Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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On Sep 2018




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"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



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Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
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Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
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Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

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Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
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In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
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Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2022 | Month : July | Volume : 16 | Issue : 7 | Page : OC01 - OC03 Full Version

Utility of Serum Markers in Obstructive Sleep Apnoea Syndrome: A Case-control Study


Published: July 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/55152.16557
R Phani Kumar, S Laxmi Kumari, Aruna Talatam, T Ramaswamy, B Chakradhar, A Kiranmayi

1. Professor, Department of General Medicine, NRI Medical College, Chinakakani, Guntur, Andhra Pradesh, India. 2. Associate Professor, Department of Respiratory Medicine, Guntur Medical College, Guntur, Andhra Pradesh, India. 3. Professor, Department of General Medicine, NRI Medical College, Chinakakani, Guntur, Andhra Pradesh, India. 4. Professor, Department of Respiratory Medicine, Government Medical College, Anantapuram, Andhra Pradesh, India. 5. Associate Professor, Department of Respiratory Medicine, NRI Medical College, Chinakakani, Guntur, Andhra Pradesh, India. 6. Assistant Professor, Department of Respiratory Medicine, NRI Medical College, Chinakakani, Guntur, Andhra Pradesh, India.

Correspondence Address :
Dr. Aruna Talatam,
Professor, Department of Respiratory Medicine, NRI Medical College and General Hospital, Chinakakani, Guntur, Andhra Pradesh, India.
E-mail: arunatalatam@gmail.com

Abstract

Introduction: Obstructive Sleep Apnoea Syndrome (OSAS) consists of cessation of breathing for at least 10 seconds during sleep in spite of inspiratory efforts. The OSAS is an independent risk factor for a number of cardiovascular diseases and cerebrovascular events. The OSAS is diagnosed and assessed by polysomnography which is time consuming and expensive. C-Reactive Protein (CRP) and Creatine Phosphokinase (CPK) are markers of systemic inflammation. Inflammatory component is present in OSA. Biomarkers like CRP and CPK may serve as diagnostic tools which are simpler, cheaper and quicker alternatives.

Aim: To study the role of serum markers CRP and CPK in the diagnosis of sleep disordered breathing.

Materials and Methods: This was a case-control study, conducted from May 2021 to October 2021, in the Department of Pulmonary Medicine, NRI Medical College, Guntur, Andhra Pradesh, India. Total 50 patients were studied for their various symptoms suggestive of OSAS and confirmed by polysomnography were selected for the study. Total 40 age and weight matched controls were included in the study. The association of serum CRP and CPK with OSA was assessed. The Z-test of difference between two proportions was used to compare gender and smoking status of study participants of the two groups. The p-value <0.05 was reported as statistically significant.

Results: The mean CRP in those suffering from obstructive sleep apnoea was 12.075±7 mg/dL with 13.89 in moderate to severe OSAS group and 10.26 in mild cases. The CRP showed statistically significant association (p-value=0.00344) with OSA whereas CPK levels in OSA subjects showed no statistically significant association with OSAS. Sensitivity of CRP and CPK compared to the Apnoea Hypopnea Index (AHI) in the diagnosis of OSAS was 66% and 34%, respectively. Specificity of CRP and CPK was 87.5% for both. Positive predictive value for CRP and CPK was 86.8% and 77.2%, respectively.

Conclusion: C-reactive protein, a systemic inflammatory marker has a potential role in the diagnosis of OSAS.

Keywords

C-reactive protein, Cardiovascular diseases, Creatine kinase, Polysomnography

Sleep Disordered Breathing (SDB) is characterised by abnormal respiratory pattern during sleep mostly associated with repetitive episodes of transient oxygen desaturation. It affects 4-9% of adult population and 3% of children (1). The SDB includes Obstructive Sleep Apnoea Syndrome (OSAS) which consists of cessation of breathing for at least 10 seconds during sleep in spite of inspiratory efforts (2). OSAS is an independent risk factor for a number of cardiovascular diseases and cerebrovascular events (3). The OSA is diagnosed and assessed using polysomnography, which is a time-consuming and expensive tool.

The OSAS is associated with both inflammatory etiology and repetitive episodes of upper airway obstruction. Inflammatory markers are elevated in OSAS. Hence serum markers like CRP (4), Creatine phosphokinase (CPK) (5), homocysteine (6), Lipoprotein-A (7), fibrinogen (8), C-Reactive Protein (CRP), serum amyloid A, leptin may serve as biomarkers in detecting the presence of OSA. These markers are simpler, cheaper and quicker alternatives in the diagnosis of OSAS.

