Ways to reduce the frequency of exacerbations of COPD: anti-inflammatory therapy, immunoregulators, pulmo-rehabilitation. Part 2


Despite advances in modern medicine, respiratory tract infections remain among the major sources of morbidity, mortality, and economic costs worldwide. In 25–50% of patients with COPD, the lower respiratory tract is colonized by bacteria, mainly Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis. Microbial contamination of the respiratory tract often provokes and supports exacerbations of chronic bronchitis and COPD. At the same time bacterial inflammation develops, sputum secretion increases, pulmonary function worsens. One of the functional and safe approaches to the prevention of recurrent respiratory tract infections and exacerbations of COPD is the activation of the adaptive and innate immune response that can be achieved using polyvalent bacterial mechanical lysates (PBL). These drugs have been known for about 40 years (OM-85 Broncho-Vaxom, OM-85 Broncho-moon) are a standardized immunoactive lyophilized extract of eight types (21 strains) of respiratory pathogens: Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, Staphycus-ecococcus ecococcus, Strophococcus ecococcus ecococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans. pneumoniae, Klebsiella ozaenae, Moraxella catarrhalis, Haemophilus influenzae. The standard regimen is to take a daily capsule (7 mg) in the morning on an empty stomach for 10 days. Such 10-day courses are repeated three times with a three-week intervals 2 times a year (spring-autumn). The drug has a high safety profile.

  1. Zagolski, comparing the effects of PBL and autovaccines on potentially pathogenic nasopharyngeal microorganisms, showed that in cases of colonization of the Haemophilus influenzae respiratory tract, PBL is more effective than autovaccine (p <0.01).

The immunomodulatory effect of PBL is associated with the activation of the Th1 response, manifested in increased production of interferon-gamma, suppression of the Th2 response (decrease in the production of interleukin (IL) IL-4 and the level of IgE antibodies), with an increase in the activity of macrophages and monocytes (increase in the production of IL- 6, IL-11 and IL-12), with an increase in antibody production (increased levels of immunoglobulins (Ig) – secretory IgA, as well as IgA, IgM and IgG (IgG4) in serum), activation of phagocytosis (increased production of nitric oxide, superoxide -anion, expression of adhesion receptors), increased active spines of NK cells.

Even in elderly patients with COPD, administration of PBL leads to an effective immune response associated with a reduction in the number of exacerbations.

To date, the efficacy and safety of PBL OM-85 (mainly Broncho-Vaxoma) in patients with COPD have been demonstrated in a number of randomized clinical trials. In a double-blind, placebo-controlled study, 190 out of 381 patients with COPD received PBL from Broncho-Vax (BV), and the rest received placebo. The results of the study showed that the use of BV led to a 30% reduction in the risk of hospitalization (16% vs. 23%, p = 0.089) and 55% of their duration (p = 0.037). This effect did not depend on the severity of pulmonary function disorders.

Another study confirmed that BV use in patients with COPD (49 people) compared with placebo (41 people) was associated with a significant decrease in the incidence, duration and severity of exacerbations (p <0.05), a decrease in symptoms (cough, sputum, shortness of breath, wheezing in the lungs (p <0.05) Similar results were obtained by M. Soler in patients with chronic bronchitis and COPD mild course.

In their work, H. Tang showed that the number of COPD patients who underwent two or more exacerbations was significantly lower in the BV group compared with placebo (38.7% versus 73.1%, p <0.01), and antibacterial therapy was required much less frequently (37.0% and 63%, respectively, p <0.05). The addition of PBL to the standard treatment of patients with severe COPD with the risk of frequent exacerbations (groups C and D) reduced the number of exacerbations (2.1 versus 2.8) and the duration of hospitalizations by 35% [38].

The use of PBL BV in addition to antiretroviral therapy in the group of HIV-infected patients who have a high risk of recurrent respiratory infections and a higher incidence of COPD, reduced the frequency of exacerbations of respiratory infections, the number of hospitalizations associated with them and the need for repeated courses of antibiotic therapy. This effect was especially pronounced in patients with COPD and in smokers without significant signs of COPD.

Thus, the use of Broncho-Vaxoma as a supplement to standard therapy is a promising approach to the prevention of exacerbations in patients with COPD (including HIV-infected).

