*112304*
S. A. Syurin, MD, DrMedSci.
Kola Research Laboratory for
Occupational Health, Kirovsk, Russia
Differences of immune system disorders
in chronic bronchitis and chronic obstructive pulmonary disease
Introduction. The immune system plays a key
role in protecting respiratory organs against infectious and other environmental harmful effects, which is
implemented in close balanced cooperation of immune cells, humoral and nonspecific resistance factors. It was found that the
formation of secondary immunodeficiency is one of the major causes of chronic
inflammatory process in chronic bronchitis (CB) and chronic obstructive pulmonary
disease (COPD) [1, 2]. However, it remains unclear what disorders of the immune
system are characteristic of each of these two similar in pathogenesis, but
independent nosological diseases. In particular, the failure to
resolve these issues does not make it possible to justifiably recommend regular
use of immunomodulators in the treatment of CB and COPD patients [4].
The
aim of the study was to
examine the characteristics of immune system disorders in CB
and COPD patients.
Material and methods. The
studies were performed in 84 CB
patients and in 78 COPD
patients in a phase of remission of the disease. Of the 162 people there were 87 men
and 75 women. At the time of the survey, a regular drug therapy was
non administered to CB patients while COPD patients continued their baseline
bronchodilator therapy. The reference group included 30 healthy individuals
(16 men and 14 women) who did not differ significantly by sex, age and duration of the disease
from the patients
of the study group.
Evaluation of immune system
status was carried out by conventional methods of
the first and second levels of investigation, which
included the identification of peripheral blood B-lymphocytes
(Bl), T-lymphocytes (Tl) and their subpopulations with surface antigens of CD20 + (B-lymphocytes mature - Bl (CD20 +),
CD3 + (T-lymphocytes mature - Tl (CD3+), CD4+ (T-helper cells - Th (CD4+), CD8+
(T- lymphocytes cytotoxic - Tc (CD8+), the determination of
immunoregulatory index (IRI), the determination of the
major classes of serum immunoglobulins concentrations (IgA, IgM, IgG),
total IgE, the titer of normal heterophile antibodies (HAB) in serum
and saliva (SalHAB), the level of circulating
immune complexes (CIC) in blood
serum, phagocytic number (PhN) and
index (PhI) of neutrophils, secretory IgA
in saliva (SalIgA), lysozyme in serum (Lys)
and in saliva (SalLys).
MicroSoft
Excel 2007 was applied for statistical analysis of the
collected data with determination of Student's t-criterion and Pearson’s
correlation coefficient (r). Differences were
considered significant at p<0,05.
The
results. The average age of the
examined patients was 44.7±1.1 and 46.6±1.4 years (p>0.5), and the average
duration of the disease was 10.1±0.5 and 11.2±0.8 years
(p>0.2), respectively. The
number of exacerbations requiring changes in treatment and release from work,
in COPD patients was higher than in patients with CB: 2.41±0.03
and 1.34±0.02
(p<0.05).
The study of the
immune system in patients with CB and COPD
in the phase of partial remission revealed
significant changes of cellular, humoral and phagocytic links of
immunity (Table). Compared with healthy individuals, the
most typical disorders were observed in the cellular link: reduction in the number of Tl (CD3+) and Th (CD8+)
while the number of Tc (CD8+) remained unaffected. Among other changes, decrease in phagocytic activity of
neutrophils (PhN and PhI), decrease in
the level of serum IgM and increase in total IgE
level were the most noteworthy. Only the nonspecific and humoral factors of
local immunity determined in the saliva (SalIgA, SalLys and SalHAB) were
not significantly different in healthy subjects and patients with
bronchopulmonary disorders.
Differences in immune status between
patients with CB and COPD were less significant
than their differences with healthy individuals. Although in
COPD patients the majority of
indicates characterizing cellular,
humoral and phagocytic links of
immunity demonstrated a tendency to
deterioration compared with CB patients,
only the number of Tl (CD3+) and PhI were reduced to the
degree of statistical significance (p
<0,05-0,01)
Indicators of immune
system in healthy individuals and patients with CB
and COPD (̱m)
|
Indicaters |
Healthy individuals |
CB patients |
COPD patients |
|
Òl(ÑD3+),
% |
63.8±1.2 |
59.0±0.8* |
53.4±0.9*# |
|
Âl(CD20+),
% |
24.0±0.7 |
23.0±0.6 |
23.4±0.7 |
|
Òh(CD4+),
% |
47.3±1.2 |
42.1±1.2* |
39.3±1.2* |
|
Òñ(CD8+),
% |
16.6±1.0 |
16.7±1.0 |
14.1±1.1 |
|
IRI, unites |
2.95±0.25 |
2.62±0.39 |
2.84±0.41 |
|
IgÀ,
g/l |
1.78±0.04 |
1.71±0.03 |
1.67±0.04 |
|
IgM, g/l |
1.11±0.03 |
1.01±0.02* |
0.99±0.02* |
|
IgG,
g/l |
9.89±0.19 |
9.88±0.18 |
9.58±0.14 |
|
IgE,
int. unites |
83.0±13.5 |
197.0±38.6* |
230.8±31.3* |
|
HAB, lg IT |
3.55±0.12 |
3.56±0.11 |
3.81±0.11 |
|
CIC, unites |
177.1±9.9 |
185.5±15.3 |
182.9±14.5 |
|
Lys, mcg/ml |
9.82±0.35 |
9.91±0.26 |
9.58±0.24 |
|
SalIgÀ, g/l |
0.20±0.05 |
0.24±0.02 |
0.19±0.02 |
|
SalLys, mcg/l |
132.1±7.0 |
121.9±5.9 |
127.9±7.8 |
|
SalHAB, lg IÒ |
1.47±0.12 |
1.34±0.10 |
1.57±0.12 |
|
PhI, % |
59.1±1.6 |
53.2±1.0 |
49.8±1.1# |
|
PhN, unites |
4.13±0.13 |
2.85±0.09 |
2.65±0.08 |
Note. * - Significance of difference (p<0.05) between healthy
individuals
and patients
with CB and COPD; # - Significance of difference (p<0.05) between patients with
CB and COPD.
