|Year : 2014 | Volume
| Issue : 3 | Page : 148-152
Plasma high sensitivity c-reactive protein level in children with asthma seen at Aminu Kano teaching hospital, Kano
BI Garba1, M Ibrahim2, A-WBR Johnson3, IA Yahaya4
1 Department of Paediatrics, Yariman Bakura Specialist Hospital, Gusau; Department of Chemical Pathology, Aminu Kano Teaching Hospital, Kano State, Nigeria
2 Department of Paediatrics, Umaru Musa Yar'adua University, Katsina State, Nigeria
3 Department of Paediatrics and Child Health, University of Ilorin Teaching Hospital, Ilorin, Kwara State, Nigeria
4 Department of Chemical Pathology, Aminu Kano Teaching Hospital, Kano State, Nigeria
|Date of Submission||20-May-2014|
|Date of Acceptance||23-Jul-2014|
|Date of Web Publication||17-Aug-2014|
B I Garba
Department of Paediatrics, Yariman Bakura Specialist Hospital, Gusau, PMB 1010, Gusau, Zamfara State
Source of Support: None, Conflict of Interest: None
Background: Exact pathogenesis of asthma is unknown, however the hallmark of asthma is airway inflammation and bronchoconstriction. C-reactive protein (CRP) participates in the systemic response to inflammation and is useful in assessing airway inflammation and asthma severity. Objectives: To measure the plasma levels of high sensitivity-CRP (hs-CRP) in asthmatic and nonasthmatic children, to assess the association between demographic parameters and peak expiratory flow rate with a high level of hs-CRP and also to determine if hs-CRP is a predictor of asthma severity. Materials and Methods: A case-control study in asthmatics and nonasthmatics aged 4-15 years at Aminu Kano Teaching Hospital, Kano. Controls were age and gender matched; without asthma or other atopic conditions. The plasma level of hs-CRP was determined by particle enhanced turbidimetric method. Statistical Analysis: Appropriate statistical tests for quantitative and categorical variables were determined using SPSS. A P value < 0.05 was considered statistically significant. Results: Of the 70 stable asthmatics and 70 controls recruited, 50 (71%) were males and 20 (29%) females. The male to female ratio in both groups was 2.5:1. Fifteen of the asthmatics had attack during the study period. Twenty-five (35.7%) stable asthmatics and 12 (17.1%) of the controls had high-plasma level of hs-CRP. All 15 (100%) asthmatics that presented with an attack had high-plasma level of hs-CRP. Mean ± standard deviation hs-CRP of asthmatics with attack was 21.67 ± 6.57 mg/L which was significantly higher than that of stable asthmatics (9.68 ± 6.85 mg/L, P < 0.0001) and control group (6.96 ± 4.30 mg/L, P < 0.0001). Conclusion: Mean plasma hs-CRP levels was significantly higher (P < 0.001) in asthmatics with attack than stable asthmatics and controls. Plasma levels of hs-CRP may be a good indicator of respiratory airway inflammation.
Keywords: Airway inflammation, asthma, children, high sensitivity-C-reactive protein
|How to cite this article:|
Garba B I, Ibrahim M, Johnson AW, Yahaya I A. Plasma high sensitivity c-reactive protein level in children with asthma seen at Aminu Kano teaching hospital, Kano. Sub-Saharan Afr J Med 2014;1:148-52
|How to cite this URL:|
Garba B I, Ibrahim M, Johnson AW, Yahaya I A. Plasma high sensitivity c-reactive protein level in children with asthma seen at Aminu Kano teaching hospital, Kano. Sub-Saharan Afr J Med [serial online] 2014 [cited 2023 Mar 27];1:148-52. Available from: https://www.ssajm.org/text.asp?2014/1/3/148/138948
| Introduction|| |
Asthma is a multifactorial disease which is, as a result, of interactions between genetic predisposition to allergic diseases and environmental factors that serve to enhance allergic inflammation and target inflammation to the lower airway.  It is a complex clinical syndrome with many clinical phenotypes in both children and adults.  Chronic inflammation causes an associated increase in airway hyper responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. These episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment. ,
The acute phase response of plasma proteins is a normal response to tissue injury hence a fundamental aspect of many diverse disease processes.  This response usually has a net beneficial function in limiting damage and promoting repair but in some circumstances, it may have pathological consequences.
