Figures
- FIGURE 1
Flowchart of the study. ICS: inhaled corticosteroids.
- FIGURE 2
Annual prescribed and dispensed inhaled corticosteroids (ICS) shown as cumulative values (mean±sem) (n=181). p-value represents difference between cumulative prescribed and dispensed ICS as defined by the area under the curve method and paired-sample t-test.
- FIGURE 3
The average annual adherence (mean±sem) during the 12-year follow-up period (n=181).
- FIGURE 4
Average annual prescribed and dispensed daily doses of inhaled corticosteroids (ICS) in the 12-year follow-up periods (mean±sem) (n=181). p-value represents difference between cumulative prescribed and dispensed ICS as defined by area under the curve method and paired-samples t-test.
- FIGURE 5
Annual adherence rates a) when using 80% adherence as a cut-off (n=181); and b) when dividing patients into high, moderate or low adherence, and non-adherence during the 12-year follow-up.
Tables
- TABLE 1
Characteristics of patients at the 12-year follow-up visit and their medication according to their 12-year adherence
12-year adherence Good adherence# Poor adherence¶ p-value Age years mean±sd 61±12 58±14 0.065§ Female sex 52 (63.4%) 56 (56.6%) 0.365ƒ BMI kg·m−2 28.1 (24.3–31.3) 28.4 (24.6–31.2) 0.640## Smokers+ 40 (48.8%) 51 (51.5%) 0.766ƒ Smoking history pack-years 18 (9–33) 17 (6–29) 0.407## Smoking history ≥10 pack-years and post-BD FEV1/FVC <0.7 12 (30%) 21 (42%) 0.276ƒ Number of comorbidities 1 (0–3) 1 (0–2) 0.487## Daily SABA 13 (15.9%) 8 (8.1%) 0.161ƒ Daily LABA 54 (65.9%) 41 (41.4%) 0.002ƒ Daily LTRA 18 (22%) 8 (8.2%) 0.011ƒ Daily theophylline 4 (4.9%) 0 (0%) 0.040ƒ Daily tiotropium 5 (6.1%) 3 (3.0%) 0.471ƒ Daily add-on drug 57 (69.5%) 44 (44.4%) 0.001ƒ Average prescribed ICS daily dose over 12 years µg budesonide equivalents 810 (611–1043) 805 (610–967) 0.496## Average dispensed ICS daily dose over 12 years µg budesonide equivalents 803 (616–1075) 320 (146–472) <0.001## Data are presented as n (%) or median (interquartile range), unless otherwise stated. BMI: body mass index; BD: bronchodilator; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; SABA: short-acting β2-agonist; LABA: long-acting β2-agonist; LTRA: leukotriene receptor antagonist; ICS: inhaled corticosteroid. #: ≥80% adherence, n=82; ¶: <80% adherence, n=99; +: including ex-smokers; §: independent-samples t-test; ƒ: Fisher's exact test; ##: Mann–Whitney U-test.
