This study aimed to evaluate the effects of long term IMT on sickle cell disease patients. In both groups: control or true load, there was a significant increase in inspiratory and expiratory muscle strength at the end of the training protocol, improvement in volumetric capnography variables, exercise tolerance and reduction of dyspnea in performing daily life activities. Regarding respiratory muscle strength, although the effects of IMT in patients with sickle cell disease have been poorly studied (17), studies conducted in individuals with chronic obstructive pulmonary disease (COPD) (13), older women (26) or with ankylosing spondylitis (14) showed an increase in PImax and PEmax after the termination of the training protocol. Ciesla includes IMT as one of the types of breathing exercises and points out several benefits these exercises, as it improves thoracic-cage mobility, increased tidal volume and increased inspiratory capacity (27). Our study however also showed a significant increase in respiratory muscle strength in the control group. We hypothesized that, as the two groups performed 10 min of deep inspiration daily, that is, they actually did breathing exercises, despite the real resistance to the inspiratory flow of home exercises for TG, the IMT was possibly able to modify the respiratory mechanics in both groups, leading to an increase of PImax and PEmax, not only for the true load group, but also for the control group.
Spirometry results here obtained showed no significant differences regarding initial and final evaluation, in neither group. No were there any changes in these variables reported for older women, COPD, and heart failure (26,28,29). On the other hand, in our study, the volumetric capnography showed significant changes in some variables after IMT, in both groups. Inspired volume (Vi), peak expiratory flow (PEF) and peak inspiratory flow (PIF) increased significantly, while the Tobin index (RSBI) decreased significantly. These changes suggest that daily deeper inspiratory exercises influenced an increase in inspired and exhaled air volume, even in the control group.
Another variable, the phase 3 slope (P3Slp), decreased significantly in both groups in the final assessment compared to the initial assessment. As phase 3 of the capnogram represents the elimination of pure alveolar gas, the greater the plateau of the curve in this phase the more homogenous is the distribution of ventilation in distal airspaces (30). Alveolar recruitment is related to reduced P3Slp (31). Therefore, the reduction in P3Slp observed in this study suggests that there was alveolar recruitment after IMT. Furthermore, considering that the higher the expired volume (Ve), the lower the P3Slp, this variable was normalized according to the expired tidal volume (P3Slp/Ve) (32), which also decreased after IMT, confirming the result presented by P3Slp.
In both groups after IMT, a significant reduction in dyspnea assessed by MRC was observed. This scale has been used for many years to classify the limitation imposed by dyspnea on DLA (21,33). The scale is a simple application tool, which allows the patient to indicate to what extent their dyspnea affects their mobility. This is a widely used scale for the assessment of dyspnea in patients with COPD, however, this scale has also been used as an instrument for the indirect measurement of dyspnea in a study of patients with sickle cell disease (5). Other studies that evaluated the effects of IMT in patients with pulmonary arterial hypertension and in COPD showed a reduction in dyspnea after the end of the training protocol in the true load group (34,35). In our study, improvement in dyspnea may have occurred due to increased respiratory muscle strength and increased post-IMT alveolar recruitment in both groups.
The MFIS, which allows indirect assess of the impact of fatigue on quality of life, did not change significantly at the end of IMT in both groups. This scale, originally developed by Fisk et al in 1994 (36), though widely used to assess the impact of fatigue on quality of life in patients with multiple sclerosis, has also been used to assess indirect fatigue, in a study of patients with sickle cell disease (5). Both groups however, had a significant increase in the distance covered during the 6MWT, which can be considered a form of direct assessment of fatigue (5) and exercise functional capacity. Some studies in patients with COPD and asthma have also reported reduced muscle fatigue and increased exercise functional capacity after IMT (34,37). There is an increase in the level of metabolites in the circulation, such as lactate and hydrogen ions because of the increase in anaerobic metabolism induced by exercise in hypoxia (16). Especially in the respiratory muscles, IMT improves clearance ability and tolerance to the levels of lactate and hydrogen ions (38,39). Therefore, strengthening of inspiratory muscles probably attenuated the metaboreflex of inspiratory muscles, which increased blood flow and oxygenation of limb muscles, reducing premature fatigue during exercise in hypoxia (16,40,41). Nevertheless, these the results must be viewed with caution, since direct metaboreflex measurements were not performed in the present study.
Regarding [Lac], normal values in healthy individuals should be between 0.5 and 2.0 mmol/l (42). However, there was a tendency for [Lac] to be higher in patients evaluated before the 6MWT, therefore at rest, when compared to normal values in healthy individuals. Some of the evaluated patients had pre-TC6 maximum values between 5.2 mmol / l and 8.1 mmol / l, i.e. well above the maximum normal value found in healthy individuals. Some authors attribute the increase of [Lac] in patients with sickle cell disease to the adaptation to lower O2 availability to body cells, caused by the change from basal to anaerobic metabolic pathway, due to the sickle cell process. Thus, anaerobic glycolysis increases the participation in cellular energy metabolism, favoring the production and increase of [Lac] (12,43).
[Lac] showed no significant change in the comparison of initial and final evaluation results. As expected, there was an increase in [Lac] after the 6MWT, probably related to the greater participation of anaerobic metabolism (11). [Lac] tends to increase significantly from levels between 50% and 60% of the maximum oxygen uptake rate (VO2max) (44). Patients with sickle cell disease may have a reduction in VO2max, due to the pathophysiological changes of the disease itself that reduce the half-life of red blood cells, leading to reduced oxygen transport. In addition, intrinsic lung disease also worsens peripheral oxygenation, contributing to the lower oxygen uptake peak in these patients (12,45). Thus, these patients tend to have a greater increase in [Lac] during exertion. Thus, IMT does not appear to have influenced an improvement in these conditions and, therefore, did not contribute to a lower elevation of [Lac].
Finally, comparison of patients grouped according to disease severity revealed no differences, suggesting homogeneity of the patients, probably due to the medical intervention in the natural history of the disease.
However, despite the important results found, we believe that other studies with a larger sample size and over a longer period should be made to test our hypothesis.