Background Most patients with amyotrophic lateral sclerosis (ALS) are treated with mechanical insufflation–exsufflation (MI-E) in order to improve cough. This method often fails in ALS with bulbar involvement, allegedly due to upper-airway malfunction. We have studied this phenomenon in detail with laryngoscopy to unravel information that could lead to better treatment. Methods We conducted a cross-sectional study of 20 patients with ALS and 20 healthy age-matched and sex-matched volunteers. We used video-recorded flexible transnasal fibre-optic laryngoscopy during MI-E undertaken according to a standardised protocol, applying pressures of ±20 to ±50 cm H₂O. Laryngeal movements were assessed from video files. ALS type and characteristics of upper and lower motor neuron symptoms were determined. Results At the supraglottic level, all patients with ALS and bulbar symptoms (n=14) adducted their laryngeal structures during insufflation. At the glottic level, initial abduction followed by subsequent adduction was observed in all patients with ALS during insufflation and exsufflation. Hypopharyngeal constriction during exsufflation was observed in all subjects, most prominently in patients with ALS and bulbar symptoms. Healthy subjects and patients with ALS and no bulbar symptoms (n=6) coordinated their cough well during MI-E. Conclusions Laryngoscopy during ongoing MI-E in patients with ALS and bulbar symptoms revealed laryngeal adduction especially during insufflation but also during exsufflation, thereby severely compromising the size of the laryngeal inlet in some patients. Individually customised settings can prevent this and thereby improve and extend the use of non-invasive MI-E.

BACKGROUND: Respiratory complications represent the major cause of death in amyotrophic lateral sclerosis (ALS). Noninvasive respiratory support is the mainstay therapy, but treatment becomes challenging as the disease progresses, possibly due to a malfunctioning larynx, which is the entrance to the airways. We studied laryngeal response patterns to mechanically assisted cough (mechanical insufflation-exsufflation) as ALS progresses. METHODS: This prospective longitudinal study of 13 consecutively included subjects with ALS were followed up during 2011–2016 with repeated tests of lung function, neurological status, and laryngeal responses to mechanical insufflation-exsufflation using video-recorded flexible transnasal fiberoptic laryngoscopy. RESULTS: Follow-up time was median 17 (range 6–59) months. In total, 751 laryngoscopy recordings from 67 individual examinations (median 4 per subject, range 2–11 per subject) were analyzed. Adverse laryngeal events that developed with disease progression during insufflation included adduction of true vocal folds in 8 of 9 spinal-onset subjects and adduction of aryepiglottic folds in all subjects, initially at the highest positive pressure and prior to onset of other bulbar symptoms in spinal-onset subjects. As cough became less expulsive with disease progression, laryngeal adduction occurred at lower insufflation pressures. Retroflex movement of the epiglottis was observed in 7 of 13 subjects regardless of insufflation pressures and independent of bulbar involvements. Backward movement of the tongue base occurred regardless of insufflation pressures in all but 1 subject. During exsufflation, constriction of the hypopharynx was observed in all subjects regardless of the presence of bulbar symptoms, after the adverse events that occurred during insufflation. CONCLUSIONS: Applying high insufflation pressures during mechanically assisted cough in ALS can become counterproductive as the disease progresses; importantly also prior to the onset of bulbar symptoms. The application of positive inspiratory pressures should be tailored to the individual patient, and laryngoscopy during ongoing treatment appears to be a feasible tool.

When the ability to cough is impaired, secretion clearance may be assisted and augmented with mechanical insufflation-exsufflation (MI-E). In some individuals, the efficacy of MI-E may be hampered by counterproductive upper airway reactions, where the airways close in response to positive pressures. To fully utilize the therapeutic potential inherent in the MI-E technology, we need a better understanding of the pathophysiology behind these untoward reactions. There is increasing interest in monitoring and measuring upper airway responses to MI-E and how such information can be used to optimize MI-E settings. The purpose of this narrative review is to increase the theoretical understanding of the larynx as a respiratory organ, summarize the current literature in the area, and provide insight into how this knowledge can affect current clinical practice.

Mechanical insufflation-exsufflation (MI-E) is a strategy to treat pulmonary exacerbations in neuromuscular disorders (NMDs). Pediatric guidelines for optimal setting titration of MI-E are lacking and the settings used in studies vary. Our objective was to assess the actual MI-E settings being used in current clinical treatment of children with NMDs and a survey was sent in July 2016 to European expertise centers. Ten centers from seven countries gave information on MI-E settings for 240 children aged 4 months to 17.8 years (mean 10.5). Settings varied greatly between the centers. Auto mode was used in 71%, triggering of insufflation in 21% and manual mode in 8% of the cases. Mean (SD) time for insufflation (Ti) and exsufflation (Te) were 1.9 (0.5) and 1.8 (0.6) s respectively, both ranging from 1 to 4s. Asymmetric time settings were common (65%). Mean (SD) insufflation (Pi) and exsufflation (Pe) pressures were 32.4 (7.8) and -36.9 (7.4), ranging 10 to 50 and -10 to -60cmH2O, respectively. Asymmetric pressures were as common as symmetric. Both Ti, Te, Pi and Pe increased with age (p < 0.001). In conclusion, pediatric MI-E settings in clinical use varied greatly and altered with age, highlighting the need of more studies to improve our knowledge of optimal settings in MI-E in children with NMDs.

Mechanical insufflation-exsufflation (MI-E) is essential for secretion clearance, especially in neuromuscular disorders. For the best outcomes, initiation of MI-E should be started at the correct time with regular evaluation to the response to treatment. Typically, cough peak flow has been used to evaluate cough effectiveness with and without MI-E. This review highlights the limitations of this and discussed other tools to evaluate MI-E efficacy in this rapidly developing field. Such tools include the interpretation of parameters (like pressure, flow and volumes) that derive from the MI-E device and external methods to evaluate upper airway closure. In this review we pinpoint the differences between different devices in the market and discuss new tools to better titrate MI-E and detect pathological responses of the upper airway. We discuss the importance of point of care ultrasound (POCUS), transnasal fiberoptic laryngoscopy and wave form analysis in this setting. To improve clinical practice newer generation MI-E devices should allow real-time evaluation of waveforms and standardize some of the derived parameters.