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

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Dr Mohan Z Mani

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Dr Mohan Z Mani,
Professor & Head,
Department of Dermatolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"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."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
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I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



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.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
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.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
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.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
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.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
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 : 2011 | Month : February | Volume : 5 | Issue : 1 | Page : 48 - 51 Full Version

Study Of Malondialdehyde As An Indicator Of Oxidative Stress And Its Modulation By N-Acetylcysteine In Chronic Obstructive Pulmonary Disease


Published: February 1, 2011 | DOI: https://doi.org/10.7860/JCDR/2011/.1119
AMEETA B PATIL*, ANITA B KALE**, SAMEER S SINGHAL***, TANVEER A KHAN****

*Assistant Professor, Deptt. Of Pharmacology, Padmashri Dr Vithalrao Vikhe Patil Foundation Medical College, Ahmednagar, Maharashtra; **Associate Professor, Deptt. Of Biochemistry, Jawaharlal Nehru Medical College, Sawangi (M), Wardha, Maharashtra. Ph: 09850620123. Email: anitachalak@rediffmail.com; ***Associate Professor, Deptt. Of TB and Chest, Jawaharlal Nehru Medical College, Sawangi (M), Wardha, Maharashtra; **** Professor, Deptt. Of Pharmacology, Jawaharlal Nehru Medical College, Sawangi (M), Wardha, Maharashtra, India.

Correspondence Address :
Anita B Kale
Deptt. Of Biochemistry, Jawaharlal Nehru Medical College, Sawangi (M), Wardha, Maharashtra.
Ph: 09850620123.
Email: anitachalak@rediffmail.com

Abstract

Background & objectives: Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease characterized by systemic and local inflammation and oxidative stress. In view of the lack of therapy that might inhibit the progress of the disease, there is an urgent need for a successful therapeutic approach. This study aims to evaluate the effects of administration of oral N-acetylcysteine (NAC) on the oxidative stress and respiratory symptoms and also to check the safety of oral NAC.
Methods: This randomized, double blind study was conducted in sixty-eight adult patients diagnosed as having COPD. All patients received standard treatment for COPD and were divided into three groups. Group I received placebo, Group II and Group III received NAC 600 mg once daily (OD) and twice daily (BID) dose respectively for two months. Efficacy parameters included assessment of serum malondialdehyde (MDA) and respiratory symptoms. Adverse drug reactions were monitored as a safety measure.
Results: Mean serum MDA levels showed significant fall in group-II (p=0.001) and group-III (P=0.023) as compared to group-I (P=0.147) and improvement in respiratory symptoms was noticeable in group-III followed by group-II from day 0 to day 60. Nausea and stomatitis were the most common adverse drug reactions experienced by the patients in all the three groups.
Interpretation & conclusions: Maximum decline in oxidative stress was with OD dose followed by BID dose which indicates that antioxidants above a certain limit may not be much beneficial. Improvement in symptoms was seen maximum with BID dose followed by OD dose. This was due to mucolytic and immunomodulating properties of NAC besides its antioxidant role. Minor adverse drug reactions confirm the safety of NAC with both the doses. This confers a new facet in management of COPD and an attempt to impede the disease progression.

Keywords

Chronic obstructive pulmonary disease, N-acetylcysteine, oxidative stress.

Introduction
Chronic obstructive pulmonary disease (COPD) is the most common respiratory illness in the elderly and is the fourth leading cause of death globally (1). The prevalence of COPD is higher in countries where smoking is highly prevalent. In India, there is an increasing tendency to abuse tobacco and COPD is emerging to be a major public health problem with significant mortality and morbidity. According to the estimate of global burden of disease study, by the year 2020, COPD is likely to become the fifth leading cause of disability-adjusted life years (DALYs), moving ahead from twelfth position it occupied in 1990 and third most common cause of death worldwide. Its prevalence is estimated to increase in years to come in India (2).
COPD has been defined by global initiative of chronic obstructive lung disease (GOLD), as a state characterized by airflow limitation that is not fully reversible.
There is considerable evidence that an increased oxidative burden occurs in the lungs of patients with COPD which plays a role in its pathogenesis. The lungs are continuously exposed to oxidants generated either endogenously or exogenously. Cigarette smoke, consisting of the gas phase and particulate phase (tar phase) is thought to contain 1017 oxidant molecules per puff (3). The inflammation in stable COPD patients is dominated by macrophages, CD8+ T lymphocytes and neutrophils. Chemical mediators like interleukins, leukotrienes and tumor necrosis factor attract the inflammatory cells and increase the oxidant production. Oxidants cannot only

