TABLE 1

Studies of gastro-oesophageal reflux treatment in asthma

First author [ref]
Study type
nTreatmentAsthma symptomsExacerbationsFEV1Other outcomes
H2RAs
 Goodall [46]
RCT crossover
18Cimetidine 200 mg 5 times a day for 6 weeksImprovement in nocturnal asthma symptom scoreN/AUnchangedImprovement in evening PEFR
 Nagel [47]
RCT crossover
14Ranitidine 400 mg four times daily for 1 weekN/AN/AUnchangedNo change in use of asthma medications
 Ekstrom [48]
RCT crossover
48Ranitidine 150 mg twice daily for 4 weeksImprovement in nocturnal asthma symptom scoreN/AUnchangedN/A
 Larrain [49]
RCT placebo or surgery parallel
27Cimetidine 300 mg four times daily for 6 monthsN/AN/AMinor improvement in FEV1 after 6 monthsN/A
PPIs
 Meier
RCT crossover [50]
15Omeprazole 20 mg twice daily for 6 weeksN/AN/A27% asthma patients with GORD had a ≥20% net improvement in FEV1 after treatmentN/A
 Teichtahl [51]
RCT crossover
20Omeprazole 40 mg once daily for 4 weeks versus placeboUnchangedN/AN/AImprovement in evening but not morning PEFR;
improved reflux symptoms
 Harding [52]
RCT crossover
30Omeprazole 20–60 mg four times daily for 12 weeksImprovedN/AImproved FEV1 and FVCImproved PEFR;
improved reflux symptoms
 Levin [16]
RCT crossover
9Omeprazole 20 mg once daily for 8 weeksImprovedN/ATrend toward higher FEV1 (mean difference 15.6%)Improved Asthma Quality of Life Score (AQLS) including sutwice dailyomains of activity limitation, symptoms and emotions
 Boeree [53]
RCT crossover
36Omeprazole 40 mg b for 12 weeks versus placeboUnchangedN/AUnchangedImproved reflux symptom scores and proportion of time with pH<4;
no effect on peak flow or reversibility
 Kiljander [54, 55]
RCT crossover
107Omeprazole 40 mg once daily for 8 weeks versus placeboImproved nocturnal asthma symptomsN/AImprovedNo effect on peak flow;
18 (35%) patients had improved pulmonary symptom scores while receiving omeprazole
 Tsugeno [56]
Prospective observational
Rabeprazole 20 mg once daily for 8 weeksUnchangedN/AN/AImproved PEFR;
improved reflux symptoms
 Jiang [57]
RCT
30Omeprazole 20 mg once daily plus domperidone 10 mg three times daily for 6 weeks versus usual careN/AN/AImprovedImproved PEFR and bronchial hyperresponsiveness
 Littner [58]
RCT
207Lansoprazole 30 mg once daily for 24 weeks versus placeboUnchangedN/AUnchangedImproved AQLS emotional function;
no change in PEFR or use of asthma rescue medications
 Stordal [59]
RCT
38Omeprazole 20 mg for 12 weeks versus placeboUnchangedN/AUnchangedImproved quality of life;
improved reflux scores on pH;
no change in asthma rescue medications
 Shimizu [60]
RCT
30Lansoprazole 30 mg·day−1 for 8 weeks versus roxatidine (H2RA), 150 mg·day−1ImprovedN/AUnchangedImproved peak flow and ACQ score
 Kiljander [61]
RCT
770Esomeprazole 40 mg twice daily versus placebo for 16 weeksUnchangedN/AUnchangedImproved PEFR in patients with GORD and nocturnal symptoms only;
no safety concerns noted
 Wong [62]
Prospective observational
30Lansoprazole 30 mg once dailyImprovedN/AUnchangedNo effect on PEFR;
improved pulmonary symptom scores
 Sharma [63]
RCT
Omeprazole 20 mg twice daily plus domperidone 10 mg three times daily versus placebo for 16 weeksImproved day and night-time symptom scoresN/AImproved FEV1 and FVCImproved reflux symptom scores;
improved PEFR;
reduction in asthma rescue medications
 Khorasani [64]
RCT
Adolescents
36Omeprazole 20 mg twice daily for 6 weeks versus placeboN/AN/AImproved FEV1 and FVCImproved reflux symptoms
 Mastronarde [65]
RCT
412Esomeprazole 40 mg twice daily for 24 weeks versus placeboUnchangedN/AUnchangedNo effect on airway reactivity, asthma control, asthma symptom scores, nocturnal awakening or quality of life;
no increase in adverse events compared to placebo
 Bucknall [66]
Prospective observational
