Systematic Review
Copyright ©The Author(s) 2019.
World J Clin Cases. Oct 6, 2019; 7(19): 2995-3011
Published online Oct 6, 2019. doi: 10.12998/wjcc.v7.i19.2995
Table 1 Empirical therapeutic trials
Ref.DesignELCharacteristicsOutcomesTreatment
Hanson et al[8], 1995Pros UncontrIIIbSuspected LPR (n = 141)Symptom and sign resolution: 51%4 wk omeprazole (20 mg, 1/d) and diet
Jaspersen et al[9], 1996Pros UncontrIIIbSuspected LPR (n = 21)Laryngeal sign improvement: 100%4 wk omeprazole (40 mg, 1/d)
Shaw et al[10], 1997Pros UncontrIIIbSuspected LPR (n = 96)Pre to post-score improvement: +12 wk omeprazole (20 mg/d)
Wo et al[11], 1997Pros UncontrIIIbSuspected LPR (n = 21)Pre to post-score improvement: +8 wk omeprazole (40 mg, 1/d) and diet
Metz et al[12], 1997Pros UncontrIIIbSuspected LPR (n = 10)Symptom and sign resolution: 60%4 wk omeprazole (20 mg/d)
Habermann et al[13], 1999Pros UncontrIIIbSuspected LPR (n = 29)Pre to post-score improvement: +6 wk pantoprazole (40 mg/d)
Havas et al[14], 1999Placebo RCTIbGr1: suspected LPR (n = 7)Pre to post-score improvement: +Gr1-2: 12 wk placebo/lanzoprazole (30 mg 2/d) and Diet
Gr2: suspected LPR (n = 8)
El-Serag et al[15], 2001Placebo RCTIbGr1: suspected LPR (n = 10)54% of symptom resolutionGr1-2: 12 wk placebo/lansoprazole (30 mg 2/d)
Gr2: suspected LPR (n = 10)
Langevin et al[16], 2001Placebo RCTIbGr1: suspected LPR (n = 14)Pre to post-score improvementGr1-2: 12 wk placebo/omeprazole (40 mg/d)
Gr2: suspected LPR (n = 16)
Hamdan et al[17], 2001Pros UncontrIIIbSuspected LPR (n = 22)Pre to post-score improvement: +4 wk pantoprazole (40 mg, 2/d), cisapride (20 mg, 2/d) and diet
Rodríguez-Téllez et al[18], 2002Pros UncontrIIIbSuspected LPR (n = 21)Pre to post-score improvement: +12 wk omeprazole (20 mg, 2/d)
Habermann et al[19], 2002Pros UncontrIIIbSuspected LPR (n = 24)Pre to post-score improvement: +6 wk pantoprazole (40 mg/d)
DelGaudio et al[20], 2003Pros UncontrIIIbGr1: LPR responder (n = 19)50% symptom improvement: 63%8 wk esomeprazole (40 mg 1/d) and diet
Bilgen et al[21], 2003Pros ContrIIIbGr1: suspected LPR (n = 36)Improvement of ≥ 1-point RSI and RFS: 68%24 wk lansoprozole (30 mg, 2/d) and diet
Gr2: CT (n = 23)
Garrigues et al[22], 2003Pros UncontrIIIbSuspected LPR (n = 91)Symptom improvement/resolution: 86-41%24 w omeprazole (20 mg, 2/d)
Laryngoscopic sign resolution: 83%
Beaver et al[23], 2003Pros UncontrIIIbSuspected LPR (n = 49)Pre to post-LPR sign score improvement: +16 wk lansoprazole (30 mg, 2/d) or pantoprazole (40 mg, 2/d) or Omeprazole/Rabeprazole (20 mg, 2/d)
Siupsinskiene et al[24], 2003Pros ContrIIbGr1: suspected LPR (n = 113)Symptom improvement of Gr1: 65%Gr1-2: 5 wk omeprazole (20 mg, 1-2/d) and diet
Gr2: healthy (n = 113)
Williams et al[25], 2004Pros UncontrIIIbSuspected LPR (n = 20)Improvement of ≥ 1-point level LGS: 63%12 wk omeprazole (20 mg, 3/d) and diet