- TABLE 2
Symptoms and burden due to asthma in patients according to their 12-year adherence
12-year adherence Good adherence# Poor adherence¶ p-value Symptoms of asthma AQ20 score 4 (2–7) 4 (1–8) 0.583 ACT score 21 (19–24) 21 (19–24) 0.790 CAT 12 (7–18) 11 (6–17) 0.473 Burden of asthma Self-reported use of oral corticosteroid courses for asthma 34 (42.5%) 26 (26.3%) 0.026ƒ Dispensed oral corticosteroid for asthma+ mg·year−1 101 (11–249) 51 (0–165) 0.019## At least one hospitalisation due to asthma 14 (17.1%) 13 (13.1%) 0.532ƒ Three or more sick leaves during the past 2 years 3 (4.8%) 4 (5.2%) >0.999ƒ Emergency department visits 0 (0–0) 0 (0–0) 0.708## Fulfils severe asthma criteria according to ERS/ATS 6 (7.3%) 6 (6.1%) 0.772ƒ Hospital days, asthma-related§ 0 (0–0) 0 (0–0) 0.051## Range 0–64 0–12 Hospital days, any respiratory reason§ 0 (0–0) 0 (0–0) 0.072## Range 0–64 0–37 Asthma control visits 7 (4–11) 6 (3–9) 0.023## Asthma-related visits to healthcare 19 (12–28) 11 (8–19) <0.001## Data are presented as median (interquartile range), unless otherwise stated. Symptoms of asthma were observed at the 12-year follow-up visit. Sick leaves were observed in the 2 years before the follow-up visit. Self-reported use of oral corticosteroids, hospitalisations and hospital days were examined during the whole 12-year follow-up period. AQ20: Airway Questionnaire 20; ACT: Asthma Control Test; CAT: COPD Assessment Test; ERS: European Respiratory Society; ATS: American Thoracic Society. #: ≥80% adherence, n=82. ¶: <80% adherence, n=99. +: data obtained from the Finnish Social Insurance Institution and were divided by the years of follow-up (supplementary material); statistical significance considering symptoms of asthma were evaluated by independent-samples Mann–Whitney U-test. §: unplanned. ƒ: Pearson Chi-squared test. ##: independent-samples Mann–Whitney U-test.
- TABLE 3
Lung function and markers of inflammation in patients according to their 12-year adherence
12-year adherence Good adherence# Poor adherence¶ p-value Lung function at follow-up Pre-BD FEV1 % pred 87 (75–99) 86 (75–94) 0.398 Pre-BD FVC % pred 97 (87–108) 96 (87–106) 0.374 Pre-BD FEV1/FVC 0.73 (0.67–0.78) 0.74 (0.65–0.79) 0.730 Post-BD FEV1 % pred 90 (79–99) 89 (81–96) 0.682 Post-BD FVC % pred 99 (85–108) 97 (88–105) 0.416 Post-BD FEV1/FVC 0.74 (0.68–0.79) 0.76 (0.68–0.81) 0.320 FEV1 reversibility mL 65 (7.5–123) 100 (40–170) 0.010 FEV1 reversibility % initial FEV1 2.7 (0.29–5.0) 3.8 (1.6–6.8) 0.039 Lung function change ΔFEV1 % pred·year–1 −0.39 (−0.88–0.40) −0.54 (−1.2–0.0) 0.026 ΔFEV1 mL·year–1 −40 (−56– −22) −46 (−81– −26) 0.050 ΔFVC % pred·year–1 0.11 (−0.47–0.82) −0.21 (−0.87–0.45) 0.034 ΔFVC mL·year–1 −32 (−56– −10) −36 (−64– −13) 0.329 ΔFEV1/FVC year–1 −0.005 (−0.008– −0.0001) −0.005 (−0.008– −0.002) 0.316 Markers of inflammation Blood eosinophils ×109 L−1 0.17 (0.09–0.28) 0.18 (0.10–0.27) 0.549 Total IgE kU·L−1 71 (24–165) 56 (26–178) 0.956 FENO (ppb) 10 (5–19) 11 (5–18) 0.683 Blood neutrophils ×109 L−1 4.2 (3.5–5.3) 3.5 (2.7–4.6) 0.001 IL-6 pg·mL−1 1.9 (1.2–3.2) 1.8 (1.1–3.3) 0.537 hsCRP mg·L−1 1.0 (0.48–2.3) 1.4 (0.62–2.9) 0.224 Data are presented as median (interquartile range) unless otherwise stated. Statistical significance was evaluated by independent-samples Mann–Whitney U-test. BD: bronchodilator; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; FENO: exhaled nitric oxide fraction; IL: interleukin; hsCRP: high-sensitivity C-reactive protein. #: ≥80% adherence, n=82; ¶: <80% adherence, n=99.
Supplementary Material
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Supplementary material 00324-2019.SUPPLEMENT
