Voluntary Cough and Swallowing Function Characteristics of Acute Stroke Patients Based on Lesion Type

Accepted Manuscript Voluntary Cough and Swallowing Function Characteristics of Acute Stroke Patients Based on Lesion Type Sook Joung Lee, MD, Kyeong Woo Lee, MD, Sang Beom Kim, MD, Jong Hwa Lee, MD, Min Kyu Park, MD, PhD PII:

S0003-9993(15)00549-3

DOI:

10.1016/j.apmr.2015.06.015

Reference:

YAPMR 56242

To appear in:

ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION

Received Date: 10 May 2015 Revised Date:

29 June 2015

Accepted Date: 30 June 2015

Please cite this article as: Lee SJ, Lee KW, Kim SB, Lee JH, Park MK, Voluntary Cough and Swallowing Function Characteristics of Acute Stroke Patients Based on Lesion Type, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2015), doi: 10.1016/j.apmr.2015.06.015. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Running head: Voluntary Cough and Swallow after Stroke

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Voluntary Cough and Swallowing Function Characteristics of Acute Stroke Patients

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Based on Lesion Type

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Authors: Sook Joung Lee, MD,a Kyeong Woo Lee, MD,a Sang Beom Kim, MD,a Jong Hwa

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Lee, MD,a and Min Kyu Park, MD, PhDb

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Affiliations:

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a

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Medicine, Busan-Ulsan Regional Cardiocerebrovascular Center, Dong-A University Hospital,

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Busan, Republic of Korea.

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Korea

Department of Physical Medicine and Rehabilitation, Dong-A University College of

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Department of Pharmacology, Dong-A University College of Medicine, Busan, Republic of

Acknowledgments: This work was supported by the Dong-A University research fund.

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2014-027

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Conflicts of interest: No commercial party having a direct financial interest in the results of

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the research supporting this article has or will confer a benefit on the authors or on any

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organization with which the authors are associated.

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Correspondence: Min Kyu Park, MD, PhD

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Address: Department of Pharmacology, Dong-A University College of Medicine,

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Deasingongwon-ro 26, Busan, 602-715, Republic of Korea.

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Tel: +82-51-240-5180, Fax: +82-51-254-8511, E-mail: [email protected]

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ACCEPTED MANUSCRIPT Abstract

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Objective: To investigate the relationship between voluntary cough and swallowing function

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according to the type of lesion in acute stroke patients.

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Design: Cross-sectional study.

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Setting: University rehabilitation hospital

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Participants: Acute stroke patients with dysphagia symptoms (n=397)

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Interventions: Not applicable

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Main outcome Measures: A peak cough flow meter was used to measure voluntary

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coughing ability. Swallowing function was evaluated using the functional dysphagia scale

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and the penetration aspiration scale based on the results of a videofluoroscopic swallowing

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study. Stroke lesions were divided into one of the following three categories: cortical,

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subcortical and brainstem. These evaluations were performed within 2 weeks after stroke

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onset.

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Results: Of the enrolled 397 patients, 207 patients were classified as cortical stroke, 106

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patients were classified as subcortical, and 84 patients were classified as brainstem. Among

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the sub-scores of the functional dysphagia scale, the amount of pharyngeal residue negatively

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correlated with peak cough flow meter results across all stroke lesion types. In the brainstem

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lesion, PCF and PAS scores were high compared with other lesions but these two functions

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are not showed correlation.

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Conclusions: This study revealed that large amounts of pharyngeal residue correlated with

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weak voluntary cough ability in all stroke lesion groups. We also showed a discrepancy

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between two functions in brainstem lesion group. Our results suggest that voluntary coughing

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exercises could be a helpful therapeutic option of dysphagia to prevent pulmonary

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complications in some types of stroke patients.