Improvement of symptom score: 40%-45%
Issing et al[26], 2004Pros UncontrIIIbSuspected LPR (n = 22)Improvement of symptom score: +8 wk esomeprazole (20 mg, 2/d)
Sereg-Bahar et al[27], 2005Pros UncontrIIIbSuspected LPR (n = 43)Pre to post-RFS improvement: +18 wk esomeprazole (40 mg/d) and diet
Park et al[28], 2005Pros ContrIIbGr1: suspected LPR (n = 30)Symptom improvement (Gr1-2):68%-46%Gr1: 16 wk lansoprazole (30 mg, 2/d) and diet
Gr2: suspected (n = 30)Sign improvement (Gr1-2): 50%-18%Gr2: Omeprazole (20 mg, 2/d) and ranitidine (300 mg/d) and diet
Gr3: suspected (n = 25)Gr3: esomeprazole (40 mg, 1/d) and diet
Vaezi et al[29], 2006Placebo RCTIbGr1: suspected LPR (n = 95)Symptom resolution: 15%Gr1-2: 16 wk placebo/esomeprazole (40 mg, 2/d)
Gr2: suspected LPR (n = 50)
Dore et al[30], 2007Pros UncontrIIIbSuspected LPR (n = 266)Symptom improvement/resolution: 68%-12%12 wk rabeprazole/pantoprazole (20 mg, 2/d), and diet or esomeprazole (20 mg, 2/d) or lanzoprazole (30 mg, 2/d),
Qua et al[31], 2007Pros ContrIIIbSuspected LPR (n = 32)Gr1-2: Symptom improvement: 67%-18%8 wk lanzoprazole (30 mg, 2/d)
Gr1: GERD (n = 21)Gr1-2: LGS improvement: 86%-36%
Gr2: non-GERD (n = 11)
Oridate et al[32], 2008Pros UncontrIIIbSuspected LPR (n = 52)> 50% improvement of RSI and GERD: 50%-78%9 wk rabeprazole (20 mg/d)
Pre to post-improvement of DLS: +
Reichel et al[33], 2008Placebo RCTIbGr1: suspected LPR (n = 30)RSI improvement: 78%Gr1-2: 12 wk placebo/esomeprazole (20 mg, 2/d)
Gr2: suspected LPR (n = 28)
McGlashan et al[34], 2009Placebo RCTIbGr1: suspected LPR (n = 24)Pre to post-RSI improvementGr1-2: 24 wk placebo/gaviscon (4/d) and diet
Gr2: suspected LPR (n = 25)
Vashani et al[35], 2010Placebo RCTIbGr1: suspected LPR (n = 16)Pre to post-RSI improvement: +Gr1: 6 wk voice therapy + Omeprazole (20 mg, 2/d)
Gr2: suspected LPR (n = 16)Gr 2: Placebo (2/d)
Fass et al[36], 2010Placebo RCTIbGr1: suspected LPR (n = 24)Pre to post-symptom improvement: +Gr1-2: 12 wk placebo/esomeprazole (20 mg, 2/d) and diet
Gr1: suspected LPR (n = 17)Pre to post-RFS improvement: -
Lam et al[37], 2010Placebo RCTIbGr1: suspected LPR (n = 42)Pre to post-RSI and RFS improvement: +Gr1-2: 18 wk placebo/rabeprazole (20 mg, 2/d) and diet
Gr2: suspected LPR (n = 40)
Ezzat et al[38], 2011Placebo RCTIbGr1: suspected LPR (n = 42)RFS improvement (Gr1-2): 48%-20%Gr1-2: 8 wk pantoprazole (40 mg/d) and itopride (50 mg, 3/d)
Gr2: suspected LPR (n = 45)Pre to post-symptom improvement: +/Pantoprazole and placebo and diet
Chiba et al[39], 2011Pros UncontrIIIbSuspected LPR (n = 27)Pre to post-GERD Score improvement: +8 wk lanzoprazole (30 mg/d) or rabeprazole (10 mg/d)
Friedman et al[40], 2011RetrospectiveIVGr1: LPR (n = 73)Improvement of main complaint Gr1-2: 49%-41%24 wk PPI (20 or 40 mg, 2/d)