Correlation analysis of the immune system showed a pronounced
decrease in associativity of immunological parameters both in patients with chronic bronchitis and COPD in
comparison with healthy individuals. In the latter group the immune system has the best
integrated nature (the so-called "type trellis"), which was formed by the presence of nine pairs of relationships: Òh(CD4+)---Òñ(CD8+), r=0.65, p<0.01;
Òl(CD3+)---IgM, r=-0.45, p<0.05; SalIgA---CIC,
r=0.44, p<0.05; Âl(CD20+)---IgM, r=0.44, p<0.05;
Òl(CD3+)---Òh(CD4+), r=-0.43, p<0.05; Òl(CD3+)---Òñ(CD8+),
r=0.40, p<0.05; Âl(CD20+)---CIC,
r=0.39, p<0.05; CIC---IgA, r=-0.36, p<0.05;
SalIgA---Òl(CD3+), r=-0.36, p<0.05).
Six pairs of correlation
parameters were found in CB patients: Òl(CD3+)---Òh(CD4+), r=0.72, p<0.01; IgM---IgG, r=0.55, p<0.01; Òh(CD4+)---Òñ(CD8+),
r=-0.49, p<0.01; IgM---SalIgA, r=0.45, p<0.05;
IgA---IgM, r=0.38, p<0.05; Âl(CD20+)---HAB,
r=0.37, p<0.05). The structure of the immune system
in COPD patients was determined also by six pairs of correlation parameters which were largely
different from those in CB patients: Òh(CD4+)---Òñ(CD8+), r=-0.74, p<0.01; Òl(CD3+)---Th(CD4+), r=0.61, p<0.01; Òl(CD3+)---Âl(CD20+), r=0.45, p<0.05; Âl(CD20+)---IgÅ,
r=-0.43, p<0.05; SalIgA---Lys, r=0.38, p<0.05; SalIgA---CIC, r=0.38, p<0.05;
CIC---SalIgA, r=0.38, p<0.05).
Qualitatively, the correlation factors of the immune system in
healthy subjects and patients with chronic bronchopulmonary diseases were
significantly different. In the former group there were characteristics of a well-functioning
system of complete interdependence between the phenotypes of lymphocytes with
CD3+, CD4+ and CD8+. In patients with CB and COPD associativity
of cellular immunity was incomplete due to the absence of correlation between Tl (CD3+) and Tc
(CD8+) and because of disorders of the relationship between factors of cellular and
humoral immunity. In CB patients the degree of the immune system disintegration was consistent with
"fractional linear-type trellis". But the most significant violations of
the immune system structure were detected in patients with COPD, which
led to its disintegration to the so-called "fractional linear type".
Discussion. The current studies have confirmed the previously
known evidence
that the development of CB and COPD is accompanied by significant changes in the
immune system [2]. However, in most cases it is impossible to say reasonably whether they
are the primary defect in the protective capacity of the respiratory tract or signs of a secondary
immunodeficiency [3]. Increased levels of total serum IgE detected both in CB and COPD patients can be seen as a sign of
the body allergization accompanying chronic inflammation in the bronchial tree
and lung tissue, even during remission of the disease.
COPD is generally recognized as a more severe health condition than CB. So, it was assumed that COPD is likely to be associated with more severely
impaired immunity. The assumption was confirmed both
at the level of individual indicators (Tl (CD3+), PhI) and at the system level. The
latter type of disorders manifested itself with poor relationships between cellular and humoral immunity.
Conclusion. Chronic obstructive pulmonary disease, compared
with chronic bronchitis, is associated with significantly more pronounced disorders of immune
system. This fact demonstrates the
feasibility of application of various
immunomodulatoty interventions in the complex treatment of this
category of patients.
References
1. Borisova A.M. Rossiyskiy medizinskiy zhurnal [Russian Medical Journal], 1997, no . pp. 15-21 [in Russian].
2. Khronicheskiy
bronkhit i obstruktivnaya bolezn´ lyegkikh //Pod red. A.N.
Kokosova [Chronic bronchitis and
chronic obstructive pulmonary disease //Ed.A.N. Kokosov. Sankt-Peterburg, Lan´. 2002. 157 p. [in
Russian].
3. Shirinskiy
V.S., Sennikova Yu.A. Terapevticheskiy arkhiv [Therapeutic Archive], 1993, no 3. pp. 35-38
[in Russian].
4.
Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy
for diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO workshop report. The 2009 report is available on:
www.goldcopd.com.