The Laryngoscope

© 2019 The American Laryngological,

Rhinological and Otological Society, Inc.

Add-on Probiotics in Patients With Persistent Allergic Rhinitis:

A Randomized Crossover Clinical Trial

Mir Mohammad Jalali, MD ; Robabeh Soleimani, MD ; Ali Alavi Foumani, MD;

Hooman Ganjeh Khosravi, MD

Objectives: Current medications for allergic rhinitis (AR) may have undesirable side effects that could affect quality of life
(QoL). Probiotics could be an alternative in these patients. The aim of this study was to assess the impact of add-on probiotics
on symptoms and QoL of patients.
Methods: In this randomized crossover clinical trial, patients with persistent AR were included. Each subject received
budesonide with probiotic supplements (BP) or budesonide with placebo for 8 weeks (B), then vice versa for a further
8 weeks. There was an 8-week washout. The primary outcome was the change of the Short Form 36-Item Health Survey
(SF-36) score. The secondary outcomes were assessed by the Sinonasal Outcome Test-22 (SNOT-22) and the Control of Allergic
Rhinitis and Asthma Test (CARAT) questionnaires.
Results: A total of 152 subjects (30.1  7.6 years) completed the study. The SF-36 score in both groups showed improve-
ment compared with baseline values. Treatment BP was more effective than that of B. The Cohen’s d and the number needed
to treat for Physical Component Scales of SF-36 were 0.40 and 10.77, respectively. These values for Mental Component Scales
were 0.33 and 12.61, respectively. Also, treatment BP showed more reduction in the score of SNOT-22 and CARAT.
Conclusion: This study showed that the addition of probiotics to budesonide significantly improved QoL in persistent AR
patients. However, the clinical situation of these patients may be not very representative of AR patients in general population.
Further studies are recommended.
Key Words: Probiotics, allergic rhinitis, quality of life, SF-36, SNOT-22, CARAT.
Level of Evidence: 1b.
Laryngoscope, 00:1–7, 2019

INTRODUCTION activate or inhibit type 1 T-helper cell and cause proin-

The prevalence of allergic diseases is a serious problem flammatory or anti-inflammatory effects. Probiotics may
in the field of modern medicine and public health. Estimates also stimulate interleukin-10, which acts primarily to
suggest that 10% to 30% of adults and up to 40% of children inhibit the inflammatory response.5,6 It is expected that
suffer from allergic rhinitis (AR),1 and the prevalence of the consuming probiotics could establish a more balanced
disorder is increasing.2 Symptoms can have significant nega- intestinal flora in AR patients, lead to milder reactions to
tive impact on the patients’ quality of life (QoL), sleep qual- inhaled allergens in these patients, and limit damages
ity, mood, learning achievement, and sexual dysfunction.3 resulting from the inflammation. Thus, the use of probio-
Treatment for AR continues to be based on allergen tics is a popular strategy to prevent or treat AR.
avoidance, medications that provide symptomatic relief, A recent meta-analysis7 provided evidence of a poten-
anti-inflammatory therapies, and allergy immunotherapy. tial benefit of probiotics in the treatment of AR. Although
Current medications for allergies may have undesirable probiotics significantly improved the total scores of QoL
side effects (e.g., dry mouth, drowsiness, sleeplessness),4 questionnaires, the degree of heterogeneity was high. The
some of which may affect QoL. It is of interest to continue researchers recommended more high-quality studies to
to look for alternatives. Then, the use of probiotics as prove the efficacy of probiotics with validated QoL tools
an alternative in the world is increasing. Probiotics can and objective measurements.
Initially, a single probiotic strain was intensively in-
From Rhino-sinus, Ear, and Skull base Diseases Research Center, vestigated in the studies of the treatment of AR. However,
the Department of Otolaryngology (M.M.J.); Kavosh Behavioral, Cognitive recent studies have begun to evaluate the treatment effect by
and Addiction Research Center, the Department of Psychiatry, Shafa
Hospital (R.S.); the Department of Pulmonary Diseases, Inflammatory using more than one strain of probiotics. The potential bene-
Lung Disease Research Center (A.A.F.); and the Department of fits of using multistrain probiotics over single-strain probio-
Otolaryngology (H.G.K.), Guilan University of Medical Sciences, Rasht, Iran. tics were suggested in several reviews.8–10 These works point
Editor’s Note: This Manuscript was accepted for publication on
January 22, 2019.
to various explanations: additive effect, synergistic effect, and
This study was supported by a grant from Guilan University of symbiosis. There is a body of evidence that various lactoba-
Medical Sciences (GUMS), Rasht, Iran. The authors have no other fund- cilli and bifidobacteria exert a high interleukin (IL)-10/IL-12
ing, financial relationships, or conflicts of interest to disclose.
Send correspondence to Jalali Mir Mohammad, Department of ratio, which lead to anti-inflammatory profile and associated
Otolaryngology, Amiralmomenin Hospital, Guilan University of Medical with protection from allergy.11,12 However, there is concern
Sciences, Rasht, Guilan, Iran. E-mail: mmjalali@gmail.com
that the antagonistic effects of multi-strain probiotics result
DOI: 10.1002/lary.27858 in reduced efficacy. The efficacy of multistrain probiotic in

