ORIGINAL ARTICLE

Validation of a Quality-of-Life Instrument

for Laryngopharyngeal Reflux
Ricardo L. Carrau, MD; Aliaa Khidr, MD, PhD; Karen F. Gold, PhD; Joseph A. Crawley, MS;
Eric M. Hillson, PhD; Jamie A. Koufman, MD; Chris L. Pashos, PhD

Objectives: To establish the reliability, validity, and re-
sponsiveness of a new, disease-specific assessment tool,
the LPR-HRQL, which assesses patient-reported out-
comes (PRO) with regard to health-related quality of life
(HRQL) of patients with laryngopharyngeal reflux (LPR).
Design: A prospective, open-label, repeated-measures
study.
Setting: Six centers in 4 states in the eastern United States.
Patients: Patients with LPR.
(Quality of Life in Reflux and Dyspepsia), used to assess
the impact of gastroesophageal reflux disease.
Results: Factor analyses of the LPR-HRQL scales con-
firmed single dimensions for each. All LPR-HRQL items
contributed to internal consistency of scales and had sub-
stantial variability permitting useful information. Sub-
stantial evidence of convergent and divergent validity with
SF-36, VHI, and QOLRAD items was observed. Test-
retest validity was adequate for the time interval tested.
Changes in domain scores of the LPR-HRQL at 4 and 6
months documented its responsiveness.

Interventions: Open-label treatment with 20 mg of
omeprazole twice daily. Clinical and PRO HRQL data were
collected. Several PRO instruments were administered to
patients at each of several time points; these instruments
included the Medical Outcomes Study Short-Form 36-
Item Health Survey (SF-36), a general HRQL tool; the Voice
Handicap Index (VHI), a symptom-specific tool for as-
sessing voice problems; and the QOLRAD instrument
Conclusions: The LPR-HRQL displays reliability, va-
lidity, and responsiveness, has face validity, and is simple
and not burdensome to administer, score, and analyze.
Accordingly, it may be used to assist physicians and pa-
tients in understanding the HRQL burden of LPR and the
impact of therapy.
Arch Otolaryngol Head Neck Surg. 2005;131:315-320

Author Affiliations are listed at
the end of this article.
Financial Disclosure: When
this work was completed, Mr
Crawley and Dr Hillson were
employees of AstraZeneca LP;
Drs Gold and Pashos were
employees of HERQuLES,
Abt Associates Inc.
Dr Hillson is now an employee
of Centocor Inc.
T
HE CLINICAL IMPACT OF LA-
ryngopharyngeal reflux
(LPR) has recently been
confirmed in a position
statement of the American
Academy of Otolaryngology–Head and
Neck Surgery by Koufman et al,1 which out-
lines symptoms, clinical manifestations, di-
agnosis, and treatment. Laryngopharyn-
geal reflux is a gastrointestinal and
otolaryngologic condition related to, but dis-
tinct from, gastroesophageal reflux disease
(GERD). It is estimated that 4% to 10% of
patients presenting to an otolaryngology
practice have symptoms and/or findings re-
lated to LPR.2,3 Laryngopharyngeal reflux is
increasingly recognized as a probable con-
tributing factor to nonallergic asthma and
many ear, nose, and throat complaints. Stud-
ies suggest that acid reflux is present in 50%
to 80% of patients with asthma, 10% to 20%
of patients with chronic cough, up to 80%
of patients with difficult-to-manage hoarse-
ness, and 25% to 50% of patients with glo-
bus sensation.2-6
The manifestations of LPR vary con-
siderably.7 In contrast to GERD, in which
heartburn is the primary symptom, there
is no predominant sign or symptom for
LPR. Typical symptoms of LPR are chronic
but intermittent8 and may include dys-
phagia, throat clearing, hoarseness, chronic
cough, globus sensation, and laryngo-
spasm. Approximately 20% to 43% of pa-
tients with LPR experience heartburn,9 and
18% have esophagitis.10
Health-related quality of life (HRQL) has
been studied in depth for many diseases, in-
cluding gastrointestinal disorders.11-14 A va-
riety of generic and disease-specific instru-
ments have been used to measure the impact
on HRQL of GERD,15-26 and other instru-
ments have been used to evaluate the im-
pact of voice disorders.27-30 However, the
HRQL impact of LPR has only recently be-
gun to be evaluated and is not well under-