C-reactive protein (CRP) is an acute phase reactant produced by the liver, and it is a phylogenetically highly conserved plasma protein that participates in the systemic response to inflammation. Its plasma concentration increases during inflammatory states and is a highly sensitive marker of inflammation, infection and tissue damage which contributes to host defense against infection by activating the complement pathways. , Both CRP and high sensitivity CRP (hs-CRP) tests measure the same molecule in the blood, the difference is that hs-CRP measures small amount of CRP in the blood. 
Although most of the studies have been conducted in adults, ,,,, the few data arising from pediatric subjects with asthma , have shown that CRP is a useful marker of systemic inflammation in patients with asthma.
A cross-sectional study observed CRP to be higher in asthmatics than in the control group and also found asthma to be associated with systemic inflammation as indicated by an increase level of systemic markers of inflammation with a significant reduction in the levels of systemic inflammation after treatment. 
Another  study in children determined the concentration of hs-CRP to be significantly higher in patients with asthma and allergic rhinitis compared to healthy children. Similarly, another cross-sectional study done by Arif et al.  in United States demonstrated higher serum level of CRP was associated with asthma, wheezing and nocturnal cough. Subjects with asthma had higher levels of CRP than subjects without asthma.
Olafsdoltir et al.  carried out a multicenter epidemiological study in three countries and found high levels of hs-CRP to be significantly associated with respiratory symptoms and nonallergic asthma but not with allergic asthma. Soferman et al.  in Israel compared hs-CRP concentration in acute exacerbation of asthma and after treatment, and found it to be significantly higher in the acute attack as compared with posttherapeutic state.
Al Obaidi et al.  found serum CRP to be significantly higher in asthmatic patients as compared to the control group. In asthmatics with attack, it was significantly higher than in stable asthmatic patients and control subjects.
There have been no local studies done on plasma hs-CRP in asthmatic children which justified the need for the study.
| Materials and methods|| |
This was an observational case control study in 70 children with asthma aged 4-15 years conducted over a 3 months period at Aminu Kano Teaching Hospital (AKTH), Kano. The aim was to determine the plasma level of hs-CRP in asthmatic children, association between demographic parameters and peak expiratory flow rate (PEFR) with a high level of hs-CRP and also to determine value of hs-CRP as a predictor of asthma severity. Children whose parents or guardian consented to the study were recruited consecutively. Their bio-data, demographic and physical examination were documented.
The subjects were children with asthma attending emergency pediatric unit (EPU), pediatric outpatient department (POPD) and cardio-pulmonary clinic of AKTH, Kano. Asthmatic children that have intercurrent infections and those with chronic respiratory or cardiac diseases were excluded.
Children without asthma matched for sex, age and height that attended EPU and POPD of AKTH, Kano were used as controls. They included children that had no family history of asthma or other atopic diseases, those that presented to the POPD with conditions that do not commonly lead to increase in hs-CRP level.
The subjects were stratified into age groups as follows: 4-5 years, 6-10 years and 11-15 years.
Ethical approval was obtained from the Medical Ethics Committee of AKTH, Kano. The individual written informed consent was however obtained from the respective parent or guardian and children >7 years gave their assent.
Data were collected using a pretested interviewer administered questionnaire which was administered by the researcher and trained assistants to the parent/guardian and the child in both study groups. Only relevant sub-section of the questionnaire was administered to the control group.
The PEFR was determined using the mini-Wright Peak Flow Metre ® (Aimed Clement Clarke, England). This was calibrated in litre/minute (L/min) up to 900 L/min. The subjects were taught how to blow through the meter at the peak of deep inspiration with maximum effort and without air leak around the mouthpiece.
Asthmatic children presenting with attack were asked to come back after 2 weeks for another reading during the stable state, hence such children had PEFR readings done on two different occasions. It was also done on two different occasions in asthmatic children that were seen during stable state who later presented with an attack during the study period. However, it was done only once when they were seen during stable state and did not have an attack during the study period. The control group also had three readings with the highest value recorded reported as their PEFR on one occasion.
Five milliliter of blood was transferred into a labeled lithium heparin bottle and thoroughly mixed by rocking the bottle gently. Quantitative determination of hs-CRP in serum by particle enhanced turbidimetric method using COBAS INTEGRA 400 plus system (Roche Diagnostics GmbH, D-68298 Mannheim, Germany, 2007). Plasma hs-CRP level <10 mg/L was considered normal and value >10 mg/L as high.
