The Study Of Immunological Function Of Obstructive Sleep Apnea Hypopnen Syndrome

Background:Obstructive sleep apnoea hypopnea syndrome (OSAHS) is an increasingly recognised and highly to be thought of diseases, estimated to affect 4% of middle-aged men and 2% of middle-aged women in Western countries. The actual incidence of OSAHS is expected to increase considerably in the coming years(according to statistics, more than 80 percent of moderate to severe OSAHS were not to be diagnosed), the reason for this being both improving living stander caused increasing number of fatty and higher awareness of OSAS in the general public leading to more cases being diagnosed. If untreated, it will lead to increasing daytime sleepiness, impairment of cognitive function, mood and personality changes, reduction in quality of life and destroy relationship between spouses and partners. Also, OSAHS is one of the important causes for traffic accidence, which can bring a heavy burden to individual, family and society. OSAHS can cause not only hypoxia and carbon dioxide retention, but also cause or aggravate hypertension, coronary artery disease, Cardiac arrhythmias, Congestive heart failure, type 2 diabetes and insulin resistance and stroke. According to the Sleep apnea and cardiovascular disease:an American Heart Association/American College of Cardiology Foundation Scientific statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke council, and Council on Cardiovascular Nursing and Sleep disordered breathing and type 2 diabetes:a report from the International Diabetes Federation Taskforce on Epidemiology and Prevention in 2008, which point out there are some correlations between OSAHS and cardiovascular disease and type 2 diabetes even causality. To enhance the treatment of OSAHS would play a very important role on primary and secondary prevention of cardiovascular disease and stroke, deceasing mutilation rate of stroke and burden of family and society. According to statistics, the medical care costs of un-interfered treatment OSAHS was 3.4 million per year in American, the cost of health resources on OSAHS were two times more than healthy crowd. OSAHS now becomes a protruded problem which can affect public health, national economy, social development and drive the focus of many subjects of doctors.Ischemia—reperfusion has been the multiple point of last decade, and the main viewpoint is that when the ischemic tissue recover from perfusion which will aggravate damage or death of the cell. It was due to the poisonous things in blood flowing to the tissue when the cell had been reperfusion, then caused the damage of ischemia—reperfusion. The damage of ischemia—reperfusion was not only caused cardiac arrhythmias of ischemia—reperfusion, the decrease of myocardial Contraction, cerebral edema or death of brain cell, hurt of intestinal mucosa and acute renal function injury, but also the disorder of the immunological function.Because of recurrent pharyngeal collapses during sleep in OSAHS, leading to repetitive sequences of hypoxia-reoxygenation, which has a similar pathophysiological process with ischemia—eperfusion. So we have enough reason to suspect whether OSAHS also has a damage on immune function. The effect of both hypoxia-reoxygenation and ischemia—reperfusion was on producing a lot of free radicals (ex. ROS)and inflammatory factors (ex. IL-6, TNF-α), which can injury the whole system including the vascular endothelial cell, pancreas, heart, kidney and so on. There has been substantial evidence-based medicine proved that OSAHS has been recognize as a kind of disease affected multiple system and an independent risk for cardiovascular morbidity, leading to hypertension, coronary heart disease, coronary artery disease, cardiac arrhythmias, congestive heart failure, type 2 diabetes/insulin resistance, stroke and immune function injury. The early evidence had proved that the immune function of OSAHS, especially humoral and cellular immunity which the leukocytic series take part in has a certain degree of damage. Qun Yu-hua etal'study showed that when comparing with control group (healthy group), the OSAHS group had a significant increase in percentage of CD8+ cell but decrease in ratio of CD4+/CD8+; Dyugovskaya Letal, study also that the percentage of CD4+ cell decrease, CD8+ cell increase, both activities of CD4+ and CD8+ cell increase; The immune function of OSAHS had some change. Their samples were a little small size and only including the cellular immunity of OSAHS but very little about humoral immunity.So our study was to further investigated the relationship between OSAHS and its immunological function including humoral and cellular immunity and thus to further recognize OSAHS and its effect on immune function.Objective:1,To determine whether there was any changes in the immunological function (including humoral