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stood.31,32 Although 1 study has compared the general HRQL
impact of LPR with that of GERD and with a general US
population,32 use of a validated disease-specific HRQL in-
strument would provide physicians, other health care pro-
viders, and patients more information on the disease-
related HRQL impact of LPR. An LPR-specific instrument
would address the HRQL domains affected by the disor-
der (ie, it would be more specific) and would be more sen-
sitive to changes in HRQL, notably those due to treat-
ment. Ultimately, such an instrument would then have
greater utility in clinical practice as well as in research into
new therapies.
Therefore, the objective of the present study was to
evaluate the reliability, validity, and responsiveness of a
new LPR-specific HRQL instrument, the LPR-HRQL,
which was designed to be self-administered by the pa-
tient. While several related symptom scales exist, the LPR-
HRQL is the first HRQL instrument to be developed spe-
cifically for LPR.
METHODS
THE INSTRUMENT
The LPR-HRQL was developed based on a literature review, pa-
tient input obtained in focus-group settings, and input from an
expert panel of physicians specializing in otolaryngology, gas-
troenterology, and pulmonology. These 3 sources provided sup-
port for an instrument that would measure symptom distress and
the important effects of LPR on social and occupational func-
tioning, vitality, well-being, and perceived health. Accordingly,
a brief 43-item questionnaire that uses Likert response scales was
constructed that may be self-administered and fulfills these broad
measurement needs. In its field-test version, the instrument had
43 items—specifically, questions about LPR and how it affects
the patient. The recall period was the last 4 weeks.
A standard 7-point Likert scale was used to assess how much
or how often each item described the feelings of the patient.
Twelve questions assessed talking, singing, and voice (Voice/
Hoarse domain) with a 13th asking how these voice issues af-
fected overall quality of life. Six questions assessed coughing
(Cough domain) with a follow-up asking how problems with
coughing affected overall quality of life. Another 6 questions
addressed clearing the throat (Clear Throat domain) with a fol-
low-up question of how problems about clearing the throat af-
fected overall quality of life. The next 5 questions assessed glo-
bus and general throat symptoms (Swallow domain) with a
follow-up about general related problems affecting overall qual-
ity of life. The final part of the instrument, consisting of ques-
tions 34 through 43, assessed the combined impact of acid re-
flux–related symptoms (Overall Impact of Acid Reflux domain).
PATIENTS
To validate the LPR-HRQL, we enrolled patients presenting with
symptoms at 6 sites in 4 states in the southern, mid-Atlantic, and
northeastern regions of the United States. Sites included 4 aca-
demic medical centers, 1 regional medical center, and a multispe-
cialty group practice, so that the study population included vari-
ous sociodemographic groups receiving care in a variety of health
care settings. Local institutional review boards at each site re-
viewed and approved the implementation of the study protocol.
Patients were all newly diagnosed as having LPR (diagno-
sis ⬍1 month before enrollment) or were patients with re-
lapse and not under current treatment; this was confirmed by
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a physician in each case by direct patient examination, as is typi-
