Comparison of Laryngitis Patients With and Without Reflux
Comparison of Laryngitis Patients With and Without Reflux
This study is the first study to provide a thorough comparison between patients of chronic laryngitis with and without troublesome reflux symptoms using a bifurcated impedance-pH catheter in a large clinical sample. Data from this study indicate that these two groups of patients differ significantly from each other on most analyzed items. They constitute two distinctive entities with different pathophysiological mechanisms and responses to acid suppression therapy.
As the larynx is an organ that is exposed to many exogenous irritants, the pathogenesis of chronic laryngitis is complicated and sometimes subtle. It is difficult to differentiate RLS from laryngitis of other causes. In our study, we questioned our patients painstakingly to exclude laryngitis with definite causes, and we are confident that the chronic laryngitis of patients is truly "idiopathic." In addition, we did not want to exclude patients who might benefit from PPI therapy with negative results in any one of the above tests as there is no "gold standard" for the diagnosis of RLS, so consecutive patients with laryngeal symptoms and laryngoscopically proven laryngitis were enrolled.
The current practice to identify GERD as the cause of RLS is to detect increased acid exposure by 24-h pH monitoring with dual sensors, one placed at 5 cm above the upper margin of LES and the other around UES. However, laryngopharyngeal epithelium is far more susceptible to reflux-related injury than esophageal epithelium, thus the non-acid LPR (pH > 4), which could not be detected by pH monitoring, may also lead to damage of laryngeal mucosa. Also, there is a high frequency of artifacts in pH monitoring due to the drying of pH sensor, the accumulation of food on sensor or the interruption of electrical continuity caused by loss of contact of the electrode with mucosa. Therefore, in order to evaluate LPR accurately, it is essential to identify both acid and non-acid reflux around UES by 24-h MII-pH rather than pH monitoring. We used a new bifurcated impedance-pH catheter in order to allow esophageal pH electrode positioned 5 cm above the LES and laryngeal pH electrode positioned 0.5 cm above the UES simultaneously to assess the reflux profile of patients with chronic laryngitis. This type of bifurcated MII-pH catheter has been used in some studies to evaluate reflux in asymptomatic subjects. However, it was used to evaluate reflux in consecutive chronic laryngitis patients in a large sample in our study for the first time.
Recent studies found that the prevalence of GERD in patients with chronic "idiopathic" laryngitis or globus was more than 60% based on symptoms and 20–40% based on pH monitoring and EGD. We enrolled more patients with chronic "idiopathic" laryngitis and the results supported the above findings (56.5%, and 23.9%, respectively). However, a large proportion of patients with chronic laryngitis and troublesome reflux symptoms could not be diagnosed as GERD by 24-h monitoring and EGD. Reflux profile and response to acid suppression of these patients deserve further exploration. It would be simpler and more practical for doctors to evaluate patients according to symptoms rather than the diagnosis of GERD defined by objective exams in the daily clinical practice. We wished to replicate the situation in the generalists' office, where doctors would evaluate patients according to symptoms by the first impression. So patients in our study were classified by typical reflux symptoms rather than the diagnosis of GERD by objective exams.
Recent clinical trials and meta-analyses reported that a high-dose proton pump inhibitor is no more effective than placebo in producing improvement of extraesophageal symptoms. However, these clinical trials excluded patients with frequent reflux symptoms because of ethical and safety issues and concerns. Our results suggest that perhaps few patients without troublesome reflux symptoms suffered RLS. It is not surprising the response to long-term and aggressive acid suppression of these patients was poor. Nowadays, the diagnosis of RLS more often depends on subjective judgment rather than objective signs or exams. It is not surprising that some patients whose laryngeal symptoms were not caused by RLS would dilute the overall study population, resulting in reduced study power to detect a difference between PPI and placebo in randomized controlled trials. Our study could partly explain why PPI lack efficacy on suspected extraesophageal reflux symptoms in randomized controlled trials.
Our study has some limitations. First, it was not a placebo-controlled trial. It may have some placebo effects which would overestimate the efficacy of acid suppression on chronic laryngitis. However, the aim of our study was to compare the difference between patients with and without troublesome reflux symptoms. The comparative efficacy of PPI therapy between these two groups would be more important. Second, this study was conducted in a single centre and participants were mostly Cantonese, therefore selection and referral bias might exist and results may limit generalizability.
Chronic laryngitis is a disease in a heterogeneous condition. GERD may be just one of the causes or an aggravating factor. Patients with and without troublesome reflux symptoms may have different pathophysiological mechanisms and require different therapies. These could partly explain the discrepancy of response to acid suppression among patients with chronic laryngitis.
