New assessment and intervention in amyotrophic lateral sclerosis (ALS) patients
Absolute lung volumes, amyotrophic lateral sclerosis, forced vital capacity, inspiratory muscles, thoracoabdominal asynchrony.
Introduction: The assessment and early detection of respiratory muscle weakness resulting from amyotrophic lateral sclerosis (ALS) have gained more interest in the field of research in the recent decades. As the disease progresses, the decrease in respiratory muscle strength leads to a reduction in lung volume and consequent ventilatory insufficiency, making essential the use of bronchial hygiene techniques and the early detection of respiratory muscle weakness in order to monitor the progression of the disease as well as to anticipate the introduction of interventions.
Objectives: 1) To estimate the amount of gas compression (Vcomp) during the application of the air stacking technique in healthy subjects and to verify if the simultaneous measurements of chest wall volume changes (ΔVCW) and changes in lung volume (ΔVao), combined with pressure variation at the airways opening (ΔPao) during air stacking are able to provide reliable data on absolute lung volumes; 2) To assess thoracoabdominal asynchrony and the presence of paradoxical movement in patients with ALS and its relations with VCW, respiratory pattern and peak cough flow; 3) To analyze the relaxation rates and contraction properties of the inspiratory muscles of patients with ALS and compare with healthy matched-paired subjects. In addition, patients with ALS were divided into three subgroups in order to determine the best parameter linked to inspiratory muscle weakness.
Materials and Methods: 1) Twenty healthy subjects were studied during a protocol that included slow vital capacity maneuvers and application of the air stacking technique. Vcomp was calculated by subtracting ΔVao(measured by pneumotachograph) and ΔVCW (measured by optoelectronic plethysmography) during air stacking and total lung capacity was estimated by applying Boyle-Mariote's law; 2) Phase angle (θ) between pulmonary ribcage (RCp), abdominal ribcage (RCa) and abdomen (AB), as well as the percentage of inspiratory time (IP) in which RCa and AB moved in opposite directions were quantified in 12 patients with ALS through optoelectronic plethysmography during quiet spontaneous breathing and cough using control data from 12 paired-matched healthy subjects to define the normal range of movement; 3) The relaxation rates and contraction properties of the inspiratory muscles were extracted from the sniff nasal inspiratory pressure (SNIP) curve, performed non-invasively in 39 patients with ALS and compared with 39 matched-paired healthy subjects.
Results: 1) During air stacking, 0.140±0.050 L of gas was compressed with an average ΔPao of 21.78±6.18 cmH2O. No significant differences between the estimated total lung capacity (−0.03±3.0% difference, p=0.6020), estimated functional residual capacity (−2.0±12.4% difference, p=0.5172), measured inspiratory capacity (1.2±11.2% difference, p=0.7627) and predicted values were found. 2) During quiet spontaneous breathing, a higher RCa and AB θ (p<0.05), IPRCa (p=0.001) and IPAB (p=0.02) were found in patients with ALS as well as correlations between RCp and AB θ with forced vital capacity (r = −0.773, p<0.01) and vital capacity (r = −0.663, p<0.05), and between RCa and RCp θ and peak cough flow (r = −0.601, p<0.05). During cough, correlations between AB and RCp θ and peak cough flow (r = −0.590, p<0.05), peak expiratory flow (r = −0.727, p<0.01) and VCW (r = −0.608, p<0.05); as well as between RCa and AB θ and peak cough flow (r = −0.590, p=0.01) and peak expiratory flow (r = −0.713, p=0.01) were observed. Moreover, a lower forced vital capacity (p<0.05) and a greater shortening velocity of the inspiratory muscles (p<0.05) were observed in patients with paradoxical movement of the rib cage; 3) When compared to healthy ix
subjects, patients with ALS had a significantly lower (p<0.0001) maximum relaxation rate (MRR) and maximum rate of pressure development (MRPD), as well as a greater (p<0.0001) contraction time, tau (τ) and half-relaxation time (½RT). The results of the ROC curves showed that ½RT (AUC 0.720, p=0.01), forced vital capacity (AUC 0.700, p=0.03), τ (AUC 0.824, p<0.0001) and MRPD (AUC 0.721, p=0.01) were the most sensitive parameters in detecting a 3-point fall in the respiratory subscale of the ALS functional capacity questionnaire. In addition, the MRPD (AUC 0.781, p<0.001), τ (AUC 0.794, p=0.0001) and the peak pressure generated during the SNIP test (AUC 0.769, p=0.002) were the parameters capable of detecting a 30% decrease in forced vital capacity of the patients studied.
Conclusions: During AS, a significant gas compression occurs and absolute lung volumes can be estimated by simultaneous measurements of ΔVCW, ΔVao and ΔPao. In addition, the identification of altered parameters, such as thoracoabdominal asynchrony and the presence of paradoxical movement between the chest wall compartments, τ, MRPD, and ½RT, represent an early sign of inspiratory muscle weakness in subjects with ALS.