Kurzgesagt – In a Nutshell 

Sources – Smoking


We thank following experts for their feedback: 


Department of Psychiatry and Psychotherapy LMU

Clinic for Tobacco Addiction 


Nuffield Department of Primary Care Health Sciences, University of Oxford

Centre for Evidence-Based Medicine



DISCLAIMER: Please note that we chose on purpose to present this topic from the perspective of smokers and tried to give viewers a glimpse into their experience. If you are not a smoker, you might not agree with a couple of statements but we hope you still take away some useful insights.  

– Once your brain is used to nicotine, for up to 72 hours you are itchy, nervous and stressed – but one drag and instantly, you feel really good.


The duration can change from person to person but the physiological effects of abstinence are generally accepted to peak around the third day. Psychological effects can last longer.


#Ian McLaughlin. Nicotine Withdrawal. 2015. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4542051/

Quote: “An aversive abstinence syndrome manifests 4–24 h following cessation of chronic use of nicotine-containing products. Symptoms peak on approximately the 3rd day and taper off over the course of the following 3–4 weeks.

[...]

The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) reports 7 primary symptoms associated with nicotine withdrawal: irritability/anger/frustration, anxiety, depressed mood, difficulty concentrating, increased appetite, insomnia, and restlessness (American Psychiatric Association 2013). The syndrome might also include constipation, dizziness, nightmares, nausea, and sore throat. For practical purposes, nicotine withdrawal symptoms are classified as affective, somatic, and cognitive. Affective symptoms include anxiety, anhedonia, depression, dysphoria, hyperalgesia, and irritability. Somatic manifestations include tremors, bradycardia, gastrointestinal discomfort, and increased appetite. Cognitive symptoms manifest as difficulty concentrating and impaired memory (Heishman et al. 2010).”


Considering the vast difference within the individual behaviors, objectively quantifying symptoms based on self-reporting is not trivial. Following meta-analysis reviews withdrawal symptoms like irritability, depression, anger and anxiety. 


#John R. Hughes. Effects of Abstinence From Tobacco: Valid Symptoms and Time Course. 2007. 

https://academic.oup.com/ntr/article/9/3/315/1100099?login=false

Quote: “The prior review concluded that anxiety was a true withdrawal symptom. Since the prior review, several studies found anxiety increased in the first 1–3 days post cessation and most reported a duration of about 2 weeks (Gilbert, McClernon et al., 1998; Gilbert et al., 2002; Hughes, 1992; Jorenby et al., 1996; M. M. Ward, Swan et al., 2001). However, one study not included in Table 1 found a decrease in anxiety using two well-validated scales and using only smokers who had been well validated as completely abstinent (R. West & Hajek, 1997). This study hypothesized that prior studies had found increased anxiety because of their inclusion of intermittent smokers who were anxious about going back to smoking. Unfortunately, even though several objective measures are available to measure anxiety in humans (e.g., autonomic functioning, response to carbon dioxide; Zvolensky, Feldner, Leen-Feldner, & McLeish, 2005), tobacco abstinence studies using these measures have not been published. In summary, the weight of the evidence continues  to indicate anxiety is a true withdrawal syndrome.”



– Smoking helps you focus at work and is an excuse to take regular breaks, which is good for you mentally. 


#Valentine G, Sofuoglu M. Cognitive Effects of Nicotine: Recent Progress. 2018

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018192/

Quote: “A primary reason smokers cite for continued smoking is to ‘stay focused’ [6-8], and this subjective experience is likely due to the difficulty concentrating, impaired attention, and impaired working memory functions that are core sequelae of smoking abstinence [9-14].”


#Anton L. Beer. Chapter 27 - Nicotine and Cognition: Effects of Nicotine on Attention and Memory Systems in Humans. 2016. 

https://www.sciencedirect.com/science/article/abs/pii/B9780128002131000274

Quote: “In summary, nicotine facilitates working memory and the encoding processes in declarative and nondeclarative learning (see Key Facts in Table 2). Nicotinic effects on memory consolidation seem to be contingent on the type of learning: Nicotine facilitates consolidation in nondeclarative learning. For declarative learning, only low doses of nicotine promote consolidation, whereas high doses of nicotine likely inhibit consolidation. Nicotine also seems to facilitate memory retrieval. However, further research is needed in order to understand controversial findings.”

