OROPHARYNGEAL DYSPHAGIA IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE: A SYSTEMATIC REVIEW

Background: oropharyngeal dysphagia in patients with chronic obstructive pulmonary disease. Purpose: patients with Chronic Obstructive Pulmonary Disease (COPD) can be vulnerable to respiratory incompetence that may lead to swallowing impairment. A systematic review was conducted to investigate the relationship between Chronic Obstructive Pulmonary Disease and oropharyngeal dysphagia. Forty-seven articles were retrieved relating to Chronic Obstructive Pulmonary Disease and dysphagia. Each article was graded using evidence-based methodology. Only 7 articles out of the 47 addressed oropharyngeal swallowing disorders in patients with Chronic Obstructive Pulmonary Disease. This review found few studies that documented the relationship between oropharyngeal swallowing disorders and Chronic Obstructive Pulmonary Disease. There were no randomized control trials. Conclusion: although the evidence is not strong, it appears that patients with Chronic Obstructive Pulmonary Disease are prone to oropharyngeal dysphagia during exacerbations. Future studies are needed to document the prevalence of oropharyngeal dysphagia in homogeneous groups of patients with Chronic Obstructive Pulmonary Disease, and to assess the relationship between respiration and swallowing using simultaneous measures of swallowing biomechanics and respiratory function. These investigations will lead to a better understanding of the characteristics and risk factors of developing oropharyngeal dypshagia in patients with Chronic Obstructive Pulmonary Disease.

(1) Speech-Language Patologist; Department of Communicative Disorders, University of Redlands, CA, USA; Spell Desorders. (2) Speech-Language Patologist; Department of Communicative Disorders, University of Redlands, CA, USA; Degree in Bachelor of Arts with Honors in Comunicative Desorders; Ph.D., Professor and Chair.
Confl ito de interesse: Inexistente medulla 2 , and shared anatomic structures such as the mouth, pharynx and larynx. Theoretically, interruption in breathing has the potential to interfere with swallowing. Most investigations that have examined the effects of disordered respiration on swallowing have studied patients with neurologic disease [3][4][5][6][7] . These studies have examined the interaction between disordered breathing and its effect on swallowing in patients with motor neuron disease 3 , spastic cerebral palsy 5 , and Parkinson's disease 6 . Interestingly, only one study sought to compare the breathing and swallowing performance in those with neuromuscular disease and in those with respiratory failure with tracheotomy 4 . Because patients with Chronic Obstructive Pulmonary Disease (COPD) may be liable to respiratory incompetence, swallowing also may be impaired.

 INTRODUCTION
The coordinate interactions between breathing and swallowing are well known. They are linked physiologically as swallow interrupts respiration. Shared anatomic and physiologic substrates allow precise coordination of both events in tandem, and for a separation of function 1 . Shared commonalities include the location of neural control centers in the COPD is the fi fth leading cause of death in North America 8 . By 2020, the World Health Organization predicts it will be the third most diagnosed disease in the world and the fi fth most disabling 9 . COPD usually encompasses subcategories of disease such as asthma, chronic bronchitis, emphysema, and airway obstruction. If respiratory compromise secondary to COPD impacts oropharyngeal swallowing safety, then the impact on one's quality of life would be greater if eating restrictions have to be imposed.
This systematic review sought to investigate the relationship between oropharyngeal swallowing disorders and COPD. We sought to answer the following questions: (1) what is the prevalence of oropharyngeal swallowing impairment in those with COPD? (2) what are characteristics of oropharyngeal swallowing disorders in patients with COPD? (3) what are the risk factors for developing oropharyngeal swallowing disorders in patients with COPD, and (4) is there any evidence that standard medical treatments for COPD improve oropharyngeal swallowing safety?

