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UDC 616.3-07-08-036: 616.12-008.331.1:616.24-008.4 doi.org:10.31684/2541-8475.2019.1(13).46-51
CLINICAL AND EPIDEMIOLOGICAL FEATURES OF DIGESTIVE DISEASES IN PATIENTS WITH COMORBID PATHOLOGY OF RESPIRATORY AND CARDIOVASCULAR SYSTEMS
Altai State Medical University, Barnaul
E.B. Klester, I.I. Belova, A.S. Balitskaya, K.V. Klester
Research objective. To study the frequency and features of clinical implications of concomitant diseases of the digestive organs in patients with COPD, including the cases when combined with arterial hypertension. Materials and methods. Clinical and functional disorders were analysed in 319 patients, among them, 97 were diagnosed chronic obstructive pulmonary disease (COPD) (I group), 118 patients had the combination of COPD with arterial hypertension (AH) (II group), 104 patients had AH (III group).
Results. It was found that chronic gastritis is the most frequently detected digestive system disease in patients with COPD (up to 78.2% of patients), however, gastroenterological complaints are hardly expressed. HP infection ranged from 67.6% (in patients of the II group) to 83.8% (in patients of the I group). According to the morphological study, in the presence of a combined pathology, the number of patients with signs of atrophy increases, the microcirculation disorder in gastric mucosa can be observed.
Conclusion. High frequency of a concomitant digestive system pathology leads to mutual burdening of diseases,
requires additional examination and obligatory medication correction in patients with COPD.
Key words: digestive system pathology, chronic obstructive pulmonary disease, arterial hypertension.
The combination of diseases of the digestive system with pathology of respiratory and circulatory systems occurs from 8% to 80% of cases [1, 2]. In addition to the genetic predisposition and the presence of anatomical and functional relationships realized by the commonality of innervation and blood supply, the high frequency of the combination can be explained by general risk factors as well: smoking, old age, etc. [3, 4]. One of the main problems of modern medicine is the increase in the multiplicity of diseases, which reflects, first of all, involution processes (multimorbidity), while deterministic possibility of their combination (comorbidity) remains difficult to study [5, 6]. This problem fully refers to the pathology of the digestive tract in patients with diseases of the respiratory and cardiovascular systems, the association of which determines significant changes of clinical implications, trends, approaches to treatment, and outcomes of each disease [7, 8]. The world literature actively discusses "systemic manifestations" of COPD and the relationship of heart damage with the emerging and ongoing pathological processes of respiratory, digestive, genitourinary, and some other systems [9], arising from three leading mechanisms of COPD development: systemic inflammation, oxidative stress, and neurohormonal one [10, 11].
The research objective was a comparative study of the frequency of occurrence and features of clinical implications of concomitant diseases of the digestive system in patients with pathology of respiratory and cardiovascular systems.
Materials and methods
The study included 319 patients with COPD diagnosed according to GOLD (2018) [12], which determined the formation of groups: group I - 97 patients with COPD, group II - 118 patients with COPD and AH, group III - 104 patients with AH. The pathology of the digestive system was determined according to the Russian standards (protocols) of diagnosis and treatment of patients with diseases of the digestive system (order of the Ministry of Health of the Russian Federation No. 125 dated 17.04.98, taking into account standards of medical care according to nosology) [13].
Exclusion criteria are as follows: acute forms of IHD, blood circulation decompensation (IIB and III stage of CHF), any other combined pathology under decompensation. Patients were included in the study upon admission. All participants of the study signed an informed consent.
In estimating the distribution of patients by sex, the majority were men: in group I - 64.5±8.7%, in group II - 62.8±7.2%, in group III - 61.6±4.6% (p>0.05).
The mean age of patients of group I was 58.7±1.73 years, group II - 61.3±1.14, group III -59.5±1.41 (p>0.05).
Patients of study groups did not differ among themselves by the main clinical characteristics (age, sex, severity of COPD), which allowed to compare them. For example, patients of groups I and II had obstructive bronchial patency disorders, classified by the FEV1 parameter of mild and moderate severity, and the degree of risk B prevailed (according to GOLD, 2018, taking into account the presence of even one recrudescence
that led to hospitalization) [12], subject to relieved recrudescence and AH (patients of groups II and III), mainly of the II degree (according to the Guidelines for the Management of Arterial Hypertension of the European Society of Cardiology and the European Society of Hypertension, 2018) [14]. The average FC of CHF was 2.44±0.06 in patients of group I, 2.86±0.07 in group II, 2.12±0.09 in group III (pI_II. II-III<0.05). In the summary assessment of the clinical state of patients by RSCS, 4.48±0.11 points were determined in patients of group I, 4.97±0.13 points in group II, 4.22±0.11 points in group III (pt n
ii-iii<0.05).
