作者:caroline e omotil1, egbagbe eruke elizabeth2
【摘要】 objective: to assess the haematological and lipid profile assays in asthmatics. methods: eighty asthmatic subjects were prospectively studied in a major referral centre serving the niger delta region of nigeria for 12 months (20062007). clinicohaematological and serum lipid total cholesterol (tc), triglyceride (tg), and lipoproteins concentration were analyzed after adjusting for age, cigarette smoking, alcohol ingestion, hypertension and diabetes mellitus. results: eighty patients (34 males and 46 females) were seen with female predominating in the various age groups (m∶f ratio, 0.7∶1). total cholesterol and low density lipoproteinscholesterol for the asthmatics was significantly higher than the controls (p<0.000 1), while the ratio of tc∶hdlc(high density lipoproteincholesterol) in asthmatics was 3.67 compared to the control value of 3.01. tc and low density lipoproteincholesterole( ldlc) were significantly higher in females than the males (p<0.05). there was a combined hypertriglyceridemia (ht, >2.3mmol/l) and a significant hypercholesterolemia (hc, >5.2mmol/l) according to the adult treatment panel iii definition in asthmatics thereby putting them at increased risk for the development of cardiovascular disease as well as other disorders related to excess lipids. there was a significant thrombocytopenia (p<0.000 1) which may accompany allergen exposure and this persists for 24 h; that asthmatics of african descent showed a significantly increased total leucocyte count (p=0.001) similar to other studies in the western countries. conclusion: hyperlipidaemia is a prevalent medical problem among asthmatics; hence screening for fasting serum lipid levels to identify those who need early intervention is recommended.
【关键词】 asthma; lipidaemia; haematological values; hypercholesterolemia
introduction
lipid and lipoprotein assays (lpa) form one of the special investigations in vascular disease conditions[14] and in most chemical pathology laboratories worldwide. the importance of lpa is fast increasing in many developing countries including nigeria. dyslipidaemia has been found to occur as a result of change in diet to high fatty foods (high levels of saturated fats elevate serum lipids) caucasian lifestyle[57]. lpa and its application in the management of patients with cardiovascular diseases (including ischaemic heart disease) and monitoring of diabetic patients has been emphasized[8, 9]; while on the contrary there is paucity of information on lpa levels in asthmatics. alshawwa et al[10] in a recent report stated that the effect of hyperlipidaemia (hl) on asthma has not been fully addressed; and concluded that hypercholesterolemia is a potential risk factor independent of obesity. recent literature implicates a proinflammatory role for hypercholesterolemia in asthma with multiple cell types involved in the pathophysiology of asthmatics.
hyperlipidaemia, a combination of hypertriglyceridaemia (ht) and hypercholesterolemia (hc) may either primarily be due to genetically determined disorders or secondary as a result of acquired causes[1115]. these include obese individuals, alcoholics, individuals of high social status as well as malnourished children[16]. several studies, however, have shown beneficial effects of reversing hyperlipidaemia by either primary or secondary prevention[1719]. this has been well established in various disease conditions and consequently the need to have a separate reference value for asthmatics in our centre. hence this study was designed to assess the haematological and lpa order to evaluate it as a possible risk factor. the outcome of this study will enhance our perception of dyslipidaemia as a current and actively progressive medical problem that can be contained by different measures to prevent its complications.
materials and methods
a total of 80 consecutive asthmatics attending the adult medical outpatient clinic of university of benin teaching hospital (ubth), a major referral centre serving the niger delta region, nigeria were prospectively studied (20062007). diagnosis of asthma was determined by the treating physician (history and examination of patients, reversibility test and exercise test for young patients). cases who may present to the clinic with mild ailments such as cold and fever that are not known to affect lpa concentrations were included. the lpa levels of adults without a history of asthma or wheezing were included to serve as nonasthmatics ageandsex matched controls (male and female). ethical committee approval was obtained from the ethical committee of the hospital after informed consent. clinicohaematological and lp levels were analyzed after adjusting for age, cigarette smoking, alcohol ingestion, hypertension and diabetes mellitus. other personal data and medical history obtained include the gender, demographic features, drug therapy, pulse rate and blood pressure.