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Key words: Stroke, voluntary cough, dysphagia, videofluoroscopic swallowing study,

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List of abbreviations: ASHA-NOMS: American speech-language-hearing association national outcome measurement system FDS: functional dysphagia scale

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K-MBI: Korean-version of modified Barthel index

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K-MMSE: Korean-version of mini mental status examination

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NIHSS: national institutes of health stroke scale PAS: penetration aspiration scale

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PCF: peak cough flow

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VFSS: videofluoroscopic swallowing study

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ACCEPTED MANUSCRIPT Introduction

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Cough and swallowing function play important roles in airway protection.1 After a stroke,

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many patients suffer from airway infections and dysphagia due to cough and/or swallowing

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dysfunction.2-4 Coughing is an important protective mechanism for maintaining a clear

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airway, and many studies have revealed that stroke patients can experience a decrease in

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cough function.4-6 Swallowing disorders commonly occur in stroke patients, and 38 to 64% of

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stroke patients suffer from swallowing problems during the acute stage.2,3 A swallowing

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disorder due to stroke presents with various clinical manifestations and can demonstrate

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different patterns according to the stroke lesion type.7,8 Therefore, objective evaluation of

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cough and swallowing functions is important for deciding proper diet and treatment

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options.4,9,10

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There are two types of cough: reflex and voluntary. Reflex cough is a brainstem-mediated involuntary reflex. This type of cough can be initiated by aspiration, which is a serious

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swallowing problem, and often causes aspiration pneumonia.3 The afferent and efferent

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pathways of the cough reflex are shared with that of the swallowing reflex. After a stroke,

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some patients experience decreased or absent cough reflex due to swallowing reflex issues.

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Voluntary cough can be elicited intentionally, and a study by Smith et al. reported that

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adequate voluntary coughing reduces the risk of aspiration pneumonia.4 Both reflex and

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voluntary coughs are closely related to swallowing function and play an important role in

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airway protection. Previously, a study reported that both cough types are impaired in patients

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with hemispheric stroke.6

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Previous studies have demonstrated the relations between cough and swallowing function in 3

ACCEPTED MANUSCRIPT stroke patients.2-6,10-12 Several studies have reported that a low peak cough flow (PCF) may

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be a one of the predictive factors for aspiration pneumonia after stroke.5,10,12 Other studies

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have revealed that stroke patients who experience a normal cough reflex have a minimal risk

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for significant aspiration.11 These studies focused exclusively on the relationship between

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aspiration and voluntary cough. However, there are various clinical manifestations of

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dysphagia after stroke, including food aspiration and oral, pharyngeal, and esophageal

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disorders. Few studies have investigated the relationship between voluntary coughing and

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swallowing functions other than aspiration. To our knowledge, no study has analyzed these

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functions according to the stroke lesion type. We hypothesized that voluntary coughing

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would have relationship with swallowing function and that this relationship would vary

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according to the stroke lesion type because the severity and prognosis of dysphagia have been

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shown to differ according to stroke lesion types. The aim of this study was to investigate the

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relationship between voluntary cough and swallowing function according to the stroke lesion

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type. The PCF was used to measure voluntary cough function, and the functional dysphagia

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scale (FDS) and the penetration aspiration scape (PAS) based on the results of

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videofluoroscopic swallowing study (VFSS) were used for evaluate swallowing function.

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Methods

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Subjects

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This study was designed as a cross-sectional study and was performed in the rehabilitation

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center of a university hospital. Acute ischemic or hemorrhagic stroke patients with dysphagia

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symptoms admitted to the stroke or rehabilitation center were recruited. All of the included

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patients had experienced their first stroke and were evaluated VFSS and PCF within 2 weeks

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of stroke onset.

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ACCEPTED MANUSCRIPT Patients who experienced previous strokes, displayed multiple stroke lesions, or displayed

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comorbid cardiopulmonary disease or oropharyngeal cancer were excluded. Patients who had

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cognitive impairments or aphasia to an extent that prevented VFSS testing or impaired their

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ability to produce a maximal voluntary cough upon verbal direction were excluded. Patients

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with tracheostomy tubes were excluded, but the presence of a Levin tube was not considered

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an exclusion criterion if the patients could perform the VFSS and PCF tests. These patients

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were tested by VFSS and PCF after the removal of the Levin tube. After VFSS, we decided

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patients’ diet according to the results of VFSS. The study protocol was approved by the

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institutional review board, and all participants provided written informed consent (15-108).

