Резюме
Бен Аммар Сауссен. Дифференцированная терапия хронического обструктивного заболевания лёгких: учет тяжести, выраженности симптомов, риска обострений, показателей качества жизни.
По результатам комплексного исследования 120 больных ХОЗЛ доказано, что оценка степени тяжести заболевания исключительно на основании уровня ограничения воздушного потока является недостаточной, поскольку не учитывает другие клинико-функциональные параметры пациентов, в частности: степень выраженности одышки, гипервентиляции легких и толерантность к физической нагрузке, что является важным с учётом в том числе и коморбидных состояний. При этом, формирование групп дифференцированной терапии с использованием новых классификационных (GOLD, 20011) подходов обеспечивает учёт не только снижения скорости воздушного потока и форсированной жизненной ёмкости лёгких, но и степень обструкции периферических дыхательных путей, что патогномонично с выраженностью клинических симптомов и взаимосвязано с воздействием заболевания на качество жизни пациентов.
Ключевые слова: хроническое обструктивное заболевание лёгких, группы дифференцированной терапии, стратификация.
Резюме
Бен Аммар Сауссен. Диференційована терапія хронічного обструктивного захворювання легенів: урахування тяжкості, виразності симптомів, ризику загострень та показниківв якості життя.
За результатами комплексного обстеження 120 пацієнтів хронічним обструктивним захворюванням легенів доведено, що оцінка ступеня тяжкості захворювання виключно на основі ступеня обмеження повітряного потоку є недостатньою, оскільки не враховує інші клініко-функціональні параметри: ступінь задухи, гіпервентиляції легенів та толерантність до фізичних навантажень, що є важливим насамперед у за наявності комор бідних станів. При цьому, формування груп диференційованої терапії з урахування нових класифікаційних підходів (GOLD, 20011) забезпечує комплексність – урахування не тільки ступеня обмеження швидкості повітряного потоку та форсованого життєвого об’єму легенів але і ступінь обструкції периферичних дихатльних шляхів, що патогномонічно з виразністю клінічних симптомів та взаємопов’язано з впливом захворювання на якість життя пацієнтів.
Ключові слова: хронічне обструктивне захворювання легенів, групи диференційованої терапії, стратифікація.
Summary
Ben Ammar Sawssen. Differentiated treatment of chronic obstructive pulmonary disease: consideration of disease severity, symptoms intensity, risk of deterioration, indicators of life quality.
Using international classificatory approaches (GOLD, 2011-2013) for treatment assignment of patients with COPD we performed the stratification of patients according to degree of airspeed limitation, frequency of disease recurrence (for the last 12 months) and also intensity of clinical symptoms (mMRC scale) and their impact on life quality (self-actualization test questionnaire) of patients; 120 patients with COPD were involved in the investigation. The assessment of COPD severity basing only on airflow limitation is imperfect because it does not take into account other clinical functional parameters of patients particularly: extent of dyspnea intensity, hyperpnoea and exercise tolerance that is important considering comorbid states. Formation of differentiated therapy groups with the use of new classificatory approaches provides consideration of not only decrease of airspeed and forced vital lung capacity but also the degree of peripheral respiratory obstruction that is pathognomonic with intensity of clinical symptoms and is connected with disease impact on life quality of a patient.
Кey words: сhronic obstructive pulmonary disease, differentiated therapy groups, stratification.

Рецензент: д.мед.н., проф. Ю.Г. Бурмак

УДК 616.24-007.272-036.1-07 :616.127]-085.276+615.23

Харьковская медицинская академия последипломного образования

61176, г. Харьков, ул.Корчагинцев, 58

Kharkov medical academy of Postgraduate Education

61176, Kharkov, 58 str.Korchahyntsev

serg_shklyar@ukr.net

Introduction. Chronic obstructive pulmonary disease (COPD) together with arterial hypertension, ischemic heart disease (IHD) and diabetes mellitus belong to the group of leading chronic diseases; they account for more than 30% among all other malconditions of a person. Today COPD is known not only for its medical but also social values which are very important in the structure of general morbidity, disability, and mortality of population all over the world. World Health Organization (WHO) classifies COPD as the diseases with a high level of social burden; it is widely spread both in developed and developing countries. The prediction for the period till 2020, made by the experts of WHO, showed that COPD would become not only one of the most popular human diseases but would join the ranks of the leading causes of fatal cases.

