Respiratory muscle training was administered with the aid of an inspiratory expiratory system (Resp-in-out, Medinet, Milan, Italy, Supplementary Material Figure S1). This device consists of a positive pressure and volume exerciser for respiratory training, promoting inhalation and deep exhalation without interruption of the respiratory cycle. The tool is composed of a body into which the air is blown, and which contains a mobile ball; a tube with mouthpiece; and colored connectors with a grid filter, characterized by holes of different sizes (red, yellow and green), changing the resistance to airflow. The subjects, keeping their lips tightly close to the mouthpiece, exhale normally. The rising ball indicates the pressure in cmH2O. The pressure can increase according to the connector used. At the end of the exhalation, the ball goes down, and without detaching the lips from the mouthpiece, it is possible to complete the breathing exercise, making an inspiration. It is also possible to prolong inhalation and/or exhalation by keeping the ball in place, thus maintaining a certain pressure or a certain volume.
Patients were requested to perform the training on non-dialysis days (at least 4 days per week) two times per day, as follows. Using a metronome set at 30 beats per minute to guide the respiratory rhythm, patients were instructed to perform a complete respiratory cycle with inspiration synchronized with the first beat and expiration corresponding to the second beat and then wait for two consecutive beats before restarting. In one minute, patients performed 8 complete respiratory cycles. Then, the following minute, they rested without doing any training. This 1:1 min train-rest ratio was repeated five times for a total of 10 min. The training device included three different levels of resistance to the air flow, low, medium or hard, according to the dimensions and number of holes present in the connection between the mouthpiece and the device with the ball. During the first week of training, the air resistance was kept at a minimum; then, in week two, it was increased to the intermediate level, and finally, for the last two weeks, it was moved to the hardest level.
During the first week of exercise, an exercise physiologist supervised the training sessions of patients by directly administering them before the dialysis session. The following three weeks were performed at home autonomously by each patient. A daily log was provided to each patient to report the training execution and possible symptoms. Moreover, once per week on a dialysis day, a team member checked the training execution and reinforced the adherence to the program. At the end of the training period, to monitor the long-term adherence, patients of RMT group were allowed to keep the RMT device, but no recommendations were given to the patients in relation to the training continuation.
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