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Evaluation

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Voluntary cough function

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PCF was used as a parameter to measure voluntary coughing ability, which was assessed by

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having patients cough as forcefully as possible through a peak flow meter.a Prior to testing,

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patients were allowed to use the peak flow meter several times to become accustomed to the

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test, after which the patients were asked to make their maximal effort at least 3 times. PCF

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was defined as the highest point of the flow volume curve obtained during a cough. A

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maximum value of three attempts was used for analysis. PCF is the primary parameter used

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to assess voluntary cough efficacy, and many previous studies have used this parameter as a

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voluntary cough measurement tool.5,12-14

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Swallowing function

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Swallowing function was evaluated using FDS and PAS based on the results of VFSS. VFSS

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was performed with the patients in a sitting position to allow a lateral view. A modified 5

ACCEPTED MANUSCRIPT version of the protocol from a study performed by Logemann was used.15 First, 3 ml of

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barium-containing thick liquid was administered to the subject, after which pureed, semi-

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solid, solid, and thin liquid were administered in this sequence. All of the food samples

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contained barium and were administered two or three times. All patients received

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individualized feeding therapy based on the results of the VFSS.

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FDS is a scale that was developed to quantify dysphagia severity, and it correlates well with the ASHA-NOMS (American speech-language-hearing association national outcome

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measurement system) criteria.16 The FDS consists of 11 items with weighted values

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representing 4 kinds of oral (lip closure, bolus formation, residues in oral cavity, and oral

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transit time), and 7 kinds of pharyngeal (triggering of pharyngeal swallow, laryngeal

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elevation and epiglottic closure, nasal penetration, residue in valleculae, residue in pyriformis

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sinus, coating of pharyngeal wall after swallow, pharyngeal transit time) functions that can be

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observed by VFSS (Table 1). To determine whether differences exist between parameters

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according to the stroke lesion type, FDS score was divided into subsection and analyzed.

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PAS evaluates airway invasions17 and has a maximum score of 8 points. Scores are

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determined primarily based on the depth to which material passes into the airway and based

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on whether material entering the airway can be expelled. The penetration category

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corresponds to level 5 on the scale, and levels 6 to 8 correspond to laryngo-tracheal aspiration.

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PAS 8 means that material enters the airway, passes below the vocal folds, and no effort is

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made to eject. It was represent as silent aspiration which was caused by weak or absent of

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reflex cough.

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Intra- and inter-rating reliability has been established in both scores. Higher FDS and PAS 6

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scores indicate poor swallowing function. These evaluations were performed on the same day within 2 weeks of stroke onset. All test procedures were recorded, and the findings were analyzed by three physiatrists.

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Classification of stroke lesions

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Stroke was diagnosed with cerebral infarction or hemorrhage by magnetic resonance imaging

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or computed tomography of the head. Stroke lesions were divided into three categories

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(cortical, subcortical and brainstem). Previous studies have demonstrated different patterns of

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dysphagia according to the stroke lesion type.7,8,18 These studies have suggested that

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dysphagia patterns can be classified into two main divisions: supratentorial and infratentorial.

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Supratentorial lesions present different dysphagia patterns between the cortical and

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subcortical areas.7

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Statistical analysis

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SPSSb 18.0 for Windows was used for the statistical analysis. Correlation analysis between

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voluntary cough and swallowing function was assessed using Pearson’s correlation

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coefficient. Demographic characteristics of three stroke lesions were analyzed using one-way

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ANOVA. Relation between voluntary cough and swallowing functions in three groups were

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analyzed using ANCOVA, which values were adjusted mean (95% confidence interval) by

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age, days from stroke onset and NIHSS. FDS score was divided into subsection and analyzed.

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A p-value less than 0.05 was considered statistically significant. Post-hoc analysis was

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performed using the Bonferroni correction if there was a significant difference among three

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groups. The level for statistical significance in the post-hoc test was calculated as 0.05/3 =

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0.0167.

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ACCEPTED MANUSCRIPT Results

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Five hundred seventy-one patients with dysphagia symptoms were evaluated by VFSS and

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PCF within 2 weeks of acute stroke from February 2014 to February 2015. Of these patients,

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397 patients met our inclusion criteria and were enrolled in the study. Of the 397 patients,

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207 patients were classified as cortical stroke, 106 patients were classified as subcortical, and

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84 patients were classified as brainstem. Initial stroke characteristics and the functional status

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of the patients according to the stroke lesion are listed in Table 2. After evaluations, 80

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patients could eat a normal diet without food modification, and 317 patients ate a limited diet,

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such as a soft blended diet or a thickened fluid. No patients who required a non-oral diet met

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our inclusion criteria.