 METHODS
A search for relevant literature in the English language between 1980 and 2008 was conducted using the following databases: PubMed, Medline, ComDis Dome, Cochrane Library, Agency for Healthcare Research and Quality, Campbell Collaboration, and the National Guideline Clearinghouse. No other limitations were placed on the search. Keywords used alone and in combination to gather relevant literature included: "respiratory disorders", "swallowing disorders", "dysphagia", "COPD" "deglutition", "gastroesophageal refl ux disease", "complications", "oxygen saturation", "medications", and "meals". Hand searches were done on the reference lists of each article retrieved for additional relevant research.
Full text versions of articles retrieved were obtained. Articles were divided into fi ve general sections: therapy/prevention, prognosis, diagnosis, differential diagnosis/symptom prevalence, and economic analysis. Each article was graded for the level of evidence using the Oxford Centre for Evidencebased Medicine's Levels of Evidence grading chart 10 ( Table 1). It was apparent that not all studies could be easily classifi ed using the numerical scale due to overlap in design criteria. Therefore, letter grades (Column 1, Table 1) were assigned. Both authors independently assigned a level of evidence grade to each article. Interobserver agreement on assignment of the level of strength among two investigators was high (Kappa=.85).

Review of subjects
The most common exclusionary criteria in the reviewed articles included those with head and neck cancer, neuromuscular disease, esophageal disease, stroke, or central nervous system pathology 8,12,13,15 . Criteria that varied between studies were the exclusion of patients with tracheostomy 8,13 , current smokers 12 , and respiratory disorders other than COPD 8 .
In 3 of the 6 studies that tested patients with COPD, subjects were referred because oropharyngeal dysphagia had been identifi ed or there was a high suspicion for its presence [13][14][15] . The remaining 3 studies did not select patients suspected of dysphagia, but did assess them for possible disorders of swallowing 8,11,12 . While most studies had similar subject exclusionary criteria, comparison across studies is diffi cult because some patients had tracheostomy 8,13 , ventilator dependency 18 , gastrostomy and nasogastric tubes 15 , lung hyperinfl ation 8 and gastroesophageal refl ux disease (GERD) 8 . In a retrospective review of 78 patients with COPD who were referred for videofl uoroscopy swallowing studies, Good-Fratturelli and colleagues documented all accompanying medical conditions such as stroke, cervical osteophytes, and other neurologic disease 13 .
Three studies either described current medication use, or used certain medications as exclusionary criteria 8,12,14 . Two of these studies allowed the use of medications such as home oxygen therapy, oral and inhaled steroid therapy, and bronchodilator therapy during testing 8,14 . Kobayashi and colleagues excluded patients taking corticosteroids 12 . Shaker and colleagues did report that patients were studied during acute exacerbations in the emergency room prior to medication use, but details on their usual medication regime were not provided 11 .