All patients underwent the complex clinical instrumental and laboratory examination with the analysis of anamnesis data, complaints, and the objective study methods with the analysis of ECG, respiratory function (RF) examination, if medically required - clinical and X-ray studies (including gastric X-ray), methods of functional diagnostics (ECG, RF, Doppler echocardiography, ultrasound investigation of hepatobiliary zone organs), endoscopic examination (GIF-Q10, GIF-Q20, GIF-P30 units of Olympus firm were used) of the esophagus, stomach, and intestines with morphological study of biopsy materials, in patients after stomach resection - from the area
Structure of diseases of the di
of anastomosis and the preserved part with the diagnosis of Hp (the degree of contamination of gastric mucosa with Hp was assessed according to the criteria proposed by L.I. Aruin et al. [15]), and the determination of local urease activity (Clo-test). Histological changes in the gastric mucosa (GM) were evaluated according to the modified Sydney classification using a visual analog scale [15].
Statistical processing of the obtained data was carried out with the help of variation statistics methods using the Statistica 7.0 software package. At normal distribution, the statistical significance of differences in average indicators was determined with the use of Student's t-test. Non-parametric criteria were used in the analysis of distributions different from normal ones. Qualitative differences between groups were determined using the Fisher's exact test (at n<5) or c2 at n>5, including Yates's correction at n<50. The differences were considered statistically significant at p<0.05.
Results and discussion
In studying the frequency of occurrence of diseases of the digestive system, the highest frequency was revealed in group II - in 77 (65.3%) patients, less in group I - in 50 (51.5%) patients, and in group III - in 42 (40.4%) patients (pI-n. II-m<0.05).
' Table 1
five system in analyzed groups of patients
Diseases Group I (COPD) n=50 Group II (COPD+AH) n=77 Group III (AH) n=42
Abs % Abs % P Abs % P
number number number
GERD 29 51.8 60* 69.0 C2=4.83; p=0.03 24- 45.3 C2=4.70; p=0.03
Chronic gastritis 34 60.7 68* 78.2 C2=6.68; p=0.01 31 58.5 C2=3.12; p=0.08
Chronic duodenitis 27 48.2 57* 65.5 C2=4.57; p=0.03 23 43.4 C2=3.74; p=0.05
Peptic ulcer disease 15 26.8 42* 48.3 C2=6.42; p=0.01 13- 24.5 C2=5.17; p=0.02
Cholelithiasis 11 19.6 30 34.5 C2=3.25; p=0.07 10 18.9 C2=2.16; p=0.14
Chronic pancreatitis 10 17.9 28 32.2 C2=3.13; p=0.08 8 15.1 C2=3.08; p=0.08
Chronic hepatitis 9 16.1 28* 32.2 C2=4.10; p=0.04 8 15.1 C2=3.08; p=0.08
Liver cirrhosis 6 10.7 20 23.0 C2=2.83; p=0.09 6 11.3 C2=1.54; p=0.21
Chronic bowel diseases 8 14.3 27* 31.0 C2=4.61; p=0.03 7- 13.2 C2=3.65; p=0.03
Notes: * - statistically significant differences (p<0.05) between groups I and II; • - statistically significant differences (p<0.05) between groups II and III.
All patients filled in the GerdQ questionnaire themselves. The number of points ranged from 1 to
18 (the average score of group I was 9.1±3.7; group II - 10.3±4.1; group III - 9.0±3.5; p II-m<0.05). At the
sum of points of 8 and more, GERD was diagnosed, which was confirmed by the EGD data. GERD was manifested in heartburn mainly in patients of group I (79.3%), less often in patients of groups II and III (58.3 and 33.3% respectively; pI-n. n_m<0.05), which was observed in half of patients both day and night. Strong correlation (r=0.71) was revealed between the sum of the questionnaire points and the EGD results. The rate of detection of GERD moderately correlates with the points by CAT (r=0.48).
In patients of all groups, chronic gastritis was the most frequently detected disease of the digestive system (Table 1), with gastroenterological complaints being mildly expressed. In the analysis of endoscopic picture of gastric mucosa, signs of inflammation more pronounced in the antral section (in 44.1% of patients) than in the fundal one (in 14.7% of patients) were observed in patients of group I more often than in patients of groups II and III.