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Comparison between voluntary cough and swallowing function

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Figure 1 shows the correlation between voluntary cough and swallowing functions in all

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patients. Pearson’s correlation showed a significant relation between the PCF and the PAS

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(Pearson’s correlation co-efficient: -0.252, p = 0.01), and PCF and the FDS scores (Pearson’s

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correlation co-efficient: -0.360, p = 0.01). PCF showed a strong correlation with residue in

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the vallecular pouch and the piriformis sinus according to the FDS sub-scores (Pearson’s

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correlation co-efficient: - 0.654, p=0.01).

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Relationship between voluntary cough and swallowing function according to the stroke

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lesion type

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Table 3 lists the results of voluntary cough and swallowing studies according to stroke lesion

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type. Their values were adjusted mean (95% confidence interval) by age, days from stroke

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onset, and NIHSS. PCF and PAS were significantly higher in the brainstem lesion group 8

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compared with the other lesions. Post-hoc analysis using the Bonferroni correction revealed

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that (PCF- cortical group vs brainstem group: p < 0.001, PCF- subcortical group vs brainstem

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group: p < 0.01, PAS- cortical group vs brainstem group: p < 0.001, PAS- subcortical group

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vs brainstem group: p< 0.001). The total FDS scores did not show lesion-specific differences. When FDS was divided into

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subsection and analyzed, several oral phase FDS sub-scores were higher in the cortical lesion

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group compared with the other lesions.

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Correlation between voluntary cough and swallowing functions in each stroke lesion As shown in Fig. 1, significant correlations were observed regarding PCF, PAS and FDS in

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all patients include all stroke lesion type. We analyzed the relationship between voluntary

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cough and swallowing functions according to the stroke lesion type using pairwise

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correlations (Table 4). Significant correlations were found between PCF and amounts of

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pharyngeal residue within the FDS subsections in all three stroke lesions. In comparing the

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PCF with the FDS subsections or PAS, relations between two functions showed differences

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according to the stroke lesion type. In the brainstem lesion group, PCF and PAS did not

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correlate, but significantly correlated with each other in the cortical and subcortical stoke

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lesion groups. The pharyngeal phase of the FDS also did not correlate with PCF in the

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brainstem lesion group.

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Discussion

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This study aimed to demonstrate the relationship between voluntary cough and swallowing

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functions according to the stroke lesion type in acute stroke patients. Our results revealed that

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these two functions have similar and/or different characters according to the stroke lesions 9

ACCEPTED MANUSCRIPT type. Among the various swallowing factors, the amount of pharyngeal residue strongly

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correlated with PCF in all stroke lesion groups. However, lesion differences were observed.

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In the cortical stroke lesion, oral phase of FDS sub-scores were higher and PCF was lower

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than other stroke lesions. And in the brainstem lesion, PCF and PAS scores were high

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compared with other lesions but these two functions are not showed correlation.

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Cough and swallowing function in the stroke patients

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After a stroke, many patients suffer cough and/or swallowing dysfunction.2-4 According to a

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literature review, cough and swallow pattern generators are tightly coordinated because they

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share the afferent and efferent pathways.1,4,10,19,20 Because cough and swallowing functions

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share the same motor output system, decreased swallowing function can affect cough

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function in stroke patients.

Previous studies have demonstrated the relationship between cough and swallowing

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function in stroke patients.2-6,10-12 Ward et al. showed that both voluntary and reflex coughs

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are impaired in patients with hemispheric stroke.6 Other studies reported that objective

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measures of voluntary cough can identify stroke patients who are at risk for aspiration.4,5,10,12

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However, these studies focused exclusively on the relationship between cough and

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aspiration. There are two types of cough: reflex and voluntary which should be distinguished.

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And there are various clinical manifestations of dysphagia after stroke. Thus, our study aimed

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to investigate the relationship between voluntary cough and swallowing function. Swallowing

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function was evaluated using FDS and PAS, which include various swallowing features.

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Our results were generally consistent with the results from previous studies, showed 10

ACCEPTED MANUSCRIPT significant correlation between PCF with FDS and PAS (Fig.1). Furthermore, we found that

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the amount of pharyngeal residues and voluntary cough show strong correlation (Fig. 1,

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Table 4). Similar findings were seen in each stroke lesion type. To our knowledge, it is a first

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time to describe correlation between large amount of pharyngeal residues and weak voluntary

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coughing ability.

