|Ahead of print publication
A correlational study on neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in bronchial asthma
Rabia Tahseen1, Mohammad Parvez2, G Sravan Kumar3, Parveen Jahan1
1 Department of Zoology, School of Sciences, MANUU, Hyderabad, Telangana, India
2 Department of Pulmonology, Telangana Institute of Medical Sciences, Hyderabad, Telangana, India
3 Department of Pulmonology, Government and General Chest Hospital, Hyderabad, Telangana, India
|Date of Submission||26-Feb-2022|
|Date of Acceptance||19-Apr-2022|
|Date of Web Publication||17-Oct-2022|
Department of Zoology, School of Sciences, MANUU, Hyderabad, Telangana
Source of Support: None, Conflict of Interest: None
Introduction: Inflammation is an integral component of bronchial asthma associated with hyperresponsiveness and chest tightness. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been proven as independent inflammatory markers in various conditions. This study is an effort to evaluate the correlation between these two markers in asthma. Materials and Method: With the approval of the Ethical Committee, Osmania Medical College, Hyderabad, 194 subjects were enrolled for the current study. Out of which, 122 were proven asthmatics diagnosed by pulmonologist and 72 non-asthmatic healthy volunteers. Blood samples were collected from all the individuals and subjected to complete blood count. NLR and PLR were calculated and analysed for each study group. The continuous data were expressed as mean ± standard deviation and Student's t-test. The correlation analysis was performed between the various groups. Results: A statistically significant difference was noted with respect to NLR and PLR between asthma patients and non-asthmatic healthy controls (P = 0.0001). NLR alone varied significantly between responders (mild asthmatics) and poor responders (moderate asthmatics) of the patient group. Further, a positive correlation was noted between NLR and PLR in all the categories, with the highest value in the poor responders. The results are indicative of strong interdependency of NLR and PLR in a condition with higher inflammation. Conclusion: Future studies are warranted to explore this relation in understanding the disease severity/drug response to monitor or to identify the better drug target.
Keywords: Complete blood count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio
|How to cite this URL:|
Tahseen R, Parvez M, Kumar G S, Jahan P. A correlational study on neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in bronchial asthma. Adv Hum Biol [Epub ahead of print] [cited 2022 Dec 2]. Available from: https://www.aihbonline.com/preprintarticle.asp?id=358670
| Introduction|| |
Asthma is a heterogeneous chronic inflammatory airway disease associated with hyperresponsiveness, recurrent attacks, wheezing, coughing and chest tightness coupled with the multicellular influx of granulocytes and altered cellular profile, which results in a range of clinical presentations and treatment responses.,, According to GINA, asthma affects 300 million individuals worldwide, and its prevalence in India is 1%–18%, accounting for ≤15% of severe cases.,, Its aetiopathophysiology is complex, variable and exhibits different asthma phenotypes, where the interaction of extrinsic and intrinsic factors impacts the development of the disease and its severity.,,,
Inflammation is an integral element of asthma and is often characterised by morphological and physiological alterations in the leucocyte population, in particular neutrophils, eosinophils, lymphocytes and platelets, both in the peripheral blood and airways. Heterogeneity of inflammatory phenotypes is typified by predominant eosinophils or neutrophils and is represented as eosinophilic, neutrophilic, mixed granulocytic and pauci-granulocytic asthma phenotypes. Platelets exhibit a crucial role in the pathogenesis of asthma through its continuous activation and release of mediators:, the inflammatory sub-phenotypes exhibit different exacerbation risks and response variations to the administered medication. Inhaled corticosteroids (ICs) are the effective medications given daily on a long-term basis to keep asthma under clinical control, chiefly through their anti-inflammatory effects. However, 5%–10% of these patients fail to respond well to even high doses of inhaled or oral glucocorticoids along with ß-antagonists and are considered to be poor responders.