Discussion
This study is the first study to provide a thorough comparison between patients of chronic laryngitis with and without troublesome reflux symptoms using a bifurcated impedance-pH catheter in a large clinical sample. Data from this study indicate that these two groups of patients differ significantly from each other on most analyzed items. They constitute two distinctive entities with different pathophysiological mechanisms and responses to acid suppression therapy.
As the larynx is an organ that is exposed to many exogenous irritants, the pathogenesis of chronic laryngitis is complicated and sometimes subtle. It is difficult to differentiate RLS from laryngitis of other causes. In our study, we questioned our patients painstakingly to exclude laryngitis with definite causes, and we are confident that the chronic laryngitis of patients is truly "idiopathic." In addition, we did not want to exclude patients who might benefit from PPI therapy with negative results in any one of the above tests as there is no "gold standard" for the diagnosis of RLS, so consecutive patients with laryngeal symptoms and laryngoscopically proven laryngitis were enrolled.
The current practice to identify GERD as the cause of RLS is to detect increased acid exposure by 24-h pH monitoring with dual sensors, one placed at 5 cm above the upper margin of LES and the other around UES. However, laryngopharyngeal epithelium is far more susceptible to reflux-related injury than esophageal epithelium, thus the non-acid LPR (pH > 4), which could not be detected by pH monitoring, may also lead to damage of laryngeal mucosa. Also, there is a high frequency of artifacts in pH monitoring due to the drying of pH sensor, the accumulation of food on sensor or the interruption of electrical continuity caused by loss of contact of the electrode with mucosa. Therefore, in order to evaluate LPR accurately, it is essential to identify both acid and non-acid reflux around UES by 24-h MII-pH rather than pH monitoring. We used a new bifurcated impedance-pH catheter in order to allow esophageal pH electrode positioned 5 cm above the LES and laryngeal pH electrode positioned 0.5 cm above the UES simultaneously to assess the reflux profile of patients with chronic laryngitis. This type of bifurcated MII-pH catheter has been used in some studies to evaluate reflux in asymptomatic subjects. However, it was used to evaluate reflux in consecutive chronic laryngitis patients in a large sample in our study for the first time.
Recent studies found that the prevalence of GERD in patients with chronic "idiopathic" laryngitis or globus was more than 60% based on symptoms and 20–40% based on pH monitoring and EGD. We enrolled more patients with chronic "idiopathic" laryngitis and the results supported the above findings (56.5%, and 23.9%, respectively). However, a large proportion of patients with chronic laryngitis and troublesome reflux symptoms could not be diagnosed as GERD by 24-h monitoring and EGD. Reflux profile and response to acid suppression of these patients deserve further exploration. It would be simpler and more practical for doctors to evaluate patients according to symptoms rather than the diagnosis of GERD defined by objective exams in the daily clinical practice. We wished to replicate the situation in the generalists' office, where doctors would evaluate patients according to symptoms by the first impression. So patients in our study were classified by typical reflux symptoms rather than the diagnosis of GERD by objective exams.
Recent clinical trials and meta-analyses reported that a high-dose proton pump inhibitor is no more effective than placebo in producing improvement of extraesophageal symptoms. However, these clinical trials excluded patients with frequent reflux symptoms because of ethical and safety issues and concerns. Our results suggest that perhaps few patients without troublesome reflux symptoms suffered RLS. It is not surprising the response to long-term and aggressive acid suppression of these patients was poor. Nowadays, the diagnosis of RLS more often depends on subjective judgment rather than objective signs or exams. It is not surprising that some patients whose laryngeal symptoms were not caused by RLS would dilute the overall study population, resulting in reduced study power to detect a difference between PPI and placebo in randomized controlled trials. Our study could partly explain why PPI lack efficacy on suspected extraesophageal reflux symptoms in randomized controlled trials.
Our study has some limitations. First, it was not a placebo-controlled trial. It may have some placebo effects which would overestimate the efficacy of acid suppression on chronic laryngitis. However, the aim of our study was to compare the difference between patients with and without troublesome reflux symptoms. The comparative efficacy of PPI therapy between these two groups would be more important. Second, this study was conducted in a single centre and participants were mostly Cantonese, therefore selection and referral bias might exist and results may limit generalizability.
Chronic laryngitis is a disease in a heterogeneous condition. GERD may be just one of the causes or an aggravating factor. Patients with and without troublesome reflux symptoms may have different pathophysiological mechanisms and require different therapies. These could partly explain the discrepancy of response to acid suppression among patients with chronic laryngitis.
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