damage DNA, lipids and proteins, but also mediate a variety of processes that could foster the development of COPD e.g. increased production of mucus and impairment of cilia function. This might lead to pulmonary damage of greater magnitude and progression of the disease (4).
Antioxidant therapy therefore would seem to be a logical therapeutic approach in COPD, apart from standard pharmacological treatment to combat the oxidative stress (5).
The challenges in developing novel therapies include limited understanding of the molecular pathogenesis of COPD (6). Several agents with antioxidant properties such as Vitamin C, Vitamin E and beta-carotene have been tried in patients with COPD, but the evidence is still not consistent. N-acetylcysteine (NAC) is the most widely investigated drug with antioxidant properties that has been used in both experimental and clinical settings which are relevant to COPD (4). NAC is the acetylated precursor of both amino acid L-cysteine and reduced glutathione (GSH). This antioxidant has been applied in patients with COPD in order to reduce symptoms, exacerbations and the accelerated decline in lung function. In addition to this antioxidant action, NAC exhibits mucolytic properties by destroying the disulphide bridges of the mucoprotein macromolecules.
There is need for a successful therapeutic approach that might inhibit the progression of the disease. Considering these facts, this study was conducted to throw light on the effects of oral administration of NAC in patients with COPD in relation to oxidative stress and respiratory health hazards.

Material and Methods

This randomized, double blind, placebo controlled, parallel group, single centered study was carried out at Jawaharlal Nehru Medical College, Sawangi, Wardha. Recruitment of patients was started in the month of November 2008 and study was completed by the end of May 2009. Clearance from institutional ethical committee was obtained.
A questionnaire was designed to obtain information on demographic data, occupational status and respiratory complaints. Consent was taken. The smoking history was measured by the unit of “pack-year” which was defined as smoking of a pack of cigarettes (20 pieces) per day for one year. The number of pack years was calculated as: [(the number of cigarettes smoked per day/20) × (the number of years smoked)] (2). Randomization was done by a randomization plan obtained from Random Allocation software, Rando (7).
At baseline, patients were evaluated for respiratory symptoms, chest X- Ray, and serum malondialdehyde (MDA). Patients were then divided into three groups, and respective treatment was started after which, they were followed up to obtain information on symptomatic improvement (after 60 days) and monitoring of adverse drug effects (after 15, 30 and 60 days) and serum MDA estimation was done again at the end of 30 and 60 days.
Total of 68 patients diagnosed as COPD were divided into three groups and received following drugs.
Group I: Control n=23
(Receiving standard treatment for COPD)
Group II: NAC 600 mg OD n=22
(In addition to the standard treatment for COPD)
Group III: NAC 600 mg BID n=23
(In addition to the standard treatment for COPD)
Drugs and placebos were provided by Cipla Limited, Mumbai and were in the form of effervescent tablets to be taken orally twice a day, for a period of two months. Group I received placebo in BID dose, Group II received NAC 600 mg & placebo both in OD doses, whereas Group III received NAC 600 mg in BID dose.
Drug (NAC) / Placebo was randomly given to each group from boxes containing either, unknown to the investigator and to the patients.
Inclusion Criteria:
1. Patients diagnosed as COPD, between ages 35-80 yrs of either sex.
2. Patients who understand and are willing to fill the questionnaire regularly.
3. Informed written consent taken prior to the start of the study.