laboratory and assay methods
the subjects were fasted over night (1214 hours) and 10ml of venous blood was obtained from the antecubital veins after routine aseptic procedure. the lpa was assayed using already standardized and well established methodologies[2023]. all assays were performed using kits manufactured by human diagnostic laboratory (wiesbaden, germany). total cholesterol (tc) was done using the modified liebermannburchards method of abell et al[20] and high density lipoproteincholesterol (hdlc) by precipitation method[21]. triglyceride (tg) was assayed using enzymatic colorimetric method after hydrolysis of the tg[22]. low density lipoproteincholesterol (ldlc) was calculated by indirect method using friedewald et al[23] equation summarized as follows: ldlc=[tc][hdlc]tg/2.2 the current adult treatment panel (atp) iii[24] in comparing the values was adopted and all concentrations are given in millimoles per litre. blood samples collected haematological counts were analyzed using an automated coulter tm counter.
data analysis
statistical analysis was performed using instat graph pad software version 2.05a. means and sd/sem were determined for quantitative data and frequency determined for categorical values. student ttest was used to test for significant association; anova was used to compare multiple means. p<0.05 was considered statistically significant.
results
a total of 80 asthmatic patients seen during the study period (jan 2006dec 2007) were compared with 84 nonasthmatic ageandsex matched controls (male andfemale). the asthmatics comprised of 34 males (42.5%) and 46 females (57.5%) giving a maletofemale ratio of 0.7∶1; with female predominating in all the various age groups (table 1). the overall median age was 54 years (range: 2670years) with a mean of 52±13years. the age and sex distribution for the asthmatics is shown in table 1. the most frequent age group range observed was 4160years (65%) with 18 patients (22.5%) less than 40years. the patients were on various forms of asthmatic therapies which included short acting b2adrenoceptor agonists e.g. salbutamol plus a corticosteroid e.g. fluticasone propionate (34 patients), 26 patients (32.5%) each were on either salbutamol or seretide only and 2 patients (2.5%) on leukotriene inhibitors e.g. zafirlukast.
the total serum lp concentrations of asthmatics compared with controls are shown in table 2. total cholesterol and ldlc for the asthmatics were significantly higher than the controls (p<0.0001) using the adult treatment panel iii (atp iii) classification.24 the hdlc of the patients were also higher than the controls but the difference was not significant (p>0.05). the ratio of tc: hdlc in asthmatics was 3.67 compared to the control value of 3.07. table 3 shows the median values and ranges of lp levels classified by sex. in this study tc and ldlc were significantly higher in females than the males (p<0.05). the fasting blood sugar of the female (78 mg/dl) were also significantly higher (p=0.005 5) than the male (70 mg/dl) asthmatics. the haematological counts as shown in table 4 were significantly lower than the controls while the total leucocyte count were significantly higher than the controls (p=0.001).
table 1 age and sex distribution of asthmatics at the time of presentation.
biologic featuresn(%)sex (m∶f)34∶4642.5∶57.5age (years), m∶f∶t21301∶3∶45.031405∶9∶1417.5415010∶18∶2835.0516013∶9∶2227.5>605∶7∶1215.0
mean serum lipid and lipoprotein findings of asthmatics at presentation over the study period.
parameterspatient value (n=80)control value(n=84)p valuetotal cholesterol(mmol/l)5.24.0<0.000 1triglyceride(mmol/l)2.93.0nsldlc (mmol/l)3.22.1<0.000 1hdlc (mmol/l)1.41.3nsfasting blood sugar(mg/dl)83.062.0<0.000 1
ldlc: low density lipoproteincholesterol; hdlc: high density lipoproteincholesterol; nsnot significant.
table 3 the mean, median values (and ranges) of serum lipid and lipoproteins according to sex in asthmatic patients over the study period.
parametersmale (n=34)female (n=46)meanmedianrangemeanmedianrangep valuetotal cholesterol (mmol/l)4.4167.1412455.32021532740.003 0triglyceride (mmol/l)2.595.0402303.011541178nsldlc (mmol/l)3.1118.5851773.3126592220.011 0hdlc (mmol/l)1.454.038971.66125100nsfasting blood sugar (mg/dl)73.070.05012277.078391000.005 5
table 4 summary of blood counts of the asthmatics at presentation(±sd).
