Opening the black box of mechanical insufflation–exsufflation: bringing upper airway physiology to the bedside

Extract

Mechanical insufflation–exsufflation (MI-E) has become a cornerstone of airway clearance therapy for patients with neuromuscular disorders and impaired cough. By delivering positive pressure followed by rapid negative pressure, MI-E augments cough flows, facilitates secretion clearance and reduces respiratory morbidity [1].

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Personalising cough augmentation therapy starts with understanding the larynx https://bit.ly/3SZxhj6

To the Editor:

Mechanical insufflation–exsufflation (MI-E) has become a cornerstone of airway clearance therapy for patients with neuromuscular disorders and impaired cough. By delivering positive pressure followed by rapid negative pressure, MI-E augments cough flows, facilitates secretion clearance and reduces respiratory morbidity [1]. Yet despite its widespread use and strong physiological rationale, treatment response remains remarkably heterogeneous. Some patients achieve substantial improvements in cough effectiveness and secretion clearance, whereas others derive limited benefit despite apparently adequate device settings and adherence. For many years, explanations for this variability focused primarily on the patient and the device. Disease severity, respiratory muscle weakness, bulbar involvement, insufflation and exsufflation pressures, interface selection, and synchronisation were considered the major determinants of treatment success. However, a growing body of evidence suggests that another important factor has been hiding in plain sight: the upper airway [2–4].

The larynx was long viewed as a passive conduit through which insufflation and exsufflation pressures were transmitted to the lower airways. Flexible laryngoscopy studies have fundamentally challenged this paradigm. Rather than behaving passively, the larynx actively responds to positive- and negative-pressure therapy. In some individuals, particularly those with neuromuscular disorders and bulbar dysfunction, paradoxical adduction of the larynx or supraglottic structures may impede airflow transmission and compromise the effectiveness of MI-E [3]. These observations have shifted attention from the device alone towards the interaction between the patient, the device and the upper airway. In this issue of ERJ Open Research, Andersen et al. [5] take an important step towards addressing a key translational challenge in this field: how can upper airway physiology be assessed outside specialised centres? Their study evaluated whether laryngeal ultrasonography can detect laryngeal movements during MI-E and provide a practical, noninvasive alternative to transnasal flexible laryngoscopy (TFL), the current reference standard for upper airway assessment. The recognition that upper airway behaviour influences cough-assist therapy has emerged as an important physiological advance in the field of respiratory support. Traditional models of MI-E assumed effective transmission of device-generated pressures to the lower airways. However, laryngoscopic studies have shown that the larynx is not merely a passive conduit but a dynamic structure that may facilitate or impede airflow generation during mechanically assisted cough.

This insight has important clinical implications. Two patients receiving MI-E with identical settings may experience markedly different airflow profiles because of fundamentally different laryngeal responses. In this context, upper airway physiology may represent a previously underappreciated source of treatment heterogeneity. The situation is reminiscent of other areas of respiratory medicine in which growing physiological understanding has transformed clinical practice. Recognition of patient–ventilator asynchrony changed the way clinicians approach mechanical ventilation. Similarly, understanding upper airway collapse transformed the management of obstructive sleep apnoea. The emerging appreciation of laryngeal behaviour during MI-E may represent a similar shift for cough augmentation therapies. Laryngeal ultrasonography is rapidly expanding beyond perioperative vocal fold assessment, and is increasingly being explored as a bedside imaging modality across a range of laryngeal disorders and airway applications [2].

Against this background, the study by Andersen et al. [5] is timely and clinically relevant. The investigators performed simultaneous TFL and laryngeal ultrasonography in 30 healthy volunteers undergoing MI-E with both passive and active cough manoeuvres. Using simultaneous flexible laryngoscopy and ultrasonography in healthy volunteers undergoing MI-E, Andersen et al. [5] demonstrated moderate-to-high agreement between the two techniques (78–92%), while highlighting important limitations in image acquisition and visualisation. The study therefore provides proof-of-concept evidence that laryngeal ultrasonography can detect relevant upper airway movements during mechanically assisted cough. At the same time, the authors appropriately emphasise that ultrasound does not currently match the visualisation capabilities of laryngoscopy and cannot be considered a replacement for the reference standard. These findings are important because they address a fundamental barrier to broader implementation of upper airway assessment. While flexible laryngoscopy has transformed our understanding of laryngeal responses during MI-E, its invasive nature, requirement for specialist expertise and limited availability have restricted its use largely to specialised centres and research settings.

The possibility of assessing laryngeal behaviour using a portable, noninvasive bedside technique is therefore attractive. However, important questions remain before such an approach can be incorporated into routine clinical practice. Evidence supporting laryngeal ultrasound has largely emerged from studies of vocal fold immobility following thyroid surgery, where the clinical question is typically binary and static (normal versus impaired vocal fold mobility) [2, 6–8]. In contrast, MI-E involves rapid and highly dynamic upper airway responses occurring across multiple phases of the respiratory cycle. Whether the diagnostic performance reported in perioperative vocal fold assessment can be translated to this more complex physiological setting remains uncertain [6].

Several limitations warrant caution. First, the study was conducted in healthy volunteers rather than the neuromuscular populations most likely to benefit from upper airway assessment. Second, visualisation rates remained substantially lower than those achieved with laryngoscopy, and may be influenced by anatomical factors such as sex, thyroid cartilage calcification, obesity and body habitus [7]. Third, concordance should not be interpreted as diagnostic accuracy. Finally, the challenge is not only whether laryngeal ultrasound works but whether it can be performed consistently across operators and centres. Standardised acquisition protocols, competency frameworks and quality assurance processes will be essential before the technique can move from physiological investigation to routine clinical practice [9]. The most important implication of this work may extend beyond imaging itself. The goal is not to visualise the larynx but to improve treatment effectiveness through a better understanding of patient–device interaction. In this context, upper airway behaviour may represent a novel treatable trait during MI-E. The treatable traits framework emphasises the identification of clinically relevant, measurable and modifiable characteristics that can be targeted through personalised interventions [10]. If specific laryngeal response patterns are shown to predict treatment failure and can be modified through adjustments in device settings, coaching strategies or interface selection, upper airway physiology could become an actionable therapeutic target. Such an approach would move MI-E beyond a one-size-fits-all intervention towards physiology-informed precision therapy, where treatment settings are adapted not only to respiratory mechanics but also to upper airway behaviour. In this framework, imaging becomes not merely a diagnostic tool but a means of personalising therapy. Importantly, this concept remains hypothetical but provides a compelling rationale for future research. The study by Andersen et al. [5] should be viewed as an important first step rather than a final destination. The real challenge is no longer demonstrating that upper airway physiology can be visualised during MI-E but determining whether this information can change clinical practice. Future work should move beyond feasibility and focus on identifying clinically meaningful laryngeal phenotypes, validating ultrasound in neuromuscular populations, and establishing whether physiology-guided treatment strategies improve patient-centred outcomes. Only then will it become clear whether laryngeal ultrasonography is simply a new way of seeing the larynx or a tool capable of improving care.

Flexible laryngoscopy has revealed that the larynx is not a passive conduit during mechanically assisted cough but an active determinant of treatment success. Andersen et al. [5] suggest that this physiology may now be explored using a noninvasive bedside tool. The larynx is no longer invisible. The challenge now is to determine whether bringing upper airway physiology to the bedside can transform physiological insight into better outcomes for patients who depend on cough augmentation therapies.