Respiratory system complications and abnormalities are common in patients with amyotrophic lateral sclerosis (ALS) and respiratory failure remains the most common cause of death. Extensive epidemiological longitudinal data have documented the extent, magnitude, and clinical course of these abnormalities, but few studies have provided objective information that can have prognostic significance for individual patients. In this study, the reported data represent results from a retrospective review of the medical records of 153 patients with ALS cared for at a single institution (The Penn State Milton S. Hershey Medical Center) over a 50-month period. Medical information in relation to respiratory system abnormalities and complications including pulmonary function measurements was extracted for data analyses. The intent of this review of longitudinal data from a relatively large cohort of patients with ALS was to identify clinically relevant easily-identifiable objective information and clinical milestones that could have potential prognostic significance when applied to individual patients. Demographic data including gender, survival outcome, respiratory symptoms, age of disease onset, and age at death were similar to previously published epidemiological studies: mean age at ALS disease onset was 58.9+/-12.7 years, and mean age at death was 66.7+/-10.8 years. For 151 patients with available data, the incidence of study defined respiratory complications included infectious pneumonia 13 (9%), venothromboembolism 9 (6%), and tracheostomy and mechanical ventilation 6 (4%). For 139 patients with serial measurements of forced vital capacity (FVC), median values for calculated rate of decline in FVC was 97 ml/30 days (2.4% predicted/30 days); 25% of patients had FVC rates of decline less than 52 ml/30 days (1.4% predicted/30 days) and 25% had rates of decline greater than 170 ml/30 days (4.4% predicted/30 days). Stratifying patients into two distinct clinical subgroups based upon rates of decline in FVC less than or greater than the median value of 97 ml/30 days identified an apparent two-fold increase in survival duration for ALS patients with slower rates of pulmonary physiology deterioration when referenced to either date of dyspnea onset or time from bi-level positive airway pressure (BiPAP) initiation (2.0+/-1.4 vs. 1.0+/-0.8 years; 1.9+/-1.5 vs. 1.0+/-0.9 years, respectively). We concluded that the correlation between clinically defined milestones, most importantly onset of dyspnea, and the calculated rate of decline in FVC represent obtainable and objective measurements that predict the natural course of respiratory muscle dysfunction in patients with ALS and provide important prognostic information in relation to individual patient survival duration.
"Previous studies have identified several promising candidate markers of bulbar motor decline using instrumentbased measures of speech subsystem performance. Kent et al.  measured the physiologic function of the respiratory subsystem and identified declines in maximum ventilatory volume and vital capacity as primary indicators of respiratory decline related to bulbar ALS (see also   ). Ramig et al.  studied the acoustic features related to the phonatory subsystem function and identified increased phonatory instability (e.g., increased variability in the amplitude and fundamental frequency [F0] of voice, increased jitter and shimmer, etc.) and reduced phonatory limits (e.g., F0 range) as acoustic indicators of vocal involvement (see also [16, 21– 26]). "
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To develop a predictive model of speech loss in persons with amyotrophic lateral sclerosis (ALS) based on measures of respiratory, phonatory, articulatory, and resonatory functions that were selected using a data-mining approach.
Physiologic speech subsystem (respiratory, phonatory, articulatory, and resonatory) functions were evaluated longitudinally in 66 individuals with ALS using multiple instrumentation approaches including acoustic, aerodynamic, nasometeric, and kinematic. The instrumental measures of the subsystem functions were subjected to a principal component analysis and linear mixed effects models to derive a set of comprehensive predictors of bulbar dysfunction. These subsystem predictors were subjected to a Kaplan-Meier analysis to estimate the time until speech loss.
For a majority of participants, speech subsystem decline was detectible prior to declines in speech intelligibility and speaking rate. Among all subsystems, the articulatory and phonatory predictors were most responsive to early bulbar deterioration; and the resonatory and respiratory predictors were as responsive to bulbar decline as was speaking rate.
The articulatory and phonatory predictors are sensitive indicators of early bulbar decline due to ALS, which has implications for predicting disease onset and progression and clinical management of ALS.