cal practice. Each patient gave written informed consent prior
to any study procedures. Enrolled patients were between 19
and 80 years old and had at least 1 of the following symptoms
commonly associated with LPR within the previous month:
hoarseness, chronic cough (defined as cough lasting ⬎1 month),
globus, laryngospasm, chronic throat clearing, or difficulty swal-
lowing. Patients were not enrolled in the study if they mani-
fested only GERD symptoms and not LPR.
A laryngoscopic examination documenting clinical signs con-
sistent with a diagnosis of LPR was conducted within 1 month
prior to patient enrollment for all patients. Furthermore, the
presence and severity of LPR clinical signs for each patient were
assessed using the Reflux Finding Score developed by Belaf-
sky et al.33 The Reflux Finding Score facilitated evaluation of
the presence and severity of the following clinical signs: sub-
glottic edema, ventricular obliteration, arytenoid erythema, vo-
cal fold edema, diffuse laryngeal edema, posterior commis-
sure hypertrophy, granuloma and/or granulation, and
pachydermia laryngis.
Patients with cancer, major psychiatric illness, and/or un-
stable chronic illnesses (such as diabetes) were excluded to elimi-
nate comorbidities that might confound or inhibit an assess-
ment of the effect of LPR on HRQL. In addition, patients
requiring medications with known drug-drug interactions with
omeprazole were also excluded, thus further reducing the num-
ber of participants with comorbid conditions.
STUDY DESIGN
Data were collected from patients with LPR at a baseline visit
and 3 times subsequently during regularly scheduled study vis-
its. Baseline and 2-month postbaseline data were used to es-
tablish the validity and reliability of the LPR-HRQL. Data from
the 4-month and 6-month study visits were used to establish
the instrument’s responsiveness.
INSTRUMENTATION
A battery of instruments was administered to patients at base-
line and at 2, 4, and 6 months after baseline. Aside from the LPR-
HRQL, these instruments included the Medical Outcomes Study
Short-Form 36-Item Health Survey (SF-36), the Voice Handi-
cap Index (VHI), the QOLRAD instrument (Quality of Life in
Reflux and Dyspepsia), and Overall Treatment Effect (OTE) ques-
tionnaires. The SF-36, a self-administered, generic HRQL ques-
tionnaire containing 36 items, measures health in 8 multi-item
dimensions, covering functional status, well-being, and overall
evaluation of health. The reliability and validity of the SF-36 is
well documented.34,35 The 30-item VHI measures the impact of
voice problems on a person’s life.36 The QOLRAD measures the
HRQL associated with GERD and dyspepsia.22 The 4-item OTE
enables patients to rate whether and how their symptoms have
changed since they began treatment, how much better or worse
they feel, and how important this change is.37
Physicians evaluated each patient’s symptom severity sub-
jectively on a scale of 0 to 3 (0, no symptoms; 1, mild; 2, mod-
erate; and 3, severe). All patient-completed assessments were
done prior to the performance of physical examinations or any
other clinical procedures at baseline and follow-up visits. The
physician assessments were completed at the end of the visit,
independently of the patient-completed assessments and with-
out reference to them.
To understand the instrument’s responsiveness, we treated all
patients on an open-label basis with 20 mg of omeprazole taken
twice daily for the duration of their enrollment in the study. The
selection of an initial dose of 20 mg twice daily taken for 6 months
