Study population
Patient disposition is presented at Figure 1. A total of 392 patients screened for Phase I, 315 were enrolled, and 77 were excluded as ineligible. Of 315 patients, 106 visited sites during the enrollment period and gave consent for study participation.
Characteristics of patients included in the study are presented in Table 1. There were numerically more female (n=211, 67.0%) than male patients (n=104, 33.0%) in the study. Majority of patients were older than 50 years. Most enrolled patients were Caucasians (n=257, 84.3%) and were either obese with a body mass index (BMI) ≥30 kg/m2 (n=103, 39.8%) or overweight with a BMI between 25 and < 30 kg/m2 (n=94, 36.3%). More than half of the patients were non-smokers (n=193, 64.5%); the remaining patients were either past smokers (n=66, 22.1%), current smokers (n=38, 12.7%), or passive smokers (n=2, 0.7%). Among the current and past smokers, the mean (SD) number of cigarettes smoked per day was 17.7 (7.9), and the mean (SD) pack-years was 25.4 (17.7). The overall mean (SD) number of years as a smoker among past and current smokers was 27.7 (12.6) years.
Table 1
Summary sociodemographic data for patients who entered Phases I and II
Parameter | Study population from Russia (n=315) |
Sex, n (%) Female Male | 211 (67.0) 104 (33.0) |
Age at entry, median (range) | 60.0 (24.0–83.0) |
BMI, n (%) Underweight (BMI < 18.5 kg/m2) Normal weight (18.5 ≤ BMI < 25 kg/m2) Overweight (25 ≤ BMI < 30 kg/m2) Obese (BMI ≥ 30 kg/m2) Missing | 2 (0.8) 60 (23.2) 94 (36.3) 103 (39.8) 56 |
Height, cm median (range) | 164.0 (140.0–195.0) |
Ethnicity, n (%) Caucasian Asian Other Unknown/missing | 257 (84.3) 5 (1.6) 43 (14.1) 10 |
Education, n (%) Some high school High school graduate Technical postsecondary Some college College graduate Post graduate degree Unknown/missing | 12 (7.6) 26 (16.5) 22 (13.9) 66 (41.8) 29 (18.4) 3 (1.9) 157 |
Employment status, n (%) Employed full or part time Homemaker Unemployed/Retired Disabled or too ill to work Unknown/missing | 83 (29.6) 9 (3.2) 145 (51.8) 43 (15.4) 35 |
Household income, n (%) Less than minimum wage Minimum wage 2 x minimum wage More than 2 x minimum wage Unknown/missing | 6 (5.7) 59 (56.2) 24 (22.9) 16 (15.2) 210 |
Smoking status, n (%) Current smoker Past-smoker Non-smoker Passive smoking at home/other Unknown/missing | 38 (12.7) 66 (22.1) 193 (64.5) 2 (0.7) 16 |
Notes: BMI – body mass index; percentages in the table were calculated for available data (excluding unknown/missing). |
Medical history
Among the 315 patients enrolled in Phase I, 303 (96.2%) patients had at least one comorbidity. Overall, the mean (SD) number of all comorbidities, disease comorbidities, allergic conditions, and other comorbidities were 3.0 (1.4), 2.2 (1.0), 1.8 (0.8), and 1.0 (1.0), respectively. The most common comorbidity was cardiovascular disease (n=217, 71.4%), followed by chronic respiratory disease (n=198, 68.8%) (including chronic obstructive pulmonary disease [COPD, n=99, 31.5%], allergic rhinitis [n=94, 30.4%], or other [n=62, 20.9%]), respiratory allergies (n=64, 22.6%), drug allergies (n=57, 21.3%), gastrointestinal disease (n=55, 19.3%), and other allergies (n=36, 12.7%). Renal disease, rheumatological disease, diabetes with/without end-organ damage, malignancy disease, immunological disease, and food allergies were each reported in less than 10% of the patients. There were nine other comorbidities also reported, including obesity, osteochondrosis, benign prostatic hyperplasia, iron deficiency anemia, dyslipidemia, gout, hyperlipidemia, osteoarthritis, and sinusitis; 56 (57.1%) patients had other comorbidities.
Asthma history data is presented in Table 2. Among the 315 patients, the median (range) age at diagnosis of asthma or severe asthma was 45.0 (1.0–79.0) and 55.5 (15.0–82.0) years, respectively. The median (range) age at the first symptoms of asthma was 42.0 (1.0–76.0) years. The mean (SD) time between asthma diagnosis and severe asthma diagnosis was 10.1 (11.1) years. Most patients did not have a familial first-degree history of asthma (n=150, 62.0%).