 

#Ernst et al. Effect of nicotine on brain activation during performance of a working memory task. 2001.

https://www.pnas.org/doi/10.1073/pnas.061369098#sec-3

Quote: “Nicotine influences cognition and behavior, but the mechanisms by which  these  effects  occur  are  unclear.  By  using  positron  emission tomography, we measured cognitive activation (increases in relative regional cerebral blood flow) during a working memory task [2-back task (2BT)] in 11 abstinent smokers and 11 ex-smokers. Assays were performed  both  after  administration  of  placebo  gum  and  4-mgnicotine gum. Performance on the 2BT did not differ between groups in either condition, and the pattern of brain activation by the 2BT was consistent  with  reports  in  the  literature.  However,  in  the  placebo condition, activation in ex-smokers predominated in the left hemi-sphere,  whereas  in  smokers,  it  occurred  in  the  right  hemisphere.When nicotine was administered, activation was reduced in smokers but  enhanced  in  ex-smokers.  The  lateralization  of  activation  as  a function of nicotine dependence suggests that chronic exposure to nicotine or withdrawal from nicotine affects cognitive strategies used to perform the memory task. Furthermore, the lack of enhancement of activation after nicotine administration in smokers likely reflects tolerance.”


#Levin. Complex relationships of nicotinic receptor actions and cognitive functions. 2013

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797209/#R1

Quote: “The relative roles of nicotinic stimulation vs. desensitization in cognitive function are not well understood. Nicotine, is the prototypic agonist of nicotinic receptors, however, stimulation is not nicotine’s only action. It also potently desensitizes nicotinic receptors. Desensitization is an inherent property of nicotinic receptors. Nicotinic receptor activation is followed by a period of desensitization during which it cannot be activated by either the endogenous ligand acetylcholine or exogenous drug ligands like nicotine and other nicotinic agonists. Therefore, every nicotinic agonist is also a desensitizing agent. Desensitization is not merely the cessation of an agonist effect; it has physiological consequences of its own through a more prolonged limitation of the actions of acetylcholine. The degree to which agonist or desensitizing effects of nicotinic agonists contribute to their pharmacodynamic effects is currently poorly understood. Classically, it was thought that the cognitive enhancing effects of nicotine was due to its receptor stimulation and that receptor desensitization only diminished the efficacy of nicotine or other nicotinic agonists.”



– It is a tool against boredom, it suppresses your appetite, it makes bad moments feel less bad and good moments better. 


Below some selected publications regarding the effects of smoking on boredom and appetite.


Boredom: 

#Martínez-Vispo et al. Boredom susceptibility as predictor of smoking cessation outcomes: Sex differences. 2019.

https://www.sciencedirect.com/science/article/abs/pii/S0191886919301941

Quote: “In addition, it has been found that an individual is more likely to smoke in a low rewarding environment due to the expectation of positive reinforcement offered by cigarette smoking (Perkins, Karelitz, & Boldry, 2017). In line with this, van Tilburg and Igou (2012) suggested that the boredom susceptibility trait promotes stimulation seeking and the maintenance and/or restoration of meaningful activities. This is relevant, as, for most smokers, cigarette consumption is an important activity that provides stimulation (Fagerstrom, 2011). In consequence, when an individual quits, he loses not only a rewarding activity, but also the stimulating effect of tobacco. Therefore, in the absence of rewarding activities other than smoking, individuals with greater boredom susceptibility may be more likely to continue to smoke or to relapse after cessation.”



Appetite: 

#Audrain-McGovern J, Benowitz NL. Cigarette smoking, nicotine, and body weight. 2011 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3195407/

Quote: “The release of hormones such as norepinephrine, dopamine, serotonin and γ-aminobutyric acid by the central nervous system influences brain chemicals that suppress eating and increase metabolic rate (such as pro-opiomelanocortin and cocaine-amphetamine-regulated transcript) as well as those that suppress eating and decrease metabolic rate (such as neuropeptide Y, Agouti-related peptide, melanin-concentrating hormone, and orexin).21 Nicotine has complex effects on these hormones; the acute response is consistent with activation of systems that decrease appetite and increase body metabolism, whereas the chronic changes are consistent with activation of systems that increase appetite and decrease metabolic rate.20 Like nicotine, drugs that increase central nervous system levels of norepinephrine, dopamine and/or serotonin (such as phentermine, sibutramine, and bupropion) suppress appetite and facilitate weight loss.22”


#Jo YH, Talmage DA, Role LW. Nicotinic receptor-mediated effects on appetite and food intake. 2002.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2367209/

Quote: “The literature is clear with respect to the effects of nicotine and nicotinic receptors in the regulation of appetite. Smokers are leaner and smoking cessation in the absence of nicotine replacement therapy typically results in significant and sustained hyperphagia and weight gain.”