The mortality from COPD ranks the forth place out of all causes of mortality in general population (GOLD, 2011). According to the prediction of WHO concerning economic damage in 2012 COPD will be the fifth as opposed to its current position which is the twelfth and it will outrun other diseases of respiratory system. It has been currently established that numerous risk factors of COPD can be investigated as predictors of manifestation of different diseases including cardiovascular ones. Thus, many experts suppose that it is impossible to consider COPD only as a multimorbid state. It is established that comorbide background against which COPD manifests often involves metabolic disorders (peripheral myopathy, weight loss, cachexia) and diabetes mellitus, arterial hypertension, ischemic heart disease, cardiac failure, infiltrative diseases and pulmonary tumors, and also primary pulmonary hypertension. COPD almost never proceeds without serious comorbidities.

The importance of COPD problem is determined by high cost of this pathology for Health Services and society as a whole. According to the data of Global Initiative for Chronic Obstructive Lung Disease (GOLD) in EC annual assignable expenses for COPD reach 38,6 bln euro. In USA in 2005 this ratio equaled to 21,8 bln USD and indirect costs exceeded by 17 bln USD.

There is one more important problem in Ukraine which deals with insufficient consideration of morbidity and prevalence of COPD that is an obstacle to quality increase in delivery of health care for these patients. In order to improve health care delivery for patients with respiratory diseases particularly COPD the Ministry of Health of Ukraine elaborated Decree №128 dated 19.03.2007 “Approval of clinical protocols for provision of medical care.”

In 2010 the Ministry of Health of Ukraine recorded 420083 cases of COPD disease among adult population (age 18 up) that is 11% greater than in 2009. The report provided by Medical Statistics Centre of the Ministry of Health of Ukraine showed that the index of hospital mortality of COPD is 12,6 higher than of bronchial asthma (BA). High rate of mortality and incapacitation is determined by under-diagnosis and undertreatment of COPD patients.

The book represents a completely revised report of GOLD work group (Global Initiative for Chronic Obstructive Lung Disease) – revision of 2011. The book is concerned with the definition of chronic obstructive pulmonary disease, its damage, risk factors, pathogenesis of chronic obstructive pulmonary disease, diagnosis, classification and training of medical workers and patients. The author paid much attention to the management of patients with chronic obstructive pulmonary disease namely introduced a universal plan of treatment of chronic obstructive pulmonary disease aimed at decrease of morbidity, prevalence rate and untimely death.

The goal of research is stratification of COPD patients into groups of differentiated anti-inflammatory and broncholytic therapy with the use of international classificatory approaches. 

Materials and methods of investigation.

Using international classificatory approaches (GOLD, 2011-2013) for treatment assignment of patients with COPD we performed the stratification of patients according to degree of airspeed limitation, frequency of disease recurrence (for the last 12 months) and also intensity of clinical symptoms (mMRC scale) and their impact on life quality (self-actualization test questionnaire) of patients; 120 patients with COPD were involved in the investigation.

The research involved clinical observation of COPD patients with chronic heart failure (CHF) comorbidity. 115 men and 5 women (middle age (58,5±4,1)) took part in investigation. All patients were active smokers. Entry criteria included COPD patients of II-IV stages with CHF comorbidity of II-IV functional classes. Chronic heart failure (CHF) is classified in accordance to recommendations of New York Heart Association (NYHA, 1964).

Exclusionary criteria included bronchial asthma, old myocardial infarction, AV-block (atrioventricular block) of II-III stages, atelocardia and acquired valvular disease, cerebral blood flow acute disturbances.

