Role of serum Immunoglobulin E level in diagnosis of severity of cough variant asthma

© 2018 The Authors; Tabriz University of Medical Sciences This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Role of serum Immunoglobulin E level in diagnosis of severity of cough variant asthma

Cough variant asthma (CVA) is known by airway Hyper responsiveness and nonproductive chronic cough without wheezing for a minimum duration of 8 weeks.It is less common form of asthma.This study was conducted aiming to diagnose the role of serum Immunoglobulin E (IgE) in diagnosis of cough variant form of the disease.
In this cross sectional study, 80 patients with an age range of 5-14 years were included with clinical criteria for CVA who referred to pulmonology clinic of Tabriz Children Hospital, Tabriz, Iran.Serum IgE level was measured and severity of CVA based on Global Initiative for Asthma (GINA) classification was determined, finally the relationship between serum IgE level and severity of CVA was evaluated.
In patients with CVA without history of allergic disease, mean serum titer of IgE was 138.2 ± 17.5.Significant difference of serum IgE level in different severities of CVA was detected (P = 0.001).
Serum IgE level in patients with CVA is a reliable marker for diagnosis and evaluation of the severity of disease.Cough is a prevalent compliant among individuals referring to the medical sites. 1 Chronic cough is defined as a cough that lasts more than 8 weeks. 2 Coughing may affect the quality of life (QOL). 3Asthma is a common chronic respiratory disease with significant morbidity.The incidence of asthma is higher among boys and families with a poor economic level. 4Children asthma is one of the most common caucuses of emergency referrals and school absence. 5In several studies carried out in different countries, an increasing incidence rate of asthma has been reported reaching about 50%.Causes of asthma are not completely clear, however combination of environmental exposure and genetic predisposition have been considered of the causes. 6,7ough variant asthma (CVA) is a subtype of asthma in which cough is the predominant or sole symptom. 8CVA is known by airway Hyper responsiveness and dry chronic cough for a minimum of 8 weeks, which stops by bronchodilator. 9Unlike classic asthma, patients do not experience wheezing, shortness of breathing, and chest tightness. 10ujimura et al. defined diagnostic criteria for CVA as follows:

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1. Nonproductive cough more than 8 weeks 2. Absence of wheezing 3. Absence of postnasal discharge 4. Presence of airway hyperresponsiveness 5. Response to bronchodilator  11 According to Global Initiative for Asthma (GINA) classification, asthma has been divided into four categories based on daily or night symptom and spirometry values: Intermittent, mild persistent, moderate persistent, and severe persistent asthma (Table 1). 12ased on the knowledge of the researchers, no study has been conducted on the evaluation of serum IgE level and severity of CVA.Thus, this study was accomplished aiming to evaluate the relationship between serum IgE level and severity of CVA.
In this cross sectional study, 80 patients aged 5 to 14 years old with chronic cough more than 8 weeks and two diagnostic criteria for CVA (previously mentioned) were included.This study was performed from June 2016 to August 2017 on patients who referred to pulmonology clinic of Tabriz Children Hospital, Tabriz, Iran. 4 patients who had cough due to another reason such as cystic fibrosis, bronchiectasis, respiratory tract infection (RTI), which were diagnosed during the study or they couldn't do spirometry, were excluded.
Based on physical examination and spirometry values and clinical history, patients were divided into four groups based on severity of asthma: intermittent, mild persistent, moderate persistent, and sever persistent asthma, and then the serum IgE level was measured among them.
The results were expressed as mean ± standard deviation (SD).Statistical analysis were performed using the SPSS software (version 16, SPSS Inc., Chicago, IL, USA) and a P value of < 0.050 was considered to be statistically significant.
Of 80 patients enrolled in this study, 4 (5.0%)patients who had cough but lacked CVA criteria or couldn't perform spirometry, were excluded.28 (36.8%) and 48 (63.2%) of the patients were women and men, respectively.Mean age of the patients was 7.3 ± 0.3 years (5-14 years).
No statistically significant differences were obtained in age, sex, exposure to cigarette smoke, atopic status, and urban or rural and familial history of allergies among the patients.
The mean of serum IgE level was obtained as 138.2 ± 17.5 (IU/ml).Serum IgE level in different severity of CVA was measured.The study showed significant differences between Serum IgE level and severity of CVA (P = 0.001) (Table 2).
Mean of serum IgE level among men and women was 156.0 ± 22.9 and 107.0 ± 26.6 (IU/ml), respectively, and no significant difference was observed between the two groups (P = 0.120).This study indicated that in CVA, not only the serum Ig E level was high, but also it had different level in different severity of disease.Asthma is a chronic respiratory disease due to chronic inflammation and immune response causing reversible airway bronchospasm and air flow limitation.Cytokines and immunoglobulins play an essential role in pathogenesis of asthma. 13n this study, the serum IgE level was evaluated in patients with CVA based on severity of the disease.Mean serum IgE level was obtained as 138.0 ± 17.5 (IU/ml) and significant increase was observed with increasing severity of the disease.
Wang et al. reported that serum interleukins 4 5 (IL-4, IL-5) level in CVA were similar to classic asthma but serum IgE level was variable.In addition, serum IgE level in acute phase of CVA was higher than control phase and further studies was recommended. 14n another study, serum IgE, IL-4, and IL-13 levels were studied among patients with CVA and control group.They found that serum IgE, IL-4, and IL-13 level were significantly higher in CVA group. 13owever, none of them has measured IgE level in different severity of CVA.
A study reported that nerve growth factor (NGF) and IL-4 in sputum and serum was higher than control group, which was significantly decreased with treatment. 12L-12, IL-4, IL-5, and transforming growth factor beta (TGFB) and IgE serum level in CVA were also measured in other studies and it was reported that these markers had a great role in pathogenesis of asthma and they decreased with treatment.4,5 According to the present study and other similar studies, it can be asserted that IgE, IL, and other markers such as NGF increase in CVA, so they can be used for diagnosis and determination of severity of disease and response to treatment.
Limitations: The most important limitation of this study was sensitivity of laboratory diagnostic kits to IgE measurement.
Based on this study, serum IgE level can be used for diagnosis, classification and evaluation of response to treatment in CVA.

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Bilan N, Orang-Poor H, Dastranji A. Role of serum Immunoglobulin E level in diagnosis of severity of cough variant asthma.J Anal Res Clin Med 2018; 6(4): 149-52.Doi: 10.15171/jarcm.2018.024 This study was supported by the Pediatric Health Research Center of Tabriz University of Medical Sciences.N. Bilan designed and supervised the study.H. Orang-Poor performed the data collection.A. Dastranji performed data analysis and drafting the article.No funding.Authors have no conflict of interest.This study was registered by the Medical Ethics Committee of Tabriz University of Medical Sciences (5/D/988080-1395/10/14). 1. Irwin RS, Baumann MH, Bolser DC, Boulet LP, Braman SS, Brightling CE, et al.Diagnosis and management of cough executive summary: ACCP evidence-based clinical practice guidelines.Chest

Table 1 .
Global Initiative for Asthma (GINA) classification for severity of cough variant asthma (CVA)

Table 2 .
Serum Immunoglobulin E (IgE) level in different level of cough variant asthma (CVA)