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was based on a recommendation by a panel of otolaryngologists
with a high volume of referred patients with LPR as the mini- Table 1. LPR-HRQL Item-Level Response Scores
mum required to achieve relief of symptoms. For the purposes Grouped by Domain at Baseline
of homogeneity of effects in testing the sensitivity of the instru-
ment to change, patients were instructed that no other prescrip- Quality of Life Factor Mean (SD) Range
tion therapy for acid-related symptoms was permitted during the Voice/Hoarse
study. Previous use of antisecretory or promotility agents was per- 1. Difficult to work 1.94 (2.01) 0-6
mitted, as long as these treatments were discontinued at least 10 2. Satisfied with sound 2.57 (2.01) 0-6
days prior to study enrollment and the baseline evaluation. 3. Hard to communicate 2.24 (2.02) 0-6
4. Others uncomfortable 1.36 (1.82) 0-6
5. Cannot sing 2.90 (2.37) 0-6
STATISTICAL ANALYSIS 6. What others think 0.66 (1.30) 0-6
7. Sound upset when not 1.06 (1.75) 0-6
Validity 8. Strain is tiring 1.87 (2.00) 0-6
9. Embarrassed by voice 1.55 (1.99) 0-6
Face validity was established by the evaluation of the substan- 10. Avoid talking 1.21 (1.64) 0-6
tive content by a panel of physician experts. In addition, in- 11. Difficult to do job 1.39 (1.91) 0-6
formation was collected from patients during the pilot test to 12. Fear permanent voice loss 0.96 (1.63) 0-6
assess the patient perception of the face validity of the instru- 13. Overall Voice/Hoarse effect 3.97 (2.92) 1-10
ment. Statistical, construct, and concurrent validity were as- Cough
sessed. The primary tools for assessing statistical validity were 14. Cough embarrassing 1.88 (1.93) 0-6
descriptive statistics and distribution graphs. In the assess- 15. Avoid social events 0.78 (1.41) 0-6
ment of construct validity, factor analysis was conducted of all 16. Need to leave room 0.95 (1.40) 0-6
domains to determine if they reflected individual, coherent fac- 17. Perceived as sick 1.31 (1.74) 0-6
tors. Zero order correlations among the items and subscale scores 18. Hear me in the halls 1.21 (1.77) 0-6
were examined for discriminant and convergent validities, which 19. Worry about timing 1.49 (1.84) 0-6
provided an assessment of concurrent validity. Concurrent va- 20. Overall Cough effect 3.06 (2.52) 1-10
lidity was further examined by analyzing the relationships be- Clear Throat
tween the LPR-HRQL and the VHI, SF-36, and QOLRAD. 21. People notice 2.73 (2.03) 0-6
22. Disrupts sex life 0.57 (1.27) 0-6
Reliability 23. Friendships affected 0.60 (1.32) 0-6
24. Makes it hard to talk 1.98 (1.81) 0-6
Reliability was established through item analysis. To assess in- 25. Frustrating frequency 2.96 (2.12) 0-6
26. Avoid social events 0.79 (1.41) 0-6
ternal consistency reliability, we computed a Cronbach ␣ for each
27. Overall Clear Throat effect 3.85 (2.88) 1-10
domain of the LPR-HRQL. To ensure that the questionnaire was
stable across time, we performed a test-retest reliability analysis Swallow
by examining Pearson correlations and comparing 4-month and 28. Hard to swallow 2.66 (2.13) 0-6
6-month evaluations. These time points were selected to co- 29. Avoid public eating 0.67 (1.38) 0-6
incide with the time subsequent to treatment initiation when the 30. Fear choking in sleep 0.73 (1.50) 0-6
therapy should have achieved full efficacy (ie, month 4 and later) 31. Burning in throat 2.83 (2.13) 0-6
and the patient could be considered “treatment stable.” 32. Awaken gasping 0.76 (1.43) 0-6
33. Overall Swallow effect 4.72 (2.85) 1-10

