Biochemical Changes in Patients with AsthmaCorrespondence Address :
Dr Amina Hamed Ahmad Al Obaidi Department of Biochemistry,Medical CollegeTikrit University, Email: email@example.com
Background: The changes that occur in diseases in chemical constituents and biochemical mechanisms are of vital importance for homeostasis within the human body.
Aim: The study was performed on asthmatic patients and healthy non asthmatic control subjects to determine the changes in serum levels of some biochemicals in asthma.
Setting and design:A cross â€“ sectional study with matched control.
Methods and materials: A total of 178 sera were used for determination of iron, calcium, very low density lipoprotein (VLDL), lactate dehydrogenase (LDH) and creatine kinase (CK) . The effect of Immunotherapy on serum iron, calcium, VLDL, LDH and CK was evaluated in 169 asthmatic patients after one year of hyposensitization. All the above were determined using a commercial kits and procedures were performed according to manufacturer instructions.
Statistical analysis:Student t test was used to determined the significance of differences.
Results: The iron and calcium serum levels were significantly lower in stable asthmatic group as compared to that in exacerbation asthmatic . Also, serum iron and calcium levels during asthma exacerbation were significantly higher than that in control. Very low density lipoprotein serum level in stable asthmatic patients was significantly higher (P<0.02) than that of asthmatic patients with exacerbation, but it was lower than that in control (P<0.05). Iron, calcium , LDH, and CK serum levels were significantly reduced following vaccination. However, serum VLDL was significantly higher following immunotherapy as compared to that before vaccination.
Conclusions: Serum iron, calcium levels were higher during asthma exacerbation than in stable asthma and control, while VLDL serum level was lower. Immunotherapy for one year reduce serum iron, LDH, CK and calcium levels and increased VLDL serum level.
Asthma, VLDL, LDH, Iron, Calcium, CK
Homeostasis is the name given to the dynamic processes that enable optimum conditions to be maintained for constituent cells, in spite of continual changes taking place both internally and externally.
Whenever an imbalance occurs, regulatory systems become active to restore the optimum conditions. The changes that occur in diseases in chemical constituents and biochemical mechanisms are of vital importance for homeostasis within the human body. These changes may be either underlying cause of the disease or the outcome sequences. Thus body fluids analysis for determination of the above changes was an important approach that aid clinicians for diagnosis, treatment, monitoring of the disease and elucidation of disease pathogenesis.
Generally, Iron metabolism is of crucial importance in the biology and pathophysiology of the lower respiratory tract. As with many other factors involved in inflammation, it is very important that an appropriate iron balance is maintained. Local deficiency could impair growth and proliferation of cells responsible for the inflammatory response and tissue repair and the synthesis of mediators(1). In contrast, excessive accumulation of iron, especially in free form that is, not bound to one of the specific iron-binding proteins facilitates the generation of potentially toxic hydroxyl radicals (2).
Surfactant synthesis is critically dependent on the availability of fatty acids. One fatty acid source may be circulating triglycerides that are transported in very low density lipoprotein (VLDL), and hydrolyzed to free fatty acids by lipoprotein lipase. Indeed, surfactant phospholipids synthesis is stimulated by VLDL (3).
Interest in the pathogenetic mechanisms of lung injury has focused on the cellular and biochemical mediators considered as potential biological markers of lung injury. Cytoplasmic cellular enzymes, like lactate dehydrogenase (LDH) in the extra cellular space, although of no further metabolic function in this space, are of benefit because they serve as indicators suggestive of disturbances of the cellular integrity induced by pathological conditions. If cell lyses occurs, cytoplasmic enzymes, such as LDH are released into the extra cellular space. Therefore, the extra cellular appearance of LDH is used to detect cell damage or cell death (4).
