The retrograde movement of stomach contents into the esophagus, larynx, and pharynx, known as laryngopharyngeal reflux (LPR), is thought to be an extraesophageal symptom of gastroesophageal reflux disease (GERD), causing tissue damage in these regions and symptomatizing as odynophagia, pharyngeal globus, throat clearing, dysphonia, dry cough, and laryngospasm crisis [12]. It became to be significant and increasingly common disease seen by an otolaryngologist, with an estimated range from 18 to 80% [13].
The mean age of the studied participants was 37.56 ± 9.51 years and ranged from 18 up to 60 years. In agreement with our study, Gaber et al. [10], Patigaroo et al. [14], Mosli et al. [15] found that the mean age of the LPR cases was 38, 40.1 ± 11.8 and 43 ±16 years, respectively.
It is well known that advancing age has been inconsistently associated with an increased risk for GERD symptoms. In a meta-analysis, the summary odds ratio for 50 years or more versus less than 50 years of age was 1.32 [16]. In our study, we only included GERD cases who attended our clinic before starting any treatment; this explains the younger age at the time of GERD diagnosis among our studied participants.
No sex predilection was found in our study among studied GERD cases, as 38 (47.5%) were males and 42 (52.5%) were females out of 80 studied GERD cases. In line with our research, Gaber et al. reported that 50% of the studied cases were males with a male to female ratio of 1:1 [10]. Also, in line with our study, GERD symptoms are not associated with sex in North America or Europe, but in South America and the Middle East, women are almost 40% more likely to report GERD symptoms than males [16].
The manifestations of GERD were divided into esophageal and extraesophageal disorders, and the association between laryngopharyngeal reflux disease (LPR) and GERD has been established according to the Montreal Consensus Conference [17]. In this current study, in order to determine the prevalence of laryngeal reflux in GERD cases, all studied participants were evaluated by laryngoscopic examination using the Reflux Finding Score (RFS). RFS is an 8-item clinical severity scale that depends on the fiberoptic laryngoscopy findings. The scale ranges from 0 which means no abnormal findings to 26 which is the worst possible score.
Also, complaints of GERD patients were evaluated with Reflux Symptom Index (RSI), first described by Belafsky et al., as a self-administered and validated 9-item scoring system designed to assess the symptoms related to LPR (throat clearing, excess throat mucus or postnasal drip, hoarseness, breathing difficulties, dysphagia, globus pharyngeus, coughing after eating or lying down, troublesome or annoying cough, and heartburn) [2]. An RSI score quantifies the severity of LPR symptoms on a scale of 0–5, with a total score of 45 indicating the most severe form. RSI levels above 13 are considered abnormal and suggest LPR, which is used as the diagnostic cutoff point. Farahat et al. developed an Arabic version of the RSI which was used in the current study [18].
In this study, 80 patients with confirmed GERD were examined and 70 patients (87.5%) of them were diagnosed with LPR. In line with our study, many previous studies reported a strong correlation between the two conditions (laryngopharyngeal disorders and GERD). Tauber et al. reported 69% of patients with GERD had laryngitis confirmed by inter-arytenoid edema and erythema diagnosed by laryngoscopic examination [19]. Also, a study by Vardar et al. had similar results as LPR was reported in 70% of patients diagnosed with GERD [20]; recently, Mosli et al. reported that 71% of confirmed GERD patients had LPR [15]; and lastly, Silva et al. reported that 82.8% of confirmed GERD cases had LP [12].
According to RFS, all studied participants at the baseline examination were suffering from ventricular obliteration, erythema or hyperemia, diffuse laryngeal edema, vocal fold edema, and posterior commissure hypertrophy. 61.2% suffered from subglottic edema, 44.8% suffered from granuloma or granulation, and 73.1% suffered from thick mucus endolaryngealy, and the mean RFS was about 14.12 ± 2.87 and ranged from 1 up to 21.
Other studies have also found that the most common laryngeal finding “as assessed by RFS” was found to be erythema/hyperemia like studies of Book et al., Mesallam et al., Karkos et al., Toros et al., Patigaroo et al., and Osman et al. [13, 14, 21,22,23,24]. Also, other authors have noted that the most common laryngoscopic signs are posterior commissure hypertrophy as by Belafsky et al. and partial ventricular obliteration as by Tezer et al. [11, 25].
After 3 months of gastric reflux treatment with PPIs, significant improvement was noticed in all abovementioned findings (P<0.001 for all) except for ventricular obliteration, erythema or hyperemia, vocal fold edema, diffuse laryngeal edema, and posterior commissure hypertrophy as 100% of the studied participants still suffered from it. However, there was a significant decrease in the mean values of the used RFS for all these items from before to after treatment (P<0.001), and the mean RFS was significantly decreased from 14.12 ± 2.87 to 7.49 ± 4.80, P<0.001.
Our study showed similar results to other studies done for the response of RFS to PPI like studies of Belafsky et al., who reported that the mean of RFS at entry was 11.5 (± 5.2 SD) and improved to 9.3 (± 4.7 SD) at 2 months, 7.3 (± 5.5 SD) at 4 months, and 6.1 (± 5.2 SD) at 6 months of treatment with PPIs [11]. Bilgen et al. reported that the RFS before the start of the therapy was 14.8±3.8 and improved significantly to 7.7±3.8 at the second month, to 4.5±2.3 at the fourth month, and to 1.4±0.9 at the sixth month of treatment with proton pump inhibitors [26]. Also, our study was supported by the recent study of Silva et al., who reported that the RFS assessment showed a reduction in the values when compared with the pre- and post-treatment with 90 days with PPI [12].
