Investigation of the Effects of Standard Rehabilitation Program and Inspiratory Muscle Training on lncRNA HOTAIR Expression in Patients With Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic, inflammatory, and autoimmune disease characterized by inflammation of synovial tissue in the joints, which can lead to joint destruction. Although the pathogenesis of the disease is not yet fully understood, it is thought that genetic and environmental factors contribute to the pathological activation of the immune system. The presence of autoantibodies has been demonstrated in the serum of RA patients, including rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), anti-carbamylated protein antibodies, and anti-acetylated protein antibodies. The presence of these autoantibodies provides critical insights into the pathophysiology of the disease. RA follows an inflammatory pathway characterized by the overexpression of proinflammatory cytokines. Specifically, TNF-α, IL-6, and IL-1b play significant roles in triggering joint destruction and synovial inflammation, ultimately leading to bone erosion and cartilage damage.

In addition to joint involvement, RA can also involve extra-articular organs and tissues, which may lead to significant increases in morbidity and mortality. The lungs are the primary organ affected by extra-articular involvement in RA. Pulmonary involvement in RA negatively impacts prognosis and often necessitates treatment modification. Pulmonary manifestations can present as pleural, parenchymal, or vascular involvement. Among the types of pulmonary involvement associated with RA, interstitial lung disease (ILD) is one of the most common parenchymal manifestations. However, the prevalence of ILD in RA (RA-ILD) patients varies depending on the diagnostic methods used and the populations studied. Studies have shown that ILD significantly worsens the overall prognosis of RA and often requires specific therapeutic approaches, including modifications to immunosuppressive treatments or the addition of antifibrotic therapies.

Respiratory dysfunction in RA is not solely limited to parenchymal damage. Inflammatory involvement of respiratory muscles, as well as reduced pulmonary function due to systemic inflammation, are common findings. Pulmonary function tests (PFT) in RA patients often reveal restrictive or obstructive patterns, with significant reductions in forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO). Moreover, seropositive RA patients, particularly those with high titers of RF or ACPA, are more likely to exhibit pulmonary abnormalities compared to seronegative patients. Factors such as age, smoking status, disease duration, and body mass index also contribute to variations in PFT outcomes.

The primary treatment goals for RA patients are remission or achieving a state of low disease activity. Disease-modifying antirheumatic drugs (DMARDs) and biological agents are employed to meet these objectives. These therapies aim to suppress systemic inflammation, reduce joint damage, and prevent extra-articular complications. In addition to pharmacological treatments, exercise training is recommended to improve patients' quality of life, enhance functional recovery, and reduce cardiovascular risks. Aerobic and resistance exercises have been shown to be both feasible and effective for RA patients, significantly improving muscle strength, joint mobility, and overall physical function without exacerbating disease activity.

Particularly in RA patients with pulmonary involvement, respiratory exercises are gaining attention for their potential to improve respiratory muscle strength and pulmonary function. Studies on respiratory training have demonstrated improvements in inspiratory and expiratory muscle strength, as well as reductions in dyspnea severity. These interventions are especially beneficial in patients with coexisting ILD, where optimizing pulmonary function can contribute to better clinical outcomes and quality of life.