  Patients were hospitalized because of COPD recurrence in Kharkiv Municipal Pulmonology Centre; 34 patients (28,3%) were diagnosed with COPD of  II stage, 55 patients (45,8%) suffered from COPD of III stage, 31 patients (25,8%) had COPD of IV stage, their diagnostics and treatment were performed in accordance with active clinical protocols.

In order to evaluate the function of external respiration we analysed the dynamics of forced expiratory volume in 1 sec (FEV1 – forced expiratory volume in 1 sec), forced vital lung capacity (FVC), FEV1 and FVC ratio. Dimensioning was performed using MS-22 spirometer (Microprocessor spirometer Controlled, Hungary); such speed index as FEV1 (forced expiratory volume in 1 sec) was determined; it is expressed as a percentage of forced vital lung capacity. A special index expressing the ratio of FEV1/FVC (FEV1/FVC=Index Gaenslar) was calculated; FEF₂₅ (Forced expiratory flow) at the level of 25% of forced vital lung capacity, the same with FEF₅₀ and FEF₇₅.

The evaluation of dyspnea was performed with the help of modified questionnaire of British Medical Research Council (mMRC); the questionnaire is well associated with other methods of health assessment and allows predicting the risk of death.

COPD test (self-actualization test) represents 8 items and allows quantitizing patient’s life quality decrease connected with COPD; the number of grades can be from 0 to 40.

Statistical processing analysis was performed by the methods of analysis of variance using “Microsoft Excel”, “Statistica” application problem packages with the help of one-tailed student’s t-test (t), data are represented in absolute and relative values for which mid-values (M), average error of mid-value (±m) were calculated, differences were considered to be valid by p<0,05.

Results of investigations and their discussion. As it is represented in table 1 Patients’ allocation depending on COPD severity, patients are allocated as follows: 34 COPD-II patients, 55 COPD-III patients and 31 COPD-IV patients. It is necessary to admit that in every clinical group according to degree of airflow limitation (AFL) the patients were various. Thus, in COPD-II group degree of AFL in 19 patients was greater than 60% and averaged (67,2±1,1)% and degree of AFL in 15 patients ranged within (60÷51)% and averaged (54,5±0,6)%, p≤0,05. In this example the use of more detailed stratification of patients according to the level of AFL allows singling out people with different original (before treatment) levels of respiratory function disorder even in the limits of one clinical group. The use of such standardized criterion as Index Gaenslar (I_G) allowed confirming an identified clinical heterogenicity of patients in the limits of COPD-II clinical group emphasizing that I_G mid-value of the patients belonging to this group did not differ significantly from referential ones. 

In COPD-III group degree of AFL in 26 patients ranged within (50÷41)%  and averaged (41,7±1,3)% and degree of AFL in 29 patients ranged within (40÷31)% and averaged (38,8±1,1)%, p≥0,05. In this example the group of patients was similar according to the level of the FEV1, however it has been found that these subgroups differed significantly (р≤0,05) in accordance to I_G mid-value (70,9±4,8 and 59,3±2,8 respectively). The presence of these differences determines the necessity of their consideration while analyzing the effectiveness of broncholytic and anti-inflammatory therapy.

In COPD-IV group degree of AFL in 25 patients ranged within (30÷21)%  and averaged (25,0±0,7)% and degree of AFL in 6 patients was at the level of less than 20,0% and averaged (18,9±1,3)%, p≤0,05. The presence of these differences determines the necessity of their consideration while analyzing the effectiveness of broncholytic and anti-inflammatory therapy. In such case it is necessary to admit that COPD-IV group of patients was similar in accordance to the I_G level (49,4±2,5 and 42,1±5,6  ).

The analysis of disease recurrence frequency determined that out of 120 COPD patients significantly p≤0,05 the largest ratio was characteristic for the patients with 3 recurrences that is (40,8±4,5)% people and basing on the number of recurrences with  less than three and more than three for the last 12 months the patients were classified with similar frequency.

