Background
Pneumonia is a common event after strokes and is associated with morbidity and mortality in stroke patients. It reportedly occurs in one-third of all stroke victims and is the most common respiratory complication in this population [
1]. The risk factors for aspiration pneumonia include silent aspiration caused by old age and neuromuscular disorders, but not cerebral stroke. The identification of patients who are at risk of developing pneumonia is thus important in terms of morbidity and mortality as well as cost of care.
The videofluorographic swallowing study (VFSS) is the definitive test to identify aspiration and other swallowing abnormalities [
2]. Previous studies have shown that aspiration observed on VFSS indicates a risk of developing aspiration pneumonia. The laryngeal cough reflex protects the laryngeal aditus from significant aspiration of food, fluids, and secretions, and reduces the risk of aspiration pneumonia [
3,
4]. However, VFSS is not routinely used to assess the laryngeal cough reflex. Dysphagia and the cough reflex are separate physiologic and neurologic issues and should therefore be independently assessed. Furthermore, several screening tests, including the water test, food test, and saliva swallowing test, cannot detect silent aspiration in patients without a cough reflex.
Previous research has suggested that adding a cough sensitivity test to clinical swallowing evaluations has the potential to reduce the risk of pneumonia after stroke. A clinical guideline for cough assessment produced in 2007 by the European Respiratory Society Task Force highlighted the lack of standardization of cough testing protocols using cough-stimulating agents [
5]. In the reflex cough test (RCT) the patient inhales citric acid and tartaric acid from low to high concentrations and the presence of a cough is assessed. Studies have shown that the inhalation of tartaric acid stimulates coughs in normal subjects [
3,
6,
7], and that the RCT is useful for the detection of silent aspiration [
8,
9]. In these studies, nebulized tartaric acid was shown to be safe and did not produce systemic or adverse side effects. However, the RCT results were evaluated in terms of the presence and number of coughs, but not cough strength. Voluntary cough strength can be measured with a spirometer, but up to this point no devices have been able to measure involuntary cough strength as part of the RCT. Another drawback of the RCT is the subjective evaluation of cough strength by the examiner, because it is important to determine whether the cough generated by the stimulating agent is effective, and whether the subject can cough up secretions.
To overcome these shortcomings, we developed a device to quantify the cough reflex. This paper describes the use of an objective examination system, called the modified RCT (mRCT), to quantify both a tartaric-acid-stimulated involuntary cough and the time until the cough reflex. The study also investigated whether screening with this new instrument would be feasible for evaluating the risk of aspiration pneumonia.
Discussion
Silent aspiration is defined as aspiration without coughing or other obvious distress, and has been linked to an increased prevalence of pneumonia and mortality [
13,
14]. The risk of pneumonia was found to be increased 10-fold in patients with profound aspiration and 13-fold in those with silent aspiration [
15]. However, patients with silent aspiration have no symptoms, including coughing, and dysphagia is therefore more likely to be identified late in disease development. Early identification of silent aspiration and prevention of pneumonia are thus essential in view of the high mortality associated with these conditions.
VFSS is the definitive test for identification of aspiration and other swallowing abnormalities, but it cannot be performed at every institution. This makes swallowing screening tests essential. These tests consist of the water screening test, food test, saliva swallowing test, and RCT. Tohara et al. reported that the water swallowing test (3 ml of water) and the food test (4 g of pudding) had a sensitivity of 90% and specificity of 56% [
16], while Nishiwaki et al. found that the sensitivity of the saliva-swallowing test was 28% and the specificity was 76% [
17]. However, since patients with silent aspiration have difficulty coughing, a simple screening test cannot be used to detect their condition in the clinical setting. The RCT is reportedly the method of choice for detecting silent aspiration, and uses citric acid and tartaric acid to trigger the cough [
9].
The RCT using citric acid demonstrated a diminished cough reflex in patients with aspiration pneumonia [
9]. An impaired cough reflex may play a role in the pathogenesis of aspiration pneumonia, and it was suggested that the early detection of a diminished cough reflex in patients with a predisposition to aspiration helped prevent aspiration pneumonia [
9]. A previous study reported that the RCT fail rate for patient cohorts with suspected dysphagia was 25% for VFSS and 23% for fiber optic endoscopic evaluation of swallowing [
18].
However, the RCT using citric acid takes a long time, and the procedure and decision criteria are complicated, thus making it difficult to use this test to examine patients in debilitated condition. The RCT using tartaric acid is an alternative method that is simple and quick and can thus be more appropriate for such patients. Addington et al. reported that using the tartaric acid RCT after a neurological event was essential for determining the appropriate clinical treatment plan for prescription of food, fluids, and medications. Moreover, the RCT helps to stratify pneumonia risk and improves outcomes by reducing morbidity, mortality, and cost [
8]. One major problem with the conventional RCT method is that cough strength is subjectively evaluated by the examiner, thus results may differ among providers.
