Effect of Physiotherapy Applications on Inflammatory Markers in Asthma Disease

It is estimated that there are 300 million individuals diagnosed with asthma worldwide. Asthma is a chronic inflammatory heterogeneous disease with clinical symptoms such as wheezing, nocturnal cough, dyspnea, expiratory airflow limitation

response in the airways [2].The increase in systemic inflammation markers in asthma patients plays a role in the development of hypoxia and dynamic hyperinflation [3].The presence of inflammatory cells in the airway causes an altered repair response of the airway with the secretion of cytokines and growth factors that induce structural changes in the airways.In the case of airway remodeling, there is an increase in inflammatory cell count, hypertrophy of submucosal glands, hyperplasia of goblet cells and airway smooth muscle, and accumulation of collagen and fibronectin in the subepithelial basement membrane/submucosa around or in airway smooth muscle bundles [4].Clinical symptoms of asthma are wheezing, nocturnal cough, dyspnea, expiratory airflow limitation, and bronchial spasm [5].
Airway tone is regulated by the autonomic nervous system.The autonomic nervous system acts on mucociliary clearance.Mucociliary clearance; impaired by airway inflammation, excessive mucus production, and changes in mucus viscosity or osmolality [6].
In the pathophysiology of asthma, changes in autonomic, endocrine, immunological, and central nervous system mechanisms and psychosocial factors; motivation, sense of self, lifestyle are negatively affected [7].Due to the perception of dyspnea and

Introduction
Asthma is a common disease known to have approximately 300 million individuals worldwide [1].It is seen that 50% of a mild or severe type of asthma, which is an inflammatory disease, has a type 2 inflammatory cytokines, interleukin (IL)-4, IL-5 and IL-6, IL-13-16, monocyte, chemoattractant protein 1, and keratinocyte chemoattractant protein (mouse homolog human IL-8) inhibition of nuclear factor kappa B (NFκB) activation and an increase in the anti-inflammatory cytokines IL-10, IL-1ra and circulating regulatory T cells [20].
Exercise has also been found to improve patency of bronchioles through epithelial stimulation and mucociliary clearance, and smooth muscle function through deep inspiration and sigh rate [21].
Several randomized controlled trials in the literature have found that aerobic exercise training is beneficial for functional capacity, airway inflammation, asthma exacerbation, control, healthcare utilization, psychological state, and quality of life [22].
There is evidence that aerobic exercise training reduces bronchial hyperresponsiveness through a mechanism involving β2-adrenergic receptors [23].

Physical Activity and Inflammation
Physical activity is effective in preventing the development of chronic diseases and managing disease symptoms [24].In the literature, it has been proven that good asthma control, a decrease in the number of exacerbations and attacks, and a decrease in the need for health care use are associated with the level of physical activity participation [8].
Sedentary life plays an important role in the development of obesity, which is one of the risk factors for asthma disease in individuals.Obesity causes decreased lung volume, more pronounced asthma symptoms, increased work of breathing, less favorable response to controller medications, and increased airway inflammation [25].It also has a negative effect on the immune system of individuals.Physical inactivity contributes to poor asthma control and consequent increase in symptoms, risk of exacerbations, and airway inflammation in asthmatics [26].It is known that an active life provides an increase in the physical fitness level of individuals and a decrease in body mass index.An increase in physical activity is effective in weight loss and reduces sleep disorders [27].
Physical activity causes a decrease in the level of pro-inflammatory mediators and an increase in antiinflammatory mediators and their mediators.Rahimi, et al. according to their study, it was determined that physical activity reduces CRP concentration and decreases other inflammation markers [28].
Based on cross-sectional data, it is reported that it is effective in increasing physical activity levels, reducing inflammation, and lowering susceptibility to obesity and type 2 diabetes [29].