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Fig. 1. Participant flow diagram. [Color figure can be viewed in the online issue, which is available at www.laryngoscope.com.]

persistent allergic rhinitis (PAR) is unclear. It is worth at initial screening visit. Volunteers were excluded from the study
stressing the paucity of such studies reporting the efficacy when presenting any medical condition, such as pregnancy, respi-
of multistrain probiotics on the QoL of patients with AR, ratory tract infection, that could influence the study; uncontrolled
particularly the persistent type of AR. asthma (peak expiratory flow <20% of volunteer’s best personal
value); taking antihistamine, leukotriene receptor antagonist, and
Familact (Zist Takhmir Co., Tehran, Iran) is a probi-
decongestant within the week prior to the study; consumption of
otic mixture supplement that has shown efficacy in several corticosteroids within the month prior to the study; or having no
diseases.13–18 Therefore, we conducted this randomized medical compliance.
crossover clinical trial. The aim of this study was to assess The trial was registered at the Iranian Registry of Clinical
the impact of add-on probiotic supplement on PAR symp- Trials (IRCT) (IRCT201501251138N13). The survey protocol was
toms and on the QoL of patients. approved by the ethical committee of Guilan University of Medical
Sciences (GUMS), Rasht, Iran (1930459703) and complied with the
rules delineated in the Helsinki Declaration. Written informed con-
MATERIALS AND METHODS sent was obtained from each subject before the start of the study.

Patients
Included patients were 18 to 45 years of age with a diagnosis
of moderate-to-severe PAR (according to the Allergic Rhinitis and Study Design
Its Impact on Asthma classification) for at least 1-year duration. This was a randomized, double-blind, placebo-controlled,
Allergic rhinitis was confirmed by positive findings on physical crossover study was conducted in Rasht, Iran, between April
examination and a positive skin prick test (weal diameter ≥3 mm) 2015 and October 2015. The subjects were recruited from patients

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 TABLE I.
Subjects’ Baseline Characteristics.
Budesonide/ Budesonide/
Overall Probiotic Placebo
Variable (n = 152) (N = 76) (N = 76)