Gr2: suspected LPR (n = 70)Resolution of main complaint Gr 1-2: 14%-3%
Lee et al[41], 2011Pros UncontrIIIbSuspected LPR (n = 455)Reduction of > 50% of RSI: 75%12 wk rabeprazole (10/20 mg/d) and diet
Masaany et al[42], 2011Pros UncontrIIIbSuspected LPR (n = 47)Reduction of ≥ 10-point of RSI: 79%16 wk pantoprazole (40 mg, 2/d)
Naiboglu et al[43], 2011Pros UncontrIIIbSuspected LPR (n = 50)Pre to post-RSI and RFS improvement: +12 wk lansoprazole (30 mg/d) and diet
Patigaroo et al[44], 2011Pros UncontrIIIbSuspected LPR (n = 50)Pre to post-RSI and RFS improvement: +16 wk esomeprazole (20 mg, 2/d)/pantoprazole (40 mg/d)
Lansoprazole (30 mg, 2/d)
Habermann et al[45], 2012Pros UncontrIIIbSuspected LPR (n = 1044)Pre to post-RSI and RFS improvement: +12 wk pantoprazole (20 or 40 mg, 2/d)
Park et al[46], 2012Pros ControIIIbGr1: suspected LPR (n = 50)Reduction of ≥ 5-point of RSI Gr1-2:46-68%Gr1: 12 wk omeprazole (20 mg, 2/d)
Gr2: suspected LPR (n = 50)Reduction of ≥ 3-point of RFS Gr1-2:18-50%Gr2: Omeprazole + voice therapy
Becker et al[47], 2012Pros UncontrIIIbSuspected LPR (n = 30)Reduction of RSI: 20%12 wk pantoprazole (40 mg, 2/d)
Hunchaisri et al[48], 2012Pros ControIIbGr1: suspected LPR (n = 32)RSI reduction: 73%Gr1: 12 wk domperidone (10mg, 3/d) and omeprazole (20 mg, 2/d) and diet
Gr2: suspected LPR (n = 33)> 50% of RSI reduction: 67%Gr2: Omeprazole (20 mg, 2/d) and diet
Chung et al[49], 2012Pros ControIIbGr1: suspected LPR (n = 22)Pre to post-RSI and RFS improvement: +Gr1: 8 wk Lanzoprazole (30 mg/d)
Gr2: suspected LPR (n = 20)Gr2: Lanzoprazole + SGB
Oridate et al[50], 2012Pros ControIIbGr1: suspected LPR (n = 60)Pre to post-RFS improvement: -Gr 1: 4 wk rabeprazole (10 mg/d)
Gr2: suspected LPR (N=13)Gr 2: No treatment
Chun et al[51], 2013Pros ControIIbGr1: suspected LPR (n = 32)Pre to post-RSI and RFS improvement: +Gr1: 12 wk lanzoprazole (30 mg/d)
Gr2: suspected LPR (n = 29)Gr2: Lanzoprazole and itopride (50 mg 3/d)
Beech et al[52], 2013Pros UncontrIIIbSuspected LPR (n = 74)Reduction of ≥ 1-point of RSI: 71%24 wk lansoprazole (30 mg 2/d) and diet
Improvement of pre to post-VSS: +
Vailati et al[53], 2013Pros UncontrIIIbSuspected LPR (n = 22)Reduction of ≥1-point of RSI: 59%12 wk pantoprazole (40 mg, 2/d)
Lee et al[54], 2014Pros UncontrIIIbSuspected LPR (n = 180)Pre to post-RSI and RFS improvement: +12 wk lansoprazole (15 mg, 2/d) and diet
Chappity et al[55], 2014RCTIIbGr1: suspected LPR (n = 117)Pre to post-score improvement: +Gr1: 12 wk omeprazole (20 mg, 2/d) and diet
Gr2: suspected LPR (n = 117)Gr2: Diet
Wan et al[56], 2014Pros ControIIbGr1: suspected LPR (n = 35)Pre to post-RSI and RFS improvement: +4 wk esomeprazole (20 mg, 2/d) and diet
Gr2: LPR (n = 23)
