Effectiveness of proton pump inhibitor in unexplained chronic cough

Hye Jung Park, Yoo Mi Park, Jie-Hyun Kim, Hye Sun Lee, Hyung Jung Kim, Chul Min Ahn, Min Kwang Byun, Hye Jung Park, Yoo Mi Park, Jie-Hyun Kim, Hye Sun Lee, Hyung Jung Kim, Chul Min Ahn, Min Kwang Byun

Abstract

Background: Current guidelines recommend that patients with unexplained chronic cough undergo empirical proton pump inhibitor (PPI) treatment, but scientific evidence for this treatment is lacking. We investigated the effectiveness and appropriate dose of PPI therapy in chronic cough.

Methods: We included 27 patients with unexplained chronic cough after excluding subjects with positive response to postnasal drip medication. Subjects were randomized to a placebo, standard, and high dose of PPI groups with blinding. The drug or placebo was administered orally for 8 weeks, and the Leicester Cough Questionnaire (LCQ) score and visual analogue scale (VAS) scores were collected.

Results: The LCQ score in the PPI group significantly improved from 0 weeks (11.4 ± 1.4) to 4 weeks (14.8 ± 1.4) and to 8 weeks (17.1 ± 1.4), whereas that in the placebo group did not improve from 0 weeks (13.7 ± 1.1) to 8 weeks (11.8 ± 1.4); the difference between the 2 groups was significant (P < 0.001). In subgroup analysis according to reflux, significant improvements in the LCQ score were observed in the PPI group regardless of reflux (P < 0.001 in the reflux group and P < 0.001 in the no reflux group, respectively; P = 0.188 between the 2 groups). In addition, improvements in LCQ and VAS scores between the standard- and high-dose PPI groups were not significantly different; however, adverse reactions were induced by only the high dose (16.7%).

Conclusions: The results of this pilot study support the empirical use of the standard dose of PPI for 8 weeks in patients suffering from unexplained chronic cough regardless of whether reflux is present.

Trial registration: ClinicalTrial.gov NCT01888549 www.clinicaltrials.gov; cris.nih.go.kr KCT0000543 cris.nih.go.kr/.

Conflict of interest statement

Competing Interests: The authors declare receipt of funding from Hanmi Pharmaceutical Co., Ltd. There are no other declarations relating to employment, consultancy, patents, products in development or marketed products. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Study flow.
Fig 1. Study flow.
PND, postnasal drip; PPI, proton pump inhibitor.
Fig 2
Fig 2
Change in LCQ (A) and VAS (B) scores according to time and group. The LCQ and VAS scores are significantly improved through 8 weeks in the PPI group, but not in the placebo group (between-group comparison: LCQ score, P < 0.001; VAS score, P = 0.063). PPI, proton pump inhibitor; LCQ, Leicester Cough Questionnaire; VAS, visual analog scale; SE, standard error. * P-value < 0.05 according to time; † P-value < 0.05 according to time between the 2 groups; obtained by linear mixed model analysis after adjustment for age, sex, hypertension, and atopy.
Fig 3
Fig 3
Change in LCQ and VAS scores according to time and reflux in the placebo group (A, B) and PPI group (C, D). Significant improvement was seen in the PPI group with and without reflux, but not in the placebo group. LCQ, Leicester Cough Questionnaire; VAS, visual analogue scale; PPI, proton pump inhibitor; SE, standard error. * P-value < 0.05 according to time; obtained by linear mixed model analysis after adjustment for age, sex, hypertension, and atopy.
Fig 4
Fig 4
Change in LCQ (A) and VAS (B) scores according to time and dose of PPI. Improvement in LCQ and VAS scores is seen in both standard- and high-dose PPI groups, and there is no difference between the standard- and high-dose PPI groups (LCQ score, P = 0.842; VAS score, P = 0.803). LCQ, Leicester Cough Questionnaire; VAS, visual analogue scale; PPI, proton pump inhibitor; SE, standard error. * P-value < 0.05 according to time; obtained by linear mixed model analysis after adjustment for age, sex, hypertension, and atopy.

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