Asthmatic subjects were sampled during stable state; those who later presented with an attack had another blood sampling done. Asthmatic subjects who presented initially with an asthma attack also had blood samples taken, but with repeat sampling done 2 weeks after resolution of symptoms. However, blood sampling was done once when seen during the stable state and did not present with attack later during the study period. Blood sampling was also done once in the control group.
Data were entered into a Statistical Package for Social Sciences version 16 for cleaning and analysis. Quantitative variables were summarized using mean and standard deviation (SD). Categorical variables were summarized using frequency and percentages. Means were compared using Student's t-test while Chi-square test and Fisher' exact test (for sample size <5 in a cell or more) were used for association between categorical variables. ANOVA was used to compare the three groups. Relationship between continuous variables was described using Pearson correlation co-efficient. A P value < 0.05 was considered statistically significant.
| Results|| |
Seventy stable asthmatic subjects of which 15 presented with an attack and 70 controls were enrolled into the study.
Demographic Characteristics of Study Population
The age ranged from 4 to 15 years with a mean ± SD of 8.97 ± 2.88 years in the asthmatic group and 9.01 ± 3.04 years in the control group. In [Table 1], the 6-10 years age-group constituted the highest percentage of subjects in the study groups, followed by those aged 11-15 years. There were 50 (71.4%) males and 20 (28.6%) females giving male to female ratio of 2.5:1. Asthmatic subjects that presented with an attack included 11 (73.3%) males and 4 (26.7%) females.
Plasma hs-CRP Level of Asthmatic Subjects and Control
[Table 2] shows the mean hs-CRP level was significantly higher among asthmatic subjects with attack when compared to children with stable asthma or control group. The maximal level of hs-CRP which was 33.0 mg/L was seen in asthmatic subjects with attack. When all the three groups were compared, there was statistically significant difference (F = 39.69, df = 2, P = 0.0001).
Comparison between the two-study groups as shown in [Table 3] shows the mean hs-CRP level of asthmatic subjects with attack was significantly higher than that of stable asthmatics. Similarly, mean hs-CRP level of asthmatic subjects with attack when compared with control was also significantly higher, significant difference was also observed between hs-CRP level of stable asthmatic subjects and those in the control group.
[Table 4] shows the mean hs-CRP levels of study populations according to age group. Among the stable asthmatic group, age group 4-5 years had a higher level of hs-CRP. The age group 11-15 years was found to have a higher level of hs-CRP in both asthmatics with attack and the control group.
Amongst the asthmatics that were seen during stable state, 25 (35.7%) had high hs-CRP, while 45 (64.3%) had normal hs-CRP. The 6-10 years age-group had 13 subjects with high hs-CRP in stable asthmatic subjects, 8 in the 11-15 years age-group and 4 in the 4-5 years age-group. There was however no association between hs-CRP and age (χ2 = 0.956, df = 3, P = 0.812). All 15 (100%) asthmatics with attack had high hs-CRP.
|Table 4: The hs-CRP levels (mean ± SD) of study population according to age group |
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In the control group, 12 (17.1%) had high hs-CRP level, while 58 (82.9%) had normal levels. The age groups 11-15 years had a higher number of subjects with high hs-CRP in the controls with six subjects, four in the 6-10 years age-group and two in the 4-5 years age group. No significant association was also observed between hs-CRP and age in control subjects (χ2 = 0.815, df = 2, P = 0.665).
Twenty males and five females had higher levels of hs-CRP in asthmatic subjects with only eight males and four females in the control group having high hs-CRP. There was however no significant association between hs-CRP and gender in both study groups. High hs-CRP (χ2 = 1.400, df = 1, P value = 0.237), normal hs-CRP (χ2 = 2.810, df = 1, P value = 0.596).
Mean PEFR in stable asthmatics was 177.6 ± 57.2 L/min, with a range of 60-300 L/min. That of asthmatics with attack was 119.3 ± 45.2 L/min, ranged from 50 to 190 L/min. For the control group, it was 221.6 ± 72.2 L/min and 100-450 L/min respectively.
The PEFR did not correlate with hs-CRP level in stable asthmatic subjects (r = −0.024, P = 0.843) nor with that of asthmatics with attack (r = −0.083, P = 0.768). The hs-CRP also did not correlate with PEFR in controls (r = −0.097, P = 0.423).
| Discussion|| |
C-reactive protein is a highly sensitive marker of inflammation, infection and tissue damage which contribute to host defense against infection by activating the complement pathway.  This study determined the plasma level of hs-CRP in asthmatic children. There were more males than females in the present study. The male preponderance for asthma before adolescence appears to be a universal finding as similar observations were made by Aderele,  Abdurrahman and Taqi ,, factors responsible for a male preponderance are not clear. The reason for the male preponderance may be partly because males are more adventurous and more likely to come in contact with trigger factors.  Females tend to present with asthma at a later age; hence they constitute a considerable part of adult asthma cases. 
