Respiratory resistance and reactance in adults with sickle cell anemia: Part 2—Fractional-order modeling and a clinical decision support system for the diagnosis of respiratory disorders

Abstract

Background A better understanding of sickle cell anemia (SCA) and improvements in drug therapy and health policy have contributed to the emergence of a large population of adults living with this disease. The mechanisms by which SCA produces adverse effects on the respiratory system of these patients are largely unknown. Fractional-order (FrOr) models have a high potential to improve pulmonary clinical science and could be useful for diagnostic purposes, offering accurate models with an improved ability to mimic nature. Part 2 of this two-part study examines the changes in respiratory mechanics in patients with SCA using the new perspective of the FrOr models. These results are compared with those obtained in traditional forced oscillation (FOT) parameters, investigated in Part 1 of the present study, complementing this first analysis. Methodology/Principal findings The data consisted of three categories of subjects: controls (n = 23), patients with a normal spirometric exam (n = 21) and those presenting restriction (n = 24). The diagnostic accuracy was evaluated by investigating the area under the receiver operating characteristic curve (AUC). Initially, it was observed that biomechanical changes in SCA included increased values of fractional inertance, as well as damping and hysteresivity (p<0.001). The correlation analysis showed that FrOr parameters are associated with functional exercise capacity (R = -0.57), pulmonary diffusion (R = -0.71), respiratory muscle performance (R = 0.50), pulmonary flows (R = -0.62) and airway obstruction (R = 0.60). Fractional-order modeling showed high diagnostic accuracy in the detection of early respiratory abnormalities (AUC = 0.93), outperforming spirometry (p<0.03) and standard FOT analysis (p<0.01) used in Part 1 of this study. A combination of machine learning methods with fractional-order modeling further improved diagnostic accuracy (AUC = 0.97). Conclusions FrOr modeling improved our knowledge about the biomechanical abnormalities in adults with SCA. Changes in FrOr parameters are associated with functional exercise capacity decline, abnormal pulmonary mechanics and diffusion. FrOr modeling outperformed spirometric and traditional forced oscillation analyses, showing a high diagnostic accuracy in the diagnosis of early respiratory abnormalities that was further improved by an automatic clinical decision support system. This finding suggested the potential utility of this combination to help identify early respiratory changes in patients with SCA.

Combined forced oscillation and fractional-order modeling in patients with work-related asthma: a case-control study analyzing respiratory biomechanics and diagnostic accuracy

“…A comparison between the present results and those of a preliminary study, including all asthma phenotypes [29], con rms the ability of this parameter to describe the presence of heterogeneous peripheral ventilation in the speci c phenotype of WRA. Additional supports of this interpretation are provided by other studies performed recently in patients with sickle cell anemia [28], chronic obstructive pulmonary disease [23,27], and asbestos-exposed workers [26]. The hysteresivity increases with the hysteresis area of the pressure-volume loop [45], which associates this parameter with the work of breathing [21,22].…”

“…In recent years, various fractional-order models have been developed and introduced [15, [21][22][23][24][25] to increase our understanding of cystic brosis [25], asthma in children [24], asbestos-exposed workers [26], chronic obstructive pulmonary disease [22,23,27], and sickle cell anemia [28]. Thus, there is a growing body of literature that recognizes the importance of fractional-order models in the interpretation of respiratory system functioning.…”

Combined forced oscillation and fractional-order modeling in patients with work-related asthma: a case-control study analyzing respiratory biomechanics and diagnostic accuracy

“…A comparison between the present results and those of a preliminary study, including all asthma phenotypes [29], confirms the ability of this parameter to describe the presence of heterogeneous peripheral ventilation in the specific phenotype of WRA. Additional supports of this interpretation are provided by other studies performed recently in patients with sickle cell anemia [28], chronic obstructive pulmonary disease [23,27], and asbestos-exposed workers [26]. The hysteresivity increases with the hysteresis area of the pressure-volume loop [45], which associates this parameter with the work of breathing [21,22].…”

“…In recent years, various fractional-order models have been developed and introduced [15,[21][22][23][24][25] to increase our understanding of cystic fibrosis [25], asthma in children [24], asbestos-exposed workers [26], chronic obstructive pulmonary disease [22,23,27], and sickle cell anemia [28]. Thus, there is a growing body of literature that recognizes the importance of fractional-order models in the interpretation of respiratory system functioning.…”

Combined forced oscillation and fractional-order modeling in patients with work-related asthma: a case–control study analyzing respiratory biomechanics and diagnostic accuracy

“…A comparison between the present results and those of a preliminary study, including all asthma phenotypes [28], confirms the ability of this parameter to describe the presence of heterogeneous peripheral ventilation in the specific phenotype of WRA. Additional supports of this interpretation are provided by other studies performed recently in patients with sickle cell anemia [27], chronic obstructive pulmonary disease [22,26], and asbestosexposed workers [25]. The hysteresivity increases with the hysteresis area of the pressure-volume loop [43], which associates this parameter with the work of breathing [15,21].…”