Research Protocol Design and Practice

Discuss about the Research Protocol Design and Practice.

Smoking has turned out to be an alarm for public health worldwide as it is a key risk factor for many diseases. Considerable lung weakness demonstrated by a decrease in the vital capacity of the lungs has been observed in smokers as compared to non-smokers (Santos, Echeveste, & Vidor, 2014). Breathing problems, chronic obstructive pulmonary disease (COPD), pneumonia, and lung cancer have also been associated with smoking.

A complex mixture of many genotoxic lung carcinogens and their DNA addition products (adducts) comprises the cigarette smoke (Hecht, 2012). Earlier studies using biomarkers have revealed that adolescents and adults exhibited almost similar level of exposure to lung carcinogens (polycyclic aromatic hydrocarbons) (Hertsgaard et al., 2008). Though nicotine found in tobacco smoke is not a carcinogen, it is highly addictive (Hecht, 2012). Hence, nicotine metabolism needs to be studied in detail to conclude whether it is similar in all people belonging to different races and ethnicities. This will help to conclude on the various aspects of population specific measures to reduce the risk of lung cancer in populations that are more prone to it because of slower nicotine metabolism.

What is already known

Australia has a mild climate and a relatively unpolluted atmosphere. So, gross bacterial infection of the airways is less likely to be the cause of chronic bronchitis in patients than tobacco smoking. Smoking affects people of all age groups as well as people of all racial/ ethnic groups.

Different studies published in biomedical journals and the PubMed central database was searched using the search terms “lungs”, “tobacco”, “race”, “ethnicity”, “genetics”.  Publications in English language were referred. Randomised trials, qualitative studies, metaanalysis and review articles, for which full text was available, were considered. Twenty two articles were shortlisted and on further reading and after checking the relevance to the topic ten were used in this study.

Studies have shown that from early life, i.e., foetal stage, lung development is adversely affected by exposure to environmental tobacco smoke. This is the reasonwhy smoking is contraindicated during pregnancy. Nuclear factor (NF)-?B, activity and activation pathway, is inhibited by exposure to environmental tobacco smoke, thereby promoting lung apoptosis (Zhong, Zhou, Joad, & Pinkerton, 2006; Zhong, Zhou, & Pinkerton, 2008). This pathway involves many genes and interleukins included in the process.

On exposure to mainstream tobacco smoke, 79 genes in mice were significantly differentially expressed and connected with many biological processes that cause lung damage such as inflammation, xenobiotic metabolism, redox reactions, and oxidative stress (Halappanavar, Russell, Stampfli, Williams, & Yauk, 2009). This shows that the constituents of tobacco smoke alter the structure of susceptible genes, thereby altering their structure and causing damage to the body organs.

It has been found that genetic variation in certain genes (such as GSTM2-5 genes) may inhibit the decontamination of environmental compounds (such as tobacco smoke) (Alexander et al., 2013). The detoxification of the harmful compounds in the environment is necessary for normal functioning of lungs. The exposure of lungs to these harmful substances may alter the functioning of the lungs that may do great harm to the lungs over the years.

Tobacco smoke not only causes carcinogenic DNA damage, but also hinders the same DNA repair pathway (Holcomb et al., 2016). This increases the the load of DNA damage on cells exposed to tobacco smoke.

It is also known that race is a prognostic factor associated with lung cancer risk, fluctuating between different races and ethnicities (Furrukh, 2013). After adjusting the age of participants, the incidence rates for lung cancer in Afro-Americans and Caucasians were found to be higher as compared to Alaskans, Indians, Asians, Pacific Islanders and Hispanics, among the natives of America.

Another study used biomarkers to study tobacco smoke exposure among native Hawaiians, Filipinos, and Whites groups that have different possibility of occurrence of lung cancer (Fagan et al., 2015). It was found that nicotine metabolism is slower in racial/ethnic groups suffering more commonly from lung cancer.

Thus, the available literature clearly shows that genetic constitution of individuals greatly determines the effect tobacco will have on their lungs. As the genetic constitution varies in different racial/ethnic groups. There is need to study the metabolism of the constituents of tobacco smoke in these groups individually to ascertain the limit of exposure they can tolerate.

Gap in knowledge

As nicotine is the main addictive component in tobacco associated with the carcinogenic substances, the metabolism of nicotine and other components of tobacco smoke need to be known in greater details. The genes metabolising nicotine and other polycyclic aromatic compounds present in tobacco smoke in different races need to be studied further. A comparative analysis of different races needs to be done for establishing clear cut points of slow and fast metabolism of nicotine and other associated constituents of tobacco smoke.