Apart from the clinical symptoms, asthma is usually diagnosed through a spirometry reversibility test upon exposure to bronchodilators. Spirometry and bronchial alveolar lavage fluid are not accessible for routine monitoring to all patients, especially in developing countries like India. Asthma is a chronic condition that requires constant monitoring. Although the presence of inflammatory cells in the airways is not a part of the diagnosis of asthma, their measurement is principally useful for the clinical assessment/monitoring, guiding treatment with corticosteroids and long-term therapy of asthma patients.
In clinical practice, peripheral leucocyte count is used as a non-invasive technique to quantify inflammatory cells to detect the inflammatory subtypes of asthma. Recently, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been realised to serve as reliable, inexpensive and sensitive inflammatory markers that are well studied in several diseases such as sepsis, cardiac diseases, cancer and pulmonary disorders.,,, However, there are not many studies in relation to asthma and no studies from India. The purpose of the current study was firstly, to examine the systemic inflammatory markers such as NLR and PLR between asthma patients and non-asthmatic healthy controls. Secondly, to see their link with severity and drug response amongst asthma patients and further, to assess the correlation between NLR and PLR among the sub categories of patients.
| Materials and methods|| |
We recruited a total of 194 subjects that include 122 asthma patients and 72 non-asthmatic healthy controls from Hyderabad. The pulmonologist of Government General Chest Hospital, Erragadda, Hyderabad, had diagnosed the patients with bronchial asthma based on the bronchodilator reversibility test and prescribed them a combination inhaler (ICS + β-antagonist). During the sampling, no patients were in exacerbation. The non-asthmatic healthy controls were volunteers from the same ethnic group. Clinical, familial and demographic information was obtained from all the subjects included in the study through a questionnaire before the sample collection. The blood samples were drawn from each participant in ethylenediaminetetraacetic acid Vacutainer and subjected to a complete blood count (CBC). Based on the frequency of the asthma symptoms experienced and the response to treatment, the patients were divided as responders and poor responders. The responders had milder symptoms of asthma, whereas the poor responders had moderate symptoms; thus, in the present study, the responder's term is inter-exchangeable with milder and poor responders with moderate. From the Complete blood count (CBC) data, NLR (absolute neutrophil count ÷ absolute lymphocyte count) and PLR (absolute platelet count ÷ absolute lymphocyte count) were calculated and analysed for each category.
The present study has approval from the Ethical Committee (Ref. No. IEC/OMC/HYD/2020/13), Osmania Medical College, Hyderabad, Telangana state, India, and informed consent from the study subjects.
The clinical, demographic and haematological data were compiled, analysed and expressed as mean ± standard deviation for continuous variables, and categorical data were reported using frequencies and percentages. Independent Student's t-test was performed to test the difference between two sample means of patients and controls and various study groups with respect to the parameters considered, and the results were reported significant when P ≤ 0.05. Correlation between inflammatory markers was performed in MS-Excel.
| Results|| |
[Table 1] shows the characteristic features of 122 asthma patients and 72 non-asthmatic healthy controls recruited in this study. There were 41% versus 61% males and 59% versus 38% females in the patient and control groups respectively. The non-asthmatic healthy group and asthma group did not vary with regard to mean age and body mass index (P ≥ 0.05). The mean age at onset of the clinical symptoms in asthma patients was 30 ± 16.85 years, and the patients with an early age at onset (<30 years) were 41% and with late onset (≥30 years) were 59%, and the family history of asthma was seen in 41% of the patients. Parental consanguinity in patients and healthy controls did not vary significantly.
|Table 1: Characteristic feature of asthma patients and non-asthmatic healthy controls|
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[Table 2] refers to the analysis of the systemic inflammatory profile of asthma patients versus non-asthmatic healthy controls and responders versus poor responders. First, patients and controls showed a significant variation with respect to NLR (2.23 ± 0.90 vs. 1.63 ± 0.70; P = 0.0001) and PLR (154.04 ± 52.09 vs. 98.26 ± 46.30; P = 0.0001). Amongst the asthma patients, 64% were responders, and 36% were poor responders. Second, responders and poor responders were compared and found a significant difference with regard to only NLR (2.05 ± 0.53 vs. 2.54 ± 1.20; P = 0.002). Amongst the asthma patients, non-neutrophilic and neutrophilic responders were 51.6% versus 48.4%, and non-neutrophilic and neutrophilic poor responders were 57.7% versus 42.3%. The odds ratio (OR) between the study groups is as follows: OR = 3.06; P = 0.007; 95% confidence interval: 1.35–6.94.