According to RSI, at baseline, the most common symptom in the study was found to be clearing throat and postnasal drip in 100% of the study population, followed by coughing after eating or lying down documented in 98.5%, sensation of something sticking in throat 97.0%, then chest pain, heartburn, stomach acid coming up, or indigestion documented in 83.6%; the mean RSI was 19.84 ± 4.96 and ranged from 14 up to 32.
In line with our results, Toros et al. found frequent clearing of the throat as the most common symptom [24], while some studies have found other most common symptoms of LPR like the study of Patigaroo et al. who found the most common symptom to be globus sensation in 74% of patients followed by the frequent clearing of the throat in 64% of patients and annoying coughing in 56% of the study population and the least common symptom was breathing difficulties [14]. Studies of Issing et al., Mesallam et al., Karkos et al., and Osman et al. also found that the most common symptom like our study was globus pharyngeus [13, 22, 23, 27].
After 3 months of gastric reflux treatment with PPIs, we observed significant improvement in all laryngopharyngeal reflux symptoms “as assessed by RSI” except hoarseness of voice and breathing difficulty. However, there was a significant decrease in the mean values of the used RSI for hoarseness of voice, but not for breathing difficulty, which was still a problem facing our patients, from before to after treatment (P<0.001), and the mean RSI was significantly decreased from 19.84 ± 4.96 to 11.94 ± 10.61, P<0.001.
Similar results were obtained in other studies like the study by Belafsky et al. who reported that the mean RSI of LPR patients improved from 21.2 ± 10.7 to 12.8 ± 10.0 after 6 months of treatment with PPI [2]. Also, the study of Patigaroo et al. reported that the mean of RSI before treatment for all patients was 24.75, and after 8 weeks of treatment with PPI, it decreased to 13.5 and after 16 weeks dropped to 13.25 [14]. Osman et al. reported reflux symptoms markedly improved at the end of 2 months and 6 months of PPI therapy with significant [13]. Also, our study was supported by the recent study of Silva et al. who reported that the RSI assessment showed a decrease in the values when compared to the pre- and post-treatment values with PPI for 3 months (p <0.001) [12].
We reported a 22.4% resistance rate among our studied participants. Some studied patients still have persistent signs, as 100.0% still have erythema or hyperemia, vocal fold edema, diffuse laryngeal edema, and posterior commissure hypertrophy; 22.4% still have ventricular obliteration; 19.4% still have subglottic edema; 17.9% still have thick mucus endolaryngealy; and three cases (4.5%) still have granuloma. Persistent symptoms such as throat cleaning in 86.6%, 82.1% still suffering from hoarseness of voice, 67.1% from postnasal drip, 67.2% from globus pharyngeus, 61.2% from heartburn, 53.7% from difficult swallowing, 52.2% from coughing post-prandial or on lying down or annoying cough, and 49.3% still suffering from breathing difficulties were still detected 3 months post-PPI therapy.
Osman et al.’s study detected the persistence of some of the presenting signs after still 6 months post-therapy: partial ventricular obliteration was still detected in 8 (13.1%) of included patients, mild vocal fold edema in 10 (16.4%) of patients, mild laryngeal edema in 7 (11.5%) of patients, and granuloma in 6 (9.8%) of them [13].
On the other hand, other studies show higher response rates like studies of Jaspersen et al. and Patigaroo et al. which demonstrated completely (100%) symptom-free patients after treatment with 40 mg omeprazole per day, and Kamel et al. found the response rate was 92% [14, 28, 29].
The difference between this study and the previously mentioned studies leads us to question the duration of treatment, which in the present study led to a discrete reduction in the overall sum of the RFS from 14.12 to 7.49 and RSI from 19.84 to 11.94. Perhaps a longer follow-up time could change the profile of these scores since our follow-up was of only 3 months. Also, it is well known that unlike GERD, response to PPI in patients with LPR has been described to be highly variable. This may be due to that LPR require prolonged and more aggressive therapy, which may last for several months, than GERD [30]. This finding was confirmed by Belafsky et al. in 2001 and 2002 who found a more improvement in the scores of individuals treated with PPIs for 6 months, double the time used in our study [2, 11].
One of the limitations of our study was the small sample size, so larger prospective studies are needed to confirm the role of PPI in controlling the laryngeal disorders associated with GERD disease and evaluate its long-term side effects. Another limitation of our study may be the subjectivity of RFS, as these signs can be present in up to 86% of asymptomatic subjects, because both the interobserver and interobserver reproducibility of laryngeal signs due to LPR is poor, which may lead to overdiagnosis of laryngopharyngeal reflux; evaluation of the patients by two examiners is needed. There is a vital need for the implementation of RSI and RFS in daily use to decrease time consumption and expensive examinations for patients and to help in early diagnosis of LPR with a subsequent decrease in serious complications such as laryngeal granuloma, subglottic stenosis, and laryngeal cancer.
