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Objective: To systematically assess decline in respiratory measures in amyotrophic lateral sclerosis (ALS) and to examine the impact of sex, disease onset type and baseline morbidity on progression. Methods: The REVEALS study (Registry of Endpoints and Validated Experiences in ALS) was conducted between April 2018 and February 2021 in six European ALS centers. Slow and forced vital capacity (S/FVC), sniff nasal inspiratory pressure (SNIP), peak cough flow, amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS-R), and respiratory morbidity were collected. Data were analyzed using a Bayesian multiple outcomes random effects model. Results: Two hundred and eighty participants had a median of three assessments (IQR 2.0, 5.0) over a median of 8 months (IQR 2.3, 14.1). There were 974 data collection timepoints. Differences in respiratory measures and rates of decline between disease-onset and sex subgroups were identified. Females had lower scores in all respiratory measures and females with bulbar onset ALS had faster decline compared with other sub-groups. These differences were not detected by the ALSFRS-r respiratory subscale. Dyspnea, orthopnea, and a higher King's stage at baseline were associated with lower respiratory scores throughout follow-up, while having a regular productive cough at baseline was associated with lower peak cough flow scores. Conclusion: Respiratory function declines more quickly in females with ALS compared with males when measured by FVC, SVC, SNIP, or PCF, but not the ALSFRS-R respiratory sub-score. Higher baseline King's staging and the presence of clinical respiratory symptoms at baseline were associated with worse respiratory function. The ALSFRS-R respiratory sub-score is poorly correlated with objective respiratory measurements. [ABSTRACT FROM AUTHOR]

Background: An ongoing longitudinal study in six European sites includes a 3-monthly assessment of forced vital capacity (FVC), slow vital capacity (SVC), peak cough flow (PCF), and Sniff nasal inspiratory pressure (SNIP). The aim of this interim analysis was to assess the potential for SNIP to be a surrogate for aerosol generating procedures given COVID-19 related restrictions. Methods: This was a prospective observational study. Patients attending six study sites with King's Stage 2 or 3 ALS completed baseline FVC/SVC/SNIP/PCF and repeated assessments 3 monthly. Data were collected from March 2018 to March 2020, after which a COVID-19 related study suspension was imposed. Correlations between the measures were calculated. A Bayesian multiple outcomes random-effects model was constructed to investigate rates of decline across measures. Results: In total, 270 cases and 828 assessments were included (Mean age 65.2 ± 15.4 years; 32.6% Female; 60% Kings stage 2; 81.1% spinal onset). FVC and SVC were the most closely correlated outcomes (0.95). SNIP showed the least correlation with other metrics 0.53 (FVC), 0.54 (SVC), 0.60 (PCF). All four measures significantly declined over time. SNIP in the bulbar onset group showed the fastest rate of decline. Discussion: SNIP was not well correlated with FVC and SVC, probably because it examines a different aspect of respiratory function. Respiratory measures declined over time, but differentially according to the site of onset. SNIP is not a surrogate for FVC and SVC, but is a complementary measure, declining linearly and differentiating spinal and bulbar onset patients. [ABSTRACT FROM AUTHOR]

Objective: Sniff nasal inspiratory pressure (SNIP) is a commonly used clinical measure of respiratory impairment in amyotrophic lateral sclerosis (ALS), which is used to guide the initiation of noninvasive ventilation (NIV). SNIP can be completed with either an occluded or an un-occluded contralateral nostril. The aim of this study was to compare occluded and un-occluded SNIP measurements and to examine the decline in occluded SNIP over time compared to the ALSFRS-R respiratory subscore. Methods: This was a prospective longitudinal study examining occluded and un-occluded SNIP scores in ALS and PLS patients recorded between 2001 and 2018. Bland and Altman graphs were plotted for occluded vs. un-occluded SNIP measurements taking account of the repeated measures nature of the data. Longitudinal models were constructed as linear mixed effects multi-level models with follow-up in ALS limited to 6 years. Results: SNIP measured with an occluded contralateral nostril was systematically higher than with an un-occluded nostril. SNIP measured using both methods declined non-linearly, particularly after 2–3 years. The best fit model for decline in occluded SNIP included a main effect and interaction between site of onset and time, with age and diagnostic delay as independent variables. This showed a linear decline in spinal onset with a floor effect in bulbar-onset ALS. Conclusion: SNIP measured with an occluded and un-occluded contralateral nostril is not interchangeable, which is relevant in interpreting thresholds for initiation of NIV. SNIP declines non-linearly, which is explained in spinal onset ALS by age and diagnostic delay, but an apparent floor effect remains in bulbar onset. [ABSTRACT FROM AUTHOR]