Age [years; mean (SD)] 30.1 (7.6) 29.4 (6.7) 30.7 (8.4)
Sex [male; n (%)] 82 (53.9) 43 (56.6) 39 (51.3)
Rhinitis duration [years; 5.4 (0.7) 5.4 (0.6) 5.5 (0.8)
mean (SD)]
Pre-study medications
[n (%)]
Oral antihistamine 70 (46.1) 32 (42.1) 38 (50)
Topical corticosteroid 41 (27.0) 22 (28.9) 19 (25.0)
Topical antihistamine 26 (17.1) 11 (14.5) 15 (19.7) Fig. 2. Mean and 95% confidence intervals of Physical (light gray
Antileukotriene 20 (13.2) 8 (10.5) 12 (15.8) bar) and Mental (dark gray bar) Component Summary scores of
Decongestant 8 (5.3) 4 (5.3) 4 (5.3) the Short Form 36-Item Health Survey Questionnaire in the
periods 1 and 2. B = budesonide/placebo; BP = budesonide/pro-
Cromolyn sodium 5 (3.3) 4 (5.3) 1 (1.3) biotic. [Color figure can be viewed in the online issue, which is
No drug 51 (31.6) 23 (30.3) 28 (36.8) available at www.laryngoscope.com.]
History of current smoking 46 (30.3) 30 (39.5) 16 (21.1)
[n (%)]
History of asthma [n (%)] 52 (34.2) 27 (35.5) 25 (32.9) with placebo supplement containing 500 mg maltodextrin once
daily (identical in appearance to Familact, Zist Takhmir Co.). There
Mild 11 (7.2) 6 (7.9) 5 (6.6)
was an 8-week washout between treatments. During the run-in
Moderate/severe 41 (27.0) 21 (27.6) 20 (26.3)
and washout periods and throughout the study, cromolyn sodium
SF-36 [mean (SD)] (Nasocrom, Sina Darou) was used as required for symptomatic
PCS 45.4 (5.4) 45.3 (5.4) 45.4 (5.4) relief. The symptomatic use was recorded on a diary card, and the
MCS 49.1 (10.1) 49.0 (9.7) 49.1 (9.7) number of puffs was considered. Visit 3 was conducted after the first
treatment. Visits 4 and 5 were conducted before and after the sec-
SNOT-22 [mean (SD)] 49.0 (15.6) 49.0 (16.1) 48.9 (15.1)
ond treatment, respectively.
CARAT (U) [mean (SD)] 7.21 (0.93) 7.2 (1.0) 7.2 (0.9)
Each probiotic supplement—Familact (500 mg capsule, Zist
Spirometry Takhmir Co.)—contains seven different gram-positive organisms:
FEV1 [%; mean (SD)] 84.9 (11.6) 84.4 (11.7) 85.4 (11.5) 9 * 109 colony-forming units (CFU)/g of viable, lyophilized lactoba-
FVC [%; mean (SD)] 90.6 (8.4) 90.2 (8.4) 91.0 (8.5) cilli (L. acidophilus, L. casei, L. delbrueckii subsp. L. bulgaricus,
and L. rhamnosus), 1.25 * 1010 of bifidobacteria (B. longum, and
FEV1/FVC [%; mean (SD)] 93.3 (5.1) 93.1 (5.3) 93.4 (4.9)
B. breve), and 1.5 *1010 of Streptococcus salivarius subsp. thermo-
AR = Allergic Rhinitis; CARAT(U) = Control of Allergic Rhinitis and philus and 38.5 mg fructooligosaccharide. Rhinocort (AstraZeneca
Asthma Test (upper airway subscale); FEV1 = Forced Expiratory Volume in AB Company, Sodertalje, Sweden), an intranasal corticosteroid
the first second; FVC = Forced Vital Capacity; MCS = Mental Component spray (INCS), is a micronized suspension of budesonide in an aque-
Summary; PCS = Physical Component Summary; SD = Standard Deviation;
SF-36 = Short Form 36-Item Health Survey Questionnaire; SNOT-22 = Sino-
ous medium.
nasal Outcome Test-22. At each visit, the subjects’ diary cards were reviewed, and a
physical examination and spirometry were conducted. The pri-
mary endpoint was mean total score of the Short Form 36-Item
already receiving treatment at the outpatient clinics of Amiralmo- Health Survey Questionnaire (SF-36) on week 8 of treatment fol-
menin and Razi Hospitals. lowing budesonide with probiotic supplement versus budesonide
All participants were evaluated in five visits (Fig. 1). Visit and placebo. The secondary outcomes were the effect on AR
1 (screening) determined inclusion and exclusion status. A medical symptoms at the Sinonasal Outcome Test-22 (SNOT-22) and the
history was taken, and nasal endoscopy and skin prick tests were Control of Allergic Rhinitis and Asthma Test (CARAT) question-
performed. In addition, forced vital capacity (FVC) and forced expi- naires. In addition, asthma control in subjects who had coexist-
ratory volume in 1 second (FEV1) responses were measured. ing asthma was estimated based on the Global Initiative for
Participants stopped any usual therapy with antihistamines, antil- Asthma (GINA) recommendations.19
eukotrienes, decongestants, and nasal steroids, and were given
cromolyn sodium nasal spray as rescue medication. Participants
attended visit 2 after 2 weeks without their usual treatments to
establish baseline measurements. The subjects were allocated to Measurements
groups A or B. Both groups participated in two regimens, namely The SF-36 is a general QoL instrument measuring eight
budesonide/probiotic (BP) and budesonide/placebo (B); each regimen health-related concepts, including physical function (PF), role
had a duration of 8 weeks. Patients in group A were assigned to par- physical (RP), body pain, general health (GH), vitality (VT),
ticipate in the BP regimen first, followed by an 8-week B regimen. social function (SF), role emotional (RE), and mental health
Patients in group B were assigned to participate in the B regimen (MH).20 The interval level scoring for all eight scales ranges from
first, followed by the 8-week BP regimen. The BP regimen included 0 (for worse health) to 100 (best possible health as measured by
256-μg budesonide nasal spray (one puff on each side, twice daily; the questionnaire). These eight scales can be aggregated into two
Rhinocort Aqua, AstraZeneca AB Company, Sodertalje, Sweden) summary measures: the Physical (PCS) and the Mental (MCS)
with probiotic supplements once daily (Familact cap, Zist Takhmir); Component Summary scores. The component scores are stan-
whereas the B regimen included 256-μg budesonide nasal spray dardized with a mean of 50 and a standard deviation (SD) of 10.

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Fig. 3. Mean score of SF-36 subscales at baseline and after budesonide/probiotic or budesonide/placebo. Paired t tests between two regi-
mens were shown by the connectors (*: P < 0.05; **: P < 0.001). SF-36 = Short Form 36-Item Health Survey Questionnaire.

A difference of 3 to 5 points has been proposed as the minimal is the difference between period 1 and period 2 irrespective of treat-
clinically important difference (MCID).21 ment order. The period effect is the difference between period 1 and
The SNOT-22 questionnaire is a validated tool to assess period 2 irrespective of treatment order. This bias may result from
nasal symptoms as well as their impact on psychological status, a change of patient characteristics during the study that modifies
sleep, ear and facial symptoms. The range of the total score is response to different interventions. The pkcross procedure of the
0 to 110, with lower scores implying a better QoL.22 Stata 13.0 software (StataCorp LLC, College Station, TX) was used
The CARAT questionnaire is a validated tool to measure for the crossover analysis.
disease control of asthma and AR in the last 4 weeks. It is We calculated Cohen’s d effect size for all primary and sec-
composed of 10 questions divided into two scores: upper airway ondary outcomes. The Cohen’s d was defined as the difference
(U) and lower airway (L). Each score includes four questions.23 between the means at postintervention, divided by the pool
All the questions are scored on a Likert scale of 4 points. The SD. Cohen defined effect sizes as “small, d = 0.2,” “medium, d =
CARAT (U) score >8, is indicative of good control.24 0.5,” and “large d = 0.8.” Additionally, we calculated the number
Asthma control is defined as the extent to which the various needed to treat (NNT) for all significant interaction effects.27
manifestations of asthma are reduced or removed by treatment.25

RESULTS
Randomization and Blinding
A total of 172 AR patients were randomized to treat-
Randomization and blinding were carried out by an inde-
pendent pharmacist unrelated to the study. Block randomization ment, and 152 (88%) completed the study as planned
(size of four) was conducted with a computer-generated random (Fig. 1). The mean age of the total population was
allocation sequence. This was administered by using sealed 30.1  7.6 years; the majority were male (53.9%). About
coded envelopes at the Rhino-Sinus, Ear and Skull Base Disease 30% percent of enrolled subjects were current smokers,
Research Center of GUMS. The probiotic supplement and pla- with an average 9  2 cigarettes per day. The number of
cebo were made identical in external appearance and content to smokers in group 1 (BP then B) was more than that of
double blind and double dummy the trial. smokers in group 2 (B then BP) (P = 0.009). Demographic
data are presented in Table I. No significant differences
existed between baseline values before each randomized
Statistical Analyses treatment for any of the primary or secondary outcome
According to a previous study, a sample size of 150 subjects measures evaluated by treatment or sequence. There was
allows to detect a 2-point difference in score SF-36, a power of no significant difference between patients taking BP or
90%, and a type I error of 0.05.26 Taking into account a dropout B. Therefore, all analyses were subsequently performed
rate of 15%, 172 subjects were planned to be enrolled. compared with pooled baseline values.
Descriptive analysis of the pattern of distribution of each
The summary measures of SF-36 (PCS and MCS)
variable was performed. Qualitative variables were reported as
showed an insignificant difference between baseline and
frequencies and quantitative variables as means and SD. Intention-
to-treat analyses were conducted. The baseline characteristics and beginning of the period 2 (paired t test; P value: 0.89 and
outcomes of interest were compared by Student t test or χ2 test. We 0.11, respectively). The component scores in both groups
carried out analysis of variance to evaluate differences in intraindi- showed improvement after intervention compared with
vidual responses between treatments for each response variable. baseline values. Treatment with BP was more effective
We estimated the sequence and period effects: The sequence effect than that B (Fig. 2). After supplementary analyses, a

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 TABLE II.
Results of Outcome After Budesonide/Probiotic Versus Budesonide/Placebo in AR Patients (n = 152).*
Treatment Effect
Within-Individual Sequence Effect Period Effect
Outcome BP B Difference Effect Size NNT F P Value (P Value) (P Value)

Primary outcome
SF-36
PCS 57.14 (5.40) 55.35 (5.64) 1.79 (4.52) 0.40 10.77 23.88 <0.01 0.30 0.38
MCS 60.21 (6.86) 58.02 (7.59) 2.19 (6.61) 0.33 12.61 16.57 <0.01 0.24 0.49
Secondary outcomes
SNOT-22 16.71 (5.92) 27.47 (4.90) −10.76 (7.61) 1.41 5.32 306.86 <0.01 0.59 0.12
CARAT(U) 10.33 (0.67) 8.78 (0.53) 1.55 (1.03) 1.14 5.67 20.28 <0.01 0.89 0.19
Spirometry
FEV1 86.37 (9.02) 85.54 (10.38) 0.81 (5.38) 0.15 25.44 15.44 <0.01 0.96 0.85
FVC 92.81 (7.29) 92.17 (7.95) 0.64 (5.28) 0.12 31.37 2.27 0.13 0.91 0.36
FEV1/FVC 92.91 (3.97) 92.54 (4.35) 0.37 (3.35) 0.11 34.07 1.82 0.18 0.93 0.08

*Mean (SD).
AR = Allergic Rhinitis; B = budesonide/placebo; BP = budesonide/probiotic; CARAT(U) = Control of Allergic Rhinitis and Asthma Test (upper airway sub-
scale); FEV1 = Forced Expiratory Volume in the first second; FVC = Forced Vital Capacity; MCS = Mental Component Summary; NNT = number needed to treat
given the control group’s event rate of 80%; PCS = Physical Component Summary; SD = Standard Deviation; SF-36 = Short Form 36-Item Health Survey Ques-
tionnaire; SNOT-22 = Sinonasal Outcome Test-22.

significant higher score was detected in physical function groups, treatment BP showed more reduction of the
(PF), vitality (VT), and social function (SF) subscales SNOT-22 in most items than did treatment B during the
(Fig. 3). The Cohen’s d effect size of PCS between two both periods. The CARAT (U) subscale measures four items:
groups was 0.40, which signifies that about 66% of the BP nasal congestion, sneezing, nasal itching, and runny nose.
group had a higher PCS score than the B group. If we The mean CARAT (U) score showed a significant decrease
assume that 80% of the B group have favorable outcomes, in the BP group (P value: 0.03). The evaluation of CARAT
that is, control group’s event rate (CER) is set to 80%, (U) items in BP versus B groups showed that scores of nasal
NNT will be 10.77. The Cohen’s d for MCS was 0.33. itching and runny nose items were significantly improved
Given CER 80%, NNT will be 12.61. after 8-week intervention (Fig. 4).
The mean of puff number usage of cromolyn sodium as The value of FEV1 and FVC, as well as EV1/FVC
symptomatic relief in BP and B groups was 76.2 (median ratio, increased in both groups; however, a significant
72.5) and 81.2 (median 78.5), respectively. After logarithmic difference in two groups was observed only in FEV1
transformation of the variable, statistical analysis showed a (P < 0.01). It should be noted that only 52 cases were
significant difference between two groups (geometric mean diagnosed comorbid asthma. According to the GINA cri-
difference 1.11; paired t test, P < 0.01). This result is proba- teria, asthma conditions were well controlled in 47 sub-
bly not clinically important. jects in two periods. This finding may attenuate the effect
The change score of variables from baseline (i.e., visit of intervention on the spirometry tests. A planned sub-
point 3 or 5) is illustrated in Table II. Comparing between group analysis was performed for the 52 patients with

Fig. 4. Mean score of four items of CARAT (U) at baseline and after the intervention. The 95% confidence interval of the mean score is marked with
a box bar (subscale 1: nasal congestion; subscale 2: sneezing; subscale 3: nasal itching; subscale 4: runny nose). CARAT(U) = Control of Allergic
Rhinitis and Asthma Test (upper airway subscale). [Color figure can be viewed in the online issue, which is available at www.laryngoscope.com.]

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comorbid asthma. The baseline values of SF-36 (PCS and explained why the effect size of the SF-36 is lower than the
MCS) in subjects with or without asthma were similar. values of the SNOT-22 and CARAT (U).
Similar to the results found in the study population, the The SNOT-22 items can be divided into four domains
treatment BP was more effective than that of B in these (rhinological, ear/facial, sleep, and psychological).39 Hoehle
patients (P < 0.01 and 0.05, respectively). In addition, et al.40 pointed out that among the different symptoms of
subjects who received BP, had a significantly higher value AR, otologic and sleep quality symptoms were most domi-
in FEV1, FVC, and FEV1/FVC ratio than did B (P values nantly associated with a decreased QoL; however, there
0.01, 0.003, and 0.04, respectively). was no association between QoL with nasal symptoms.
Considering a significant clinical difference of QoL and
SNOT-22 between the two groups, a possible explanation
DISCUSSION may be that INCS produces the greatest improvement in
Intranasal corticosteroid sprays are first-line ther- nasal symptoms in AR patients; thus, more room exists for
apy for moderate-to-severe AR and are the most effective action of probiotics on extranasal symptoms. In agreement
medication for controlling AR symptoms.28 The most with our finding, Lin et al.31 showed no add-on effect of
important concern in management of AR is patient’s Lactobacillus paracasei as a supplement to levocetirizine in
adherence to treatment. It has been proposed that probio- managing PAR children.
tics improve the intestinal microbial balance and may The PAR patients with comorbid asthma showed no
modulate immune responses. In a recent systematic significant further deterioration of the QoL compared to
review and meta-analysis, Guvenc et al.7 found only five that of patients without asthma. The results of the pulmo-
studies29–33 that evaluated the impact of probiotics on nary function tests of FEV1 and FVC indicated that probio-
patients with PAR. These studies have shown that pro- tics may have partially improved the effect of budesonide.
biotics may be useful in the treatment or prevention of In our study, only one-third of patients had asthma, and a
PAR in children. Only one clinical trial has explored the ceiling effect may exist in the results due to baseline pulmo-
clinical effects of probiotic administration on PAR in nary function tests of our patients. Therefore, the effect of
adults.33 However, there are no conclusive studies for the probiotics on pulmonary function test could be disappeared.
treatment of PAR adults with probiotics.34 Further studies with larger populations are needed to
We found that during the run-in period, physical and determine the role of probiotics on lung function tests and
mental health were reduced about 5% and 1% below the the QoL of patients with asthma.
norms, respectively. Considerable evidence now exists that There were some limitations associated with this
the symptoms of AR negatively affect the QoL of patients.35 study that must be considered. First, we used the SF-36
This study revealed that PCS and MCS improved signifi- and SNOT-22 as PROMs to estimate health-related
cantly after adding probiotics to INCS. However, the differ- QoL. There are concerns regarding outcome measures in
ence of component summary scores between two groups did allergy. Although many researchers used SNOT-22 in
not exceed the minimal clinically important difference. The research settings, several tools such as Total Nasal Symp-
greatest improvements were observed in the subscales that tom Score exist that have better specificity in allergic con-
focus more on MH (VT and SF) as opposed to physical ditions. Second, assessments were performed during the
health (PF). It is possible that some patients could not dis- intervention, and the stability of these findings was not
criminate between RP limitations and RE limitations. Thus, evaluated through time. Third, this trial was an add-on
we could interpret the results of SF-36 as health conditions design without a real control group (no INCS). Because of
rather than those of mental health. this, it was difficult to establish the degree to which clini-
In this study, we used CARAT (U) and SNOT-22 to cal improvements were due to probiotic supplementation.
determine nasal symptom scores and global scores of sub- Fourth, the self-report recall nature of the SF-36 ques-
jects, as well as lung function tests to assess the lower air- tionnaire is prone to reporting bias and has a ceiling
way status. We indicated more reduction of AR symptoms effect that may limit the ability to detect subtle changes
in the BP group compared to the B group. These results in response to the addition of probiotics in subjects.
confirm the study of Bousquet et al.36 We found a signifi- Finally, our sample was comprised of the moderate-to-
cant within-individual difference in SNOT-22 score (mean severe PAR patients. The clinical situation of these
10.8, P < 0.01, NNT 5.32). The MCID of SNOT-22 is patients may be not very representative of AR patients
9-point.37 But, the within-individual difference of CARAT (intermittent and persistent) in the general population.
(U) was 1.55, which did not meet the accepted MCID of 3.5
in CARAT.38 However, the Cohen’s d was similar for
SNOT-22 and CARAT (U). These questionnaires are dis- CONCLUSION
ease-specific patient-reported outcome measures (PROMs) This study has shown that the addition of the probi-
for allergic rhinitis. In contrast to disease-specific tools, SF- otic compound, Familact (Zist Takhmir), to INCS signifi-
36 is a generic PROM to assess GH. The generic PROMs cantly improved QoL and extranasal symptoms compared
allow comparisons between conditions or treatments and with INCS alone in PAR patients. Noteworthy, this find-
therefore can be used to determine not only the impact of ing adds to the growing body of evidence to support the
different diseases on patient groups but also the relative benefits of probiotics in management of AR in adults. We
cost utility of different interventions. However, generic recommend further studies in intermittent and persistent
instruments may be unresponsive to small changes in AR to determine the efficacy of probiotics on symptoms
health-related QoL that are important to the patient. It is and the QoL of these patients.

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Acknowledgment 19. Global Intitiative for Asthma. Pocket guide for health professionals,
updated 2015. Available at: http://www.ginasthma.org. Accessed
This study was supported by a grant from Guilan Univer- November 10, 2018.
sity of Medical Sciences, Iran. 20. Montazeri A, Goshtasbi A, Vahdaninia M, Gandek B. The short form health
survey (SF-36): Translation and validation study of the Iranian version.
Qual Life Res 2005;14:875–882.
21. Hays RD, Morales lS. The RanD-36 measure of health-related quality of life.
Ann Med 2001;33:350–357.
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