and cellular immunity) of obstructive sleep apnea hypopnea patients.2,To further recognized OSAHS and its effect on immune function.Methods: 1,We carried out a retrospective study of 187 OSAHS and 20 examined healthy who stayed in Nan Fang Sleep Center of Nan Fang hospital from Sep 2008 to Dec 2010. All the patients must be exclude from innate immunity defect or hypofunction, chronic diseases and drug taking history of anti-immunity and rejection that affected immunity.2,All the patients underwent a overnight polysomnography study in sleep lab at least 7 hours. Firstly, all were divided into 4 groups according to AHI and LSpO2(see in severe grade classification of OS AHS):normal, mild, moderate, severe. At last, for convienience, we divided the patients into control group(AHI<5, LSPO2≥90%), mild group (AHI 5-14/hr, LSPO2 85-89%), moderate-severe group(AHI≥15/hr, LSPO2<84%).3,For all patients, a medical history was taken using a standard protocol including personal sleep habit; occupation; use of tobacco and alcohol; mental status of daytime and cardiovascular and cerebrovascular history. The point to determined were neck collar, height(NC), weight body mass index(BMI), apnoea hypopnea index(AHI) and lowest pulse oxyhemoglobin saturation(LSPO2).4,The diagnostic criteria of OS AHS:mainly according to medical history, sighs and measure of polysomnography (PSG) during sleep. With typical clinical feature of snoring, irregular breathing during sleep at night, daytime sleepiness (ESS >9 socre) and measurement of PSG show apnoea hypopnea happen repeatedly more than 30 times per night in 7 hours or AHI>5/hr.5,The severity of OS AHS can be divide into three gades:mild AHI 5-14/hr, LSPO2 85-89%), moderate AHI 15-30/hr, LSPO2 80-84%), severe AHI>30/hr, LSPO2<80%) according to AHI and LSPO2, while AHI for the mainly diagnostic criteria, LSpO2 for reference.6,Apnea and hypopnea was defined as follows:a) apnea (absence of oronasal airflow for at least 10 seconds); b) hypopnea (reduction of oronasal airflow by 50% or more accompanied by desaturation and/or arousal); c) desaturation (decrease in LSpO2 of 4% or more compared to previous reading).7,After finishing PSG monitoring in the next day morning, humoral and cellular immunity analysis was performed on peripheral venous blood extracted from a superficial vein in the arm. Nephelometry was used to testing humoral immunity (including C4,C3,IgM,IgA,IgG,CH50) and flow cytometry to cellular immunity including(CD3,CD3+CD4,CD3+CD8,NK).8,207 patients performed humoral immunity testing, while 102 patients cellular immunity with reason of economy.9,Statistical analysis was performed using version 13.0 of the Statistical Package for Social Sciences (SPSS13). Results are expressed both as means (SD) and as absolute values. For the comparison of quantitative variables in three groups, we used analysis of variance(ANOVA), applying LSD method in multiple comparisons when the variance was homogeneity; when the variance was not homogeneity, we used the robust test of equality of means of Welch, applying Dunnett's T3 method in multiple comparisons.The correlations between quantitative variables were assessed using Pearson's correlation coefficient. Significance was set at a value of P less than 0.05.Result:1,Of the 207 patients enrolled in the study,190 were(91.8%) men and 17(8.2%) were women. Mean(SD) age was 44.6(11.7) years, mean BMI was 28.21(5.00) kg/m2, mean NC was 40.59(3.74) cm, mean AHI was 37.47(27.40)/hr and mean LSpO2 was 75.80(11.90)%.2,The test of homogeneity variance of Age, NC and BMI using Levene test showed the variances were homogeneity (P=0.46, P=0.47 and P=0.20),while heterogeneity in AHI and LSpO2 (both P<0.01); The total variance of age had no significant difference when comparing with each other in the three groups (F=0.169, P=0.844), but a significant difference in NC and BMI (F=8.268, P<0.01和F=29.706, P<0.01) which needed multiple comparison; The robust test of equality of means of AHI and LSpO2 using Welch method showed there was a significant difference between the three groups (F=342.305,P<0.01 and F=119.852,P<0.01) and then needed multiple comparison. LSD test was used in NC and BMI to compare with each other in three groups:there was a significant difference in NC when comparing the moderate-severe groups with control and mild groups(both P<0.01), when comparing the control group with mild group there was no significant difference (P>0.05); there was a significant difference in BMI when comparing the moderate- severe groups with control and mild groups(P=0.001 and P=0.004), when comparing the control group with mild group there was no significant difference (P>0.05); Dunnett's T3 method was used in AHI and LSpO2 to compare with each other:there was a significant difference in AHI when comparing the moderate-severe groups with control and mild groups