|Table 2: Systemic inflammatory profile of asthma patients and non-asthmatic healthy controls|
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In addition, the correlation between NLR and PLR was highly significant (P = 0.0001) amongst all the study groups, with the correlation value (r) being 0.55 in healthy controls, 0.72 in asthma patients, 0.66 in responders and 0.80 in poor responders [Figure 1].
|Figure 1: Correlation between NLR and PLR amongst the study groups. NLR: Neutrophil-to-lymphocyte ratio, PLR: Platelet-to-lymphocyte ratio.|
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| Discussion|| |
The steady increase in the prevalence of asthma is contributing to poor quality of life and high economic burden worldwide. The heterogeneous nature of asthma is a major theme of concern for the development of targeted drugs. Understanding the pathophysiology and identifying inexpensive biomarker(s) is valuable in the management of asthma. NLR and PLR are the two non-specific, convenient and economically feasible inflammatory biomarkers obtained from the simple CBC test, which clearly reflects the host immune-inflammatory status. Studies have shown that alteration of these indices is associated with poor prognosis in various diseases.,,
The present study is an effort to explore the role of NLR and PLR in asthma severity and drug response. First, we found a statistically significant difference in terms of both NLR and PLR between asthma patients and non-asthmatic healthy controls. These results are supported by eight other studies from different ethnic populations establishing inflammation in the pathophysiology of asthma.,,,,,,,
Second, the analysis of inflammatory markers between responders (milder asthma) and poor responders (moderate asthma) revealed a significant variation only in terms of NLR but not PLR. The elevated NLR may be due to the administration of corticosteroids to the asthma patients, which alters the leucocyte population mainly by depleting the lymphocyte count and recruiting the neutrophils as observed by Olnes et al., 2016. The reports from Turkey, China and Japan have similar observations suggesting NLR as a useful marker to monitor not only inflammation but also drug response and severity. PLR is another inflammatory marker that remained slightly elevated amongst the poor responders over the responders (P > 0.05). However, Beyhan Sagmen and Kıral and Shi et al. reported significantly elevated PLR in uncontrolled asthmatics as compared to controlled asthmatics.
Fourth, considering the reports on the interdependency of NLR and PLR in various types of cancers by Chen et al. in hepatocellular carcinoma, Wu et al. in lung cancer and Feng et al. in oesophageal cancer and absence of such approach in asthma, we evaluated our data and found a positive correlation between NLR and PLR in all categories of our study groups and noted a gradual increase in correlation values from non-neutrophilic poor responders to neutrophilic poor responders (NNPR < NNR = HC < NR < NPR). Our observations could be explained based on the suggestions of Stark and Lisman that the interplay of platelets and neutrophils triggers neutrophil extracellular traps' formation, which could generate inflammatory responses that may have an association with the aggravated asthmatic condition and disease progression.
These results specify the role of both NLR and PLR combined in drug response variations. However, this contention needs to be confirmed through multicentre studies with a large sample size, as the limitation of the present study is the restricted sample size.
| Conclusion|| |
Our study supports that inflammation is a significant component of asthma pathophysiology. NLR and PLR may serve as quick and easily accessible inflammatory markers. We realised that routine monitoring of inflammatory markers would help in the assessment of the risk of exacerbation and drug–response in patients with uncontrolled asthma. Large studies are required from multiple centres to realise the importance of these emerging markers in the clinical setup and in search of novel management and therapeutic options.
Financial support and sponsorship
UGC non-NET fellowship to Rabia Tahseen.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]