APPENDIX

Low use and adherence to maintenance medication in

chronic obstructive pulmonary disease in the general population

Truls S. Ingebrigtsen,1,2,3 MD, Jacob L. Marott,2 Statistician, Børge G. Nordestgaard,2,3,4 MD, D.M.Sc., Peter Lange,2,3,5,6 MD, D.M.Sc., Jesper Hallas,7 MD, D.M.Sc., Morten Dahl,8 MD, D.M.Sc., Jørgen Vestbo,1,9 MD, D.M.Sc.

Appendix-table 1.Recommended daily dosages for combinations of inhaled corticosteroids with long-acting β2-agonists (ICS/LABA), long-acting anti-cholinergics (LAMA), or long-acting β2-agonists (LABA) used to calculate adherence.

DOSAGES / RECOMMENDED DAILY DOSAGES
50 µg Salmeterol + 100 µg Fluticasone / 2 puffs daily
50 µg Salmeterol + 250 µg Fluticasone / 2 puffs daily
50 µg Salmeterol + 500 µg Fluticasone / 2 puffs daily
25 µg Salmeterol + 50 µg Fluticasone / 4 puffs daily
25 µg Salmeterol + 125 µg Fluticasone / 4 puffs daily
25 µg Salmeterol + 250 µg Fluticasone / 4 puffs daily
4.5 µg Formoterol + 80 µg Budesonide / 4 puffs daily
4.5 µg Formoterol + 160 µg Budesonide / 4 puffs daily
9 µg Formoterol + 320 µg Budesonide / 2 puffs daily
18 µg Tiotropium Bromide / 1 capsule daily
2,5 µg Tiotropium Bromide / 2 puffs daily
25 µg Salmeterol / 4 puffs daily
50 µg Salmeterol / 2 puffs daily
4.5 µg Formoterol / 4 puffs daily
6 µg Formoterol / 4 puffs daily
9 µg Formoterol / 2 puffs daily
12 µg Formoterol / 2 puffs daily
10 mg Bambuterol / 2 pills daily
20 mg Bambuterol / 1 pill daily

Appendix-table2.Description of variables utilized in multivariable analyses of adherence in the Copenhagen General Population Study.

Characteristics of COPD / Variables associated to adherence
according to previous literature
  • FEV1: forced expiratory volume in one second, % of predicted
  • Smoking status: current/former/never
  • Breathlessness: a score on The Modified Medical Research Council scale equal to or larger than two, mMRC≥2
  • Moderate exacerbation: at least one treatment with oral corticosteroids and/or the combination of oral corticosteroids with antibiotics.
  • Severe exacerbation: at least one admission with a discharge diagnosis of COPD.
  • The number of previous self-reported respiratory infections within the last ten years requiring consulting a doctor and/or staying home from work (none/1-5/6-10/>10)
  • Self-reported chronic bronchitis
  • Physical activity in leisure time
  1. Low: less than two hours per week
  2. Intermediate: 2-4 hours per week
  3. High: more than four hours per week
/
  • Gender (males/females)
  • Age at the examination
  • Previous adherence to fixed dose combinations of inhaled corticosteroids with long-acting beta2-agonists (ICS/LABA) in the year before the examination.
  • Previous adherence to long-acting anti-cholinergics (LAMA).
  • Previous adherence to long-acting beta2-agonists(LABA).
  • Length of self-reported education in years (<8/8-10/>10). These categories correspond to lower primary school, higher primary school and secondary school, or college and university in Denmark.
  • Comorbidity: yes/no variable constructed according to the questionnaires: answering yes to previous deep venous thrombosis, and/or pulmonary embolism, and/or cardiovascular disease, and/or CNS disease including cerebrovascular disease, and/or diabetes, and/or cancer,and/or answering yes to ‘Other chronic diseases’.
  • Psycho-social variables (reporting a feeling of stress, feeling tired, not having accomplished much recently, difficulty concentrating, a tendency to quit tasks, or reporting to feel fine)
  • Visits to the general practitioner: reported number of visits to their general practitioner.
  • Cohabitation (living with spouse or life companion/living alone/living with others)
  • Household income (low/intermediate/high)
  • The year of cohort entry.

Appendix Figure 1 - Adherence calculated among the subgroups of 383 users (72% of all users) of only one type of maintenance medication. Shows average adherence to ICS/LABA (fixed-dose combinations of inhaled corticosteroids with long-acting beta2-agonists), LAMA (long-acting anti-cholinergics) and LABA (long-acting beta2-agonists) in percent, graded according to GOLD 1, GOLD 2, and GOLD 3+4.

Appendix Figure 2 - Adherence calculated from the first dispensing andwith first dispensing dosage included. Shows average adherence to ICS/LABA (fixed-dose combinations of inhaled corticosteroids with long-acting beta2-agonists), LAMA (long-acting anti-cholinergics) and LABA (long-acting beta2-agonists) in percent, graded according to GOLD 1, GOLD 2, and GOLD 3+4. A subgroup of 493 users who had one year of possible follow-up from their first dispensing was included in the analyses.