– Your lips are one of the most sensitive parts of your body and putting something between them is deeply satisfying.


Lips and fingers are among the most sensitive parts in our body and unfortunately smoking involves both. 


#Giulia Corniani and Hannes P. Saal. Tactile innervation densities across the whole body. 2020.

https://journals.physiology.org/doi/full/10.1152/jn.00313.2020

Quote: “We estimate that around 43,000–46,000 tactile afferents innervate the hairy facial skin and the lips, excluding the oral cavity, which is likely to be innervated by around 16,000–19,000 fibers.

[...]
Innervation density is not uniform across the face: we estimate an innervation density of 48 units/cm2 for the forehead, eyes, and nose (V1); 67 units/cm2 for the central part of the face (V2); and 84 units/cm2 for the lower lip, the chin, the jaw, and an area around the ears (V3). Locally, some regions such as the area immediately surrounding the mouth and the lips are likely to exhibit much higher innervation densities.

[...]

Forty-three percent of tactile afferent fibers or around 7,310 fibers are fast-adapting type I fibers (FAI). FAI afferents are densely packed in the human fingertip with 141 units/cm2 at its distal end.

[...]

SAI fibers are densely concentrated in the fingertips at around 70 units/cm2 at its distal end, and less so in the more proximal area of the hand with 46 units/cm2 in the middle phalanx and 10 units/cm2 in the palm (see Fig. 1A).”

– A cigarette is dried tobacco leaves mixed with chemicals that make it burn slowly, helping you to absorb nicotine, and flavors that make the smoke less harsh. 


#Geiss O, Kotzias D. Tobacco, Cigarettes and Cigarette Smoke - An Overview. EUR 22783 EN. 2007. 

https://publications.jrc.ec.europa.eu/repository/handle/JRC37472

Quote: “Definition of Additives: "Additive" means any substance, chemical or compound, other than tobacco, water or reconstituted tobacco sheet, that is introduced by a manufacturer into the tobacco, paper or filter of a cigarette or into cigarette tobacco during the processing, manufacturing or packing of the cigarette or cigarette tobacco.

Casings

Before the leaves are cut, a “sauce” is added to the tobacco. This sauce contains a variety of ingredients, such as sugars, humectants (2.5-3.5%) and aromatic substances. The addition of sugars to tobacco (4-6%) results in acidic smoke (pH 5.2-6.2) by neutralizing the alkalinity of the nitrogenous compounds.

Aims of Additives

nicotine "hit" and improve the chances of addicting a smoker).”



#National Cancer Policy Forum; Board on Health Care Services; Institute of Medicine. Reducing Tobacco-Related Cancer Incidence and Mortality: Workshop Summary. Washington (DC): National Academies Press (US); 2013 Apr 16. TOBACCO USE AND CANCER.

https://www.ncbi.nlm.nih.gov/books/NBK206898/#sec_016

Quote: “Cigarette smoke contains more than 7,000 compounds, at least 60 of which are known carcinogens, said Pechacek and Graham Warren, a clinical radiation oncologist who treats cancer patients and director of the Tobacco Assessment and Cessation Program at Roswell Park Cancer Institute (HHS, 2010b). Approximately 600 compounds are added to tobacco to enhance flavor or nicotine absorption. Inhaling this mix of chemicals through smoke induces tissue injury and changes in the cellular environment that foster proliferation and transformation into cancer cells (HHS, 2004, 2010b).”


#Winnall, WR. 12.6 Additives and flavourings in tobacco products. Tobacco in Australia: Facts and issues. Melbourne: Cancer Council Victoria; 2022. 

https://www.tobaccoinaustralia.org.au/chapter-12-tobacco-products/12-6-additives-and-flavourings-in-tobacco-products

Quote: “Combustion aids are used to control the smoking mechanics of cigarettes, such as by controlling the burning properties of cigarette paper. These can affect the rate at which burning occurs, and therefore the temperature. They include ammonium phosphate, sodium phosphate, sodium citrate and potassium citrate, which help to keep the cigarette lit.1 ,34 ,49”


#Ghasemi et al. Cigarette butts as a super challenge in solid waste management: a review of current knowledge. 2022.

https://link.springer.com/article/10.1007/s11356-022-20893-9

– Cigarette smoke is 95% gases like carbon dioxide and water vapor. The remaining 5% are particles called tar and they contain the magic sauce: carbon or nitrogen compounds filled with nicotine. 