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Voluntary cough and swallowing function according to the stroke lesion

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Previous studies have demonstrated that swallowing dysfunction differs according to the type

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of stroke lesion.7,8,18 Coughing ability also differs according to the stroke lesion type.21

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Therefore, we compared voluntary cough and swallowing functions using FDS sub-scales

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among the stroke lesion types.

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Cortical or subcortical strokes can cause pseudobulbar palsy. Previous studies have revealed that the clinical findings associated with swallowing dysfunction in hemispheric stroke

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patients predominantly involved oral dysfunction that resulted from weakened facial and

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tongue muscles.7 22 In this study, cortical stroke patients displayed more abnormal findings

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relative to the other lesions in oral function (Table 3).

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Brainstem lesions may directly affect the lower motor neurons of the swallowing center. Thus, brainstem stroke patients, when compared with other lesion groups, had a higher

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frequency of pharyngeal phase abnormalities based on VFSS results.7,8,18,22

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pharyngeal phase FDS sub-scores did not show stroke lesion differences when compared

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after adjusting covariates (Table 3). But, PCF and PAS score were highest in the brainstem

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group among three groups. Interestingly, these two parameters did not show significant

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correlation only in the brainstem lesion.

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In our results,

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Correlation between voluntary cough and swallowing function according to the stroke

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lesion

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Among pairwise correlations between voluntary cough and swallowing functions, there are

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both significant and non-significant correlations according to the lesion. As mentioned above, in all stroke lesion groups, PCF was negatively correlated with the

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amount of pharyngeal residue. Pharyngeal muscle weakness or decreased sensory function

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after stroke can result in residue in the vallecular pouch or the pyriformis sinus after

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swallowing. The amount of pharyngeal residue is related to aspiration.16 We found that

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patients who showed large amounts of pharyngeal residue had weak voluntary coughing

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ability.

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There are non-significant correlations between two functions. Especially in the brainstem

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lesion, discrepancy was observed between voluntary cough and swallowing functions. In our

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study, which contrasts with results from the previous studies,4,6,10 some patients, particularly

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in patients with brainstem stroke, showed higher PCF; however, the higher PCF scores did

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not correlate with PAS. These patients showed strong voluntary cough function but weak

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reflex cough, which could result in silent aspiration. After stroke, some patients show

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decreased or absent cough reflex due to problems in the swallowing reflex. In this case, silent

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aspiration could occur and involves a discrepancy between the voluntary cough and

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swallowing functions.

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In this point, voluntary cough should be distinguished from reflex cough. Although the two

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types of coughs could correlate with each other because they share the same motor output

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system, they have different mechanisms of initiation.13 Voluntary cough is elicited 12

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intentionally, whereas reflex cough is a brainstem-mediated involuntary reflex that can be

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initiated by mechanical stimulation of the chemo-irritant receptors in the trachea or pharynx.

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1,23,24

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in some patients with stroke lesions that affected the cough or swallowing reflex pathways.

Thus, a discrepancy between voluntary cough and swallowing function was observed

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Voluntary coughing exercise as a therapeutic option for dysphagia

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Our results demonstrated that patients who showed large amounts of pharyngeal residue had

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weak voluntary coughing ability in all stroke lesions. And we found that a discrepancy

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between voluntary cough and swallowing functions occurs in patients with brainstem strokes.

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Patients with large amounts of pharyngeal residue or silent aspiration exhibited a high risk of

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aspiration pneumonia. Therefore, encouraging voluntary cough in these patients is a good

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therapeutic option for dysphagia treatment to promote airway protection. Smith et al. reported

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that adequate voluntary coughing reduces the risk of aspiration pneumonia.4 Moreover, Pitts

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et al. demonstrated the therapeutic efficacy of voluntary cough by expiratory muscle strength

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training on swallowing function in patients with Parkinson’s disease.19

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would like to establish the effect of voluntary coughing exercises in stroke patients with

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dysphagia.

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Study Limitations

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A selection bias existed in our study design because we enrolled patients who were able to

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conduct the VFSS and PCF tests. Many patients had difficulty conforming to conventional

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cough evaluation techniques using PCF. Based on these criteria, our study sample was not

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representative of the general stroke population. Moreover, several parameters of the VFSS,

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FDS, and PAS test can be subjective. And we tried to conduct the VFSS as soon as possible 13

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before patients started their swallowing therapy. However, some patients already had

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received swallowing therapy and this variable might contaminate the results. Finally, our

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study did not evaluate the occurrence of aspiration pneumonia.