Responsiveness Overall Impact of Acid Reflux

34. Effect on energy 4.28 (3.05) 1-10
The responsiveness index was calculated as the change from 35. Job productivity effect 3.41 (2.79) 1-10
36. Social relations effect 3.01 (2.70) 1-10
baseline to end point to represent the improvement in func-
37. Intimate relations effect 2.44 (2.50) 1-10
tion under a known effective treatment regimen. A paired t test
38. Sexual relations effect 2.15 (2.30) 1-10
compared baseline and 6-month scores. To facilitate a mean- 39. Sleep effect 4.31 (3.06) 1-10
ingful clinical interpretation of domain score changes, we cal- 40. Lying down problems 4.46 (3.08) 1-10
culated the minimum clinically meaningful change in each do- 41. Self-perception effect 3.74 (2.93) 1-10
main to correspond to a significant (1-point) decrease in the 42. Lifestyle effect 4.34 (3.11) 1-10
physician-reported symptom severity score. 43. Affects ability to enjoy 4.05 (3.05) 1-10

Burden Abbreviation: LPR-HRQL, Laryngopharyngeal Reflux Health-Related

The ability of respondents to complete the instrument was evalu-
ated, and factors of time needed for completion and language
complexity were considered.
RESULTS
In the assessment of the patient perception of the face
validity of the instrument, no items were flagged by sub-
jects as inappropriate or unclear.
Of the 117 subjects enrolled, 78 (66.7%) were women,
101 (86.3%) were white, and the mean (SD) age was 48.4
Quality of Life questionnaire.
(14.6) years. Overall, 28.2% of the sample were younger
than 40 years; 31.6% were aged between 40 and 50 years;
and 40.2% were older than 50 years. This age group dis-
tribution did not differ significantly between men and
women. At baseline, 85.5% reported chronic throat clear-
ing, 82.1% globus, 80.3% hoarseness, 53.9% difficulty swal-
lowing, 44.3% chronic cough, and 33.3% laryngospasm.
Table 1 lists the item-level descriptive statistics
grouped by domain for the LPR-HRQL. All items showed
good variability, and the ranges spanned all possible val-

