Table 1
General characteristics of the study participants
Parameters
|
Vaccinated PCV13, n = 324
|
Unvaccinated, n = 176
|
p*
|
|
Group
|
1
|
2
|
3
|
|
Number of patients, n
|
COPD
n = 149
|
COPD + CHD n = 175
|
COPD, n = 176
|
|
Gender
|
male
|
male
|
male
|
-
|
Age (years), median (Q25-Q75)
|
61.00 (58.00–64.00)
|
62.00 (59.00–65.00)
|
65.00 (61.00–68.00)
|
|
Smoking history (years), median (Q25-Q75)
|
16.00 (12.00–21.00)
|
13.00 (11.00–15.00)
|
15.00(12.00–20.00)
|
|
COPD duration (years), median (Q25-Q75)
|
13.00 (11.00–15.00)
|
9.00 (7.00-10.50)
|
13.00 (11.00–15.00)
|
p < 0.05
|
COPD stages (GOLD), n
|
|
|
|
|
II
|
22
|
33
|
26
|
|
III
|
65
|
54
|
68
|
|
IV
|
62
|
88
|
82
|
|
Functional class of angina pectoris, n
|
-
|
-
|
-
|
|
FC 2
|
-
|
31
|
-
|
|
FC 3
|
-
|
95
|
-
|
|
FC 4
|
-
|
49
|
-
|
|
Rate of COPD exacerbations per year
|
148
|
229
|
142
|
|
Number of hospitalizations per year
|
141
|
235
|
159
|
|
Number of pneumonias per year
|
25
|
44
|
24
|
|
MRC dyspnea scale (points), median (Q25-Q75)
|
3.00 (3.00–3.00)
|
3.00 (3.00–3.00)
|
3.00 (3.00–4.00)
|
|
SpO2 (%), median (Q25-Q75)
|
91 (90–92)
|
88 (86–89)
|
94 (92–95)
|
p < 0.05
|
FEV1 (%), median (Q25-Q75)
|
48.00 (45.00–51.00)
|
46.00 (35.00–58.00)
|
51.00 (47.8–56.00)
|
p < 0.05
|
6-minute walk distance test (6MWD, m), median (Q25-Q75)
|
230.00 (190.00-300.00)
|
217.00 (190.00-245.00)
|
218 (190–240)
|
p < 0.05
|
The main characteristics of patients are presented in the Table 1. At the time of enrollment in the study protocol, severe and extremely severe patients prevailed in the structure of patients with COPD: with moderately severe stage in the observation group there were 22 patients (14.8%), with severe COPD 65 (43.6%) and with GOLD IV 62 patients (41.6%) (Table 1). In patients with a combined course of COPD and CHD, the distribution of observed patients was as follows: 33 (18.8%) were with moderately severe COPD, 54 (30.8%) with severe and 88 (50.4%) with extremely severe disease. 31 (17.8%) patients were with grade II FC of angina pectoris, 95 (54.2%) with III FC and 49 (28%) with IV FC.
In accordance with the purpose of the study, the effectiveness of PCV13 vaccination against the development of CAP in the first year after vaccination, in the fifth year and 10 years later. The direct positive impact of PCV13 demonstrated in Figs. 1 and 2, showing the distribution of the number of CAP developed during 10 years of follow-up and incidence rate CAP per 1000 patients. A cumulative analysis shows that after administration PCV13 in the first year there is a significant decrease in episodes of CAP, and 5 and 10 years of follow-up maintain this trend in Groups 1, 2. Unvaccinated surviving patients showed higher recurrent pneumonia incidence.
When constructing the proportional hazards model (Cox regression) taking into account the number of exacerbations, hospitalizations and CAP, the high quality of the selected parameters was demonstrated with a sufficient degree of reliability (p < 0.005) (Fig. 3; Table 3). The survival curves presented in Fig. 3 show a significant reduction in years of survival in unvaccinated patients compared with vaccinated by PCV13 patients with COPD and with comorbidities. At the same time, there is a significant difference in survival curves in patients with COPD and COPD with CHD in favor of patients with isolated nosology.
CAP (without specifying the etiology) was the leading cause of mortality in Group 3 (61,2%). In Groups 1 and 2 (patients received PCV13) the cause of mortality from CAP was 5,5% and 6,2% accordance. The structure of causes of mortality presented in Table 2. Among patients with comorbid COPD&CHD was registered cordial cases of death (29,7%), such as Heart attack, Chronic heart failure (CHF).
Table 2
The structure of causes of mortality
Cause of mortality (%)
|
Group 1
|
Group 2
|
Group 3
|
CAP
|
5,5
|
6,2
|
61,2
|
Progressive respiratory failure
|
12,8
|
14,6
|
31,6
|
Chronic heart failure
|
0
|
23,2
|
0
|
Heart attack
|
0
|
6,5
|
0
|
Other reasons
|
81,7
|
49,5
|
7,2
|
Table 3
Coefficients of the proportional hazards model (Cox regression) and assessment of the quality of the proportional hazards model.
Model coefficients
|
|
|
|
Parameter
|
Hazard Ratio
|
95% CI
|
P value
|
Group 1 (COPD PCV13)
|
-1.28
|
(-1.59;-0.98)
|
< 0.005
|
Group 2 (COPD and CHD PCV13)
|
-1.36
|
(-1.68;-1.04)
|
< 0.005
|
Exacerbations_baseline
|
0.69
|
(0.43;0.94)
|
< 0.005
|
Age
|
0.06
|
(0.04;0.08)
|
< 0.005
|
Parameters of model
|
|
|
|
Concordance
|
0.73
|
|
|
log-likelihood ratio test
|
132.74 on 4 df
|
|
|
P value
|
< 0.005
|
|
|
Levels of dyspnea, as measured by the MRC scoring system, were initially comparable in patients with COPD and those with co-morbidities, before vaccination with PCV13: 3.0 (3.00–3.00) The dyspnea level was 3.5 (3–4) points among unvaccinated patients.
Among vaccinated patients, dyspnea decreased by the first year of observation and maintained the same trend after 5 and 10 years of observation, in contrast to unvaccinated patients (Fig. 4).
The combination of nosologies determines the severity of the patient's condition and presents certain diagnostic difficulties, as it is often impossible to distinguish the true nature of dyspnea in this case (Fig. 4).
Parameters of pulmonary function, particularly FEV1, behave unidirectionally with dyspnea levels. The lowest value was recorded in the Group 2 46.00% (35.00–58.00) of the normal value (Table 1). After 1.5 and 10 years of observation, stable FEV1 levels observed in vaccinated patients. In unvaccinated patients, there was trend towards a decrease in the level of functional indicators (Fig. 5).
The 6-minute walk distance test in COPD patients provides a more accurate assessment of disease severity and prognosis than FEV1. The risk of death in COPD patients increased for every 50 m decrease in 6MWD, and a reduction in 6MWD less than 289 m raised the risk of death 2-fold [17]. The distance in 6MWD was minimal in patients with a combined COPD&CHD, 217.00 (190.00-225.00) m. The negative dynamics of 6MWD is most noticeable in unvaccinated patients, starting from the 5th year of observation and the minimum values recorded by the 10-year period (Fig. 6).
The data presented in Fig. 7, 8 show a decrease in the number of recurrent exacerbations in vaccinated patients groups during the very first year after vaccination, and taking into account the deceased patients, we can see more unvaccinated patients with recurrent exacerbations by the 10th year of follow-up.
The hospitalizations dynamics also indicates a higher frequency of inpatient treatment for various reasons in unvaccinated patients (Fig. 9).