Since calcium is the major second messenger regulating ASM contraction, investigators (5) hypothesized that abnormalities in calcium homeostasis, manifested by increases in the flux of calcium or alteration in calcium regulatory proteins, may play a critical role in inducing ASM hyper reactivity in asthma. Thus this study was conducted to determine serum levels of different biochemical parameters in asthma and the effect of immunotherapy on their levels.
The study was performed on asthmatic patients and healthy non asthmatic control subjects. A total of 178 sera were used for determination of iron, calcium, VLDL, LDH and CK. The effect of Immunotherapy on serum iron, calcium, VLDL, LDH and CK was evaluated in 169 asthmatic patients after one year of hyposensitization. Their age range was from 17 to 52 years. The subjects included in the study were outpatients from the Asthma and Allergy Centre or Samara General Hospital outpatients Clinic. The diagnosis and classification of asthma was performed by specialist physician and was established according to the National Heart Blood and Lung Institute / World Health Organization (NHLBI/WHO) workshop on the Global Strategy for Asthma (6). Subjects were considered atopic by positive skin tests to at least one common aeroallergen. Patients were excluded if they were smokers, if they had respiratory infection within the month preceding the study, a rheumatological illness, malignancy, diabetic, heart failure, history of venous embolisms, coronary heart disease and liver or kidney diseases.
At enrolment, they all underwent full clinical examination, pulmonary function test, and blood sampling. Sputum samples were collected from patients when indicated. Normal volunteers were also enrolled in the study as a healthy control. None of them had any previous history of lung or allergic disease and were not using any medication. They had a normal lung function test (FEV1 > 80%) and negative skin allergy test. General stool examination was performed for all patients and control to exclude parasitic infections. Acute asthma exacerbation was defined as dyspnea and wheezing with or without increased coughing (6). The sampling performed during the period from May 2004 to December 2005. All samples collected at morning following overnight fasting. The study was approved by the college ethics committee and a written informed consent was taken from subjects.
Determination of Biochemical Parameters:
Serum levels of Determination of iron, calcium, Triglycerides, LDH, and CK were determined using commercial kits, and the procedures performed according manufacturer instructions.
The values are reported as mean Â± SD and 95% confidence interval. For statistical analysis between groups paired t test was used. The levels of each marker were compared between the study groups and control group, using SPSS computer package. P values of < 0.05 were considered significant.
Biochemical Changes in Asthma:
The iron serum level was significantly lower (P<0.0001) in stable asthmatic group (78.21 Â± 26.24 Âµg/dl) as compared to that in exacerbation asthmatic (113.23 Â± 45.47 Âµg/dl). However, no significant difference from that for control group (83.25 Â± 29.43 Âµg/dl) was achieved. Also, serum iron level during asthma exacerbation (113.23 Â± 45.47 Âµg/dl) was significantly higher (P<0.0001) than that in control (Table/Fig 1).
Calcium serum concentration in stable asthmatic patients was significantly lower (8.21 Â± 2.28 mg/dl, P<0.0001) than that of asthmatic with exacerbation (10.98 Â± 2.53 mg/dl). In addition, serum calcium concentration was significantly higher (P<0.001) in asthmatic during exacerbation (10.98 mg/dl) than that of control (8.23 Â± 3.46 mg/dl). However, calcium serum concentration in stable asthmatic was similar to that of control.
Very low density lipoprotein serum level in stable asthmatic (31.89 Â± 17.02 mg/dl) not significantly different (P>0.05) from that of control (31 Â± 13.9 mg/dl). However, VLDL serum of stable asthmatic patients was significantly higher (P<0.02) than that of asthmatic patients with exacerbation (25.19 Â± 12.69 mg/dl). Furthermore, VLDL serum level in asthmatic with exacerbation was significantly lower (P<0.05) than that of control subjects.