Among 34 COPD-II patients the largest ratio is characteristic for people with single recurrence and there are significantly less patients with two and three COPD recurrences for the last 12 months ((64,7±8,2)%,  (29,4±7,8)% and (5,9±4,0)%,  respectively by р≤0,05). The assessment of interaction between recurrence frequency and FEV1 allowed to determine that patients with COPD-II and three recurrences had significantly less indices of FEV1 ((64,7±1,3)% by one recurrence and (55,9±4,9)% by three recurrences, р≤0,05). Thus, COPD-II patients with three and more recurrences have FEV1 overriding criteria (table 2).

Among 55 COPD-III patients the largest ratio is characteristic for people with three recurrences and there are significantly less patients with two and four COPD recurrences ((56,4±6,7)%,  (18,2±5,2)% and (25,5±5,9)%, respectively, by р≤0,05). Among patients of this group ratio of patients with three recurrences is practically 10 times more than by COPD-II (table 2). The assessment of interaction between recurrence frequency and FEV1 of COPD-III patients did not determine significant differences in the indices of FEV1 (ranges within (40,9±1,3)% by four recurrences and (41,8±1,9)% by two recurrences, р≤0,05).

Among 31 COPD-IV patients there were no significant differences in recurrence frequency and dependence of FEV1 on repetition factor of disease recurrences. Thus, we admit that the ratio of patients with three recurrences was the same as in COPD-III group ((51,6±9,0)% and (56,4±6,7)%, respectively, р≥0,05), and there were significantly more patients with four and more recurrences by COPD-IV (table 2). As a whole recurrences were characterized by seasonality: with prevalence of their frequency in spring (31,5%) and autumn (37,9%) periods.

The study of clinical symptoms intensity (dyspnea appearance) in groups of patients with different severity of COPD showed (table 3.3) that dyspnea intensity in 34 COPD-II patients is evaluated in limits of 1÷3 grades by mMRC scale. At that time among the patients of this group there was domination of people with clinical symptoms intensity of 1 and 2 grades ((41,2±8,4)% and (47,1±8,6)%) and significantly (р≤0,05) less patients with clinical symptoms intensity of 3 grades (their ratio equaled to (11,8±5,5)%.

Among 55 COPD-III patients the largest ratio was characteristic for people with clinical symptoms intensity of 1 grade while the symptoms intensity of 2 and 3 grades was recorded with similar frequency ((47,3±6,7)% and (23,6±5,7)%, (21,8±5,6)% respectively); only four people of this clinical group that is (7,3±3,5)% had four and more COPD recurrences.

By COPD-IV similar ratio was characteristic for the patients with clinical symptoms intensity of 3 and 4 grades ((41,9±8,9)% and (51,6±9,0)% respectively, while there were significantly (р≤0,05) less people with the intensity mark of two grades that is (6,5±4,4)%, four times less than by COPD-III and eight times less than by COPD-II (table 3).

Life quality investigation associated with the disease and evaluated using self-actualization test showed that among the COPD-II patients people with assessment of disease impact on life quality within (11÷20) grades dominated while there were significantly (р≤0,05) less patients that is (41,2±8,4)% within (0÷10) grades.       

In COPD-III group of patients (20,0±5,4)% that is 11 people were characterized by high degree of disease impact on life quality though like by COPD-II there is the same ratio of patients with low impact of disease on life quality ((41,2±8,4)% and (47,3±6,7)% respectively, р≥0,05). The average level of disease impact on life quality in COPD-III patients was found in (32,7±6,3)%. 

 In COPD-IV group of patients the largest ratio was characteristic for patients with high degree of disease impact on life quality that is (71,0±8,2)% while the average degree was found in (9,7±5,3)% patients and very high degree was in (19,4±7,1)% that is significantly more, р≤0,05. Thus, more than 90% patients of this group had high and very high degree of disease impact on life quality.