CRP is an important inflammatory marker synthesized in the liver in response to Interleukin 6 (IL-6). Adipose tissue is a potent source of IL-6. Nocturnal hypoxemia and sleep disturbances lead to increased CRP in OSA patients (4). An elevated CRP level is a strong predictor of cardiovascular risk (9). CPK is an energy transfer enzyme and is elevated in conditions associated with increased muscle activity. Repeated attacks of hypoxemia and its effects on respiratory and skeletal muscles in OSA leads to elevated levels of CPK (5). The elevation of CPK is either due to distintegration of muscle cells or due to leakage from muscle membranes (10),(11).

Several studies have shown that CRP was significantly elevated in OSA (12),(13),(14). Bhattacharjee R et al., have also found an association between CRP and OSA in children. However, other diseases with increased CRP levels like, asthma, and allergic rhinitis, were not ruled out (15). Similarly, serum CPK was found to be associated with OSA. CPAP therapy in OSAS patients resulted in a significant decrease in CPK level (16). Hence, this study was undertaken to evaluate the utility of these markers in the diagnosis of OSAS.

Material and Methods

This was a case-control study, conducted from May 2021 to October 2021, in the Department of Pulmonary Medicine, NRI Medical College, Guntur, Andhra Pradesh, India. The study was carried out after approval from Institutional Ethics Committee (IEC NRIMC365).

Inclusion criteria:

• Patients with symptoms suggestive of OSAS and Apnoea Hypopnea Index (AHI) >5/hr.
• All those above the age of 18 years.
• Those who gave the informed consent.

Exclusion criteria:

• Patients with cardiac illness, chronic obstructive pulmonary disease, recent trauma, neuromuscular diseases or other systemic illnesses.
• Patients who were on medications.

Procedure

Cases: Fifty OSA patients were selected based on their symptoms like snoring, apnoeic spells during sleep, excessive daytime sleepiness, fatigue and Apnoea Hypopnea Index (AHI) of >5/hour on polysomnography. Body Mass Index (BMI) (kg/m2), neck circumference (cm) were measured. All the patients were evaluated for thyroid dysfunction. Epworth Sleepiness Scale (ESS) (17) scoring was done for the cases. All the cases underwent PSG in sleep laboratory using Alice-5, 54 channel Polysomnography (PSG). AHI is the total number of respiratory events per hour of sleep:

• AHI >5 (18) on PSG diagnostic of OSA,
• AHI= 5-15/hr were considered as mild
• AHI >15/hr as moderate to severe.
• Lowest oxygen saturation (SpO2) was measured on PSG, with pulse oximetry.

Controls: Total 40 weight and age-matched controls were selected for the comparison. Attenders of the patients and hospital staff of NRI Medical College with no systemic illnesses were included in the control group. None of the subjects did not exercise on the day of the study, because exercise may alter the values of CRP and CPK.

Serum samples of all the subjects were taken by venepuncture from antecubital fossa by standard method and sent for laboratory for CRP and CPK measurements. Cut-off value for CRP was taken as <0.6 mg/dL (RHELAX-CRP slide agglutination test). The standardization of detection limit of the test is traceable to the international reference standard (19). CPK was measured on VITROS analyser and <200 IU/L was taken as cut-off value (20).

Statistical Analysis

The baseline characteristics of the subjects and CRP and CPK levels are expressed as mean±SD. t-test of difference between two means was used to compare mean age, BMI, CRP and CPK of cases and controls (MedCalc statistical software). Z-test of difference between two proportions was used to compare gender and smoking status of study participants of the two groups. The p-value <0.05 was reported as statistically significant.

Results

The total number of cases diagnosed as OSA were 50, out of which males were 42 and females were 8. The number of controls matched for age and weight were 40, out of which 30 were males and 10 were females. Out of the 42 male patients, 35 were smokers (Table/Fig 1).

The OSA patients were divided into two groups based on AHI (apnoea hypopnea index), those with 5-15/hr as ‘mild’, and those above >15/hr as ‘moderate to severe’. The mean and SD of ESS score was 10±2.6 in OSA patients. The ESS score was significantly higher in moderate-severe OSAS group compared to mild group. However, the neck circumference was not significantly different between the two groups. The AHI was significantly higher in the moderate-severe OSAS group. The lowest oxygen saturation was significantly lower in the moderate-severe group (p-value<0.0001) (Table/Fig 2).

The mean CRP in those suffering from obstructive sleep apnoea was significantly higher compared to control group (p-value=0.00344). The CPK values were however similar in both the groups (Table/Fig 3).