Effect of Immunotherapy on Iron, Calcium, VLDL, LDH, and CK Serum Levels in Asthmatic Patients:
Iron serum level was significantly reduced (P<0.001) from 88.44 Âµg/dl (Â± 38.56) before vaccination to 66.19 Âµg/dl (Â± 3.75) after vaccination. Calcium serum level was significantly reduced (P<0.001) from 9.02 mg/dl (Â± 2.74) before vaccination to 8.15 mg/dl (Â± 3.49) after vaccination. However, serum VLDL was significantly higher (P<0.02) following immunotherapy (33.97 Â± 19.61 mg/dl) as compared to that before vaccination (29.28 Â± 14.49 mg/dl) (Table/Fig 2).
Serum LDH was reduced significantly(P<0.001)from 334.6 IU/l (Â±120.9) before vaccination to 197.53 IU/l (Â± 67.82) after immunotherapy. Also creatine kinase reduced significantly (P<0.001) following immunotherapy, so it was reduced from 239.7 IU/l (Â± 135.8) to 106.3 IU/l (Â± 96.4) following immunotherapy(Table/Fig 2).
Asthma is a chronic inflammatory disease of the airways and ROS/RNS are suggested to contribute to its pathology. Data on several ROS/ NOS profile as well as the presence of iron and iron binding proteins in different lung compartments, also the amount of iron and its distribution in different pulmonary diseases have already been reported (1),(7),(8). However, more studies on the matter are needed in view of the increasing incidence of asthma and because many questions about iron metabolism and its relation with the metabolisms of other related parameters in the lung remained unanswered (9). For example, the relationship between nitric oxide and iron as well as the participation of myeloperoxidase (MPO) in to this association and role of iron in the defense against infectious agents in the lung is not fully understood (9).
Indeed, Catalase which is an antioxidant enzyme contains iron and therefore iron is a critical element in much oxidative reaction (2). Free irons as a transition metal that participate in the generation of free radicals catalyze the transformation of H2O2 to the highly reactive hydroxyl radical via the Fenton and Haber- Weiss reactions (1). Thus high body iron stores increase free radical production and may elevate asthma risk (10).
Our findings, indicated that serum iron in stable asthmatic patients not differ significantly from that of control. However, in patients with exacerbation, the serum level of iron was significantly higher than that in patients with stable asthma and control. This results is in agreement with that found by others (9),(10). Whereas, Vural et al (11) reported that serum iron level in asthmatic not significantly different from control group.
In fact, mediators, including NO released during chronic inflammation were shown to increase heme oxygenase expression in asthmatic patients (9). Heme oxygenase reaction, with its products bilirubin, carbon monoxide and free iron, is interpreted as an antioxidant defense mechanism due to release of bilirubin (10). However, free iron, a catalyst during ROS production, is another product of this reaction and therefore may possess some inflammatory effects (9). The usual source of iron in the lung is serum iron, which is derived from catabolized erythrocytes and absorbed iron (1). Metabolism of Iron is of a crucial importance in the biology and pathophysiology of the lower respiratory tract . As with many other factors involved in inflammation, it is very important that an appropriate iron balance is maintained. Excessive accumulation of iron exerts toxic effects through its ability to catalyze formation of highly reactive hydroxyl radicals (1).
Studies have reported that nitric oxide synthase can bind transition metals, however, only iron increased the rate of the reaction, whereas others, e.g. nickel and cobalt inhibited the reaction or without effect like manganese. On the other hand, NO was reported to cause iron release from erythrocytes (1). Serum iron levels were reported to have only limited importance for diagnosis and prognosis of bronchial asthma and the estimation of this parameter were recommended in special cases only (12).
Reports on serum iron levels in bronchial asthma are scare [9-12]. In one report, no change was detected in serum iron levels in patients with asthma as compared to controls (11). However, significantly increased serum iron levels in asthmatic patients were found in this study, and our finding was consi
In Conclusions, serum iron, calcium levels were higher during asthma exacerbation than in stable asthma and control, while VLDL serum level was lower. Immunotherapy for one year reduced serum iron, LDH, CK and calcium levels and increased the VLDL serum level.
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