As the result of investigation which involved 120 COPD patients it is necessary to admit that patients with low, middle and high degrees of disease impact on life quality were represented with similar frequency. An important indicator of patient’s state, besides dyspnea, is an index of life quality (by self-actualization test scale), the results of our investigations showed decrease of life quality combining with increase of disease severity. However, individual evaluation of the same parameters within one stage of disease demonstrates, as in dyspnea, wide fluctuations range. Life quality in accordance to all domains of the questionnaire became worse (by COPD severity) demonstrating logical interaction between decrease level of life quality and COPD severity. Basing on the tasks of investigation we performed the stratification of 120 COPD patients (into clinical groups B, C, D in accordance to GOLD, 2011) considering airspeed, frequency of recurrences, intensity of symptoms and degree of disease impact on patient’s life quality for subsequent differentiated treatment.      

Group “B” includes 22 patients (low risk, more symptoms belong to GOLD-2 class) which were characterized with decrease of airspeed at the level of: FEV1=(64,7±1,3)% by the average level of forced vital lung capacity of (72,1±2,9)% and Index Gaenslar within I_G=(82,95±3,9) units with peripheral respiratory obstruction of (FEF₂₅=(44,8±3,3)%, FEF₅₀=(35,4±2,5)% EFF₇₅=(47,6±5,5)%); average intensity of clinical symptoms in these patients equaled to: mMRC=2,23±0,9 g., and the average level of disease impact on life quality equaled to: self-actualization test⁴=15,0±0,04 g.

Group “C” includes 38 (n_С=38) patients among which: the first ²n_C=26 subgroup of patients classified as GOLD-3 (high risk of recurrence, less symptoms), the second ¹n_C=12 subgroup of patients classified as GOLD-2 (exception: high risk of recurrences, more symptoms). These 38 patients were characterized by decrease of airspeed at the level of: FEV₁=(47,7±1,5)% by the average level of forced vital lung capacity of (56,8±1,5)% and Index Gaenslar within I_G=(71,8±4,1) units with peripheral respiratory obstruction of (FEF₂₅=(37,3±4,1)%, FEF₅₀=(29,1±2,9)% FEF₇₅=(27,8±2,1)%); all patients had low intensity of clinical symptoms: mMRC=1,0 g., and the average level of disease impact on life quality equaled to: self-actualization test⁴=(8,11±0,17) g.

 Group “D” included 60 (n_D=60) patients among which: the first ¹n_D=29 subgroup of patients classified as GOLD-3 (high risk of recurrence, more symptoms), the second ²n_D=31 subgroup of patients classified as GOLD-4 (high risk of recurrences, more symptoms). These 60 patients were characterized by decrease of airspeed at the level of: FEV₁=(32,4±1,1)% by the average level of forced vital lung capacity of (54,3±2,3)% and Index Gaenslar within I_G=(54,5±1,8) units with peripheral respiratory obstruction of (FEF₂₅=(14,6±1,8)%, FEF₅₀=(11,4±0,8)% FEF₇₅=(17,7±1,3)%); with average level of clinical symptoms intensity: mMRC=(3,8±0,1) g., and the average level of disease impact on life quality of: self-actualization test⁴=(22,3±1,3) g.

Conclusions.

1. The assessment of COPD severity basing only on airflow limitation (FEV1) is imperfect because it does not take into account other clinical functional parameters of patients particularly: extent of dyspnea intensity, hyperpnoea and exercise tolerance that is important considering comorbid states.

2. Formation of differentiated therapy groups with the use of new classificatory approaches provides consideration of not only decrease of airspeed and forced vital lung capacity but also the degree of peripheral respiratory obstruction that is pathognomonic with intensity of clinical symptoms and is connected with disease impact on life quality of a patient.

3. Obtained data as for stratification of examined patients into groups of differentiated therapy allow not only individualizing of treatment policy but also studying the impact of anti-inflammatory and broncholytic therapy on systemic inflammation and myocardium remodeling in COPD patients.

Prospects of further investigations should be aimed at the study of comorbid states particularly chronic cardiac failure and impact of anti-inflammatory and broncholytic therapy on systemic inflammation and myocardium remodeling in COPD patients.

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