Airway protection is the ability to prevent aspiration of foreign or endogenous material into the airway (aspiration prevention) and, if aspiration occurs, detect and remove the material (aspiration correction). It includes a continuum of highly coordinated behaviors, ranging from swallowing (primary preventative behavior) to cough (primary corrective behavior) [1, 2]. Deficits in airway protection are associated with decreased quality of life and increased risk of immediate or delayed sequelae, such as choking, asphyxiation, malnutrition, dehydration, and aspiration pneumonia (AP). The anatomic focal point of aspiration prevention is the pharynx, which bifurcates in the caudal part into the esophagus posteriorly and larynx anteriorly, and serves as a conduit for both air and various bolus materials . Essential in mitigating the aspiration risk inherent in this cross-system use is adequate pharyngeal swallowing function, i.e., the ability to move the bolus through the pharynx around the larynx and into the esophagus without material entering the trachea and bronchi . Pharyngeal swallowing is a sensorimotor behavior that includes a precisely patterned sequence of motor events, e.g., glottal closure, arytenoid adduction, and epiglottal folding. It requires coordination with breathing (e.g., apnea during swallowing) and other processes, such as vocalization . It is physiologically complex and prone to malfunction. Therefore, aspiration is not uncommon, even in healthy populations. However, severe complications or death are relatively rare due to the aspiration correction mechanism, whose primary behavior is cough. Cough removes aspirated material by generating high-velocity shearing forces in larger airways and squeezing actions in smaller airways . Induction occurs by cortically mediated voluntary activation, on command, or by conscious effort (voluntary cough), or secondary to stimulation of multiple types of sensory nerves innervating the airways in different densities (reflex cough) .
The debate over the exact subtypes of primary sensory neurons participating in cough generation and modulation is ongoing. In their dual-sensory neuron model, Canning et al. identify chemo-sensitive, unmyelinated C-fiber nociceptors and myelinated Aδ fibers, which are insensitive to most chemical mediators (except rapid changes in pH), but highly sensitive to mechanical stimuli [6,7,8]. Cough-inducing, or tussigenic, stimuli include aspirated foreign or intrinsically produced materials (e.g., food, liquids, sputum, gastric content), inhaled particulate matter, inflammatory mediators (e.g., bradykinin), and irritants (e.g., citric acid, aerosolized capsaicin) . In the past two decades, our understanding of airway protection neurophysiology has evolved from swallowing and cough as separate reflexive behaviors expressed by separate central pattern generators (CPGs) in the brainstem to a continuum of highly coordinated behaviors intimately connected via a sensorimotor control network with shared neural substrates in the brainstem as well as in cortical and subcortical regions [2, 9,10,11]. Given the potential of shared neural circuitry, it is reasonable to hypothesize that disease and damage have distributed effects . A consequence of this may be the high prevalence of dystussia (impaired cough) and atussia (absence of cough) in neurogenic dysphagia (ND).
The airway protection deficits associated with the concurrence of swallowing and cough impairments can have deleterious effects on patients’ health and quality of life [13,14,15,16,17,18]. Of particular concern is AP, a leading cause of mortality in ND [19, 20]. Historically, AP has been attributed almost solely to dysphagia-related aspiration . Accordingly, AP prevention strategies have focused mainly on preventing aspiration by improving swallowing safety. While aspiration is undoubtedly a prerequisite for AP pathogenesis, a growing body of literature identifies impaired cough function as a critical factor and, consequently, a clinically relevant therapeutic target.
The absence of reflex cough in response to aspiration is termed silent aspiration . Dysphagic patients with silent aspiration are at a significantly increased risk of developing pneumonia [22, 23]. In comparison, dysphagic patients with adequate cough function rarely develop AP . Nevertheless, protussive therapies for this patient population are minimal . Thus, we investigated methods to treat dystussia and atussia in ND.
Earlier studies have attributed cough impairments in ND to sensory and cognitive, rather than motor, deficits . Indeed, some irritant chemicals are known to readily elicit cough in ND patients with dystussia and atussia and have been used for decades in diagnostics and research, e.g., to measure cough reflex sensitivity in order to identify swallowing dysfunction or assess the risk of AP [5, 27,28,29,30]. A well-known example of such an irritant is capsaicin, the pungent extract of Capsicum annuum fruits (chili peppers), which, in aerosolized form, induces cough in a dose-dependent and safe manner. It also has good short- and long-term reproducibility [31, 32]. The ability of aerosolized capsaicin (AC) to induce cough in ND patients with cough impairments suggests that the potential to produce cough is present but “inaccessible” due to neurological disorder. We termed this unrealized potential “cough potential” (CP).
This study aimed to assess the use of AC as a therapeutic tool in treating ND-related cough impairments. For this, the cough response to AC was quantified. Spirometry was used to measure peak cough flow (PCF) of voluntary cough (cough on command) and reflexive, or AC-induced, cough. PCF is an indicator of cough efficacy in terms of its tracheobronchial clearance capabilities . It ranges from 6 to 14 L/s in healthy individuals. Cough with a PCF above 4.5 L/s is defined as effective, and between 2.7 and 4.5 L/s as partially effective. Cough with a PCF below 2.7 L/s is considered ineffective and associated with increased risk of AP [34,35,36]. In addition, we introduced a novel application method that allows AC treatment to be performed at home by the patients themselves or their caregivers.
The a priori hypothesis was that in ND patients with dystussia and atussia, a CP is present but inaccessible due to neurological disorder. It was further hypothesized that AC would allow this patient population to access their individual CP and perform adequate tracheobronchial clearance.