51Omeprazole up to 80 mg dailyN/AN/AN/AImproved GORD symptoms and pH readings with increased therapy dose
 Kiljander [67]
RCT
828Esomeprazole 40 mg once/twice daily for 26 weeksUnchangedN/AImproved FEV1 in 40 mg TWICE DAILY group after 26 weeks compared to controlNo effect on PEFR;
improved AQLS score in both treatment groups compared to control
 Adamko [68]
Infants
RCT
19Combined omeprazole 10 mgonce daily plus bethanacol versus either treatment alone versus placeboImproved daytime coughing and respiratory symptom scoresN/AN/AImproved GORD symptoms and GORD measured by pH;
no adverse events noted
 Holbrook [69]
Children
RCT
306Lansoprazole 15 mg·day−1 if <30 kg or 30 mg·day−1 if ≥30 kg versus placeboImprovedN/AUnchangedImproved ACQ score but no effect on asthma-related quality of life or rates of episodes of poor asthma control;
in the subgroup with a positive pH study, no treatment effect was observed for any asthma outcome;
increased respiratory infections noted in treatment group
 Sandur [70]
Prospective observational
28Omeprazole 40 mgonce daily for 3 months; increased to 60 mgonce daily at 2 months if pH study remained abnormalImproved pulmonary symptom and night-time asthma symptom scoresN/AImproved FEV1Improved reflux symptom score and peak flow readings
 Yamaji [71]
RCT
60Omeprazole 10 mgonce daily plus mosapride 5 mg three times daily versus omeprazole alone for 4 weeksN/AN/AN/ANo additional amelioration of GORD symptoms when combined
Surgery
 Perrin-Fayolle [73]
Prospective observational
44Nissen fundoplicationImprovedN/AN/APulmonary improvement classified as total cure 25%, marked improvement 16%, moderate improvement 25%, no improvement 34%
95% long-term improved reflux symptoms
 Larrain [49]
RCT
26Nissen fundoplicationImprovedN/AN/AClinical improvement and reduced use of asthma rescue medications
 Spivak [74]
Prospective observational
39Nissen fundoplication (median follow-up 2.7 years)ImprovedN/AN/AImproved asthma scores;
reduction in use of systemic steroids
 Ekstrom [75]
Prospective observational
13Transabdominal/ laparoscopic fundoplicationN/AN/AUnchangedN/A
 Sontag [76]
RCT
62Antacids p.r.n. versus ranitidine 150 mg three times daily versus Nissen fundoplication for follow-up of 2 yearsSurgery improves asthma symptomsN/AUnchangedNo effect of PEFR, rescue medications or survival
 Khoshoo [77]
Children
Prospective observational
18Medical treatment
(lifestyle changes, proton pump inhibitors and prokinetics) or surgical treatment (Nissen fundoplication)
ImprovedN/AN/AReduction in need for rescue medications
 Khoshoo [78]
Children
Prospective observational
44Esomeprazole plus metoclopraminde 10 mg three times daily versus ranitidine versus Nissen fundoplicationN/AIncreased exacerbations in ranitidine group compared to other treatment groupsN/AN/A
 Kiljander [79]
Prospective observational
69Esomeprazole 40 mg twice daily versus Nissen fundoplication after 3 monthsImproved cough and dyspnoea with both treatment groupsN/AUnchangedImproved SGRQ quality of life after fundoplication
 Silva [80]
Retrospective observational
30Nissen fundoplicationImprovedN/AN/AImprovement in daily crises of asthma
 Hu [81]
Prospective observational
137Stretta radiofrequency (n=82) or laparoscopic Nissen fundoplication (n=55)ImprovedN/AN/AImproved reflux, respiratory and ENT symptoms in both groups, better in Nissen fundoplication group at both 1 and 5 years follow-up

Abbreviations: FEV1: forced expiratory volume in 1 s; H2RAs: histamine-2 receptor antagonists; PEFR: peak expiratory flow rate; RCT: randomised controlled trial; GORD: gastro-oesophageal reflux; FVC: forced vital capacity; AQLS: Asthma Quality of Life Score; ACQ: Asthma Control Questionnaire; SGRQ: St. George's Respiratory Questionnaire; ENT: ears, nose and throat; N/A: not available.