#Brokl et al. Multivariate analysis of mainstream tobacco smoke particulate phase by headspace solid-phase micro extraction coupled with comprehensive two-dimensional gas chromatography–time-of-flight mass spectrometry. 2014. 

https://www.sciencedirect.com/science/article/pii/S0021967314016483?via%3Dihub

Quote: “Tobacco smoke is an aerosol containing an extremely complex mixture of chemicals [1]. It consists of liquid/solid droplets, called the particulate phase (PP), suspended in a mixture of gases and semi-volatiles – the vapor phase (VP). Although the majority (95%) of whole cigarette smoke is gaseous phase by weight, with the remainder (5%) being particulates [2], the latter part contains most of the 6000+ identified compounds [3]. Based on gas chromatographic (GC) scans, various investigators have estimated that for each component identified in tobacco smoke there were 5–20 components present at extremely low levels that have not yet been identified, and the total number of tobacco smoke components might reach up to 100,000 [4].”


#Schwartz et al. Carbon dioxide is largely responsible for the acute inflammatory effects of tobacco smoke. 2010. 

https://www.tandfonline.com/doi/abs/10.3109/08958370903555909

Quote: “Mainstream smoke can been divided in two parts: the particulate phase and the gas/vapor phase. Most published research has been focused on the particulate phase, which is primarily composed of tar, a complex mixture of thousands of different chemicals, including known carcinogens such as tobacco-specific nitrosamines or benzo[a]pyrene (Hammond and OConnor, 2008; Hecht, 2006). The gas phase has been less well studied. In the gas phase, apart from nitrogen and oxygen (respectively 62% and 13% by weight of mainstream smoke), carbon dioxide prevails (about 12.5%), followed by carbon monoxide (4%) and water (1.3%) (Dube and Green, 1982; Norman, 1977). ”


#Centers for Disease Control and Prevention (US); National Center for Chronic Disease Prevention and Health Promotion (US); Office on Smoking and Health (US). How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General. Atlanta (GA): Centers for Disease Control and Prevention (US); 2010.

https://www.ncbi.nlm.nih.gov/books/NBK53014/

Quote: “The gas phase of cigarette smoke includes nitrogen (N2), oxygen (O2), carbon dioxide (CO2), CO, acetaldehyde, methane, hydrogen cyanide (HCN), nitric acid, acetone, acrolein, ammonia, methanol, hydrogen sulfide (H2S), hydrocarbons, gas phase nitrosamines, and carbonyl compounds (Borgerding and Klus 2005; Rodgman and Perfetti 2009). Constituents in the particulate phase include carboxylic acids, phenols, water, humectants, nicotine, terpenoids, paraffin waxes, tobacco-specific nitrosamines (TSNAs), PAHs, and catechols. Mainstream smoke contains only a small amount of nicotine in the gas phase (Johnson et al. 1973b; Pakhale et al. 1997), but the fraction of nicotine in the gas phase is higher in side-stream smoke because of the higher pH (Johnson et al. 1973b; Brunnemann and Hoffmann 1974; Adams et al. 1987; Pakhale et al. 1997).”


#Action on Smoking and Health (ASH). What's in a cigarette? 2022

https://ash.org.uk/resources/view/whats-in-a-cigarette

Quote: ““Tar”, also known as total particulate matter, is inhaled when the smoker draws on a lighted cigarette. In its condensate form, tar is the sticky brown substance, which can stain smokers’ fingers and teeth yellow-brown. All cigarettes produce tar but the brands differ in amounts.”


#Jebet et al. Environmental inhalants from tobacco burning: Tar and particulate emissions. 2018. 

https://www.sciencedirect.com/science/article/pii/S2468227618300450

Quote: “Depending on their origin, fine particulates of cigarette smoke may serve as carriers for carcinogens such as benzo[a]pyrene by absorbing them on the surface of particulates [7]. Both long-term and short-term exposure to inhalable particulate matter [8] are linked to injurious effects on human health such as cardiovascular, pulmonary, neurological morbidity and mortality in addition to premature delivery, birth defects and death [9,10]. Although a single cigarette is small in size and typically weighs less than 1 g, it is capable of emitting between 7 and 23 mg of PM2.5 when smoked, depending on the smoking conditions and the type of cigarette brand [11]. It is estimated that one cigarette exposes the human respiratory tract to between 10–40 mg particulate matter [8], and have a mean diameter of between 0.1 and 2 μm [12].”