and when comparing the control group with mild group (both P<0.01); there was also a significant difference in LSpO2 when comparing the moderate- severe groups with control and mild groups and when comparing the control group with mild group (both P<0.01).3,Of the 207 patients in humoral immunity testing,20 were control group,32 were mild group,155 were moderate- severe group; and 102 patients in cellular immunity testing,20 were control group,25 were mild group,57 were moderate- severe group.4,About humoral immunity:The test of homogeneity variance of C4, C3, IgM, IgG and CH50 using Levene test showed the variances were homogeneity (P=0.95, P=0.22, P=0.18, P=0.83 and P=0.46),while heterogeneity in IgA (P=0.04); The total variance of C4, IgG and CH50 had no significant difference when comparing with each other in the three groups(F=0.120, P=0.887 and F=0.589, P=0.556 and F=1.294, P=0.276), while needed not multiple comparison; but a significant difference in C3 and IgM(F=7.307, P=0.001 and F=4.523, P=0.012), which needed multiple comparison; The robust test of equality of means of Ig A using Welch method showed there was no significant difference between the three groups (F=1.177,P=0.318) and needed not multiple comparison. LSD test was used in C3 and IgM to compare with each other in three groups:there was a significant difference in C3 when comparing the moderate-severe groups with mild and control groups(P=0.001 and P=0.042), when comparing the control group with mild group there was no significant difference (P>0.05); there was a significant difference in IgM when comparing the control groups with mild and moderate- severe groups(P=0.013 and P=0.003), when comparing the mild group with moderate-severe group there was no significant difference (P>0.05)。5,About cellular immunity:The test of homogeneity variance of CD3+, CD3+CD4+ and CD3+CD8+ using Levene test showed the variances were homogeneity (P=0.71, P=0.41 and P=0.06,),while heterogeneity in NK cell (P<0.01); The total variance of CD3+, CD3+CD4+ and CD3+CD8+ had no significant difference when comparing with each other in the three groups (F=2.329, P=0.103 and F=1.153, P=0.320 and F=1.580, P=0.211), while needed not multiple comparison; The robust test of equality of means of NKcell using Welch method showed there was a significant difference between the three groups (F=10.838,P<0.01)and needed multiple comparison. Dunnett's T3 method was used in NK cell to compare with each other in the three groups:there was a significant difference in NK cell when comparing the control group with mild and moderate-severe groups (P=0.038 and P=0.001); there was also a significant difference when comparing the mild group with moderate- severe group (P=0.025).6,Correlation between AHI, LSpO2 (stand for severity of OSAHS) and level of C3, IgM, and NK cell:The correlation between AHI and C3(r=0.403,P<0.01) was statistical significance with positive correlation; correlation between LSpO2 and C3(r=-0.364,P<0.01) was also statistical significance but with negative correlation. There was no significant correlation between AHI and IgM(r=-0.107, P=0.124), though a statistical significance correlation between LSpO2 and IgM(r=0.154,P=0.027) with weak positive correlation; correlation between AHI and NK cell(r=-0.296,P=0.003) was also statistical significance with weak negative correlation; There was no significant correlation between LSpO2 and NK cell(r=0.117,P=0.076).Conclusions:1,There was a increasing trend on level of C3 and a decreasing on IgM when comparing OSAHS with the healthy in humoral immunity.2,We also found a decreasing trend on level of NK cell when comparing OSAHS with the healthy in cellular immunity.3,AHI and LSpO2 which stand for severity of OSAH had some correlations between level of C3,IgM and NK cell:The correlation between AHI and C3(r=0.403,P<0.01) was statistical significance with a positive correlation; correlation between LSpO2 and C3(r=-0.364,P<0.01) was also statistical significance but with a negative correlation. There was no significant correlation between AHI and IgM(r=-0.107, P=0.124), though a statistical significance correlation between LSpO2 and IgM(r=0.154,P=0.027) with a weak positive correlation(r absolute value 0.154); correlation between AHI and NK cell(r=-0.296,P=0.003) was also statistical significance with a weak negative correlation(r absolute value 0.297); There was no significant correlation between LSpO2 and NK cell(r=0.117,P=0.076). 4,OSAHS was a chronic low grade of inflammatory condition at systemic levels and there were some changes in immunological function, and there maybe had a decreasing on immunological function of OSAHS.5,The deceasing in level of IgM and NK cell in patients of obstructive sleep apnea hypopnea syndrome may lead to an increased incidence of some diseases, such as infection and tumor and so on.