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Conclusion

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In this study, characteristics and correlations were different between voluntary cough and

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swallowing functions according to the stroke lesion type. The current study has clinical value,

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as our results revealed that large amounts of pharyngeal residue correlated with weak

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voluntary cough ability in all stroke lesion groups. We also showed a discrepancy between

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two functions in brainstem lesion group. Our results suggest that voluntary coughing exercise

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could be an effective therapeutic option for dysphagia treatment to prevent future pulmonary

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complications. This approach may be applied to patients who show large amounts of

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pharyngeal residue, facial muscle weakness, and decreased swallowing reflex or silent

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aspiration.

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Pitts T, Rose MJ, Mortensen AN, et al. Coordination of cough and swallow: a metabehavioral response to aspiration. Respiratory physiology & neurobiology 2013;189:543-51. Mann G, Hankey GJ, Cameron D. Swallowing function after stroke: prognosis and prognostic factors at 6 months. Stroke; a journal of cerebral circulation 1999;30:744-8. Daniels SK, Brailey K, Priestly DH, Herrington LR, Weisberg LA, Foundas AL. Aspiration in patients with acute stroke. Archives of physical medicine and rehabilitation 1998;79:14-9. Smith Hammond CA, Goldstein LB, Zajac DJ, Gray L, Davenport PW, Bolser DC. Assessment of aspiration risk in stroke patients with quantification of voluntary cough. Neurology 2001;56:502-6. Kimura Y, Takahashi M, Wada F, Hachisuka K. Differences in the peak cough flow among stroke patients with and without dysphagia. Journal of UOEH 2013;35:9-16. Ward K, Seymour J, Steier J, et al. Acute ischaemic hemispheric stroke is associated with impairment of reflex in addition to voluntary cough. The European respiratory journal 2010;36:1383-90. Han DS, Chang YC, Lu CH, Wang TG. Comparison of disordered swallowing patterns in patients with recurrent cortical/subcortical stroke and first-time brainstem stroke. Journal of rehabilitation medicine 2005;37:189-91. Gonzalez-Fernandez M, Kleinman JT, Ky PK, Palmer JB, Hillis AE. Supratentorial regions of acute ischemia associated with clinically important swallowing disorders: a pilot study. Stroke; a journal of cerebral circulation 2008;39:3022-8. Bach JR, Saporito LR. Criteria for extubation and tracheostomy tube removal for patients with ventilatory failure. A different approach to weaning. Chest 1996;110:1566-71. Smith Hammond CA, Goldstein LB, Horner RD, et al. Predicting aspiration in patients with ischemic stroke: comparison of clinical signs and aerodynamic measures of voluntary cough. Chest 2009;135:769-77. Addington WR, Stephens RE, Gilliland KA. Assessing the laryngeal cough reflex and the risk of developing pneumonia after stroke: an interhospital comparison. Stroke; a journal of cerebral circulation 1999;30:1203-7. Bianchi C, Baiardi P, Khirani S, Cantarella G. Cough peak flow as a predictor of pulmonary morbidity in patients with dysphagia. American journal of physical medicine & rehabilitation / Association of Academic Physiatrists 2012;91:783-8. Lee SC, Kang SW, Kim MT, Kim YK, Chang WH, Im SH. Correlation between voluntary cough and laryngeal cough reflex flows in patients with traumatic brain injury. Archives of physical medicine and rehabilitation 2013;94:1580-3. Trebbia G, Lacombe M, Fermanian C, et al. Cough determinants in patients with neuromuscular disease. Respiratory physiology & neurobiology 2005;146:291-300. Palmer JB, Kuhlemeier KV, Tippett DC, Lynch C. A protocol for the videofluorographic swallowing study. Dysphagia 1993;8:209-14. Han TR, Paik NJ, Park JW. Quantifying swallowing function after stroke: A functional dysphagia scale based on videofluoroscopic studies. Archives of physical medicine and rehabilitation 2001;82:677-82. Rosenbek JC, Robbins JA, Roecker EB, Coyle JL, Wood JL. A penetration-aspiration