Research question

What are the cut points of nicotine metabolism rate in different races of people that determine their susceptibility to lung damage?

What needs to be known

For this study, the natives of Australia belonging to different racial/ ethnic origins need to be selected. The different genes in various races responsible for nicotine metabolism need to be studied. There is a need to study how these genes affect the rate of nicotine metabolism and if other environmental factors in different races contribute to different rates of nicotine metabolism.

The amount of nicotine and associated components inhaled and the duration of exposure needs to be assessed using questionnaires and quantitative measures. The extent of damage caused to lungs needs to be measured using the lung function tests. Data needs to be recorded and analysed using statistical tools.

Project aims and expected benefits

This project aims to have better knowledge of nicotine and associated compounds metabolism in different human races and how the rate of nicotine metabolism will affect the rate of damage to lungs in different human races.

This can help in preventing the damage caused by nicotine and associated compounds in tobacco as the most appropriate population-based interventions can be assessed using this data. These interventions may include decreasing the quantity of nicotine in cigarettes or using modified medicine approaches for different racial/ethnic groups to reduce the harm caused by smoking to the lungs. Designing customized interventions for different racial groups will highly benefit the particular groups and prevent lung damage which is one of the most probable cause of mortality.

References

Alexander, M., Karmaus, W., Holloway, J. W., Zhang, H., Roberts, G., Kurukulaaratchy, R. J., … Ewart, S. (2013). Effect of GSTM2-5 polymorphisms in relation to tobacco smoke exposures on lung function growth: a birth cohort study. BMC Pulmonary Medicine, 13, 56. http://doi.org/10.1186/1471-2466-13-56

Fagan, P., Moolchan, E. T., Pokhrel, P., Herzog, T., Cassel, K. D., Pagano, I., … Clanton, M. S. (2015). Biomarkers of Tobacco Smoke Exposure in Racial/Ethnic Groups at High Risk for Lung Cancer. American Journal of Public Health, 105(6), 1237–1245. http://doi.org/10.2105/AJPH.2014.302492

Furrukh, M. (2013). Tobacco Smoking and Lung Cancer. Sultan Qaboos University Medical Journal, 13(3), 345–358.

Halappanavar, S., Russell, M., Stampfli, M. R., Williams, A., & Yauk, C. L. (2009). Induction of the interleukin 6/ signal transducer and activator of transcription pathway in the lungs of mice sub-chronically exposed to mainstream tobacco smoke. BMC Medical Genomics, 2, 56. http://doi.org/10.1186/1755-8794-2-56

Hecht, S. S. (2012). Lung Carcinogenesis by Tobacco Smoke. International Journal of Cancer. Journal International Du Cancer, 131(12), 2724–2732. http://doi.org/10.1002/ijc.27816

Hertsgaard, L. A., Hanson, K., Hecht, S. S., Lindgren, B. R., Luo, X., Carmella, S. G., … Hatsukami, D. K. (2008). Exposure to a Tobacco-Specific Lung Carcinogen in Adolescent vs. Adult Smokers. Cancer Epidemiology, Biomarkers & Prevention?: A Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology, 17(12), 3337–3343. http://doi.org/10.1158/1055-9965.EPI-08-0307

Holcomb, N., Goswami, M., Han, S. G., Clark, S., Orren, D. K., Gairola, C. G., & Mellon, I. (2016). Exposure of Human Lung Cells to Tobacco Smoke Condensate Inhibits the Nucleotide Excision Repair Pathway. PLoS ONE, 11(7). http://doi.org/10.1371/journal.pone.0158858

Santos, K. W. dos, Echeveste, S. S., & Vidor, D. C. G. M. (2014). Association between Lung Function and Vocal Affections Arising from Tobacco Consumption. International Archives of Otorhinolaryngology, 18(1), 11–15. http://doi.org/10.1055/s-0033-1358586

Zhong, C.-Y., Zhou, Y. M., Joad, J. P., & Pinkerton, K. E. (2006). Environmental Tobacco Smoke Suppresses Nuclear Factor-?B Signaling to Increase Apoptosis in Infant Monkey Lungs. American Journal of Respiratory and Critical Care Medicine, 174(4), 428–436. http://doi.org/10.1164/rccm.200503-509OC

Zhong, C.-Y., Zhou, Y. M., & Pinkerton, K. E. (2008). NF-?B Inhibition is Involved in Tobacco Smoke-Induced Apoptosis in the Lungs of Rats. Toxicology and Applied Pharmacology, 230(2), 150–158. http://doi.org/10.1016/j.taap.2008.02.005