Exclusion Criteria:
1. Any decompensated cardiovascular, endocrine, hepatic or renal function.
2. Parenchymal lung pathology or active infection due to Mycobacterium tuberculosis.
3. H/O allergy to NAC.
4. Clinically proven gastric or duodenal ulcer in the previous six months.
5. Participation in any clinical trial in the past six months.
6. Pregnancy / Lactation.

Serum MDA Estimation
Serum MDA estimation was done on day 0, 30 and 60 i.e. prior to the administration of drug (NAC or Placebo), and subsequently repeated twice at one-monthly intervals after initiating the drug treatment. Blood samples were collected under all aseptic precautions using disposable syringes, in non-heparinized bulbs and serum was separated.
Lipid peroxidation end product MDA was estimated by Thiobarbituric Acid Reactive Substances (TBARS) method, as described by Ohkawa et al (8).
The detailed data was analyzed statistically by One-way ANOVA and Paired t-test, using SPSS version 13.0.

Results

Serum MDA levels showed significant difference in mean values from baseline (0 day) to post-treatment (60 days), in group II (p=0.001) and group III (p=0.023). No significant decrease in mean serum MDA levels was demonstrated in group I (p=0.147). (Table/Fig 1). The observations are also depicted in (Table/Fig 2). Patients were assessed for respiratory symptoms at the baseline and their improvement, if any, post-treatment. It was observed that all the groups showed improvement in symptoms like cough, sputum production and expectoration, dyspnoea, throat irritation and chest tightness. In group II and group III there was noticeable improvement in all the respiratory symptoms from day 0 to day 60. Maximum improvement in respiratory symptoms was seen in group III. In group I there was no improvement in cough, throat irritation and chest tightness from day 0 to day 60, while little improvement was seen in sputum production and dyspnoea. The observations are illustrated in (Table/Fig 3). The results are also depicted in (Table/Fig 4)(Table/Fig 5)(Table/Fig 6) Fig 2, 3 and 4 for group I, II and III respectively. Adverse drug reactions were monitored as a safety measure. Nausea and stomatitis were the most common adverse reactions experienced by the patients in all the three groups.