We developed an objective measuring device to simultaneously quantify cough strength and the time until the cough reflex occurs. This equipment is a novel device that can assess the relationship between aspiration pneumonia and PCF, the latter measured with the RCT using tartaric acid. The merits of our device are that it can quantify the triggered involuntary cough and measure the time until the cough reflex; there are no adverse reactions, and the examination takes only a short time.
An electromyography-based RCT system that can also evaluate the risk of aspiration pneumonia was patented in the United States in 2004 (https://www.google.com/patients/us20040181161). However, the use of electromyography to measure cough strength is an indirect approach. If patients have upper respiratory tract conditions that impair effective cough expulsion, such as laryngeal paralysis and head and neck cancer, electromyography cannot accurately measure cough strength. In contrast, our device is able to directly evaluate cough strength.
The results of our screening test showed that there was a significant difference in the PCF of patients with and without a history of pneumonia. Thus, the PCF value may indicate the risk of pneumonia and suggests that our equipment permits objective quantification and evaluation.
Hammand et al. reported that peak flow during the inspiration phase and the sound pressure level of voluntary cough was significantly impaired in severe aspirators as compared with non-aspirators [
19]. Beck et al. evaluated voluntary cough and found that in patients with severe respiratory muscle insufficiency and a PCF of less than 160 L/min, decannulation was unsuccessful due to difficulty in keeping the airway clear after extubation and decannulation [
20]. Lasserson et al. reported that PCF of involuntary cough was less than that of voluntary cough, explaining that this was related to differences between the two types of cough in terms of the functional organization of muscle activation [
21]. Tartaric acid is thought to induce coughing by stimulating irritant receptors and C-fiber receptors [
5]. Unlike a voluntary cough, the stimulus that induces an involuntary cough is delivered to the cough center, located in the nucleus tractus solitarius of the medulla oblongata, via sensory nerves ending through the vagus nerve afferent pathway sensory nerve ending, and not under cerebral cortex control. As explained above, quantification and evaluation of involuntary cough are indispensable for the assessment of aspiration. Since the novel measurement system developed in this study overcomes various difficulties and can measure the PCF of involuntary cough, it can provide a realistic assessment of the risk of aspiration pneumonia.
Our device can also measure the sensitivity threshold of the airway mucosa. Moreover, its use showed that there was a significant difference in the time until cough reflex between normal subjects and patients with dysphagia, making it possible to determine the relationship between the time until cough reflex and dysphagia.
There was no significant difference in the time until cough reflex between patients with and without a previous history of pneumonia. There are actually two distinct types of reflexive, non-voluntary cough with different underlying neurological mechanisms: a primary cough reflex occurring at the level of the vocal folds, often referred to as the laryngeal cough reflex, and a deeper tracheobronchial cough reflex that tends to be delayed and less productive [
22]. The receptors in the larynx and trachea are extremely sensitive to mechanical stimuli, with very rapid adaptation. Deeper into the airways, the receptors become more chemosensitive and less mechanosensitive. The aerosol can thus penetrate deeper into the lung and stimulate the more chemosensitive cough receptors there. In other words, the chemosensitive stimulation of the tartaric acid aerosol differs from the mechanosensitive stimulation of food and saliva. Thus, the time until the cough reflex may not be accurately assessed by mechanosensitive stimulation.
VFSS is the gold standard for evaluating swallowing. However, VFSS showed no significant differences in peak flow between patients with and without dysphagia. Since VFSS evaluates swallowing dynamics, it is suggested that there was no relationship between swallowing dynamics and cough strength, and the cough reflex test should be used in combination with VFSS to compensate for limitations of each test.
There are certain limitations to our study. First, patients with trismus or disordered consciousness were excluded from this study because the device was not suitable in these populations. Further development of our device is required to generalize its use. Second, PCF and time until cough reflex were retrospectively evaluated based on past history of aspiration pneumonia, and no prospective cases of aspiration pneumonia were studied in this report. In the near future, we plan to prospectively evaluate the risk of aspiration pneumonia using our novel device. Third, since differences in cough reflex may be age related rather than disease specific, further work will need to be undertaken in the future with age-matched controls to ensure this is not the case. Future studies of the diagnostic accuracy of this device will ideally recruit participants using a single-gate design in order to more accurately identify the test characteristics that are applicable to clinical practice. It has been demonstrated that increasing age contributes far more to reduced local sensitivity than do neuromuscular disorders, which explains the higher prevalence of dysphagia in older patients [
23]. Moreover, several studies have shown that silent aspiration is associated with advancing age [
24‐
26]. This means that there are many patients at risk of silent aspiration, and if a method could easily assess this risk it would be in great demand. Furthermore, if our method becomes more prevalent, it will make it easier for patients at risk of silent aspiration to gain access to specialized medical care. We would like to miniaturize and simplify our device to make it available not only to medical staff but to any qualified personnel.