#van Amsterdam et al. Effect of ammonia in cigarette tobacco on nicotine absorption in human smokers. 2011. 

https://www.sciencedirect.com/science/article/abs/pii/S0278691511004911

Quote: “A large variety of chemicals are added to tobacco mainly to improve the attractively of the product and to give the brand a specific and unique flavor. One of the many tobacco additives used is ammonia (and its salts). According to tobacco industry, ammonia is added to Virginia tobacco to improve the aroma and flavor of the product and as processing aid in the manufacture of tobacco sheet.”



– As you inhale, billions of particles interact with everything they pass through, getting stuck on your throat, tongue and trachea. 


The particulate matter inhaled with cigarette smoke stuck on the airways depending on their size, bigger particles holding on the upper respiratory tract while the tiny ones can make their way all the way into alveoli. 


#Centers for Disease Control and Prevention (US); National Center for Chronic Disease Prevention and Health Promotion (US); Office on Smoking and Health (US). How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General. 2010.

https://www.ncbi.nlm.nih.gov/books/NBK53021/

Quote: “The respiratory system extends from the nose and upper airway to the alveolar surface of the lungs, where gas exchange occurs. Inhaled tobacco smoke moves from the mouth through the upper airway, ultimately reaching the alveoli. As the smoke moves more deeply into the respiratory tract, more soluble gases are adsorbed and particles are deposited in the airways and alveoli. The substantial doses of carcinogens and toxins delivered to these sites place smokers at risk for malignant and nonmalignant diseases involving all components of the respiratory tract including the mouth.”


Yalcin E, de la Monte S. Tobacco nitrosamines as culprits in disease: mechanisms reviewed. 2016.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4868960/

 Quote: “Besides nicotine and tobacco-specific nitrosamine exposures, smoking causes tissue buildup of tar, a harmful, highly toxic, partially combusted particulate, resinous substance. Tar contains most of the carcinogenic and genotoxic substances in tobacco smoke [37]. Tar damages and kills ciliated respiratory epithelial cells, impairing their ability to trap airborne toxic particulate matter. Consequently, tar descends into the lower respiratory tract and alveoli where it exerts its carcinogenic effects. Moreover, tar is responsible for toxic lung injury, tooth blackening and rotting, gum damage, and desensitization of taste buds. It is not yet known whether health threats are lowered in individuals who consume cigarettes that contain substantially lower levels of tar and nicotine [37].”


Despite the clearing efforts in the airways, 60 to 80% of the particulate matter from smoke remains in the lungs, kicking off the very first step of all the diseases that will follow. 


#Baker and Dixon. The Retention of Tobacco Smoke Constituents in the Human Respiratory Tract. 2005. 

https://www.tandfonline.com/doi/full/10.1080/08958370500444163

Quote: “The bulk of the studies indicate that, on average, 60 to 80% of the mainstream smoke particulate matter is retained in the lungs after inhalation. For nicotine, carbon monoxide, nitric oxide, and aldehydes the total retentions are of the order of 90–100, 55–65, 100, and approximately 90%, respectively, during cigarette smoke inhalation. For most smoke constituents the retentions in the mouth only are considerably smaller than in the whole respiratory tract. The lung retention values for smoke particulate matter are dependent on the depth of inhalation, hold time in the lungs, exhalation volume, and other factors. However, the degree of nicotine retention following inhalation is not markedly influenced by changes in respiratory parameters.”

Quote: “5. Based on size and the behavior of other aerosols, only about 20% of fresh mainstream smoke entering the respiratory tract would be expected to be retained. The observed retentions of 60–80% are due to the growth of the smoke aerosol particles by water absorption in the humid environment of the lung, and the subsequent deposition of the larger aerosol particles. Typically, the smoke particles grow such that their mass is increased about 5 times and their diameter by about 70%. 

