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tically significant better improvement was noted for PPI-
treated patients. In our opinion, it is not surprising that in
this study laryngeal signs of LPR showed no stronger im-
provement in PPI recipients compared to control within two
months, as the physical findings of LPR improve more
slowly than the symptoms In our study we could also find
no statistically significant difference in the laryngeal ap-
pearance (reflected by the total RFS) between the esome-
prazole and placebo group after a short treatment period of
six weeks . Another critical point for the men-
tioned study is the fact that patients were not instructed on
when to take the medication. This could have seriously
affected the results of this study. In a randomized, double-
blind, placebo-controlled trial, Wo et al evaluated the effi-
cacy of single-dose pantoprazole 40 mg for 12 weeks in
newly diagnosed LPR The response was similar between
the pantoprazole and placebo group. As 60% of the study
subjects had additional abnormal distal esophageal reflux
and the single-dose PPI was not sufficient to reach a pH-
documented measurable suppression of hypopharyngeal
acid reflux, the results of this study are not adequately
comparable to those of our study with a double-dose PPI
design. Noordzij et al performed another prospective, pla-
cebo-controlled, randomized, and double-blind study to de-
termine the efficacy of 40 mg omeprazole twice daily for
two months in the treatment of LPR The authors could
demonstrate a significant improvement of a composite la-
ryngeal symptom score in the omeprazole group but not the
placebo group. Again, the endoscopic laryngeal signs did
not change significantly over the course of the study for
either treatment group. As mentioned above, the two-month
follow-up period may not have been sufficient to detect
changes in laryngeal appearance. Another study investigat-
ing the therapeutic benefit of lansoprazole 30 mg twice daily
for treating LPR, by El-Serag et al, provided evidence that
lansoprazole therapy for three months achieved significantly
better symptomatic response than placebo Due to a se-
lected referral study population with a high likelihood of
GERD, the authors suggested not to generalize their results
to patients with LPR in a primary care setting.
The analysis of the respective RFS subscores in our
study revealed a highly significant reduction of posterior
commissure hypertrophy in the esomeprazole but not in the
placebo group after a treatment period of 12 weeks (P
0.01). This laryngeal sign is supposed to be one of the
mucosal alterations most related to LPR The fact that the
most significant difference in laryngeal appearance between
the two study groups after 12 weeks could be detected in
this special area in our opinion strongly indicates the effi-
cacy of a PPI treatment in patients with symptoms and signs
associated with LPR. The improvement of posterior com-
missure hypertrophy was not significantly better in the es-
omeprazole group compared to control at the first follow-
up. This result underlines the importance of a PPI treatment
for at least three months in patients with suspected LPR.
Another striking result was that we found heartburn to be
the only RSI subscore with a statistically significant differ-
ence in improvement between the two study groups after
both six weeks and three months. This finding, in our
opinion, clearly demonstrates that PPI therapy has achieved
an earlier and stronger reduction of distal reflux episodes
potentially causing heartburn compared to placebo. This
result also reflects the well-known fact that esophagitis
caused by reflux shows an earlier resonse to PPI treatment
than reflux-induced laryngitis
Several issues should be addressed. As we did not ran-
domize our otolaryngologic evaluations performed by only
one examiner, the term double-blind can only be used to
describe the medication randomization. Another critical as-
pect of our trial may be the fact that we did not perform
24-hour pH monitoring to diagnose LPR objectively before
patient inclusion. According to reports of other authors,
patient tolerance is poor for this procedure As such, we
decided to assess LPR-related symptoms and signs alone
with the use of RSI and RFS. Moreover, Vaezi et al, in the
above-mentioned study, found that only a small proportion
of their patients undergoing pH monitoring had documented
pharyngeal acid exposure despite typical LPR symptoms
and laryngoscopic signs From this finding they concluded
that sensitivity of pH monitoring for detection of proximal
esophageal or hypopharyngeal reflux episodes might not be
more than 50% Another argument against performing pH
monitoring before inclusion was the fact that more and more
authors doubt that 24-hour pH monitoring, although sup-
posed to be the gold-standard test for LPR, is the preferable
initial step in the work-up of most patients with LPR
A third limitation of our study might be the short follow-up
of 12 weeks. The significance of our study results probably
would have been higher after a treatment period of six
months. However, only Vaezi et al performed a trial with a
follow-up of more than three months Another critical
aspect might be the dose of esomeprazole used (20 mg). It
can be hypothesized that the differences in RSI and RFS
improvement between the study groups would have been
even more significant with a dose of 40 mg twice daily. This
is the dose generally recommended for treating LPR How-
ever, we chose a dose of 20 mg esomeprazole twice daily as
many institutions and general practitioners in Germany pre-
fer to start with the lower dose. Nevertheless, we suppose
our results clearly demonstrate a therapeutic effect of PPI
treatment for LPR-related symptoms and signs. This esti-
mation is confirmed by the subjective opinion of our study
patients concerning the drug effect, with only 42% of pla-
cebo recipients and more than 78% of the esomeprazole
group being free of symptoms (P 0.006).
CONCLUSION
Especially during the first weeks of PPI therapy, a signifi-
cant placebo effect appears to exist in the treatment of
LPR-related symptoms. However, compared to placebo,
Reichel et al Double-blind, placebo-controlled trial with . . .
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