Semmanaselvan et al[57], 2015Pros UncontrIIIbSuspected LPR (n = 50)Reduction of ≥ 1-point of RSI/RFS: 87%-98%12 wk rabeprazole (20 mg/d) and domperidone (30 mg/d)
Ozturan et al[58], 2016Pros ControIIbGr1: suspected LPR (n = 65)Pre to post-RSI and RFS improvement: +8 wk esomeprazole, (20 mg, 2/d) and diet
Gr2: Control (n = 35)
Gupta et al[59], 2016RetrospectiveIVSuspected LPR (n = 188)Pre to post-RSI and RFS improvement: +10 wk PPIs (2/d)
Nennstiel et al[60], 2016RetrospectiveIVGr1: LPR (n = 21)Symptom VAS improvement: 60%12 wk pantoprazole (40 mg, 2/d) and diet
Cross-sectionalGr2: suspected LPR (n = 24)
Batıoğlu-Karaaltın et al[61], 2016Pros UncontrIIIbSuspected LPR (n = 84)Reduction of ≥ 1-point of RSI/RFS: 21%-56%12 wk lansoprazole (30 mg, 2/d)
Dulery et al[62], 2016Pros UncontrIIIbSuspected LPR (n = 24)Symptom resolution: 10%8 wk esomeprazole (40 mg, 2/d)
Joshi et al[63], 2017Pros UncontrIIIbSuspected LPR (n = 100)Pre to post-RSI and RFS improvement: +24 wk omeprazole (20 mg, 2/d) and diet
Pullarat et al[64], 2017Pros UncontrIIIbSuspected LPR (n = 30)Pre to post-RSI and RFS improvement: +8 wk pantoprazole (40 mg/d)
Zalvan et al[65], 2017RetrospectiveIVGr1: suspected LPR (n = 85)Reduction of ≥ 6-points of RSI Gr1-2: 54-63%Gr1: 6 wk PPI (1 or 2/d) and diet
Gr2: suspected LPR (n = 99)Gr2: Diet
Carroll et al[66], 2017RetrospectiveIVSuspected LPR (n = 97)RSI < 13: 49%12 wk omeprazole (40 mg/d) and ranitidine (300 mg/d)
Lechien et al[67], 2018Pros UncontrIIIbSuspected LPR (n = 80)Post-therapy RSI < 13 and RFS < 7: 74%12 wk pantoprazole (20 mg, 2/d) and diet
Mozzanica et al[68], 2018Pros UncontrIIIbSuspected LPR (n = 34)Pre to post-RSI, RFS, VoiSS improvement: +8 wk omeprazole (20 mg, 2/d) and diet
Wilkie et al[69], 2018Pros ControIIbGr1: suspected LPR (n = 39)Reduction of RSI: 94%Gr1: 12 wk gaviscon advance (4/d) and diet
Gr2: suspected LPR (n = 33)Pre to post-RSI improvement: -Gr2: Gaviscon (4/d) and PPI (NA) and diet
Yang et al[70], 2018RetrospectiveIVSuspected LPR (n = 105)Reduction of ≥ 1-point of RSI: 91%8 wk PPI (40 mg/d) ± H2 blocker (300 mg/d) and diet
Kirti et al[71], 2018Pros UncontrIIIbSuspected LPR (n = 80)Unblinded RFS < 7: 95%8 wk PPI (2/d) and diet
Suzuki et al[72], 2019Pros ControIIbGr1: suspected LPR (n = 20)Pre to post-RSI, RFS improvement: +Gr1: 8 wk esomeprazole (20 mg/d)
Gr2: suspected LPR (n = 20)Gr2: 8 wk famotidine (20 mg/d)
1No statistical analysis. CT: Control; DLS: Dysmotility-like symptoms; GERD: Gastroeosophageal reflux disease; GI: Gastrointestinal; Gr: Group; LGS: Laryngitis grading system; LPR: Laryngopharyngeal reflux; PPI: Proton pump inhibitor; Pros Contr: Prospective controlled study; Pros Uncontr: Prospective uncontrolled study; RCT: Randomized controlled trial; RFS: Reflux finding score; RSI: Reflux symptom index; VAS: Visual analog scale; VoiSS: Voice symptom scale; VSS: Voice subjective score.