"ALS inevitably results in weakening of the respiratory musculature characterized by symptoms of dyspnea on exertion, orthopnea, and early morning headaches with fatigue. Respiratory failure remains the leading cause of death (16). The average rate of decline in vital capacity is reported to be 1.8% per month in patients with slowly progressive ALS and 3.5% per month in rapidly progressive disease (17,18). "
[Show abstract][Hide abstract] ABSTRACT: Bulbar motor deterioration due to amyotrophic lateral sclerosis (ALS) leads to the eventual impairment of speech and swallowing functions. Despite these devastating consequences, no standardized diagnostic procedure for assessing bulbar dysfunction in ALS exists and adequate objective markers of bulbar deterioration have not been identified. In this paper, we consider objective measures of speech motor function, which show promise for forming the basis of a comprehensive, quantitative bulbar motor assessment in ALS. These measures are based on the assessment of four speech subsystems: respiratory, phonatory, articulatory, and resonatory. The goal of this research is to design a non-invasive, comprehensive bulbar motor assessment instrument intended for early detection, monitoring of disease progression, and clinical trial application. Preliminary data from an ongoing study of bulbar motor decline are presented, which demonstrate the potential clinical efficacy of the speech subsystem approach.
[Show abstract][Hide abstract] ABSTRACT: Resumen Virtualmente todos los pacientes con esclerosis lateral amiotrófica tendrán disnea, que es quizá el síntoma más penoso de esta devastadora enfermedad. El objetivo de este estudio fue correlacionar la dimensión respiratoria de la escala ALSFRS-R, la capacidad vital forzada y las presiones estáticas máximas bucales. Se estudiaron prospectivamente 20 pacientes consecutivos sin disnea durante 24 meses. El puntaje total de la escala ALSFRS-R disminuyó de 34.3 ± 10.3 a 22.1 ± 8.0 (p = 0.0325); la contribución de la dimen-sión respiratoria fue insignificante. En quienes refirieron disnea (n: 12), la capacidad vital forzada cayó un 41 ± 21 % del valor inicial pero con similar caída (46 ± 23%), 8 pacientes no refirieron disnea. La correlación entre la escala ALSFRS-R con la capacidad vital forzada (litros) fue r: 0.73, (p = 0.0016) y con la presión inspiratoria máxima (cm H 2 O), r: 0.84, p = 0.0038. La correlación entre la capacidad vital forzada (%) con la disnea fue r s : 0.23, p = 0.1400. La correlación de la disnea con la presión inspiratoria máxima (%) fue r s : 0.58, p = 0.0300 y con la presión espiratoria máxima (%), r s : 0.49, p = 0.0400. La dimensión respiratoria de la escala ALSFRS-R no permitió predecir el grado de deterioro funcional respiratorio. Esto sugiere que dicha dimensión no reemplaza a las mediciones funcionales respiratorias y, debido a que la insuficiencia respiratoria puede no ser evidente, la rea-lización de dichas pruebas provee una base objetiva de seguimiento y permite planear medidas con anticipación. Palabras clave: esclerosis lateral amiotrófica, disnea, insuficiencia respiratoria, pruebas de función pulmonar, capacidad vital, músculos respiratorios Abstract Respiratory domain of revised amyotrophic lateral sclerosis. Functional Rating Scale. Virtu-ally all patients with amyotrophic lateral sclerosis will complain of dyspnea, which is perhaps the most distressing symptom of this devastating disease. The objective was to correlate respiratory domain of ALSFRS-R with forced vital capacity and maximal static pressures in the mouth. We designed a prospective study in 20 consecutive patients without dyspnea during 24 months. The global decline of ALSFRS-R was from 34.3 ± 10.3 to 22.1 ± 8.0 (p = 0.0325), the contribution of respiratory domain was irrelevant. Those who referred dyspnea (n: 12), forced vital capacity fell 41 ± 21% of the initial value but with similar value of fall (46 ± 23%) 8 patients did not referred dyspnea. Total score of ALSFRS-R correlated with forced vital capacity (litres), r: 0.73, p = 0.0016 and maximal inspiratory pressure (cm H 2 O), r: 0.84, p = 0.0038, but the fall of the forced vital ca-pacity (%) did not correlate with dyspnea (r s : 0.23, p = 0.1400). There was a moderate correlation between dyspnea and maximal inspiratory pressure (%), r s : 0.58, p = 0.0300 and between dyspnea and maximal expiratory pres-sure (%), r s : 0.49, p = 0.0400. We concluded that the respiratory functional deterioration could not be predicted using respiratory domain of ALSFRS-R. This suggests that respiratory domain of this scale does not replace to respiratory function testing measurements and, due to the respiratory insufficiency could not be clinically evi-dent; performing pulmonary function tests provides an objective view and permit to make anticipatory actions.
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