Table 2
Histological changes of gastric mucosa in analyzed groups of patients
Nature of changes Group I (COPD) n=34 Group II (COPD+AH) n=68 Group III (AH) n=31
Abs number % Abs number % P Abs number % P
Inflammation
in particular: mild 11 32.3 11 16.2 X2=2.62; p=0.10 12 38.7- X2=4.86; p=0.03
moderate severe 16 47.1 24 35.3 %2=0.87; p=0.35 12 38.7 %2=0.01; p=0.92
7 20.6 33 48.5* X2=6.30; p=0.01 7 22.6- X2=4.93; p=0.03
Activity
in particular: absent 6 17.6 10 14.8 %2=0.01; p=0.92 3 9.7 p=0.75
mild 7 20.6 9 13.2 X2=0.45; p=0.50 11 35.5- X2=5.23; p=0.02
14 41.2 20 29.4 X2=0.93; p=0.33 11 35.5 %2=0.14; p=0.71
moderate severe 7 20.6 29 42.6* %2=3.91; p=0.04 6 19.3- X2=4.09; p=0.04
Atrophy
in particular: absent 9 26.5 5 7.4* p=0.01 8 25.8* p=0.02
mild 7 20.6 9 13.2 X2=0.45; p=0.50 5 16.1 p=0.76
moderate 10 29.4 22 32.3 %2=0.01; p=0.94 8 25.8 %2=0.18; p=0.67
severe 8 23.5 32 47.1* %2=4.32; p=0.04 10 32.3 X2=1.35; p=0.24
Intestinal metaplasia 4 11.8 22 32.3* p=0.03 4 12.9 p=0.05
Notes: * - statistically significant differences (p<0.05) between groups I and II; • - statistically significant differences (p<0.05) between groups II and III.
Pangastritis was found in 41.2% of patients of group I. Against the background of hyperemia and edema, hemorrhages in the form of petechial rashes and punctulate erosions were revealed (in 64.7% of patients). Erosive defects of different
depths were revealed in 44.1% of patients, among them the "full" ones in 29.4%. The outbreaks of atrophic changes were localized most often in the antral section (in 50.0% of patients).
In patients of group II, with EGD, diffuse stomach lesion was more often revealed in the presence of large areas of pale mucous membrane with thinning or complete loss of gastric folds, hyperemia and edema of mucous membrane in the body and antral section, contact bleeding.
In endoscopic examination of patients of group III, gastritis with predominant antral lesion was diagnosed in 22.6%, common gastritis - in 71.0%, while isolated lesion in the body and gastric fundus was observed in only 6.4% of patients. According to the data of the complex application of cytological, histological, and urease tests, the infection of the Kelicobacter pylori (Hp) ranged from 67.6% (in patients of group II) to 83.8% (in patients of group I), indicating a high degree of association of the studied diseases with the Hp.
The results of the morphological study showed that the activity of inflammation (neutrophil infiltration) of various degrees of severity was revealed in almost all infected patients (94-100%), while active gastritis was less likely in uninfected patients. The frequency of occurrence of intestinal metaplasia (27.9%) prevailed in patients of group II.
The obtained results conform to the data of other researchers, which showed that in 10-40% of cases, foci of complete and incomplete intestinal metaplasia in GM are found in persons with chronic gastritis [16, 17].
In patients with nonatrophic gastritis, the level of colonization of the mucous membrane of Np correlated with indicators of activity and inflammation degree. At the same time, the moderate (p=0.44) direct correlation was found in patients of group I, and the average one (p=0.70; p=0.61) was found in patients of groups II and III.
In patients with atrophic gastritis, the moderate direct correlation was found between atrophy and activity, inflammation degree. Feedback was found between atrophy and degree of colonization of Np (in patients of group I, p=-0.61; in patients of group II, p=-0.76; in patients of group III, p=-0.53).
Chronic duodenitis was secondary in all examined patients.
Comparative analysis of inflammatory and atrophic changes of the mucous membrane of the gastroduodenal zone showed that in the presence of a combined pathology, the number of patients with signs of atrophy was greater, dystrophic processes were found both in the cells of the glands and in the cells of the cover epithelium, as well as microcirculation disorder in the gastric mucosa was observed. According to the morphological study, these changes were much more common than in the visual examination during the endoscopic examination.
The ulcer anamnesis averaged to 18.4±7.8 years in patients of group I, 25.3±8.5 years in patients of group II (pI-II<0.05), 21.7±5.9 years in patients of group III (pII-III<0.05). In patients of group I, duo-
denal localization of ulcers prevailed (in 40% of patients). Hp was found in 10 (66.7%) patients of group I.
Localization of ulcerative process in the stomach prevailed in patients of group II. The stomach ulcer was characterized by large size, its formation against the background of mucous membrane ischemia, the detection of Helicobacter pylori in 19 patients (45.2%). In assessing the results of endoscopic examination in patients of group III, ulcers were also more often located in the stomach than in the duodenum and often (in 31%) were multiple.
As COPD course worsened, the proportion of stomach ulcers increased: the ratio of stomach and duodenal ulcers increased from 1:4.2 (CHF I FC) to 1:2 (CHF III FC). 80.3% of patients with combined pathology were characterized by chronic recurrent course of PUD.