Review of procedures
Six of the 7 studies relevant to oropharyngeal swallowing and COPD used patients as subjects. Three of these 6 provided general descriptions of the swallowing impairment 8,13,15 . Two focused on specifi c abnormalities of swallowing such as cricopharyngeal dysfunction 14 and impairment of the swallowing refl ex 12 . Shaker, Li, and Ren et al.
was the only study that compared the relationship between disordered respiration (respirography) and swallow (surface electromyography) using simultaneous measures 11 . Their data focused on the timing relationships between respiratory cycles and swallowing onset, peak and offset. Three studies investigated the relationship between swallowing and respiratory exacerbations 11,12,14 . One study tested their subjects during an acute exacerbation 11 , while the other 2 studied patients who were described as prone to frequent exacerbations 12,14 .
The most commonly used test to assess swallowing was videofl uoroscopy 8,[13][14][15] . Two of these studies followed Logemann's 52 suggested protocol for performing videofl uorographic swallowing studies 13,15 . The remaining 2 studies that used videofl uoroscopy as the measurement tool varied in procedure from 1 to 3 different bolus types, amount of bolus delivered, and in bolus consistency. Whether swallowing was spontaneous or elicited by command was not noted 2 studies 8,14 . Physical examination included a general physical evaluation 8 , head and neck evaluation 14 , and an examination specifi c to the oral musculature 15 . Additional instrumental evaluations to assess swallowing function included chest radiographs 8 , cineradiographs 14 , and spot fi lms 14 . Mokhlesi, Logemann, Rademaker, Stangl, and Corbridge included a dysphagia symptom questionnaire in addition to videofl uoroscopy and chest radiographs 8 . Two investigations used alternative tools to investigate swallowing. Kobayashi and colleagues used a nasal catheter to inject distilled water into the patients' pharynx to measure swallow delay in the elicitation of the swallowing response 12 . Shaker, Li, and Ren et al. did simultaneous recording of the sEMG muscle activity associated with swallowing and the corresponding muscular activity of respiration using chest respirography 11 .
There was considerable variance in the length of the examination of swallowing function. Shaker, Li, and Ren et al. included a 40 minute baseline monitoring period that was followed by a succession of swallowing tasks for normal young and elderly control groups 11 . Tasks for normals included reaching three different levels of exertion on a stationary bicycle that were determined by increasing respiratory rates while performing thirty swallowing tasks at each level. These swallows were compared to subjects in acute exacerbation who dry swallowed spontaneously (mean=14) in the emergency room prior to receiving medications to control their exacerbation. Ten patients were then retested between one week and one month in periods of respiratory stabilization 11 .
Coelho followed 14 patients with COPD and oropharyngeal dysphagia for 18 months 15 . During this period they were given compensatory, behavioral swallowing strategies to obviate the risk of aspiration. However, details of the retesting results with videofl uoroscopy, and the progress or lack of progress in swallowing competencies were not reported in those who did not aspirate. In a retrospective chart review of patients referred for COPD and suspected dysphagia, Good-Fratturelli and colleagues analyzed data collected over a 3-year period 13 . Stein and colleagues followed 10 patients with COPD using videofl uoroscopy who underwent cricopharyngeal myotomy for restrictions of fl ow through the pharyngeal esophageal segment (PES) 14 . The exact time periods of post-operative evaluations were not reported.

