A recent study (H-C Lien et al. Clin Gastroenterol Hepatol 2020; 18: 14-66-74) adds a bit more insight into the topic of larygnpharyngeal symptoms (related blog post: Gastroestophageal Reflux Phenotypes and Where ‘Rome, Lyon, and Montreal Meet’ provides more information on treatment outcomes).
Methods: In this prospective multi-center observational study with adults aged 20-70 years, n=142 completed study), enrollment required chronic laryngitis symptoms >3 months and “laryngoscopic” signs suggestive of reflux. Subsequently, patients were examined with multiple modalities, including 24-pH testing, manometry, and Bernstein test followed by treatment with omeprazole 40 mg twice a day.
- Pathologic reflux was identified in 146/252 (58%) of those meeting inclusion criteria. Thus, approximately 40% did NOT have objective findings of reflux despite suspicion of laryngopharyngeal reflux (LPR); this is similar to other studies.
- In those with documented reflux, those with and without typical reflux symptoms had improvement in LPR with omeprazole therapy: 57% and 63% respectively; whereas, omeprazole therapy was effective in 32% in those without objective (pH probe) findings of reflux. In previous studies, reflux laryngitis response to PPIs has been similar to placebo.
My take: Typical reflux symptoms are not needed for patients with LPR to respond to PPIs. However, more than 40% of individuals with LPR do NOT have objective evidence of reflux; in this subset, response to PPI therapy is low.
Related blog posts:
A useful review (DA Katzka et al. Clin Gastroenterol Hepatol 2020; 18: 767-76) discusses the phenotypes of gastroesophageal reflux and related disorders. The authors note that consensus initiatives (Montreal, Rome, and Lyon) have looked at these disorders from different perspectives and their goal was to merge their perspectives.
Table 1 lists the major phenotypes:
- Nonerosive reflux disease
- Reflux hypersensitivity
- Functional heartburn
- Erosive esophagitis (low grade and high grade). LA grade A esophagitis “can be found in approximately 6% of asymptomatic controls”
- Barrett’s esophagus
- Reflux chest pain syndrome
- Regurgitation-dominant reflux disease: “need to differentiate from rumination and achalasia”
- Laryngopharyngeal reflux
- Chronic cough “although reflux may contribute, it is rarely the dominant pathophysiology… more amenable to GERD therapy when accompanied by typical reflux symptoms”
Figure 1 provides a model for the pathogenesis of GERD. Figure 2 describes the relationship between reflux phenotypes and PPI responsiveness:
In those with typical reflux symptoms:
- esophagitis healing 84% with PPI Rx compared to 28% with placebo (NNT =1.8)
- heartburn relief (with and without esophagitis) 56% with PPI Rx compared to 16% with placebo (NNT =4.4)
- heartburn relief without esophagitis 40% with PPI Rx compared to 13% with placebo (NNT =3.7)
- regurgitation relief (with and without esophagitis) 47% with PPI Rx compared to 30% with placebo (NNT =5.9)
In those with atypical reflux symptoms:
- chest pain relief with objective GERD 74% with PPI Rx compared to 20% with placebo (NNT =1.6) (Studies used a 50% reduction in pain as opposed to complete elimination…opens the door for a greater placebo response)
- chest pain relief without objective GERD 29% with PPI Rx compared to 23% with placebo (NNT =16.7) (Studies used a 50% reduction in pain as opposed to complete elimination…opens the door for a greater placebo response)
- chronic cough with objective GERD 33% with PPI Rx compared to 9% with placebo (NNT =4.2)
- chronic cough without objective GERD 31% with PPI Rx compared to 27% with placebo (NNT =25)
- reflux laryngitis (without heartburn, complete resolution) 15% with PPI Rx compared to 16% with placebo
- poorly-controlled asthma (without heartburn)-exacerbations per year: 2.5 with PPI Rx compared to 2.3 with placebo
- *references for this figure provided
Other useful points:
- “An exception to the de-emphasizing the relationship of GERD to an extraesophageal syndrome is with lung transplantation, which …has unique considerations…the sequelae of untreated GERD …may lead to accelerated mortality from allograft injury…data have suggested that PPIs may be effective at prolonging allograft survival.”
- The authors state that escalating PPI/antisecretory treatments for esophagitis is often effective but this approach has limited applicability for other indications and can result in overuse. “Similarly, failing to recognize the modulating effects of anxiety, hypervigilance, and visceral and central hypersensitivity on symptom severity has greatly oversimplified the problem.”
My take (borrowed in part from authors): PPIs work well for esophagitis and documented reflux; “the broad spectrum of syndromes [are] much less amenable to PPI therapy in any dose.”
Related blog posts:
Many gastroenterologists suspiciously view a diagnosis of laryngopharyngeal reflux (LPR) as assessed by an Ear, Nose, and Throat (ENT or otorhinolaryngologist) physician. This is due to a high degree of variability of these visible findings in a number of studies. A recent pediatric study reaches the same conclusion (J Pediatr 2014; 165: 479-84).
In this study, the authors recruited 52 infants in an effort to establish a reflux finding score for infants (RFS-I). This infant scale was modified based on a previous RFS developed in adults (Laryngoscope 2001; 111: 1313-7). In these infants, scored videos were evaluated by 3 pediatric ENTs, 2 adult ENTs, and 2 gastroenterology fellows.
- “laryngeal erythema/edema showed the lowest observer agreement…it is often speculated that laryngeal edema is caused by LPR, but no convincing evidence is available to support this theory.”
Bottomline: “Only moderate interobserver agreement [of the RFS-I] was reached with a highly variable intraobserver agreement…the RFS-I and flexible laryngoscopy should not be used solely to clinically assess LPR related findings of the larynx, nor to guide treatment.”
Related blog post: