Abstract
Objective
Allergic rhinitis is an IgE-mediated inflammatory disease which effects 10%–50% of the normal population. The mechanism of its formation and the circadian rhythm of cortisol and melatonin in allergic rhinitis have not been investigated.
Study design
Salivary levels of melatonin and cortisol were measured by radioimmunoassay in 35 newly diagnosed allergic rhinitis patients and in 23 control subjects matched for age and gender.
Results
In the study group; amplitude, baseline and peak levels of salivary melatonin were significantly decreased compared with healty controls (p < 0.001). No differences were found in the acrophase and the peak duration of salivary melatonin between the study and control groups (p > 0.05).
In the study subjects, the circadian rhythm of cortisol was flattened when compared with the control group. The amplitude and the 24 h mean levels of salivary cortisol in the study group were significantly lower than in the control group and the acrophase was delayed in patients compared with control subjects (p < 0.001).
Conclusion
The circadian rhythms of salivary melatonin and cortisol were found to be disrupted in patients with allergic rhinitis. These results may also be contributive data to explain the pathogenesis of allergic rhinitis and also they can be applicable as adjunctive therapeutic tools in the future and melatonin drugs might be an alternative in the therapy of resistant allergic rhinitis patients or allergic rhinitis patients who cannot use cortisol drugs.
1
Introduction
Allergic rhinitis (AR) is an inflammation of the nose. The typical symptoms of AR are rhinorrhea, itching, sneezing and nasal blockage. The severity of nasal congestion follows a circadian rhythm, being worst at night and in the early morning . Also sneezing and rhinorrhea secondary to AR are also greater in intensity during the morning in approximately 70% of sufferers . The mechanism involved in circadian rhythm of AR is not clearly understood yet. Asthma, nasal polyposis and AR frequently coexist in the same patient and are thought to share common predisposing genetic factors which interact with the environmental influences .
Clinical guidelines for AR have identified sleep impairment as a significiant problem . Also AR leads to sleep impairment . In addition, sleep impairment is accompanied by a damaged circadian rhythm, which affects cortisol and melatonin secretion.
Melatonin is the main hormone product of pineal gland and it coordinates the circadian rhythm in humans. Also, it has an important role in the immunomodulation, anti-inflammatory cascade and the antioxidative defense system . Cortisol is a hormone which shows a cyclic secretion. It has a typical circadian pattern with higher levels in the early morning . Cortisol excretion is coordinated via the hippocampus and the hypothalamic–pituitary–adrenal axis . There is a considerable affiliation between the plasma/serum and salivary levels of melatonin and cortisol .
Disturbed circadian rhythm of body may have a role in the development of AR. To our knowledge, no studies to date have searched the circadian rhythm of cortisol and melatonin in patients with AR without asthma. Therefore, this study was conducted to appreciate the circadian rhythm of melatonin and cortisol in this patient group.
2
Patients and methods
2.1
Study population
Thirty-five newly diagnosed AR patients without asthma (age range 18–37 years (mean ± SD age, 25.3 ± 6.6)) who presented at the Otolaryngology Clinic of Erzurum Education and Research Hospital between January 2009 and March 2011 were included in this study. Twenty-four age and gender matched volunteer control subjects (age range 18–39 years (mean ± SD age, 26.1 ± 7.2)) were chosen among healthy patients attending the same hospital during the same period. We received approval by the Local Hospital Ethical Committee and also obtained the informed consent from the patients before study.
At study entry, all subjects were examined in detail. And also; routine blood and urine analyses, electrocardiographs, spirometry, chest and sinus X-rays were performed in all subjects.
Study patients and control subjects with any clinical or laboratory evidence of inflammation, infection or asthma, those who had received hormone therapy and/or steroid therapy in the one month prior to the study, or those who were taking any drugs that might affect melatonin and cortisol levels (including antidepressants, antipsychotic medications, benzodiazepines, calcium channel blockers, beta-blockers, anticoagulants, interleukin-2, non-steroidal anti-inflammatory drugs) were also excluded from the study.
All subjects had given written informed consent to participate and the aim of the study and possible risks were fully explained. This study was acknowledged by the Ethical Committee of Erzurum Education and Research Hospital.
2.2
Saliva collection
The sampling process was started at 12:00 in all cases and samples were taken at 4 hourly intervals. Saliva samples were taken under indoor light conditions. The intensity of light was limited to 300 lux in full light, but at 00:00 and 04:00 only flashlight (about 50 lux) was used to light up the mouth. Approximately 10–20 ml of saliva was taken from each subject. Saliva was collected prior to meals using a sugarless gum to stimulate saliva flow if necessary. The samples were inserted into 50 ml tubes and placed in the refrigerator at ± 4 °C for 24 h. The samples were then centrifuged for 10 min at 2000 × g to remove mucins from the saliva and all samples were kept at − 40 °C until chemical analysis.
2.3
Saliva assay
Melatonin in the saliva was evaluated by a radioimmunoassay (RIA) using kits obtained from BÜHLMANN Laboratories AG (Baselstr. 55 CH-4124, Schönenbuch, Switzerland) (RK-DSM2). The standard range of melatonin in this kit was 0.5–50 pg/ml). Day time (baseline) level, night time (peak) level, acrophase (clock time at which the melatonin reaches peak level), amplitude (difference between peak and baseline level) and peak duration (time interval during the periodic curve deviates from the baseline level) were used as parameters to assess the melatonin rhythm.
Salivary cortisol was evaluated by ELISA. The kit is manufactured by Eagle Biosciences, Inc. (82 Broad Street, Suite 383, Boston, USA) (COR32-K01). The standard range of the cortisol kit was 0.1–30 ng/ml. The 24-h mean level, amplitude (distance from mean to peak levels) and acrophase (clock time at which the cortisol levels reaches highest level) were used as parameters to assess the cortisol rhythm.
2.4
Statistics
Statistical analyses were performed by using the SPSS® software package, version 17.0 (SPSS Inc., Chicago, IL, USA) for Windows®. Categorical variables are presented as percentages and continuous variables are presented as mean ± SD. Data continuous variables were analyzed statistically using nonparametric tests, using the Friedman two-way ANOVA to establish whether melatonin levels differed in the samples taken at the various times to evaluate both the ENP patient and control groups. After confirmation, the Wilcoxon matched-pairs signed-rank test was used to determine the differences between sample times, and a repeated-measures ANOVA with between subject factors was used to compare the cases with the control group. Finally, we used the Mann–Whitney test to compare peak values between the patient and control groups. A value of P < 0.05 was considered to be statistically significant.
2
Patients and methods
2.1
Study population
Thirty-five newly diagnosed AR patients without asthma (age range 18–37 years (mean ± SD age, 25.3 ± 6.6)) who presented at the Otolaryngology Clinic of Erzurum Education and Research Hospital between January 2009 and March 2011 were included in this study. Twenty-four age and gender matched volunteer control subjects (age range 18–39 years (mean ± SD age, 26.1 ± 7.2)) were chosen among healthy patients attending the same hospital during the same period. We received approval by the Local Hospital Ethical Committee and also obtained the informed consent from the patients before study.
At study entry, all subjects were examined in detail. And also; routine blood and urine analyses, electrocardiographs, spirometry, chest and sinus X-rays were performed in all subjects.
Study patients and control subjects with any clinical or laboratory evidence of inflammation, infection or asthma, those who had received hormone therapy and/or steroid therapy in the one month prior to the study, or those who were taking any drugs that might affect melatonin and cortisol levels (including antidepressants, antipsychotic medications, benzodiazepines, calcium channel blockers, beta-blockers, anticoagulants, interleukin-2, non-steroidal anti-inflammatory drugs) were also excluded from the study.
All subjects had given written informed consent to participate and the aim of the study and possible risks were fully explained. This study was acknowledged by the Ethical Committee of Erzurum Education and Research Hospital.
2.2
Saliva collection
The sampling process was started at 12:00 in all cases and samples were taken at 4 hourly intervals. Saliva samples were taken under indoor light conditions. The intensity of light was limited to 300 lux in full light, but at 00:00 and 04:00 only flashlight (about 50 lux) was used to light up the mouth. Approximately 10–20 ml of saliva was taken from each subject. Saliva was collected prior to meals using a sugarless gum to stimulate saliva flow if necessary. The samples were inserted into 50 ml tubes and placed in the refrigerator at ± 4 °C for 24 h. The samples were then centrifuged for 10 min at 2000 × g to remove mucins from the saliva and all samples were kept at − 40 °C until chemical analysis.
2.3
Saliva assay
Melatonin in the saliva was evaluated by a radioimmunoassay (RIA) using kits obtained from BÜHLMANN Laboratories AG (Baselstr. 55 CH-4124, Schönenbuch, Switzerland) (RK-DSM2). The standard range of melatonin in this kit was 0.5–50 pg/ml). Day time (baseline) level, night time (peak) level, acrophase (clock time at which the melatonin reaches peak level), amplitude (difference between peak and baseline level) and peak duration (time interval during the periodic curve deviates from the baseline level) were used as parameters to assess the melatonin rhythm.
Salivary cortisol was evaluated by ELISA. The kit is manufactured by Eagle Biosciences, Inc. (82 Broad Street, Suite 383, Boston, USA) (COR32-K01). The standard range of the cortisol kit was 0.1–30 ng/ml. The 24-h mean level, amplitude (distance from mean to peak levels) and acrophase (clock time at which the cortisol levels reaches highest level) were used as parameters to assess the cortisol rhythm.
2.4
Statistics
Statistical analyses were performed by using the SPSS® software package, version 17.0 (SPSS Inc., Chicago, IL, USA) for Windows®. Categorical variables are presented as percentages and continuous variables are presented as mean ± SD. Data continuous variables were analyzed statistically using nonparametric tests, using the Friedman two-way ANOVA to establish whether melatonin levels differed in the samples taken at the various times to evaluate both the ENP patient and control groups. After confirmation, the Wilcoxon matched-pairs signed-rank test was used to determine the differences between sample times, and a repeated-measures ANOVA with between subject factors was used to compare the cases with the control group. Finally, we used the Mann–Whitney test to compare peak values between the patient and control groups. A value of P < 0.05 was considered to be statistically significant.
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