Materials and Methods
This is an open label, multi-center, non-interventional, non-comparative, observational, prospective study (NCT03300076) of adult patients diagnosed with asthma of variable severity. In total, 716 patients were enrolled and followed-up for up to 6 months in 53 institutions and private practices throughout Greece, commencing from February 2018 and up to June 2018. The study was performed in accordance with the principles of the Declaration of Helsinki and was approved by the Ethics Committees of the Sotiria Chest Disease Hospital and the General Hospital of Chalkida. Written informed consent was obtained from all participants. Patients were treated with budesonide/formoterol FDC (Pulmoton Elpenhaler), according to routine clinical practice. The majority of the enrolled patients were treatment naive, and the ones already on treatment were either not satisfactorily controlled with ICS (Inhaled Corticosteroids) and on demand use of SABAs (Short Acting Beta Agonists), or were patients already satisfactorily controlled with both ICS and LABA, though administered with 2 different devices. We excluded patients meeting any of the following criteria: diagnosis of Chronic Obstructive Pulmonary Disease (COPD) at any stage, use of any fixed combination of ICS/LABA at least 1 month prior to study initiation, and/or prior use of systemic corticosteroids within 3 months from study initiation. Patients with a history of improper use of inhaled therapies or failing to comply with the study procedures, were also excluded. After study initiation, patients used a fixed dose arrangement of the inhaled treatment as instructed by the treating physician.
The primary objective of this study was to evaluate the adherence to treatment with FDC budesonide/formoterol at 3 and 6 months after treatment initiation. Adherence to treatment was assessed at 3 and 6 months since treatment initiation based on the 8-item Morisky Medication Adherence Scale (MMAS-8),[15–19] which has been elsewhere used primarily in chronic diseases, e.g. type II diabetes, hypertension, etc. This self-reported scale contains 7 items answered with a yes or no and 1 item with a 5-point Likert scale, with scores ranging from 0 to 8. The respective MMAS-8 scores were trichotomized into the following 3 levels of adherence: high adherence (HA, score = 8), medium adherence (MA, 6 ≤ score < 8), and low adherence (LA, score < 6).
Quality of life (QoL) was assessed using the validated Greek version Mini Asthma Quality of life Questionnaire (Mini AQLQ) at baseline, 3 and 6 months, depicting the impact of asthma in the patient's QoL. This 15-item questionnaire consists of 4 domains: (i) symptoms, (ii) environment, (iii) emotions, and (iv) activities, and covers a 2 week period. Scores range from 1–7 (lower is worse).
Spirometry was also performed in the same visits, using the ERS/ATS guidelines and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and their ratio (FEV1/FVC) were recorded. Moreover, asthma related exacerbations after 3 and 6 months since treatment initiation were recorded for each patient. In terms of safety, adverse events were reported throughout the study; the most current version of Medical Dictionary for Regulatory Activities (MedDRA v21.1) was used for the medical coding of the recorded adverse events.
Descriptive statistical analysis was performed on all patients in terms of patient demographics (sex, age, weight, height, smoking status, etc.) and spirometric data. Other characteristics such as history of asthma and prior medications were also summarized. Continuous variables were summarized with the use of descriptive statistical measures [mean value, standard deviation (SD), median, IQR] and categorical variables were displayed as frequency tables (N, %). Association between categorical variables was presented by contingency tables and assessed using Chi-square test or Fisher exact test, when appropriate. Furthermore, in order to examine possible differences between continuous variables, paired t-test for related samples was applied. All the statistical tests were two-sided and were performed at a 0.05 significance level. Analysis was performed on the basis of non-missing information and no imputation methods were applied.
For the primary objective of the study, i.e. adherence to treatment with Pulmoton Elpenhaler, the MMAS-8 scale was used. Continuous scale score (0–8) was descriptively summarized at 3 and 6 months and change in score between study visits was evaluated by paired t-test. The MMAS-8 score was also categorized into "high" (score = 8), medium (score = 6–7), and "low adherence" (score = 0–5) and summarized by absolute and relative frequencies (N, %). According to Muntuner et al., the minimal detectable change for MMAS-8 score is 1.98.
Quality of life was assessed with the Mini AQLQ at 0, 3 and 6 months of the study. Individual scores per question, total score and 4 domain scores (symptoms, environment, emotions, activities) were descriptively summarized and changes in the total score at 3 and 6 months from baseline were further assessed by paired t-test. Efficacy of the study drug was assessed in terms of spirometry results at 0, 3 and 6 months of the study. Additionally, changes in the Mini AQLQ questionnaire between 3 and 6 months have been evaluated with analyses of covariance (ANCOVA), using baseline values as covariates. All spirometry data (FEV1 measured in L, FEV1% predicted, FVC measured in L, FVC % predicted, and FEV1/FVC ratio) were summarized by mean, SD, median and IQR and changes in key spirometry data were further assessed by paired t-test. The minimal clinically important difference in patients with asthma has not been rigorously established in asthma, but a report from the US NIH suggests that changes of 100–200 mL are likely to be clinically important. Statistical analysis was performed by means of IBM-SPSS v24.0 statistical software.
BMC Pulm Med. 2022;22(254) © 2022 BioMed Central, Ltd.