Chest Physiotherapy and Inflammation
The inflammatory process clogs the bronchial lumen There are studies in the literature that asthma patients are more obese than healthy individuals due to limitations in physical activity [9].Tumor Necrosis Factor-alpha (TNF-α) and Interleukin 6 (IL 6) inflammation cytokines secreted from adipose tissue in obese individuals increase the production of C-Reactive Protein (CRP), which is an inflammation mediator, in the liver [10].Chronic infection and inflammatory response cause lung tissue damage.The aim of the treatment of lung diseases is to prevent or slow the progression of the disease.
In addition to medical treatment, alternative treatment methods (yoga, Tai Chi, exercise, etc.) are also frequently used in asthma [11].It has been determined that exercise has an effect on the nervous and immune systems with its endocrine activity, thus activating various complex interacting mechanisms in the psychoneuro-immune-endocrine pathways [12].
Exercise provides an increase in plasma antiinflammatory cytokine concentration and receptor antagonists.Exercise has a significant contribution to the reduction of IL6 and TNF-α [13].Regular physical training can alter the autonomic balance and accelerate the physiological recovery of vagal sympathetic interaction [14].Physiotherapy is thought to help clear inflammatory exudates, tracheobronchial secretions, airway obstructions and reduce airway resistance to improve respiration and increase gas exchange [15].
It is known that regular exercise in patients with asthma has positive effects on improvement in clinical symptoms, functional capacity, and quality of life in patients [16].This review aims to determine the effects of physiotherapy applications on adipose tissue, which causes an increase in inflammation markers and inflammatory cytokines, which increase asthma symptoms and cause attacks, and present evidence.

Aerobic Exercise and Inflammation
Aerobic exercise appears to reduce airway remodeling with reduced airway smooth muscle hypertrophy and hyperplasia, reduction in leukocyte infiltration, proinflammatory cytokine production, adhesion molecule expression, and enhanced regulatory T cell (Treg) responses [17].Regular exercises to increase aerobic condition (swimming etc.) increase the ventilatory threshold and decrease the minute volume.As a result, the feature of exercise as a trigger for symptoms disappears [18].
It has been determined that exercise training mediates the activity of immune and metabolomic pathways as a beneficial effect on asthma [19].
Airway inflammation is one of the main factors that increase the risk of exacerbation and severity of asthma in asthma.Potential mediator mechanisms by exercise include reductions in serum Th2 proinflammatory three groups during the 10-day dialysis process.They divided the first group as respiratory muscle training (n = 11), the second group as peripheral muscle training (n = 14), and the third group as control (n = 14).Compared with the control group, the group that received respiratory muscle training and the group that received peripheral muscle training had a significant decrease in CRP levels [40].
As a result, it is stated in our review that physiotherapy applications in asthma patients reduce the inflammation markers that cause an increase in the symptoms of the disease and the number of attacks, and also have an important role in the reduction of adipose tissue, which causes the increase in inflammation markers.In this respect, it is important to include physiotherapy applications in the treatment process of patients, both in terms of clinical and future research.and causes the accumulation of secretions [30].The primary purpose of chest physiotherapy is to help clear accumulated secretions, restore respiratory condition, thereby lowering airway resistance, increasing gas exchange, and facilitating breathing [15].
Chest physiotherapy is an important aid in the treatment of respiratory diseases.Chest physiotherapy techniques can be classified as traditional, modern, and instrumental techniques [31].
Modern techniques; exercises include forced expiration, active respiratory cycle, autogenic drainage, assisted autogenic drainage, prolonged expiration, increased expiratory flow, total slow expiration with glottis open in lateral posture, and inspiratory controlled flow exercises [33].In addition to clearing secretions in respiratory tract diseases, the positive contributions of exercise and breathing exercise are stated in increasing mucus viscosity and elasticity [21].
El Dein, et al. in a study conducted, applied conventional chest therapy applications and pneumatic compression to the study group of fifteen children aged 6-12 years, who were diagnosed with thirty pneumonia, while they applied only conventional chest physiotherapy to the control group of fifteen people.When they compared the study group and the control group, they found that the study group had more decreases in inflammation markers.However, it was observed that the patients in the control group had a decrease in inflammation markers (CRP, WBC, etc.) after treatment compared to before treatment [34].

Respiratory Muscle Training and Inflammation
Inspiratory muscle training (IMT) affects the autonomic nervous system and provides adaptation by stimulating stretch receptors in the lung, thus taking an active role in inflammation [35].Inspiratory muscle training weakens the chemoreceptor activities in the diaphragm and has a positive effect on the immune system [36].There are studies on the effectiveness of IMT in improving functional capacity [37].In the literature, it is stated that IMT is effective in reducing IL6 [38].
Figueiredo, et al. followed thirty-seven hemodialysis patients in three groups as IMT, aerobic training, and combined training, for initial, 8-week, and 16-week periods.In conclusion, they concluded that eight weeks of IMT improved the functional and inflammatory parameters of patients on hemodialysis treatment, similar to the effect of low-intensity aerobic training [39].
Pellizzaro, et al. in a randomized controlled study, thirty-nine hemodialysis patients were evaluated in