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scale. Dysphagia 1996;11:93-8. Galovic M, Leisi N, Muller M, et al. Lesion location predicts transient and extended risk of aspiration after supratentorial ischemic stroke. Stroke; a journal of cerebral circulation 2013;44:2760-7. Pitts T, Bolser D, Rosenbek J, Troche M, Okun MS, Sapienza C. Impact of expiratory muscle strength training on voluntary cough and swallow function in Parkinson disease. Chest 2009;135:1301-8. Pitts T, Bolser D, Rosenbek J, Troche M, Sapienza C. Voluntary cough production and swallow dysfunction in Parkinson's disease. Dysphagia 2008;23:297-301. Addington WR, Stephens RE, Widdicombe JG, Rekab K. Effect of stroke location on the laryngeal cough reflex and pneumonia risk. Cough (London, England) 2005;1:4. Ertekin C, Aydogdu I, Tarlaci S, Turman AB, Kiylioglu N. Mechanisms of dysphagia in suprabulbar palsy with lacunar infarct. Stroke; a journal of cerebral circulation 2000;31:1370-6. Addington WR, Stephens RE, Gilliland K, Miller SP. Tartaric acid-induced cough and the superior laryngeal nerve evoked potential. American journal of physical medicine & rehabilitation / Association of Academic Physiatrists 1998;77:523-6. Wang C, Saha S, Rose MJ, Davenport PW, Bolser DC. Spatiotemporal regulation of the cough motor pattern. Cough (London, England) 2009;5:12.

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ACCEPTED MANUSCRIPT Suppliers

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a. Micro Medial Ltd, PO Box 6, Rochester ME1 2AZ, UK.

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b. SPSS, Inc, 233 S Wacker Dr, 11th Fl. Chicago, IL 60606.

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ACCEPTED MANUSCRIPT Figure Legends

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Fig 1. Correlation between voluntary cough and swallowing functions. PCF showed a strong

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correlation with residue in the vallecular pouch and the piriformis sinus according to the FDS

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sub-scores. A) PCF vs PAS, B) PCF vs total score of FDS, C) PCF vs Pharyngeal residues in

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FDS sub-scores.

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ACCEPTED MANUSCRIPT Table 1. The Functional Dysphagia Scale based on Videofluoroscopic Swallowing Study Coded Value

Lip closure

Intact Inadequate None

0 5 10

10

Bolus formation

Intact Inadequate None

0 3 6

6

Residue in oral cavity

None 10% 10% - 50% 50%

0 2 4 6

6

Oral transit time

1.5s > 1.5s

Triggering of pharyngeal swallow

Normal Delayed

6

0 10

10

Normal Reduced

0 12

12

None 10% 10% - 50% 50%

0 4 8 12

12

None 10% 10% - 50% 50%

0 4 8 12

12

None 10% 10% - 50% 50%

0 4 8 12

12

Coating of pharyngeal wall after swallow

No Yes

0 10

10

Pharyngeal transit time

1.0s > 1.0s

0 4

4

EP

Residue in valleculae

TE D

Nasal penetration

AC C

Residue in pyriform sinuses

Total

3 4 5

SC 0 6

Laryngeal elevation and epiglottic closure

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Score

RI PT

Factor

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NOTE. The values are numbers

100

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Table 2. Demographic Characteristics of Patients according to the Stoke Lesion Subcortical

Brainstem

lesion

lesion

(n = 106)

(n = 84) 15.3±11.9

Cortical lesion Parameters

p-value

(n = 207)

Ischemic/hemorrhage

126/81

45/61

Gender (Male/Female)

132/75

57/49

Age (yr.)

68.5±11.7

60.1±12.8

Days from stroke onset

12.1 ± 5.6

10.1 ± 4.8

K-MMSE*

12.7±10.1

16.8±7.2

K-MBI

24.1±20.5

0.063

RI PT

5.4±7.1

47/37 50/34

68.6±10.7

SC

10.1±5.8

31.8±16.5

0.78

9.3 ± 5.1

0.531

19.3±11.2

0.02

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20.4±17.6

0.148

NOTE. The values are numbers or mean ± standard deviation.

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Abbreviations: NIHSS, national institutes of health stroke scale; K-MMSE, Korean-version of mini

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mental status examination; K-MBI, Korean-version of modified Barthel index.