Table 2 Studies that identified LPRD with objective diagnostic tools
Ref.DesignELCharacteristicsOutcomesTreatment
Noordzij et al[73], 2001Placebo RCTIbGr1: LPR (n = 15); Gr2: LPR (n = 15)Pre to post-symptom improvement: +; Pre to post-sign improvement: -Gr1-2: 8 wk placebo/omeprazole (40 mg, 2/d)
Belafsky et al[74], 2001Pros UncontrIIIbLPR (n = 39)Pre to post-RSI and RFS improvement: +24 wk omeprazole/rabeprazole (20 mg, 2/d) or lansoprazole (30 mg, 2/d) and diet
Belafsky et al[75], 2002Pros UncontrIIIbLPR (n = 25)Pre to post-RSI improvement: +26 wk PPIs (2/d) and diet
Eherer et al[76], 2003Placebo RCTIbGr1: LPR (n = 7); Gr2: LPR (n = 7)Symptom/sign improvement: 80%-100%Gr1-2: 12 wk placebo/pantoprazole (40 mg, 2/d)
Steward et al[77], 2004Placebo RCTIbGr1: LPR (n = 21); Gr2: LPR (n = 21)Symptom improvement: 53%Gr1-2: 8 wk placebo/rabeprazole (20 mg 2/d) and diet
Wo et al[78], 2006Placebo RCTIbGr1: LPR (n = 19); Gr2: LPR (n = 20)Symptom improvement: 40%Gr1-2: 12 wk placebo/pantoprazole (40 mg/d)
Jin et al[79], 2008Pros UncontrIIIbLPR (n = 40)Pre to post-RSI and RFS improvement: +20 wk lansoprazole (30 mg/d) and mosapride (5 mg, 3/d) or levosulpride (25 mg, 3/d)
Friedman et al[40], 2011RetrospectiveIVGr1: LPR (n = 73); Gr2: suspected LPR (n = 70)Improvement of main complaint Gr1-2: 49%-41%; Resolution of main complaint Gr 1-2: 14%-3%24 wk PPI (20 or 40 mg, 2/d) and diet
Lien et al[80], 2013Pros ContrIIIbGr1: GERD and LPR (n = 65); Gr2: LPR (n = 42)Reduction of > 50% of RSI (Gr1-2): 63%-17%12 wk esomeprazole (40 mg, 2/d) and diet
Wan et al[56], 2014Pros ContrIIbGr1: suspected LPR (n = 35); Gr2: LPR (n = 23)Pre to post-RSI and RFS improvement: +4 wk esomeprazole (20 mg, 2/d) and diet
Waxman et al[81], 2014RetrospectiveIVLPR (n = 43)Reduction of ≥ 1-point of RSI: 67%4 wk omeprazole (40 mg, 2/d)
Nennstiel et al[60], 2016RetrospectiveIVGr1: LPR (n = 21); Gr2: suspected LPR (n = 24)Symptom VAS improvement: 60%12 wk pantoprazole (40mg, 2/d) and diet
Cross-sectional
Tseng et al[82], 2018Placebo RCTIbGr1: LPR (n = 39); Gr2: LPR (n = 40)Pre to post-RSI and RFS improvement: +Gr1-2: 8 wk alginate/placebo and diet
Agrawal et al[83], 2018Pros UncontrIIIbLPR (n = 33)Reduction of > 50% of RSI: 45%8-12 wk omeprazole and diet
GERD: Gastroeosophageal reflux disease; Gr: Group; LPR: Laryngopharyngeal reflux; PPI: Proton pump inhibitor; Pros Contr: Prospective controlled study; PROS Uncontr: Prospective uncontrolled study; RCT: Randomized controlled trial; RFS: Reflux finding score; RSI: Reflux symptom index; VAS: Visual analog scale.
