Non‐invasive tension time index in relation to severity of disease in children with cystic fibrosis

Abstract

The non-invasive tension-time index of the inspiratory muscles at rest (TTMUS) can be used for assessing respiratory muscle function in children with cystic fibrosis (CF). This study aimed to investigate how TTMUS becomes altered with increasing pulmonary impairment, and which factors determine TTMUS changes in CF. We assessed TTMUS in 47 patients with stable CF ranging in age from 9 to 26 years and in 47 controls of same age and gender. Pulmonary impairment was assessed by the pulmonary function score (PFS) according to Cropp (PFS 0-2 = no, 3-7 = mild, 8-12 = moderate, and 13-18 = severe dysfunction). Median TTMUS was significantly higher in the entire CF-group than in controls ((0.112 (0.079-0.174) vs. 0.07 (0.052-0.094), P < 0.001)). It was nearly identical in CF-patients without (0.079 (0.056-0.114)) and mild (0.080 (0.059-0.128)) pulmonary dysfunction. It was non-significantly higher in subjects with moderate (0.118 (0.103-0.173)) and grossly elevated in individuals with severe (0.232 (0.211-0.31), P < 0.001)) respiratory impairment when compared to the other PFS-groups. TTMUS was significantly related to percent predicted airway resistance (Raw%pred) (r = 0.60, P < 0.001), percent predicted Forced Expiratory Volume in 1 sec (r = -0.49, P < 0.001), percent predicted Vital Capacity (-0.57, P < 0.001), Functional Residual Capacity in percent Total Lung Capacity (r = 0.42, P = 0.003), and transcutaneous oxygen saturation (r = -0.49, P < 0.001). By contrast, Raw%pred was the only variable that had a significant effect on TTMUS (P = 0.01), when a multivariate logistic regression was applied, using the median of the entire CF-cohort to dichotomise TTMUS. These findings suggest that subjects with stable CF and severe pulmonary dysfunction are prone to respiratory muscle fatigue, and that airway obstruction is an important factor contributing to the increase of TTMUS in CF. Regular determination of TTMUS may be clinically useful during course of disease, and may aid the decision to institute therapies like respiratory muscle training or non-invasive intermittent ventilation.

Time constant of inspiratory muscle relaxation in cystic fibrosis

“…Determinants of respiratory muscle compromise in CF have been reported in detail (1)(2)(3)9,19,20). Airway obstruction impacts on inspiratory muscle function by increasing the load against which the respiratory muscles are forced to operate (1) and hyperinflation places the respiratory muscles in mechanical disadvantage (2).…”

“…Airway obstruction impacts on inspiratory muscle function by increasing the load against which the respiratory muscles are forced to operate (1) and hyperinflation places the respiratory muscles in mechanical disadvantage (2). Moreover, malnutrition affects the diaphragmatic pressure-generating capacity (20), given that decreased somatic muscle mass indices have been consistently associated with decreased maximal respiratory pressures in CF patients (3,9). Furthermore, chronic respiratory infection (5) and nutritional deficiencies (19) might also be implicated in the pathophysiology of respiratory muscle dysfunction in CF.…”

“…Inspiratory muscle impairment in patients with CF has been studied in the literature using maximal respiratory pressures (8), diaphragmatic electromyography (10), the tension-time index of the respiratory muscles (2,3,9), and endurance testing by breathing against increased external loads (11,21,22). Although maximal respiratory pressures describe the pressure-generating capacity of the respiratory muscles at a given point of time, they would not be appropriate for the assessment or prediction of respiratory muscle function over time (14).…”

“…surface diaphragmatic electromyography can be affected appreciably by electrical "noise" from neighboring or underlying muscle groups or by levels of subcutaneous fat. Moreover, the noninvasive tension-time index of the respiratory muscles has been explored in CF patients in a number of studies and high values of TT mus have been reported, also indicating an increased risk of inspiratory muscle fatigue and respiratory failure (2,3,9). Unfortunately, measurement of the tensiontime index requires the utilization of pneumotachograph and differential-pressure transducers, i.e., a technical setup which is only found in specialized research laboratories.…”

“…Although respiratory failure in patients with CF primarily results from lower airway and lung parenchyma failure, respiratory muscle dysfunction significantly contributes to the development and the severity of the clinical picture. Respiratory muscle fatigue has been attributed to lower airway obstruction (1), lung hyperinflation (2), malnutrition (3), and chronic respiratory infection (4,5). Early recognition of respiratory muscle impairment may allow timely application of strategies aimed at preserving the functional integrity of the respiratory muscles, such as inspiratory muscle training (6) and noninvasive ventilation (7).…”