laboratory blood countsasthmatic patients (n=80)control value (n=84)p valuehaemoglobin (g/dl)12.65±0.1812.93±2.22nstotal leucocyte count (×109/l)6.08±0.245.71±0.970.001 0platelet count (×109/l)220.5±10.8304.2±61.5<0.000 1mean cell volume (fl)84.0±0.7684.5±5.26nsmean cell haemoglobin (pg)27.5±0.3030.2±3.0<0.000 1mean cell haemoglobin concentration (g/dl)32.7±0.1830.6±1.04<0.000 1
discussion
extensive research on lipids and lipoprotein profile has been carried out in various disease conditions especially cardiovascular/coronary artery disease (cad)[2527] and diabetes mellitus[28, 29]. current epidemiologic studies have even shown that dyslipoprotienaemia with low concentration of hdlc and elevated serum tg is associated with a particularly high incidence of cad[30, 31]. however, there is paucity of information on the role and pattern of lpa in asthmatics in africa and in the diaspora. the findings in this study could therefore serve to evaluate the pattern of lipid profile in relation to age and sex distribution in asthmatics.
the values of lpa in adults are consistent with the general knowledge on factors affecting biochemical analytes worldwide. factors such as age, geographical location, diet, extent of exercise regimen, obesity lifestyle and genetics influence the serum lipid levels in all categories of people[32, 33]. the common denominator would be lack of physical activity associated with unhealthy eating habits; as dietary modification has been reported to contribute to the overall health of asthmatics[34]. the serum lipid concentrations from an early age of one to 15years fluctuate after which they remain stable through to old age[35]. the mean age of the studied asthmatics was 52±13years with females predominating (57.5%). the lp concentrations have also been noted to be different at the gender level[36]. the female lp concentrations in this study were all higher than the male values probably because of the endogenous sex hormonal variations in women.
our study revealed a combined hypertriglyceridemia (ht, >2.3mmol/l) and a significant hypercholesterolemia (hc,>5.2mmol/l) according to the atp iii definition. the recommendation of atp iii adopted "the lower, the better" for cholesterol level; therefore a cutoff value of 5.2mmol/l was adopted to define hc. from the analysis of data obtained here, it shows that hl is common in asthmatics thereby putting them at increased risk for the development of cad as well as other disorders related to excess lipids. alshawwa et al. also reported that hc is a potential risk factor for asthma independent of obesity[10]. in a related study combination of cvd with asthmatics was observed in 88.3% of patients[37]; and another study detected various cvd of varying severity in asthmatic patients[38]. there was also a low hdlc level and elevated serum tg in this study which is associated with a high risk of cad; thus providing an additional risk factor in asthmatics as seen in cardiovascular diseases. it has even been suggested that hc is a significant factor in the development of atherosclerosis and that there is a correlation between the hc in childhood and the stage and extent of atherosclerotic lesions[39, 40]. this has led various organizations (national cholesterol education program and american pediatric academy) to improve cholesterol screening programs to determine individuals in early stage who were predisposed to atherosclerosis; and to recommend a reduction in the amount of cholesterol and saturated fat in the diet of the whole population[41,42]. although high plasma hdlc levels prevent the deposition of vascular cholesterol and development of atherosclerosis, the elevation of ldlc level (>3.0mmol/l) which is the major carrier of cholesterol leads to the early development of atherosclerosis. the elevated ldlc as recorded in our study has been known to be susceptible to lipid peroxidation which increases its atherogenic potential. this is due to the fact that the oxidative and peroxidative forms of ldlc could not be removed from the plasma via ldl receptors in normal cells and accumulates in the atherosclerotic lesions via alternative receptors of the macrophages and endothelial cells, thus stimulating the hypertrophy of blood vessel wall.
