethazine N = 52,800	One collection of promethazine N = 1910	Two collections of promethazine N = 540	Three collections of promethazine N = 311	Four or more collections of promethazine N = 962
HR (CI)p-value p-value	Reference	1.74 (1.60–1.89)<0.0001	2.03 (1.80–2.30)<0.0001	2.31 (1.98–2.69)<0.0001	2.15 (1.94–2.38)<0.0001

Note: Hazard ratios were calculated by adjusted Cox analysis adjusting for all variables included in the propensity score match and collection of prescriptoins of promethazine and melatonin (N = 56,523).

Gender (male vs. female) and collection of promethazine, melatonin, long-acting muscarinic receptor antagonist (LAMA) and inhaled corticosteroid (ICS) were analyzed as binary variables.

Age (≤75 years, >75 years and ≤80 years, >80 years and ≤85 years, and >85 years), Charlson comorbidity index (CCI, range 0–13), tobacco exposure (‘never smoking’, ‘passive smoking’, ‘previous smoking’, ‘active smoking’ and ‘unknown tobacco exposure’), MRC (range 1–5), BMI (≥25 kg/m², <25 kg/m² and ≥20 kg/m², <20 kg/m² and ≥15 kg/m², and <15 kg/m²) and FEV₁% GOLD stages (range 1–4) were analyzed as semi quantified variables.