Discussion

Increased oxidative stress may play a role in enhancing the inflammatory response and it is now recognized as the main pathogenic factor for progression and increasing the severity of COPD (9). A significant amount of oxidative stress is caused by the household use of solid biomass fuels, especially in rural settings in developing countries.
Domestic pollutants like particulate matter, carbon monoxide, polycyclic aromatic hydrocarbons cause bronchial irritation and decreased mucociliary clearance. Around 50% of women suffer from COPD who are non-smokers and can be attributed predominantly to biomass fuel (10). The importance of the underlying local and systemic oxidative stress and inflammation in COPD has long been established.
The study groups treated with NAC 600 mg OD and 600 mg BID showed a significant decrease in serum MDA levels from baseline to post-treatment levels with maximum decline in group II. [Table/Fig 1, 2]. High pre-treatment levels of MDA (nmol/ml) in all the groups (4.25±0.6, 5.43±1.04 and 5.30±0.97) (Table/Fig 1) indicate the presence of oxidative stress in these patients, and serves as a biomarker of lipid peroxidation.
NAC exhibits direct and indirect antioxidant properties. Its free thiol group is capable of interacting with the electrophile groups of reactive oxygen species (ROS). Its indirect effect is attributed to its role as a glutathione precursor. NAC has also been shown to increase the protective markers for oxidative stress such as glutathione peroxidase and total antioxidant capacity and thus reducing the MDA levels (11)-(12).
The clinical efficacy of NAC in COPD patients in our study was also evaluated by studying the symptomatic improvement at the end of two months. All the three groups showed improvement in symptoms like cough, sputum production and expectoration, dyspnoea, throat irritation and chest tightness at the end of two months [Table /Fig 3]. Improvement in symptoms in group II (NAC 600 mg OD) and group III (NAC 600 mg BID) were noticeable as compared to group I. Treatment with NAC causes symptomatic improvement in COPD patients, reflected by the decrease in sputum viscosity and purulence and improved sputum expectoration. NAC also has a mucolytic effect which helps in reducing the exacerbations and the days of illness (13). In animal models of chronic bronchitis, oral NAC inhibits smoke induced goblet cell hyperplasia and also improves mucociliary clearance (14). Thus NAC has been shown to improve clinical symptoms, decrease exacerbations and hospital admissions and improve the lung function parameters in COPD. Thus reducing exacerbations indirectly reduced the morbidity and healthcare costs associated with progressive disease.
The efficacy and tolerability of high dose NAC in treatment of patients with COPD was well studied by Zuin et al (13). In our study both the doses (600 mg OD and 600 mg BID) of NAC had a good outcome on the oxidative stress, and other clinical symptoms like cough intensity and frequency.
NAC also reduced the bacterial adherence to mucosal and epithelial cell structures of the airways. This action contributes to the reduction in infectious exacerbations in patients with chronic bronchitis (15).
NAC is also effective regarding the parameters related to bronchial hypersecretion (16). These patterns suggest that the protective effects of this thiol do not merely depend on its mucolytic action but are to be additionally ascribed to other mechanisms such as antioxidant and immuno-modulating, comprehensively termed as broad spectrum protection. Due to these multiple properties of NAC, group III shows maximum decline in respiratory symptoms.
Adverse drug reactions were monitored in our study as a safety measure. It was observed that, nausea and stomatitis were the most common adverse reactions experienced by the patients in all the three groups. Fever, drowsiness, diarrhea and rhinorrhea were other minor adverse effects noted. The adverse drug reactions of NAC reported in literature have been related to high doses or polypharmacy (17). It is documented that NAC is well tolerated. Mild effects like nausea and vomiting may be observed, urticaria and bronchospasm being extremely rare.
Intravenous infusion of NAC has caused hypotension by decreasing the systemic vascular resistance, but can be treated symptomatically (18). Anaphylactoid reactions, including rash, flushing, urticaria, bronchospasm and angioedema, mostly associated with very high doses of NAC (more than ten times the dose used in this study) have been described in adults (19). Thus, the use of intravenous NAC is reserved for grave conditions like paracetamol intoxication and acute myocardial infarction, to list a few.
The findings in our study indicate the important role played by NAC in combating the oxidative stress in COPD and improvement of various respiratory symptoms, at well tolerated doses. Thus, it would be relevant clinically to consider NAC as a novel therapeutic approach in the management of COPD, as add-on therapy to the standard treatment.
Nevertheless, the treatment duration in our study was 2 months and since COPD requires treatment for long duration, it would be worthwhile to conduct a study with prolonged treatment with NAC, involving a larger sample size. This approach would help to further evaluate the clinical efficacy and safety of NAC. Cost-effectiveness analysis also may be proposed by monitoring duration of disease free intervals, saved days of absence from work and cost of concomitant medications. It would be worthwhile to evaluate other parameters of oxidative stress like exhaled CO, spirometry, superoxide dismutase and glutathione levels in the future.

Key Message

1.N-acetylcysteine has a definite role in reducing oxidative stress in patients of COPD
2. N-acetylcysteine also plays important role in reducing respiratory symptoms in COPD patients.
3. N-acetylcysteine is a very safe drug with negligible adverse reactions and can be used in COPD patients

References

1.
Arshad AB, Naveed NS, Rakesh B, Zuber A, Pandey DK, Khurshid AD, et al. Effect of oral N-acetylcysteine in COPD – A randomized controlled trial. JK-Practitioner. 2007; 14(1):12-16.
2.
Premanand R, Santosh Kumar PH and Alladi M. Study of thiobarbituric reactive substances and total reduced glutathione as indices of oxidative stress in chronic smokers with and without chronic obstructive pulmonary disease. Indian J Chest Dis Allied Sci. 2007; 49:9-12.
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