6. Nicotine and semivolatile smoke constituents are retained to higher levels than particulate matter because, as the smoke is diluted as it is drawn into the lung, nicotine and other semivolatile material evaporate out of the smoke aerosol particles. There is thus an additional deposition mechanism of the absorption of the vapor-phase material. As an example, for a typical total retention of nicotine of 96%, 78% would be due to deposition of particulate-phase nicotine and 18% would be due to vapor-phase deposition.”



– Your lungs are like big inflatable sponges and have a filter and barrier; the cilia cells with hair-like extensions covered by a layer of mucus. They trap dust or bacteria to be swept away in a sort of dance. 


#The Alcohol Pharmacology Education Partnership. The Structure and Function of Lungs. Retrieved November 2023. 

https://sites.duke.edu/apep/module-4-alcohol-and-the-breathalyzer-test/biology-and-chemistry-connections/the-structure-and-function-of-lungs/

Quote: “The primary function of the lung is the exchange of gases between the body and the environment. The lungs contain a series of narrowing passageways that terminate into tiny sacs called alveoli. During respiration, oxygen enters the lungs by diffusion through the capillaries surrounding each alveolar sac. Similarly, when carbon dioxide diffuses out of the blood into the alveolar sacs, contraction of the chest muscles and diaphragm constrict the alveoli, forcing about 0.5 liters of air out of the lungs.The average adult has millions of alveoli inside each lung. These small alveoli are present in large numbers to increase the surface area available for gas exchange between the lung and the environment.”


#Science Education Enhances Knowledge (SEEK). Retrieved November 2023. 

https://sites.duke.edu/seektobacco/1-the-addictive-nature-of-nicotine/the-content/

Quote: “Each air sac is covered with tiny Capillaries (blood vessels) through which the blood flows. The large number of alveoli provides ample space (surface area) for oxygen and carbon dioxide exchange. At the site of the alveoli, oxygen, which is breathed in from the air, is absorbed into the bloodstream. At the same time, Carbon dioxide is generated by all cells, travels in the bloodstream to the lungs, where it is exhaled. Likewise, the large surface area of alveoli allows for efficient delivery of nicotine into the bloodstream. Once nicotine enters the bloodstream, it then travels very quickly throughout the body and affects many regions.”


#Science Education Enhances Knowledge (SEEK) about Tobacco. Duke University.

https://sites.duke.edu/seektobacco/1-the-addictive-nature-of-nicotine/the-content/

#Radiology Key. Large Airways. Retrieved November 2023.

https://radiologykey.com/large-airways/

The lungs are constantly exposed to the outside world. With every breath you bring some of the outside world in contact with the epithelial tissue lining your airways, from nose to deep down your lungs, which means that particles, toxicants, and microbial pathogens also scurry along.  


#Pyung, Y.J., Park, DJ., Kim, C.G. et al. Remodeling and Restraining Lung Tissue Damage Through the Regulation of Respiratory Immune Responses. 2023.

https://link.springer.com/article/10.1007/s13770-022-00516-7

#Bennet et al. Airway-On-A-Chip: Designs and Applications for Lung Repair and Disease. 2021.

https://www.mdpi.com/cells/cells-10-01602/article_deploy/html/images/cells-10-01602-g001.png

#Bustamante-Marin XM, Ostrowski LE. Cilia and Mucociliary Clearance. 2017 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378048/

Quote: “The extensive epithelial surface of the respiratory tract between the nose and the alveoli is exposed daily to viral and bacterial pathogens, particulates, and gaseous material with potentially harmful effects. In response to these challenges, humans have developed a series of defense mechanisms to protect the airways from these insults, thereby maintaining the lungs in a nearly sterile condition (Dickson and Huffnagle 2015). Lung defense involves cough, anatomical barriers, aerodynamic changes, and immune mechanisms; however, the primary defense mechanism is mucociliary clearance (MCC). Healthy airway surfaces are lined by ciliated epithelial cells and covered with an airway surface layer (ASL), which has two components, a mucus layer that entraps inhaled particles and foreign pathogens, and a low viscosity periciliary layer (PCL) that lubricates airway surfaces and facilitates ciliary beating for efficient mucus clearance (Wanner et al. 1996; Knowles and Boucher 2002). The coordinated interaction of these components on the surface of the respiratory tract results in MCC.”



– Tar particles land in the mucus and turn into a sticky brown substance that stops the dance and paralyses the cilia – allowing them to get deeper into your lungs: to the alveoli. Alveoli are little air sacs and here is where your actual breathing happens. They have very thin walls, so that the oxygen can transfer to your blood and carbon dioxide can leave. 