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 (which is attributable to a general association among symp-
Table 2. Scores on LPR-HRQL Domains, VHI, and QOLRAD toms), the magnitude of the correlation is moderate. This
indicates that the Cough, Clear Throat, Swallow, and Over-
Instrument Mean (SD) Range all Impact of Acid Reflux scores represent variability in sub-
LPR-HRQL domain ject symptoms independent of the issues represented by
Voice/Hoarse 19.71 (16.09) 0-65 the Voice/Hoarse questions.
Cough 7.61 (8.76) 0-35 Likewise, the relatively moderate or higher correla-
Clear Throat 9.63 (7.58) 0-36
Swallow 7.64 (5.84) 0-30
tions with the QOLRAD (which assesses GERD and dys-
Overall Impact of Acid Reflux 32.14 (20.93) 9-90 pepsia) are in the Swallow and Overall Impact of Acid
VHI 29.86 (25.93) 0-109 Reflux scores. The LPR-HRQL scores reflecting the symp-
QOLRAD 1.83 (1.40) 0-5.4 toms that we would expect to distinguish GERD and dys-
pepsia from LPR (Voice/Hoarse, Cough and Clear Throat)
Abbreviations: LPR-HRQL, Laryngopharyngeal Reflux Health-Related have moderate to low correlation with the QOLRAD,
Quality of Life questionnaire; QOLRAD, Quality of Life in Reflux and
Dyspepsia instrument; VHI, Voice Handicap Index.
which provides divergent validity evidence for the LPR-
HRQL. The Reflux Finding Score, documented by the phy-
sician at baseline, has somewhat limited convergent va-
lidity. It is an amalgam of symptom questions relating
Table 3. Correlation of LPR-HRQL Domains
to all the domains covered in the LPR-HRQL, so the cor-
With Validated Instruments*
relation reflects the relationship of a part (LPR-HRQL do-
Reflux
main) to the whole (overall reflux finding score).
LPR-HRQL Domain VHI QOLRAD Finding Score Table 4 reports the associations of the domains of
the LPR-HRQL with the domains of the SF-36. These as-
Voice/Hoarse 0.88 (⬍.01) 0.24 (⬍.01) 0.16 (.08)
Cough 0.45 (⬍.01) 0.37 (⬍.01) −0.06 (.52) sociations provide evidence of concurrent validation and
Clear Throat 0.56 (⬍.01) 0.41 (⬍.01) 0.24 (.01) also reveal how scores on the new disease-specific HRQL
Swallow 0.41 (⬍.01) 0.59 (⬍.01) 0.23 (.01) instrument relate to general domains of HRQL in an es-
Overall Impact 0.61 (⬍.01) 0.66 (⬍.01) 0.18 (.06) tablished instrument. The signs of the correlations are
of Acid Reflux appropriately negative. The LPR-HRQL domains are most
closely associated with the Vitality and Social Function
Abbreviations: LPR-HRQL, Laryngopharyngeal Reflux Health-Related
Quality of Life questionnaire; QOLRAD, Quality of Life in Reflux and
domains of the SF-36. Voice/Hoarse issues are substan-
Dyspepsia instrument; VHI, Voice Handicap Index. tially correlated with Social Function (r=−0.51). Cough,
*Data are reported as Pearson correlation coefficient (P value). Clear Throat, and Swallow are similarly associated with
both Vitality and Social Function (mean r=−0.41). In ad-
dition, Swallow is substantially associated with Pain, Role
ues. Histograms were examined, and no items showed Emotional, and Role Physical. There are smaller, though
evidence of multimodal distributions. There were no sub- significant, levels of association across all the LPR-
stantial floor or ceiling effects. There were no missing item HRQL domains and the Mental Health domain. Signifi-
patterns to be analyzed. Respondents completed the LPR- cant correlations across the board indicate that the LPR-
HRQL in approximately 30 minutes or less. HRQL captures the impact of LPR on the overall HRQL
All but 1 domain showed a single-factor structure with as measured by a validated, general-profile instrument.
items loading substantially on that factor. The Voice/ Finally, the Overall Impact of Acid Reflux score has the
Hoarse domain was the only domain that generated more highest correlations with the SF-36 domains compared
than a 1-factor structure. Examination of the results re- with the other LPR-HRQL domains.
vealed that the second factor, with an eigenvalue mar- The overall reliabilities of the LPR-HRQL domains tend
ginally greater than 1, was attributable to the item that to be either superior or highly acceptable (␣=.84-.93),
required reverse scoring to be integrated into the scale though the Swallow score is somewhat lower (␣ =.69).
correctly. Removal of any given single item from the score did not
Table 2 lists the descriptive statistics for the 5 do- improve the LPR-HRQL’s reliability.
mains of the LPR-HRQL instrument as well as for 2 vali- The data provide evidence of substantial test-retest re-
dated instruments used to assess convergent and diver- liability. The test-retest reliability correlation coeffi-
gent validity. Examination of the histograms of the scales cients were all significant and substantial, ranging from
indicates normal distributions with no substantial ceil- 0.90 to 0.64, indicating very high to moderate levels of
ing or floor effects. The variability, as compared with the test-retest reliability. Specifically, correlation coeffi-
potential range for each of the scores of the LPR-HRQL, cients for domains were 0.77 for Voice, 0.64 for Cough,
compares favorably with that of the VHI and the QOLRAD. 0.86 for Clear Throat, 0.83 for Swallow, and 0.89 for Over-
Table 3 outlines the evidence of substantial conver- all Impact of Acid Reflux. In comparison, the test-retest
gent validity based on the VHI and QOLRAD but not the reliability coefficients for the VHI and the QOLRAD are
Reflux Finding Score. The LPR-HRQL Voice/Hoarse score 0.70 and 0.64, respectively.
is most highly correlated with the VHI, and the magni- The final set of results establishes the responsiveness of
tude of the correlation is substantial. Both are indications the instrument to changes over time and helps establish
of convergent validity for the LPR-HRQL Voice/Hoarse do- the minimal clinically meaningful difference for the LPR-
main component. For the remaining 4 domains of the LPR- HRQL scores. Table 5 lists the dependent t test results
HRQL, while they are significantly correlated with the VHI for each of the 5 domains of the LPR-HRQL for changes

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 Table 4. Correlation of LPR-HRQL Domains With SF-36 Domains*