In this study, males had higher levels of hs-CRP than females in both study groups which is in contrast to the finding of Kasayama et al.  where female asthmatics were reported to have higher levels of CRP than the males. However, CRP level was not associated with gender, which is similar to the finding of Shima  and Sahoo et al.  where no influence between CRP and gender was seen in both asthmatics and controls.
Mean hs-CRP level was higher in 4-5 years age group in asthmatics which may be because young children are prone to respiratory tract infection hence inflammation. Children are enrolled in school now at an earlier age thereby increasing the tendency to upper respiratory tract infection, which may lead to low-grade inflammation, which may influence serum hs-CRP concentration. There was no relationship observed between hs-CRP with age which was in contrast to observations by Sahoo et al.  where they found an increase in hs-CRP level with age in atopic asthmatics but none with nonatopic asthmatics and control subjects. Shima  reported a decrease in plasma hs-CRP level with age in nonasthmatic children. Reason for these differences is not clear; however, the tendency towards infection and inflammation is not expected to increase with age irrespective of being an asthmatic or not.
Majority of the stable asthmatic subjects had normal hs-CRP level in contrast to all asthmatics with attack that had high-serum level of hs-CRP. The reason may be because of ongoing airway inflammation following asthma attack with subsequent release of acute phase reactants hence higher hs-CRP. Furthermore, with chronic inflammation a slight elevation in serum hs-CRP concentration can persist  which may now become elevated during asthma attack. The high level of hs-CRP observed in some control subjects may result from occult infection which was not obvious as at the time of data collection.
The present study found asthmatic children to have a higher plasma level of hs-CRP than the control group which is similar to what was reported by Girdhar et al.  Arif et al.,  Galez et al.,  and other studies. ,,,, This may be because asthmatics have ongoing chronic airway inflammation which is exacerbated with attacks leading to an increase in levels of hs-CRP. The control subjects are not subjected to this chronic airway inflammation.
This study also demonstrated the plasma hs-CRP level to be higher in children with acute asthma attack than that of stable asthmatics which is in agreement with other studies. , Fujita et al.  also demonstrated similar findings of asthmatic subjects with attack presenting with higher plasma hs-CRP than stable asthmatics. The findings of Soferman et al.  in Israel was also consistent with the present finding. The reason for higher level of hs-CRP during asthma attack may be because, with asthma attack, more inflammation occurs in the respiratory tract with subsequent release of the higher amount of hs-CRP.
Mean PEFR in stable asthmatics was 177.6 ± 57.2 L/min which was lower than 221.6 ± 72.2 L/min obtained in the control group. This is most likely because control subjects are not likely to have airway limitation when compared to asthmatic subjects. PEFR was not significantly associated with hs-CRP level in both asthmatic and control groups.
In conclusion, this study demonstrated that the mean plasma hs-CRP levels was significantly higher (P < 0.001) in asthmatics with attack than stable asthmatics and controls. It also showed that asthmatics with attack had higher level of hs-CRP than those with stable asthma, with males having higher levels of hs-CRP than females. Plasma levels of hs-CRP may be a good indicator of respiratory airway inflammation.
| Recommendation|| |
Further study involving a larger sample size should be undertaken to assess the usefulness of the hs-CRP measurement in classifying asthma severity.
| Acknowledgments|| |
The authors acknowledge the contributions of Professor O Oyelami of Obafemi Awolowo University Teaching Hospital, Ile Ife and Dr Ibrahim Aliyu of Department of Pediatrics, AKTH. We wish to thank Associate Professor Zubairu Ilyasu of Department of Community Medicine, AKTH for assisting with the statistics. We also Acknowledge the support of the resident doctors of the Department of Pediatrics, AKTH, Kano.