Table 3 Proton pump inhibitor therapeutic schemes used in the current literature
Drugs and durationStudy numbers
4-5 wk
Omeprazole 40mg 1/d1
Omeprazole 20mg 1/d3
Omeprazole 40mg 2/d1
Esomeprazole 20mg 2/d2
Rabeprazole 10mg 1/d1
6-7 wk
Pantoprazole 40mg 2/d1
Pantoprazole 40mg 1/d2
Lansoprazole 30mg 2/d1
Omeprazole 20mg 2/d2
8-9 wk
Omeprazole 40mg 1/d1
Omeprazole 20mg 2/d1
Omeprazole 40mg 2/d1
Esomeprazole 40mg 2/d1
Esomeprazole 40mg 1/d2
Esomeprazole 20mg 2/d2
Esomeprazole 20mg 1/d1
Lansoprazole 30mg 2/d1
Lansoprazole 30mg 1/d2
Rabeprazole 20mg 1/d1
Rabeprazole 20mg 2/d1
Rabeprazole 10mg 1/d1
Pantoprazole 40mg 1/d2
12 wk
Omeprazole 40mg 1/d1
Omeprazole 20mg 3/d1
Omeprazole 20mg 2/d4
Omeprazole 20mg 1/d1
Esomeprazole 20mg 2/d3
Esomeprazole 40mg 2/d1
Lansoprazole 30mg 2/d4
Lansoprazole 15mg 2/d1
Rabeprazole 20mg 2/d1
Rabeprazole 10mg 1/d1
Pantoprazole 20 mg 2/d3
Pantoprazole 40 mg 1/d1
Pantoprazole 40 mg 2/d6
16-20 wk
Lansoprazole 30 mg 2/d2
Esomeprazole 40 mg 2/d1
Esomeprazole 40 mg 1/d1
Esomeprazole 20 mg 2/d1
Rabeprazole 20 mg 2/d1
Pantoprazole 40 mg 2/d1
Pantoprazole 40 mg 1/d1
24 wk
Omeprazole 20 mg 2/d2
Omeprazole 20 mg 1/d1
Lansoprazole 30 mg 2/d3
Table 4 Composite treatments used in the current literature
Drugs and durationStudy numbers
PPIs and antihistamines
Omeprazole 20 mg 2/d and Ranitidine 300 mg/d (16 wk)1
Omeprazole 40 mg/d and Ranitidine 300 mg/d (12 wk)1
PPIs 40 mg/d and antihistamine 300 mg/d (8 wk)1
PPIs and gastroprokinetic
Pantoprazole 40 mg 2/d and Cisapride 20 mg 2/d (4 wk)1
Pantoprazole 40 mg 1/d and Itopride 50 mg 3/d (8 wk)1
Omeprazole 20 mg 2/d and Domperidone 10 mg 3/d (12 wk)1
Lansoprazole 30 mg 1/d and Itopride 50 mg 3/d (12 wk)1
Rabeprazole 20 mg/d and Domperidone 30 mg/d (12 wk)1
Lansoprazole 30 mg 1/d and Mosapride 5 mg 3/d (20 wk)1
PPIs and alginate
PPIs (NA) and gaviscon 4/d (12 wk)1
Aligante 3-4/d (8 wk)1
Other
Famotidine 20 mg 1/d (8 wk)1
Gaviscon 4/d (24 wk)1
Gaviscon 4/d (12 wk)1
NA: Not available; PPIs: Proton pump inhibitors.