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*: p<0.05 by One-way ANOVA

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Table 3. Voluntary Cough and Swallowing Function according to the Stroke Lesion Cortical

Subcortical

Brainstem

p-

(n=207)

(n=106)

(n=84)

value

210.5(197.2-223.7)

221.2(202.2-240.2)

282.2(261.5-302.8)

<0.001

4.3(4.0-4.7)

3.6(3.1-4.2)

4.9(3.9-5.5)

0.002

24.5(21.9-27.2)

25.8(22.0-29.6)

20.5(16.3-24.7)

0.170

FDS-(oral phase)*

2.7(2.2-3.3)

2.6(1.8-3.3)

0.3(-0.6 to 1.1)

<0.001

FDS-lip closure

0.1(0.0-0.2)

0.1(-0.0 to 0.2)

0.0(-0.1 to 0.1)

0.390

0.6(0.4-0.7)

0.5(0.3-0.7)

0.1(-0.2 to 0.3)

0.002

0.5(0.3-0.6)

0.4(0.2-0.6)

-0.0(-0.3 to 0.2)

0.003

FDS (total) , a, b, c

, a, b

FDS-bolus formation*

FDS-residue in oral cavity*

, a, b

, a, b, c

FDS-oral transit time*

FDS-(pharyngeal phase) FDS-triggering FDS-laryngeal

elevation

&

1.6(1.3-1.9)

1.6(1.1-2.0)

0.2(-0.3 to 0.7)

<0.001

20.7(19.0-22.3)

20.3(17.9-22.6)

19.8(17.3-22.4)

0.862

2.2(1.6-2.7)

2.03(1.3-2.8)

1.4(0.5-2.2)

0.268

8.7(8.0-9.4)

9.2(8.2-10.3)

9.0(7.9-10.1)

0.704

0.2(0.0-0.3)

0.3(0.1-0.6)

0.3(0.0-0.5)

0.504

3.0(2.5-3.5)

3.5(2.9-4.2)

3.5(2.8-4.2)

0.301

1.7(1.4-2.1)

1.2(0.7-1.8)

1.7(1.1-2.3)

0.334

4.8(4.1-5.5)

3.7(2.7-4.7)

3.9(2.9-5.0)

0.141

0.1(0.0-0.2)

0.2(0.0-0.3)

0.1(-0.1 to 0.2)

0.658

FDS-residue in vallecullae

FDS-coating wall

EP

FDS-residue in piriformis

TE D

epiglottic closure FDS-nasal penetration

AC C

FDS-pharyngeal transit time

SC

, b, c

PAS*

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PCF*

RI PT

Parameters

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NOTE. The values are adjusted mean (95% confidence interval) by age, days from stroke onset, and

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NIHSS. Abbreviations: FDS, functional dysphagia scale; PCF, peak cough flow; PAS, penetration

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aspiration scale.

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Post-hoc by Bonferroni correction

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a: p<0.017 indicating a significant difference between cortical and subcortical group

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b: p<0.017 indicating a significant difference between cortical and brainstem group

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c: p<0.017 indicating a significant difference between subcortical and brainstem group

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*: p<0.05 by ANCOVA.

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Table 4. Pairwise Correlations between Voluntary Cough and Swallowing Function in each

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Stroke Lesion Lesion of Stroke

Two test

Pearson’s correlation

p-value

coefficient

Subcortical

-0.368

0.001

PCF-FDS oral*

-0.279

0.003

PCF-FDS pharynx *

-0.344

0.003

PCF-FDS pharyngeal residues*

-0.547

0.001

PCF-PAS*

-0.288

0.001

PCF-FDS total*

-0.401

0.05

-0.156

0.08

-0.350

0.03

PCF-FDS pharyngeal residues*

-0.618

0.01

PCF-PAS*

-0.305

0.032

-0.219

0.047

-0.156

0.102

PCF-FDS pharynx

-0.180

0.084

PCF-FDS pharyngeal residues*

-0.571

0.001

PCF-PAS

-0.165

0.139

PCF-FDS pharynx*

PCF-FDS total*

TE D

PCF-FDS oral

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PCF-FDS oral

Brainstem

RI PT

PCF-FDS total*

SC

Cortical

NOTE. The values are Pearson’s correlation coefficient.

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Abbreviations: FDS, functional dysphagia scale; PCF, peak cough flow; PAS, penetration aspiration

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scale.

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*: p<0.05 by Pearson’s correlation coefficient.

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