According to the criteria proposed by A.A. Ilchenko [18], cholelithiasis (CL) was found in 19.6% of patients of group I, 34.5% of patients of group II, 18.9% of patients of group III, which exceeds the population level ranging from 10% to 15% [19]. Of these, stage I was more likely to be found in patients of group I (45.45%). Stage II was diagnosed without statistically significant differences in all groups (27.3%; 30.0%; 30.0% respectively). Half (50.0%) of patients of group II were determined by stage III of CL. There were no patients with stage IV among the examined ones.
Diagnosis of chronic pancreatitis (CP) was based on clinical and laboratory indicators and data obtained from transabdominal ultrasound examination, computer and magnetic resonance tomography. CP was diagnosed as defined in 17.9% of patients of group I, 32.2% of patients of group II, and 15.1% of patients of group III. According to the classification of CP [20], taking into account morphological changes of the pancreas gland, the parenchymatous variant of CP was most often determined (in 60.0%, 67.9%, 62.5% of patients of groups I, II, III respectively).
Chronic hepatitis (CH) was found in 16.1% of patients of group I, 32.2% of patients of group II, 15.1% of patients of group III. Among them, viral CH was found mainly in patients of groups I (66.7%) and III (62.5%), less often in patients of group II (42.9%). In the distribution of patients by the type of viral liver lesion, CH B was diagnosed in about half of patients without statistically significant differences in groups. The risk factors for the development of viral CH were surgical interventions (from 65.6% to 72.2% of patients).
Liver cirrhosis (LC) was diagnosed in 10.7% of patients of group I, 23.0% of patients of group II, 11.3% of patients of group III.
Functional disorders of the intestine were diagnosed in accordance with the criteria of the Rome consensus IV in 108 (33.8%) patients, among
them, with a predominance of constipation — 13.3%, with diarrhea — 21.7%, mixed — in 65.0% of patients of groups I and II mainly. Inflammatory dystrophic changes of the colon mucous membrane with disorders of its function were revealed in 38 (12.8%) patients. Of these, 7 patients were diagnosed with ulcerative colitis and 1 patient with Crohn's disease. The diagnosis is verified by the data of clinical, laboratory, instrumental, and histological methods of research. By localization of nonspecific ulcerative colitis lesion, the following was revealed: left sided - in 28.6%, total - in 14.3%, distal - in 57.1%. By severity (Truelove and Witts), the results are as follows: mild - in 42.8%, average - in 42.8%, heavy - in 14.2% of patients. Inflammatory changes were detected mainly in the rectum and the blind intestine. Changes in the mucosa were most often represented by hyperemia - in 60.5%, erosions - in 42.1%, hemorrhages - in 34.2%, contact bleeding -in 50.0%; pseudopolyps - in 15.8%, microabscesses - in 7.9%, granulomas - in 2.6%. The obtained results agree with the data of foreign researchers who presented the pathogenetic mechanism of cross-influence of pathology of respiratory and digestive systems [21, 22].
Conclusion
Concomitant pathology of the digestive system is reported in every second patient with COPD. The highest incidence of diseases of the digestive system was revealed in group II of patients. The atrophic form of chronic gastritis and gastric localization of ulcerative defect prevail. It should be noted that the nonatrophic form of chronic gastritis (with, respectively, the greatest infection of Helicobacter pylori) and duodenal localization of ulcerative defect are more often diagnosed in patients of group I. The highest frequency of complicated course of peptic ulcer disease in patients of group III can be attributed to the characteristics of the digestive system pathology. There is a mutual burden of symptoms of the disease, especially in the presence of a worsened course of COPD. The presence of clinical signs of gastrointestinal pathology in patients with COPD requires additional examination and obligatory drug correction.
Conflict of interest. The authors declare that there is no conflict of interest.
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Contacts
Corresponding author: Klester Elena Borisovna, Doctor of Medical Sciences, Associate Professor, Senior Researcher of the Central Research Laboratory, Altai State Medical University, Barnaul.
656038, Barnaul, ul. Lyapidevskogo, 1. Tel.: (3852) 689880. E-mail: klester@bk.ru
Author information
Belova Irina Ivanovna, Candidate of Medical
Sciences, Associate Professor of the Department of
Hospital Therapy and Endocrinology, Altai State
Medical University, Barnaul.
656050, Barnaul, ul. Malakhova, 53.
Tel.: (3852) 402529.
E-mail: science@agmu.ru
Balitskaya Aleksandra Sergeevna, Postgraduate
student of the Department of Faculty Therapy
and Occupational Diseases, Altai State Medical
University, Barnaul.
656038, Barnaul, ul. Molodezhnaya, 20.
Tel.: (3852) 201279.
E-mail: science@agmu.ru
Klester Karolina Vladimirovna, Resident of the Department of Therapy and Family Medicine, Altai State Medical University, Barnaul. 656045, Barnaul, ul. Lyapidevskogo, 1. Tel.: (3852) 689811. E-mail: hospital.akkb@mail.ru