A meta-analysis and systematic reviews of recent years indicated that there is as yet no conclusive (reaching statistical significance) evidence of the use of PBL for the prevention of exacerbations in patients with COPD due to the small number of studies on this topic. Nevertheless, the effectiveness of PBL in reducing the intensity of symptoms, preventing exacerbations and reducing their duration, reducing the number and duration of hospitalization is emphasized. In addition, research data indicate a reduction in the need for antibiotic treatment in patients with COPD and in a group of HIV-infected patients. The use of immunomodulators for the treatment of respiratory tract infections in patients with COPD can be economically beneficial by reducing the cost of treatment and, consequently, reducing the financial burden on the patient, on the one hand, and the entire health care system, on the other. However, before regular use of this type of therapy will be included in the GOLD recommendations, additional clinical studies with a double-blind, randomized, placebo-controlled design and a large number of patients are needed.

Pulmonary rehabilitation

Pulmo-rehabilitation (PR) is one of the key strategies in the complex treatment of patients with chronic respiratory diseases, especially patients with COPD, who have a pronounced decrease in exercise tolerance, and the effect of drug therapy can be significantly enhanced by the introduction of rehabilitation programs.

“Pulmo-rehabilitation is a complex system of measures based on a thorough examination of patients with individual selection of treatment, including physical training, training and orientation of patients to maintain health. These activities are aimed at improving the physical and psychological state of people suffering from chronic respiratory diseases, and ensuring the addiction of patients to a healthy lifestyle. ”

OL is a therapy with a high level of proven effectiveness. As a result of PR patients with COPD, positive changes are achieved that affect all aspects of the disease: the ability to exercise is improved; reduced dyspnea perception; health-related quality of life is improving; decreases the number and duration of hospitalizations; anxiety and depression associated with COPD are reduced (all this at the level of evidence A); in addition, the function of the hands is improved due to the training of strength and endurance of the upper muscle group, and the achieved positive effects persist for a long time after the training course; survival and recovery after hospitalization due to exacerbations are improved; the effectiveness of long-acting bronchodilators increases (level of evidence B); training respiratory muscles is beneficial, especially if combined with general physical training (level of evidence C).

PR is applied and effective at all stages of treatment: in the hospital, in outpatient settings, at home. The rehabilitation program depends on the severity, phase of the disease, complications of the respiratory and cardiovascular systems, and concomitant diseases.

A full rehabilitation program should include physical training, nutritional status correction, training, and psychological support, although the components of PR programs may vary significantly.

Kinesitherapy includes medical gymnastics (special complexes of respiratory and general therapeutic physical culture, aimed at maximum adaptation of the patient to the usual way of life), various types of dosed walking (simple, Scandinavian, health path, treadmill), hydrokinesiotherapy, training on simulators (cyclic and strength), respiratory training apparatus, spatial gymnastics, skiing, team sports. In Russia, rehabilitation programs also include physiotherapy (inhalations, various methods of postural drainage, magnetic therapy, laser therapy, balneotherapy, aromatherapy, acupuncture, ozone therapy).

Patient education should bring to them information about the disease, respiratory physiology, methods of drug therapy, oxygen therapy and non-invasive assisted ventilation, self-control of respiratory function, maintaining an exacerbation control protocol, methods of alleviating dyspnea, improving lung drainage, anxiety management, relaxation methods, the benefits of physical training, behavioral skills (smoking cessation, travel behavior, sexual relationships).

The rehabilitation program also includes psychological support (through education, small group discussion, and relaxation therapy) and nutritional recommendations (both excess and underweight can be a problem in patients with COPD; a decrease in body mass index is an independent risk factor for mortality these patients). It is established that at all stages in patients with COPD, there are positive changes as a result of physical training. Pulmonary rehabilitation is the cornerstone in the management of patients with stable COPD. In patients with an unstable course of the disease, recent exacerbations, early activation of rehabilitation programs can reduce the length of hospital stay, improve the quality of life and reduce mortality. For example, the PR in outpatients with COPD during the year contributed to an annual reduction in the number of exacerbations (from 2.8 to 0.8) and the number of days spent in the hospital (from 27.3 to 3.3, p <0.001), led to a significant increase in resistance to physical activity, improving the quality of life. Currently, PR is considered an obligatory component of the treatment of patients with COPD.

The goal of treating COPD is to reduce the rate of disease progression leading to an increase in bronchial obstruction and respiratory failure, a reduction in the frequency and duration of exacerbations, an increase in exercise tolerance and an increase in the quality of life. Adequate drug therapy for COPD is the main, but not the only way to combat this disease. The presence of a large arsenal of non-drug therapeutic methods, including physiotherapy, can reliably optimize the treatment and rehabilitation process.

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