Table 2
Parameter | Study population from Russia (n=315) |
Age at diagnosis, years median (range) | 45.0 (1.0–79.0) |
Age at first symptoms of asthma, years median (range) | 42.0 (1.0–76.0) |
Age at diagnosis of severe asthma, years median (range) | 55.5 (15.0–82.0) |
Years since diagnosis of severe asthma median (range) | 3.0 (0.0–43.0) |
Familial first-degree history of asthma, n (%) Yes No Missing | 92 (38.0%) 150 (62.0%) 73 |
Number of physicians that were seen before being diagnosed with severe asthma median (range) | 2.0 (1.0–10.0) |
Medical specialty of the physician that has diagnosed severe asthma, n (%) General/Family Practice Respiratory specialist Allergist Cardiologist Missing | 19 (6.7%) 189 (66.5%) 75 (26.4%) 1 (0.4%) 31 |
Medical specialty of the physician seen most often by patient for severe asthma follow-up, n (%) General/Family Practice Respiratory specialist Allergist Missing | 98 (32.7%) 161 (53.7%) 41 (13.7%) 15 |
Routine follow-up for severe asthma, n (%) Yes No Missing | 279 (94.9%) 15 (5.1%) 21 |
The most reported frequencies of nighttime awakenings due to severe asthma in the last 12 months were once a week (n=55, 23.9%), twice a week (n=40, 17.4%), and once per fortnight (n=39, 17.0%) (Figure 2).
There were 268 (85.1%) patients who experienced at least one asthma exacerbation during the last 12 months, the majority of them had 1 exacerbation during the past 12 months (n=209, 66.3%) (Figure 3). Exacerbations were most common during spring (n=116, 36.8%), followed by winter (n=91, 28.9%), summer (n=70, 22.2%), and autumn (n=54, 17.1%). The mean (SD) duration of exacerbation was 8.5 (5.3) days. For most patients, flu or common cold was the trigger for exacerbation (n=135, 46.2%).
Laboratory data
A total of 176 patients had blood eosinophil counts data available in either Phase I or II, one measurement data was available for the majority of patients (n=159, 82.0%). Therefore, eosinophil count control is not frequently used in routine practice. The highest mean (SD) eosinophil level observed was 123.9 (173.2) cells/µL. Among the 106 patients enrolled in Phase II of the study, 4 (3.8%) patients had a blood eosinophil count recorded at visit. Mean (SD) blood eosinophil count was 46.5 (86.4) cells/µL.
Data on IgE measurements were available for 88 patients, nearly all patients had only one test performed in the 12 months prior to data entry in Phase I (n=82, 93.2%). The mean (SD) last serum IgE value was 254.3 (249.7) ng/mL. Therefore, most patients’ last serum IgE value was ≤244 ng/mL, which is considered normal (n=52, 59.8%).
Retrospective spirometry data are shown in Figure 4.
Note FEV1 – forced expiratory volume in first second; last FVC – forced vital capacity; data represent mean for 279 patients.
Among the 279 patients with available data on lung function examinations in the last 12 months, the majority had only one lung function examination (n=202, 72.4%). The mean (SD) last forced expiratory volume in first second (FEV1), last forced vital capacity (FVC), and last FEV1/FVC value were 56.9 (20.4), 76.0 (21.1), and 76.0 (18.0) % of predicted, respectively. Overall, most patients had a last FEV1/FVC value between 50% and 70% (n=230, 93.9%).
No IgE evaluations were recorded in cross-sectional part of study. Spirometry data was available for 29 patients included in Phase II. The mean (SD) FEV1 value was 56.6 (21.7) % of predicted, and most patients had a FEV1 value of >50% (n=16, 55.2%). There were 15 patients with a FVC value recorded at the cross-sectional visit. The mean (SD) FVC value was 80.9 (18.3) % predicted, and most patients had a FVC value of >70% (n=10, 66.7%). The mean (SD) FEV-1/FVC ratio was 72.3 (19.4) % predicted (n=15).
Disease management
Asthma treatment related data are shown in Table 3. Among the 315 patients, the most common treatment prescribed in the last 12 months was controller/maintenance treatment (n=313, 99.4%), followed by reliever treatment (n=305, 96.8%), exacerbation treatments (short-acting β-agonists [SABA] excluded) (n=249, 79.0%), and other medication (n=245, 77.8%). In terms of the distinct number of medications prescribed for each category, exacerbation treatments (SABA excluded) had the highest mean (SD) number during the last 12 months (4.3 [3.2]), followed by other drugs (3.2 [2.3]), controller/maintenance treatment (1.9 [0.9]), and reliever treatments (1.1 [0.4]). New or ongoing reliever treatments had the longest mean (SD) treatment duration (11.1 [2.6] months), followed by controller/maintenance treatments (9.9 [3.3] months), other medications (8.0 [4.2] months), and exacerbation treatments (SABA excluded) (1.0 [2.2] months).