| References|| |
|1.||Gern JE, Lemanske RF Jr. Infectious triggers of pediatric asthma. Pediatr Clin North Am. 2003 ;50:555-75, vi. |
|2.||Sharma GD, Gupta P. Asthma (PED). eMedicine. Available from: http://www.medscape. com/articlel1000. [Last updated on 2009 Jan 15; Last accessed on 2009 Feb 21]. |
|3.||Harish R. Acute severe asthma. In: Gupte S. Textbook of Paediatrics Emergencies (Book 1: Infancy, Childhood and Adolescence). 1 st ed. New Delhi: Peepee; 2005. p. 202-6. |
|4.||Qian FH, Zhang Q, Zhou LF, Liu H, Huang M, Zhang XL, et al. High-sensitivity C-reactive protein: A predicative marker in severe asthma. Respirology 2008;13:664-9. |
|5.||Kony S, Zureik M, Driss F, Neukirch C, Leynaert B, Neukirch F. Association of bronchial hyperresponsiveness and lung function with C-reactive protein (CRP): a population based study. Thorax 2004;59:892-6. |
|6.||Pepys MB, Baltz ML. Acute phase proteins with special reference to C-reactive protein and related proteins (pentaxins) and serum amyloid A protein. Adv Immunol 1983;34:141-212. |
|7.||Girdhar A, Menon B, Vijayan VK. Systemic inflammation and its response to treatment in bronchial asthma. Chest 2007;10:132-4. |
|8.||Arif AA, Delclos GL, Colmer-Hamood J. Association between asthma, asthma symptoms and C-reactive protein in US adults: Data from the National Health and Nutrition Examination Survey, 1999-2002. Respirology 2007;12:675-82. |
|9.||Olafsdottir IS, Gislason T, Thjodleifsson B, Olafsson I, Gislason D, Jögi R, et al. C reactive protein levels are increased in non-allergic but not allergic asthma: A multicentre epidemiological study. Thorax 2005;60:451-4. |
|10.||Galez D, Dodg S, Raos M, Nogalo B. C-reactive protein in children with asthma and allergic rhinitis. Biochem Med 2006;16:163-9. |
|11.||Soferman R, Gladshtein M, Weisman Y. C-reactive protein levels, a measurement of airway inflammation in asthmatic children. XXV Congress of the European Academy of Allergology and Clinical Immunology. Austria: Vienna; 2006. p. 10-4. [Abstract book, str.59]. |
|12.||Al Obaidi AH, Al Samarai AM, Jawad AY, Al Janabi JM. Association between C-reactive protein and asthma. Turk Toraks Dev 2010;11:98-104. |
|13.||Aderele WI. Bronchial asthma in Nigerian children. Arch Dis Child 1979;54:448-53. |
|14.||Abdurrahman MB, Taqi AM. Childhood bronchial asthma in northern Nigeria. Clin Allergy 1982;12:379-84. |
|15.||Onazi SO, Orogade AA, Yakubu AM. Exercise-Induced Bronchospasm among School Children in Gusau, Nigeria. West Afr J Med 2012;31:76-80. |
|16.||Asani MO, Adeleke SI, Ibrahim M. Childhood asthma in Kano, Nigeria. Niger J Basic Clin Sci 2005;2:6-9. |
|17.||Nicolai T, Pereszlenyiova-Bliznakova L, Illi S, Reinhardt D, von Mutius E. Longitudinal follow-up of the changing gender ratio in asthma from childhood to adulthood: Role of delayed manifestation in girls. Pediatr Allergy Immunol 2003;14:280-3. |
|18.||Kasayama S, Tanemura M, Koga M, Fujita K, Yamamoto H, Miyatake A. Asthma is an independent risk for elevation of plasma C-reactive protein levels. Clin Chim Acta 2009;399:79-82. |
|19.||Shima M. Air pollution and serum C-reactive protein concentration in children. J Epidemiol 2007;17:169-76. |
|20.||Sahoo RC, Achanya PR, Noushed TH, Anand R, Acharya VK, Sahu KR. The study of high sensitivity C-reactive protein in bronchial asthma. Clin Exp Allergy 1998;Suppl 5:29-34. |
|21.||Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 1999;340:448-54. |
|22.||Fujita M, Ueki S, Ito W, Chiba T, Takeda M, Saito N, et al. C-reactive protein levels in the serum of asthmatic patients. Ann Allergy Asthma Immunol 2007;99:48-53. |
|23.||Takemura M, Matsumoto H, Niimi A, Ueda T, Matsuoka H, Yamaguchi M, et al. High sensitivity C-reactive protein in asthma. Eur Respir J 2006;27:908-12. |
[Table 1], [Table 2], [Table 3], [Table 4]