#CDC. Highlights: Scientific Review of Findings Regarding Respiratory Diseases.

https://www.cdc.gov/tobacco/sgr/2010/highlight_sheets/pdfs/scientific_respiratory.pdf

Quote: “Cilia are tiny hair-like projections that protect the body’s airways by sweeping away mucus and foreign matter such as dust particles so the lungs can remain clear. Toxicants in tobacco smoke paralyze the cilia and eventually destroy them, removing an important protection from the respiratory system.”


#Leopold PL, O'Mahony MJ, Lian XJ, Tilley AE, Harvey BG, Crystal RG. Smoking is associated with shortened airway cilia. 2009 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2790614/

Quote: “Although it is clear that smoking adversely affects mucociliary clearance, the mechanisms by which this occurs are not fully understood. One critical component is cilia, the hair-like projections on airway epithelial cells that move in metachronal waves and work in conjunction with mucus to clear the airway of inhaled particulates [9], [14]–[17]. Several reports demonstrate that cigarette smoke reduces ciliary beat frequency and interrupts the intercellular coordination of the metachronal waves [18]–[24], and ultrastructural studies have documented smoking-associated increased incidence of structural defects in cilia, including missing radial spokes, nexin links, central sheath, outer and inner dynein arms, and central microtubules, as well as more peripheral doublets and fused cilia [25]–[34].”


#Tilley et al. Cilia Dysfunction in Lung Disease. 2015.

https://www.annualreviews.org/doi/10.1146/annurev-physiol-021014-071931

Quote: “Smoking has long been recognized to suppress mucociliary clearance in most smokers, and there is documented slowing of mucociliary clearance immediately after smoking cigarettes (93, 94). Individuals with bronchitis have reduced mucociliary clearance (95). Smoking cessation improves measurements of nasal mucociliary clearance compared with baseline values obtained prior to smoking cessation (96).


Examination of the airway ciliated cells of both male and female smokers shows patches of atypical nuclei and missing cilia (97). These abnormalities increase with increasing intensity of smoking behavior and are more frequent in smokers using high-tar/nicotine cigarettes (98). Smoking induces expression of epidermal growth factor in ciliated cells, which may shift basal cell fate toward a squamous phenotype and suppress ciliated cell differentiation (99). Healthy smokers have shorter cilia in the large and small airways compared with cilia of nonsmokers, with further shortening observed in smokers with chronic obstructive pulmonary disease (COPD), a common, progressive disorder of the lung characterized by airflow limitation in response to inhaled particles or gases, including cigarette smoke (49, 50). Smoking is associated with suppression of a number of genes in the airway epithelium, likely contributing to slowing the process of regenerating cilia (Table 1).”



– Now the magic is released. Nicotine passes through the thin walls layer and enters your bloodstream reaching your brain so fast that it feels instant. The positive effect arrives right away.


Your alveoli provide a very large surface area for the nicotine to be absorbed. There on, it reaches your heart through the bloodstream where it gets pumped all around your body, including your brain. That’s why its effect is so fast. 


#Berridge, M.S., Apana, S.M., Nagano, K.K. et al. Smoking produces rapid rise of [11C]nicotine in human brain. 2010.

https://link.springer.com/article/10.1007/s00213-010-1809-8

Quote: “The rise of nicotine concentration following a single puff was rapid, reaching more than 50% of maximum brain levels within 15 s of bolus arrival in the brain in most subjects. This rate of rise was considerably faster than that seen in previous studies using intravenous administration.”


#Benowitz et al. Nicotine Chemistry, Metabolism, Kinetics and Biomarkers. 2010.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2953858/

Quote: “When tobacco smoke reaches the small airways and alveoli of the lung, nicotine is rapidly absorbed. Blood concentrations of nicotine rise quickly during a smoke and peak at the completion of smoking (Fig. 2). The rapid absorption of nicotine from cigarette smoke through the lungs, presumably because of the huge surface area of the alveoli and small airways, and dissolution of nicotine in the fluid of pH 7.4 in the human lung facilitate transfer across membranes. After a puff, high levels of nicotine reach the brain in 10–20 s, faster than with intravenous administration, producing rapid behavioral reinforcement (Benowitz 1990). The rapidity of rise in nicotine levels permits the smoker to titrate the level of nicotine and related effects during smoking, and makes smoking the most reinforcing and dependence-producing form of nicotine administration (Henningfield and Keenan 1993).”