SF-36 Domain

Physical General Role

LPR-HRQL Domain Function Role Physical Bodily Pain Health Perceptions Vitality Social Function Emotional Mental Health
Voice/Hoarse −0.33 (⬍.01) −0.38 (⬍.01) −0.25 (⬍.01) −0.23 (.01) −0.35 (⬍.01) −0.51 (⬍.01) −0.30 (⬍.01) −0.26 (⬍.01)
Cough −0.25 (⬍.01) −0.31 (⬍.01) −0.29 (⬍.01) −0.33 (⬍.01) −0.37 (⬍.01) −0.42 (⬍.01) −0.32 (⬍.01) −0.24 (⬍.01)
Clear Throat −0.28 (⬍.01) −0.36 (⬍.01) −0.29 (⬍.01) −0.23 (⬍.01) −0.40 (⬍.01) −0.43 (⬍.01) −0.31 (⬍.01) −0.29 (⬍.01)
Swallow −0.30 (⬍.01) −0.38 (⬍.01) −0.41 (⬍.01) −0.33 (⬍.01) −0.43 (⬍.01) −0.45 (⬍.01) −0.40 (⬍.01) −0.32 (⬍.01)
Overall Impact −0.32 (⬍.01) −0.55 (⬍.01) −0.39 (⬍.01) −0.40 (⬍.01) −0.55 (⬍.01) −0.64 (⬍.01) −0.54 (⬍.01) −0.42 (⬍.01)
of Acid Reflux

Abbreviations: LPR-HRQL, Laryngopharyngeal Reflux Health-Related Quality of Life questionnaire; SF-36, Medical Outcomes Study Short-Form 36-Item Health
Survey.
*Data are reported as Pearson correlation coefficient (P value).

from baseline to 4 and 6 months. For all domains of the

LPR-HRQL for both the 4- and 6-month measurements, Table 5. Test of Responsiveness of LPR-HRQL Domains
HRQL problems significantly decreased. The minimum
clinically meaningful change for each of the Voice/ Score Change, P
Domain Change Measured Mean (SD) Value
Hoarse, Cough, Clear Throat, and Swallow domains was
5 points, whereas the comparable minimum change for the Voice/Hoarse from baseline to 4 months −5.83 (13.39) ⬍.001
Overall Impact of Acid Reflux score was 10 points. The Voice/Hoarse from baseline to 6 months −6.35 (13.77) ⬍.001
Cough from baseline to 4 months −2.44 (9.39) .02
Voice/Hoarse, Swallow, and Overall Impact of Acid Re-
Cough from baseline to 6 months −3.92 (8.39) ⬍.001
flux scores of the LPR-HQRL exhibited average change in Clear Throat from baseline to 4 months −3.95 (6.83) ⬍.001
scores between baseline and 6 months that were at or greater Clear Throat from baseline to 6 months −4.73 (6.44) ⬍.001
than this clinically meaningful minimum difference. Given Swallow from baseline to 4 months −4.47 (4.51) ⬍.001
the standard deviations associated with each domain score, Swallow from baseline to 6 months −5.07 (4.70) ⬍.001
the instrument should detect this 5-point difference with Overall Impact of Acid Reflux −15.10 (17.42) ⬍.001
from baseline to 4 months
a power of 80% or better in a study comparing 2 arms each
Overall Impact of Acid Reflux −14.43 (18.02) ⬍.001
of between 20 and 30 subjects. from baseline to 6 months

COMMENT Abbreviation: LPR-HRQL, Laryngopharyngeal Reflux Health-Related

Quality of Life questionnaire.

