A Real-World Study on the Day and Night-Time Symptoms Among Greek COPD Patients Who Recently Initiated Treatment with Dual Bronchodilation: The DANICO Study

Figures & data

Figure 1 Overview of the DANICO study.

Abbreviations: CAT, COPD assessment test; COPD, chronic obstructive pulmonary disease.

Figure 2 Summary of the different treatment pathways that were followed by the study participants, either before being prescribed with aclidinium/formoterol, at visit 1 and visit 2 of the study.

Abbreviations: ICS, inhaled corticosteroids; LABA, long-acting β adrenoreceptor agonists; LAMA, long-acting muscarinic receptor antagonists; MX, methylxanthines; PDE4I, phosphodiesterase-4 inhibitors; SABA, short-acting β adrenoreceptor agonists; SAMA, short-acting muscarinic receptor antagonists.

Figure 3 (A) Patient distribution according to the physician-assessed severity of early-morning at baseline and at the follow-up visit (visit 2). Numbers indicate the percentages of patients. (B) Patient distribution according to the severity of specific early-morning symptoms as perceived by the patients at baseline and at the follow-up visit (visit 2). Numbers indicate the percentages of patients.

Figure 4 (A) Patient distribution according to the impact of daily COPD-related symptoms on the patients’ daily activities at baseline and at the follow-up visit (visit 2). Numbers indicate the percentages of patients. (B) Patient distribution according to the physician-assessed severity of night-time symptoms at baseline and at the follow-up visit (visit 2). Numbers indicate the percentages of patients. (C) Patient distribution according to whether the frequency of their nocturnal awakenings was reduced (improvement), increased (deterioration) or remained unchanged between the baseline and follow-up visit. Numbers indicate the percentages of patients.

Abbreviation: COPD, chronic obstructive pulmonary disease.

Figure 5 (Spirometric parameters - Upper panel in each ABCD group) Data shown are mean ± standard deviation. There was a statistically significant interaction between the state of bronchodilation and visit (before and after being treated with Aclidinium/formoterol) on %FEV1predicted in patients of GOLD Groups A–C (F_1,226 = 5.73, p = 0.018, partial η² = 0.025, F_1,1239 = 7.09, p = 0.008, partial η² = 0.006, and F_1,199 = 7.73, p = 0.006, partial η² = 0.037, respectively). Ιn Group A, pre-bronchodilation %FEV1predicted increased on average by 1.74%, and post-bronchodilation by 0.95%. In Group B, the corresponding percentages were 3.43% and 3.17%. In Group C, 2.9% and 2.1%. In Group D, no interaction between the study visits and the state of bronchodilation has been determined. (CAT – Lower panel in each ABCD group) Data shown are mean difference ± standard deviation. Participants on average were scoring lower to CAT in their second study visit compared to their first one, a statistically significant decrease across all GOLD ABCD groups (−1.69 with 95% CI [−2.16 to −1.21], t₂₃₄ = −6.94, p < 0.001, d = 0.45 for Group A, −5.2 with 95% CI [−5.47 to −4.93], t₁₂₇₁ = −37.84, p < 0.001, d = 1.06 for Group B, −5.93 with 95% CI [−6.91 to −4.96], t₂₀₈ = −11.99, p < 0.001, d = 0.83 for Group C and −7.15 with 95% CI [−7.78 to −6.52], t₃₆₉ = −22.25, p < 0.001, d = 1.16 for Group D).

Abbreviations: CAT, COPD assessment test; CI, confidence intervals; COPD, chronic obstructive pulmonary disease; %FEV1predicted, forced Expiratory Volume in 1 sec expressed as percentage of the predicted (based on age, height, and race); FI, functional impairment; GOLD, Global Initiative for Chronic Obstructive Lung Disease; ME, magnitude of effort; MT, magnitude of task.

Figure 6 (A) Reasons for prescribing Aclidinium/formoterol by the treating physicians. (B) Satisfaction of patients using Aclidinium/formoterol per GOLD ABCD group. (C) Compliance to the treatment scheme with Aclidinium/formoterol, and reasons for missing doses.

Abbreviations: AEs, adverse events; COPD, chronic obstructive pulmonary disease; GOLD, Global Initiative for Chronic Obstructive Lung Disease; ICS, inhaled corticosteroids.

Table 1 The 6 Cases of Adverse Events Having Occurred During the Observational Study

List of Adverse Events Recorded in This Study
N	Description/Outcome	Related to Aclidinium/Formoterol	Did the Patient Discontinue from the Study?
1	38 days after enrollment into the study (03/05/2019), the patient was diagnosed with metastatic acute lymphogenic leukemia (10/06/2019) and died 69 days later from the complications of the disease (18/08/2019).	No	Yes (deceased)
2	138 days after enrollment into the study (18/06/2019), the patient suffered from an acute episode of atrial fibrillation (02/11/2019), which led him to the ER. The episode was successfully dealt with, and the patient returned home the next day (03/11/2019).	Unlikely	No
3	4 days after enrollment into the study (20/05/2019), the patient complained about starting to be nervous/ agitated (24/05/2019), and thus discontinued aclidinium/formoterol 3 days later.	Likely	Yes
4	The next day after enrollment into the study (09/09/2019), the patient suffered nasal bleeding (10/09/2019), due to which the patient stopped aclidinium/formoterol. The episode was successfully treated by an ENT specialist and the patient returned home the next day (11/09/2019), after which he resumed pharmacotherapy with aclidinium/formoterol until the end of the study without any other medical incidences.	Probable	No
5	66 days after enrollment into the study (30/08/2019), the patient underwent surgery for lung cancer (04/11/2019), after which he suffered from cardiopulmonary arrest and died.	No	Yes (deceased)
6	Since enrollment into the study (16/09/2019), the patient was complaining about dysuria and difficulties in urination, and thus discontinued aclidinium/formoterol 35 days later (21/10/2019).	Likely	Yes

Abbreviation: ER, emergency room.