The mean CRP was significantly higher in moderate to severe OSAS group compared to mild cases. The CRP levels were proportionate to the severity of OSA (Table/Fig 4).

The sensitivity and specificity of CRP was 66% and 87.5%, respectively. Sensitivity of CPK was 34% and specificity of CPK was 87.5%. Positive predictive value of CRP and CPK was 86.8%, and 77.2%, respectively. Negative predictive value of CRP and CPK was 67.3% and 51.4%, respectively (Table/Fig 5).

Discussion

This study shows that patients with OSA had statistically significant elevated levels of CRP when compared to age and weight matched control individuals. Similar findings were found in several other studies (21),(22). Bhushan B et al., have found that OSAS patients have elevated CRP irrespective of BMI (21). However few studies have not found this association (23),(24). In a study by Barceló A et al., the CRP levels were significantly elevated in OSAS patients who were obese in comparison to non-obese OSA patients and controls; the probable reason could be association of CRP with obesity rather than nocturnal hypoxemia (23).

In the present study, the controls had no cardiac disorders, thereby strengthening the association of CRP with OSA. In a study by Drager LF et al., they have concluded that elevated CRP is independently associated with OSAS (25).

The CRP elevation is proportional with the severity of OSA (26). The mean CRP was elevated in moderate to severe OSA compared to mild cases in the present study, similar to a study done by Shamsuzzaman AS et al., and Sharma SK et al., have concluded that obesity is associated with hs-CRP, and there is no association between OSAS and elevated levels of high sensitivity CRP (hs-CRP) (27),(28). However in the present study, most of the patients were obese and CRP elevation was observed in obese OSAS patients. In a study by Taheri S et al., they have concluded that CRP levels and sleep duration were not associated significantly. The primary contributing factor attributing to relationship between CRP and sleep disordered breathing may be obesity (29).

The present study was done after close matching of cases and controls and none of them had other systemic illnesses, which further substantiates the finding that CRP is significantly increased in OSAS patients. It was also established that there was proportionate increase in CRP with severity of OSAS.

Several studies reported a strong association between CRP and cardiovascular diseases (9),(10). Thereby, measuring CRP in OSAS patients also becomes an important biomarker for cardiovascular risk.

The CPK was however not significantly associated with OSA in the present study. The probable reason for the result could be small sample size. In contrast, Lentini S et al., found that one third of study population showed mild-to-moderate elevation in CPK level, which was highly predictive of OSAS and application of positive pressure in those patients reduced CRP significantly (16). The mechanism suggested was increased activity of upper airway muscles. In a study by Sakellaropoulou A et al., they observed that a relationship exists between hypoxia and CPK concentration (30). In a study by Shah N et al., OSAS patients had lower CPK compared to non apnoeic patients (31). Further studies are needed to establish the strong association of CPK and OSAS and whether treatment of OSA lowers CPK values.

Thus, this study recommends CRP as diagnostic marker in OSA patients however it should be used in conjunction with clinical manifestations. CPK levels were not significantly elevated in OSAS patients and further studies are needed to establish it as a strong predictor.

Limitation(s)

The study is constrained by its small sample size. Another limitation is majority of OSAS patients were obese and association of CRP was not studied in relation to obesity.

Conclusion

Elevated CRP is a useful marker and can be used as a screening test to identify patients who require PSG, on a priority basis to diagnose OSA. As there is a strong association between CRP and cardiovascular disease, monitoring CRP levels also determines the patients who are at increased risk of cardiovascular complications. Further studies are needed to determine whether OSAS will improve with treatment targeted at reducing CRP.

References

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Liu Y, Zou J, Li X, Zhao X, Zou J, Liu S, et al. Effect of the interaction between obstructive sleep apnea and lipoprotein (a) on insulin resistance: A large-scale cross-sectional study. J Diabetes Res. 2019;8:2019. [crossref] [PubMed]
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Wessendorf TE, Thilmann AF, Wang YM, Schreiber A, Konietzko N, Teschler H. Fibrinogen levels and obstructive sleep apnea in ischemic stroke. Am J Respir Crit Care Med. 2000;162(6):2039-42. [crossref] [PubMed]
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DOI and Others

DOI: 10.7860/JCDR/2022/55152.16557

Date of Submission: Jan 22, 2022
Date of Peer Review: Feb 25, 2022
Date of Acceptance: Apr 07, 2022
Date of Publishing: Jul 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Jan 25, 2022
• Manual Googling: Apr 05, 2022
• iThenticate Software: Apr 11, 2022 (6%)

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