Conclusions
Six of the 7 studies documented some type of disordered swallowing in patients with COPD 8,11-15 . This is not surprising since most of these studies examined patients who were identifi ed as at risk for, or had overt signs of oropharyngeal swallowing dysfunction. Of the 78 patients studied retrospectively, Good-Fratturelli and colleagues found that 85% had oropharyngeal swallowing dysfunction 13 . The most common types of swallowing problems in their sample were oral, vallecular, and piriform sinus stasis, and a delayed swallowing response. Fortytwo percent of these patients aspirated. Coelho described similar problems with stasis in the oral and pharyngeal stages in 14 patients with COPD and suspected dysphagia 15 . In his sample, 21% of patients consistently aspirated on videofl uoroscopic examination. Mokhlesi and colleagues did not fi nd any events of aspiration in 20 patients with stable COPD who were not selected because of potential risk for dysphagia 8 . None of the patients in this series showed signs of aspiration; although compared to normals, almost half performed compensatory airway closure maneuvers. They also found a trend toward lower laryngeal resting position, and a signifi cantly lower mid-swallow laryngeal elevation in patients with COPD compared to healthy control subjects. Kobayashi and colleagues found that 22 of the 25 patients who were prone to exacerbations had delayed, and more prolonged swallowing responses; a fi nding not evident in those with stable COPD 12 . Stein, Williams, Grossman, Weinberg, and Zuckerbraun found cricopharyngeal dysfunction in 20 of 22 patients 14 . Older patients with more severe achalasia usually had poor lung function. Of the 10 patients who underwent myotomy, all 10 had improved cricopharyngeal function on postoperative videofl uorographic studies. Respiratory-related symptoms such as wheezing and coughing showed little improvement, and 6 patients failed to show any improvement on pulmonary function tests. Shaker, Li, and Ren et al.compared the respiratory and swallowing patterns in healthy young and elderly subjects to those with stable COPD in exacerbations and in stability 11 . They found that while rates of swallow were similar in all groups, the respiratory rates of both COPD groups were signifi cantly higher. The respiratory phase interrupted by swallow in both groups of COPD patients was signifi cantly different than controls. Patients with COPD were more likely to interrupt the inspiratory phase of respiration with swallowing and resume respiration with inspiration, rather than with expiration as seen in the normal controls.
What is the prevalence of oropharyngeal swallowing impairment in those patients with COPD? We could fi nd no study that documented the prevalence of oropharyngeal dysphagia in patients with COPD. What are the characteristics of oropharyngeal swallowing disorders in patients with COPD? Six studies described the characteristics of the oropharyngeal swallow in patients with COPD 8,[11][12][13][14][15] . What are the risk factors for developing oropharyngeal dysphagia in patients with COPD? Although the evidence is not strong, there is some indication that patients with COPD are more prone to oropharyngeal dysphagia during period of acute exacerbation. Is there any evidence that standard medical treatment for COPD improves oropharyngeal swallowing? We could fi nd no studies that sought to answer this question.
COPD has a high prevalence in the population, and the number of those predicted to develop this disease with accompanying disability continues to rise world-wide. Because it is a disease of the cardiopulmonary system, and because respiratory decompensation may affect swallowing, it may be important to know how COPD affects swallowing safety. An incompetent swallow accompanied by pulmonary aspiration may actually be a precipitator of respiratory exacerbation in patients with COPD. Or exacerbations of COPD may be the precursor to swallowing disability and further decompensation of respiratory function leading to increased mortality.
This systematic review has shown that little is known about the relationship between COPD and oropharyngeal swallowing disability. It also has shown that comparisons of studies that have investigated COPD and oropharyngeal swallowing are diffi cult to compare due to differences in subject selection (particularly co-morbid diagnoses), poor control for medications, and lack of pulmonary function test (PFT) data on subjects enrolled in states of exacerbation (disease severity). Only in one study of the 7 reviewed was the diagnosis of COPD defi ned by universal guidelines 53 using PFT test data 8 . Studies that focused on COPD and swallowing disorders were at evidence level B and lower. Design fl aws in level B studies such as poor subject selection criteria make generalization to the population of interest diffi cult.
Although this systematic review did not concentrate on the data pertaining to the prevalence of COPD and GERD, it is important not to ignore the high prevalence of GERD in this population as a concomitant contributor to oropharyngeal swallowing complaints 54,55 , and as an exacerbating factor in respiratory decompensation 14,30,[32][33][34]41,47 .
Future investigations into the relationship of COPD and oropharyngeal dysphagia need to focus on who may be at risk for developing dysphagia and its attendant complications. Parallel investigations should explore the question of whether undetected oropharyngeal dysphagia contributes to new exacerbations. Studies that explore the relationship between breathing and swallowing using simultaneous measures of swallow and respiration in homogenous groups of patients with COPD are particularly necessary. The use of manofl uorgraphy 56 in combination with the respiratory patterns associated with swallow will help delineate the relationships between structural displacements and the accompanying changes in pressure. Measurements of pressure are particularly important in delineating the pathophysiology of the pharyngoesophageal segment which may play a crucial role in the understanding of oropharyngeal dysphagia in patients with COPD. Finally, investigations that are designed to predict which factors of pulmonary function might precipitate oropharyngeal dysphagia and airway compromise are needed.

 CONCLUSION
Although the evidence is not strong, it appears that patients with COPD are prone to oropharyngeal dysphagia during exacerbations. Future studies are needed to document the prevalence of oropharyngeal dysphagia in homogeneous groups of patients with COPD, and to assess the relationship between respiration and swallowing using simultaneous measures of swallowing biomechanics and respiratory function. These investigations will lead to a better understanding of the characteristics and risk factors of developing oropharyngeal dypshagia in patients with COPD.