Table 3
Treatments prescribed and average duration of treatment use for severe asthma
Parameter | Study population from Russia (n=315) |
Number of distinct controller/maintenance treatments prescribed for severe asthma in the last 12 months median (range) | 1.9 (0.9) |
Number of distinct reliever treatments for severe asthma prescribed in the last 12 months, mean (SD) | 1.1 (0.4) |
Number of distinct exacerbation treatments for severe asthma prescribed in the last 12 months, mean (SD)* | 4.3 (3.2) |
Number of distinct other medications prescribed in the last 12 months, mean (SD) | 3.2 (2.3) |
Average duration of any new or ongoing controller/maintenance treatments for severe asthma in the last 12 months, months, mean (SD) | 9.9 (3.3) |
Average duration of any new or ongoing exacerbation treatments for severe asthma in the last 12 months, months, mean (SD) * | 1.0 (2.2) |
Average duration of any new or ongoing other medications in the last 12 months, months, mean (SD) | 8.0 (4.2) |
Note: SABA – short-acting β-agonist; * – excluding SABA; SD – standard deviation. |
Among the 315 patients, 199 (63.2%) patients received OCS treatment in the past 12 months. The mean (SD) overall daily dose of OCS in the last 12 months was 2.9 (5.1) mg (n=199). The mean (SD) daily dose of OCS for controller/maintenance treatment in the last 12 months was 6.1 (4.1) mg (n=16). The mean (SD) daily dose of OCS for exacerbation treatment in the last 12 months was 2.5 (4.9) mg (n=194).
Among the 313 (99.4%) patients who received controller/maintenance treatment, the most common treatments (i.e., prescribed in >5% of patients) were medium/high dose ICS/long-acting β-agonists (LABA) (n=291, 93.0%), tiotropium bromide (n=156, 49.8%), leukotriene receptor antagonist (LTRA) (n=28, 8.9%), other (n=19, 6.1%), medium/high dose ICS (n=18, 5.8%), and low dose OCS (n=16, 5.1%). The mean (SD) days of treatment among the most common treatments ranged from 239.9 (125.3) days in LTRA to 315.8 (100.0) days in medium/high dose ICS/LABA. In 12 months prior to inclusion, the most common (i.e., observed in >5% of patients) first prescribed controller/maintenance treatment started during the past 12 months was medium/high dose ICS/LABA (n=291, 92.4%), followed by tiotropium bromide (n=156, 49.5%), LTRA (n=28, 8.9%), medium/high dose ICS and other (n=19, 6.0%, for both).
Among the 305 (96.8%) patients who received reliever treatment, the most common treatments (i.e., prescribed in >5% of patients) were short-acting beta 2 agonists (n=224, 73.4%), followed by other treatments (n=70, 23.0%), and low dose ICS/formoterol (n=21, 6.9%). The mean (SD) treatment duration was 293.2 (133.7) days in low dose ICS/formoterol, 337.5 (78.0) days in other treatments, and 341.1 (75.1) days in SABA.
There were 250 (79.4%) patients with prescribed exacerbation treatment during the 12 months prior to study inclusion. The most common treatments (i.e., prescribed in >5% of patients) were systemic corticosteroid (OCS/parenteral) (n=198, 79.2%), other treatments (n=175, 70.0%), SABA (Salbutamol) (n=24, 9.6%), short-acting muscarinic antagonist (SAMA) (ipratropium) (n=22, 8.8%), and oxygen (n=16, 6.4%). Among the common exacerbation treatments for severe asthma, the mean (SD) treatment duration ranged from 22.6 (30.6) days for oxygen to 60.0 (92.0) days for SABA.
Among the 250 patients who experienced at least one exacerbation within the prior 12 months, physician consultation was the most frequent intervention (n=227, 75.4%). A total of 30 (10.6%) patients experienced at least one exacerbation which required an ER visit, and 200 (67.1%) were hospitalized with a mean (SD) of 12.3 (6.0) nights spent in hospital in the last 12 months.
Patient-Reported Outcomes
Questionnaires were completed by the patients who participated in Phase II (n=106). Most patients had an ACT score of ≤15 and fell in the category “asthma may not be under control” (n=79, 74.5%); there were 22 (20.8%) patients with an ACT score of ≥16 to ≤19 and fell in the category “asthma partially or not well controlled”; and 5 (4.7%) patients with an ACT score of ≥20 and fell in the category “asthma may be under control”. The mean (SD) ACT score was 11.4 (4.7).
The mean (SD) EQ-5D-5L utility score was 0.5 (0.3), and the mean (SD) EQ-5D visual analogue scale (VAS) score was 51.8 (20.2). The mean (SD) number of school or workdays patients reported missing due to severe asthma was 17.6 (21.8) days. The mean (SD) number of school or workdays with less productivity due to severe asthma was 44.6 (45.2) days. Overall, higher quality of life was associated with better asthma control.
Limitations
Most of the sites selected in this study were public hospitals (hence the results show that almost all patients were covered by public/social security healthcare), and thus the generalizability of the results is limited to patients treated in public healthcare settings. Physician participation in Phase I/II and patient participation in Phase II were on a voluntary basis; this may have resulted in selection bias, thereby impacting the representativeness of the final sample of participating physicians and patients. Missing data, which is a known disadvantage of observational studies, could reduce the statistical power of analyses and may potentially bias estimates. There was very limited data captured on blood eosinophil measurements in this study. Finally, it is important to consider the reliability of certain variables, e.g., smoking status may be impacted by reporting bias, due to the reluctance of patients to report smoking behavior to their doctor.