The LPR-HRQL has been shown to be a reliable and valid

instrument that poses no unusual burden on the sub-
ject, has face validity, and is simple to administer, score,
and analyze. Furthermore, it has been documented to
show significant responsiveness to changes in subjects’
HRQL associated with LPR.
Specific findings related to the LPR-HRQL are note-
worthy. That there were no missing item patterns to be
analyzed suggests that subjects understood the ques-
tions and were comfortable answering all of them. That
all subjects completed the entire instrument also indi-
cates that the instrument is not overly burdensome.
Significant correlations across the board between the
LPR-HRQL domains and those of the SF-36 indicate that
the LPR-HRQL captures the impact of LPR on the over-
all HRQL as measured by a validated, general-profile in-
strument. That the Overall Impact of Acid Reflux score
has the highest correlations with the SF-36 domains com-
pared with the other LPR-HRQL domains makes sense
in that an overall disease-specific HRQL score should have
a greater correlation with overall health domains than with
more limited aspects such as Voice/Hoarse or Cough (the
“whole to whole” correlations should be greater than the
“part-to-whole” correlations).
The overall reliabilities of the LPR-HRQL domains tend
to be highly acceptable, though the Swallow score was
in the modest range. Examination of the Swallow scale
revealed that the items had a far greater span of symp-
toms than the other scales, which would explain its re-
duced reliability. The decision was made to retain the do-
main to maintain the span of the instrument’s coverage.
Given the standard for reliability in related disease in-
struments, it was decided that maintaining all domains
would produce a more valuable instrument than one that
was shortened and thereby reduced in its span of cover-
age. The test-retest reliability correlation coefficients were
all significant and favorable compared with those of the
VHI and QOLRAD, 2 frequently used and validated in-
struments, which suggests that the test-retest reliability
for the LPR-HRQL meet the same standard of existing
instruments.
We anticipated that an instrument useful in the study
of LPR would show a significant improvement in scores
between pretreatment and posttreatment status. This oc-
curred for all domains of the LPR-HRQL at both the 4- and
6-month periods, which suggests that all LPR-HRQL do-
mains are able to capture the response to an intervention
as early as 4 months into treatment. The Voice/Hoarse,
Swallow, and Overall Impact of Acid Reflux scores of the
LPR-HRQL exhibited average changes between baseline

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and 6 months that were at or greater than the clinically
meaningful minimum difference, which suggests that the
minimum clinically meaningful difference of 5 points for
each domain score may be conservative.
The introduction of this instrument to the armamen-
tarium of disease-specific HRQL instruments will en-
able physicians and health care practitioners to assess the
HRQL of their patients with LPR and to evaluate their
response to therapy. This instrument can also assist re-
searchers who are conducting clinical studies to assess
the ability of new and/or existing therapies to reduce the
HRQL burden of reflux laryngitis.
Submitted for Publication: June 1, 2004; final revision
received November 15, 2004; accepted January 14, 2005.
Author Affiliations: Department of Otolaryngology, Uni-
versity of Pittsburgh Medical Center, Pittsburgh, Pa
(Dr Carrau); Otolaryngology Department, University of
Virginia School of Medicine, Charlottesville (Dr Khidr);
Health Economic Research and Quality of Life Evalua-
tion Services (HERQuLES), Abt Associates Inc, Cam-
bridge, Mass (Drs Gold and Pashos); AstraZeneca LP,
Wilmington, Del (Mr Crawley and Dr Hillson); and Cen-
ter for Voice Disorders of Wake Forest University, Win-
ston-Salem, NC (Dr Koufman).
Correspondence: Chris L. Pashos, PhD, HERQuLES, Abt
Associates Inc, 181 Spring St, Lexington, MA 02421 (chris
_pashos@abtassoc.com).
Funding/Support: Support for this research was pro-
vided by AstraZeneca LP.
Acknowledgment: We thank William Lenderking, PhD,
Richard Berzon, DrPh, and Abt Associates Inc for their
contributions to the design, data collection, and instru-
ment development; Sandra Sweeney, AB, for initial project
coordination; Judy Davis, MPH, MSW, for project man-
agement; and Lark Madoo, BA, for data processing and
analysis. We also thank David Moore, MD, James Rei-
bel, MD, Paul Castellanos, MD, Beverly Prince, MD, Kirk
Tolhurst, MD, and their clinic staffs as well as the clinic
staffs of Drs Carrau, Khidr, and Koufman for their assis-
tance in enrollment of the subjects into the study.
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