platelet activation is one of the aspects of cellular interaction causing inflammation in asthma, including tlymphocytes, mast cells and eosinophils[4345]. our study revealed a significant decrease in platelet count compared to the controls but was not in the thrombocytopenic range (<150×109/l). it has been suggested that persistent thrombocytopenia accompanies allergen exposure and persists beyond changes in airway obstruction at a time when airway inflammation is present. in another study of thrombocytopoesis in allergic asthma, the platelet count was found to be statistically higher in allergic asthma patients compared with healthy controls[44]. in nonallergic asthma patients the platelet count was also higher but the difference was not statistically significant. the percentage of the reticulated platelets in allergic asthma patients was statistically higher as compared to nonallergic and healthy subjects, who had similar values. the concentration of il6 was significantly elevated in allergic asthma patients as compared to healthy controls. there was no difference in il6 levels between both asthma patient groups. in nonallergic asthma patients plasma thrombopoietin levels were slightly higher, but not statistically significant, in comparison with allergic asthma patients and controls. it was therefore concluded that platelets may be involved in allergic inflammation and play a significant role in remodeling of the airways[44]. previous work has shown that allergic asthmatics have altered platelet survival[46] and that there is a fall in the circulating platelet count accompanying the airway obstruction seen after allergen inhalation in susceptible individuals[47]. one explanation for this loss of platelets from the peripheral circulation during an asthma attack is that this is due to migration of platelets from the circulation to the airways, as has been demonstrated both experimentally[48] and clinically[49,50] as part of the overall inflammatory response seen in asthma. simple postural changes are, however, known to affect platelet count, possibly by altering the blood volume in different body compartments[51]. it is therefore of importance to also consider that the immediate mechanical effects of bronchoconstriction, particularly changes in intrathoracic pressures during the respiratory cycle, might also contribute to this change in the circulating platelet count. hence, the observed thrombocytopenia following allergen challenge in atopic asthmatics that persists for 24 h, a time when bronchoconstriction has resolved, but when inflammatory changes persist. these observations add to the body of evidence suggesting an involvement of platelets in allergic asthma.
platelet activating factor (paf) holds the leading role among allergy mediators in pathogenesis of bronchial asthma. paf ability to induce bronchospasm is manifested in the presence of intact platelets. platelet function in patients with atopic and nonimmunologic aspirininduced asthma was investigated[52]. aggregation increase (platelet activation) correlating with ige level and mediator release from target cells of i order was stated to be the most important component of pathologic process in atopy. under the influence of aggregation inducers (adp and adrenaline) in platelets of patients with atopic asthma the level of camp is reduced, greater amounts of txb2 and pgf2 alpha are produced. in cyclooxygenase blockade their production is not stopped. the decrease of platelet ability to aggregate is observed in patients with nonimmunologic aspirininduced asthma. in nonstimulated platelets high levels of pgf2 alpha and txb2 are noted[52].
the bronchial epithelium in asthamatics is an important physical barrier that regulates physiological processes including leukocyte trafficking. multiple cell types have been reported to be involved in its pathophysiology. total leucocyte count was significantly higher in asthmatic patients than in controls (p=0.0011). this may be due to eosinophilia and possibly, neutrophilia which may be presented in asthma (or where allergy plays a significant role). eosinophil accumulation in peripheral blood and tissues is a hallmark of atopic disorders including asthma[5355]. blood eosinophils are known to be an indirect marker of airway inflammation in asthma.[53,54] asthmatics with exerciseinduced bronchoconstriction (eib) have been reported to show a significantly increased total eosinophil count compared with asthmatics without eib[56,57]. even in nonatopic asthmatics, those with eib showed significantly increased total eosinophil count (tec) compared with those without eib[57]. neutrophils are activated and are able to release mediators that promote and prolong asthma symptoms[58]. increasing evidence suggest that neutrophils may be central players with an important role in the pulmonary inflammatory process presented in asthma[58].the mechanisms by which neutrophils contribute to the pathophysiology of asthma remain to be elucidated; however, neutrophils may affect either accumulation or functional status of eosinophils via the generation of inflammatory mediators[59]. a recent study suggest that accumulated neutrophils may contribute to the development of eosinophilic inflammation in severe persistent asthmatics who were treated with oral and highdose inhaled corticosteroids[59]. reports suggest that the enhanced chemotactic activity of the epidermal growth factor (egf)conditioned epithelium can enhance neutrophilmediated immunity during acute injury, while during continued injury and repair, as in chronic asthma, this could contribute to persistent neutrophilic inflammation[60].
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