-An estimated 36.5 million adults in America alone smoke cigarettes.
-Smoking kills more than 480,000 Americans a year.
-For every one person who dies from smoking, an estimated 30 people survive with a crippling illness developed from smoking.
-Cigarettes and their smoke contain over 4,000 chemicals, including 43 known carcinogens.
Given the ingredients found in the ordinary cigarette, what effect do you think smoking has on the respiratory system?
Problem At Hand
-The airway epithelium is a complex layer resting upon the tracheobronchial tree. It serves as the body’s first line of defense against regularly inhaled environmental contaminants.
-Basal cells (BCs) are the stem cells which grow into various, specialized parts of the epithelial layer.
Hypothesis
With the knowledge that cigarette smoke delivers thousands of xenobiotics and chemicals as well as abnormally high levels of reactive material to the lung’s epithelial surfaces, it was hypothesized that cigarette smoke greatly disturbs basal cell metabolism.
Smoking is also proven to cause oxidative stress within the human respiratory system.
Xenobiotics - substances foreign to the body or an ecological system.
Metabolism - the chemical processes occurring within a living organism in order to maintain life.
Materials & Methods: Gathering Subjects
-Healthy nonsmokers and healthy smokers were gathered from New York City’s general population.
-Smokers were defined by >30 mg/ml urinal nicotine content or >50 mg/ml of cotinine.
-Non-smokers were classified through undetectable levels of nicotine or cotinine in their urine, at <2 mg/ml and <5 mg/ml, respectively.
-The non-smokers were used as a control group, with the smoking population representing the experimental group.
Materials & Methods: Preparation
-Airway epithelial samples were collected from each person of both groups using bronchoscopy. Airway basal cells were then isolated from the samples by selective culture methods.
-After phenotypic confirmation, BC samples were seeded at 3,000 cells per square cm in plastic flasks and stored at 37 degrees celsius.
-Once cells reached 70% confluence, they were harvested, with the reaction stopped by addition of Hepes-buffered saline.
-The resulting cells were pelleted and stored at -80 degrees C in preparation for metabolic profiling.
Results
-Of the features discovered in .50% of the 18 BC samples, 400 molecules were structurally identified based on mass and retention time, matched within a database containing 610 metabolite standards.
-Of the 400 metabolites collected and identified, 52 of them from smokers featured significantly different BC qualities compared to normal.
-These unique metabolites were classified into 5 different categories: (1) enzyme cofactors, cofactor metabolites, and citric acid cycle intermediates, (2) amino acid and protein metabolism, (3) lipid, fatty acid, and steroid metabolism, (4) amino sugar and nucleotide metabolism and (5) other metabolites.
AnalysisAnalysis
-Smoking directly correlated with a sharp decline of NAD and ADP-ribose.
-Cigarette smoke gives a heavy oxidative and nitrosative burden to the airway epithelium and mutates enzymes that contribute to general metabolism.
-475 unique enzymes contribute to the biochemical pathways that formulate smoking’s 52 abnormal metabolites. Smokers were shown to have 80 differentially expressed genes in comparison to nonsmokers.
-Cigarette smoking is the largest known risk factor and cause for COPD and lung cancer due to the extreme amount of reactive material and xenobiotics introduced to the body and specifically the respiratory system.
-Oxidative burdens overwhelm antioxidants’ defense in the lungs, leading to vulnerable lungs and injury to their overall function.
-Significant to the real world due to the high population of smokers. This research should be simplified and spread throughout the public to better educate and inform smokers.
Next Steps
-Design an experiment to fully analyze long term hindrances of smoking. (Retrospective study/comparison of subjects in later years of life)
-Develop research pertaining to mental health effects of smoking/addiction. (Psychological/brainwave surveys)
-Further analyze smoking’s effects on other parts of the body.