Exploring the Relation between Glottal Closure and Plasma Substance P: A Study Protocol

Abstract

Glottal incompetence, i.e., reduced ability to produce effective glottal closure, is a problem often associated with aging. The study protocol is presented to determine whether blood substance P (SP) serves as an indicator of glottal closure function among the elderly. SP is involved in the neuromuscular mechanisms of cough; reduced concentration of SP may be a marker for increased risk of aspiration pneumonia. The antihypertensive angiotensin-converting enzyme inhibitor, which also inhibits degradation of SP, has been found to be effective in preventing aspiration pneumonia by strengthening the cough reflex. In this study, we will employ National Hospital Organization self-controlled vocal exercise (NHOEx), which has been shown to improve glottal closure by strengthening the laryngeal adduction muscles. We hypothesize that improved glottal closure by NHOEx may lead to the increase in the plasma concentration of SP, which reflects effective cough reflex. Maximum phonation time (MPT), an indicator of glottal closure, will be measured to assess improvement of glottis-closing function. The study will include 180 patients over 65 years old with dysphonia, dysphagia, or MPT of less than 15 seconds. Based on the speculation that the improved MPT may be associated with changes in SP expression, we will measure the plasma SP before and after 6-month treatment of glottal incompetence using NHOEx. The goal is to verify the reliability of SP as an indicator for glottal closure and swallowing function. Measurement of plasma SP may be helpful for earlier detection of subjects with higher risk of aspiration pneumonia among the elderly.

Deterioration of Cough, Respiratory, and Vocal Cord Functions in Patients with Multiple System Atrophy

“…MPT is used as an indirect assessment of laryngeal and vocal cord movements, and its relationship with aspiration is known [ 31 ]. In addition, it was reported that MPT can be an indicator of the glottic closure required for intrathoracic compression in the process of coughing [ 32 , 33 ]. It is straightforward to understand that MPT depends on the vital capacity, age, and sex.…”

Exploring the relationship between plasma substance P and glottal incompetence in the elderly

“…Based on data in the protocol paper [ 14 ] associated with this study, the recommended sample size of participants was calculated using G*Power (version 3.1) [ 18 ] with power = 0.95, α = 0.05 and d = 0.5, producing an estimate of n = 105. The study included 122 patients (outpatients), all over the age of 65, each of whom provided informed written consent.…”

“…This study was registered in the Clinical Trial Registry (UMIN-CTR) as UMIN000035080. The detail was published as a protocol [ 14 ].…”

“…Coughing during ACE-inhibitor therapy to prevent aspiration is due to an increased inflammatory state in the airways for preventing reduction of SP [ 10 ]. Some reports suggested that a reduction of SP concentration in serum [ [10] , [11] , [12] , [13] , [14] ], sputum [ 15 ], or saliva [ 16 , 17 ] may be a useful predictive marker for the increased risk of developing aspiration or aspiration pneumonia. Therefore, a relationship between SP, cough reflex, and the risk of aspiration pneumonia has been established.…”

“…We measured the plasma concentration of SP and the MPT before and after the NHO-exercise to test for correlation between their changes. It was hoped that glottal incompetence, which could lead to early-stage aspiration pneumonia and is expected to occur in more patients in the future, could be reliably detected by a passive indicator using blood sampling of SP in combination with MPT [ 14 ]. This would greatly help to identify cases at risk of aspiration.…”