– If your brain had a control board, smoking would be like pressing all the buttons at once, releasing loads of transmitters and hormones that affect your whole body. 


Nicotine mimics a common neurotransmitter in your brain called acetylcholine. Acetylcholine normally binds to its specific receptors which are widely expressed in the brain (called acetylcholine receptors or nicotinic receptors). 


#Valentine G, Sofuoglu M. Cognitive Effects of Nicotine: Recent Progress. 2018

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018192/

Quote: “Prolonged activation of the nAChR leads to desensitization and upregulation of nAChR density [47, 48] and nicotine is more likely to induce these changes than the endogenous ligand acetylcholine (ACh). Following its release into the synapse, ACh is inactivated within milliseconds by the enzyme acetylcholinesterase. In contrast, nicotine is not a substrate for acetylcholinesterase and causes a prolonged activation of nAChRs [49] upon receptor binding, and with repeated nicotine exposure (i.e. from smoking cigarettes), nAChRs are readily desensitized diminishing nicotine’s effects.”


#Picciotto and Mineur. Molecules and circuits involved in nicotine addiction: the many faces of smoking. 2014.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3772953/pdf/nihms473741.pdf

Quote: “The primary reason that people smoke is that the nicotine in tobacco is addictive. Like other drugs of abuse, nicotine stimulates dopamine (DA) release from neurons in the mesolimbic system originating in the ventral tegmental area (VTA) and terminating in the nucleus accumbens (NAc). Nicotine can stimulate the firing rate of VTA neurons (Grenhoff et al., 1986; Picciotto et al., 1998), induces DA release from isolated nerve terminals (synaptosomes) (Grady et al., 1992) and increases the excitatory glutamatergic drive onto DA cell bodies in the VTA (Mansvelder et al., 2002; McGehee et al., 1995). Consistent with the ability of nicotine to potentiate DA signaling, peripheral nicotine administration can increase extracellular DA levels in the NAc of rodents for more than an hour (Benwell and Balfour, 1992; Picciotto et al., 1998). The ability of nicotine to potentiate glutamatergic signaling onto DA neurons in the VTA has been proposed as a mechanism underlying this prolonged nicotine-induced DA release, that outlasts the acute effects of nicotine on firing rate of DA neurons (Mansvelder and McGehee, 2000; Tang and Dani, 2009). Thus, nicotine is highly effective at stimulating the DA system, a circuit necessary for drug reinforcement (Koob, 1992).”



– Epinephrine and cortisol make your heart beat faster and your body ready for action. 


#NIDA.Cigarettes and Other Tobacco Products DrugFacts. 2021. 

https://nida.nih.gov/publications/drugfacts/cigarettes-other-tobacco-products

Quote: “The nicotine in any tobacco product readily absorbs into the blood when a person uses it. Upon entering the blood, nicotine immediately stimulates the adrenal glands to release the hormone epinephrine (adrenaline). Epinephrine stimulates the central nervous system and increases blood pressure, breathing, and heart rate. As with drugs such as cocaine and heroin, nicotine activates the brain’s reward circuits and also increases levels of the chemical messenger dopamine, which reinforces rewarding behaviors. Studies suggest that other chemicals in tobacco smoke, such as acetaldehyde, may enhance nicotine’s effects on the brain.”


#Wong et al. Cortisol levels decrease after acute tobacco abstinence in regular smokers. 2014. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049137/

Quote: “Several studies have documented the stimulating effects of acute doses of nicotine delivered by tobacco smoking on the HPA axis (Wilkins et al., 1982; Pomerleau et al., 1983; Kirschbaum et al., 1992; Mendelson et al., 2005), with evidence of a nicotine dose-related increase in cortisol—a key hormone involved in the HPA axis—acutely following nicotine administration (Cryer et al., 1976, Winternitz and Quillen, 1977; Seyler et al., 1984; Mendelson et al., 2005).


Nicotine may trigger cortisol production through various mechanisms. For instance, after a nicotine administration, dose-dependent increases in brain activity have been noted in regions involved in emotion regulation and HPA responses to stress (Stein et al., 1998). Thus, nicotine may modulate the neural substrates of emotional processing, which could alter subjective stress and ultimately affect HPA axis-related cortisol production.”



– Dopamine makes you feel happy and relaxed and reduces your appetite. 


#Audrain-McGovern J, Benowitz NL. Cigarette smoking, nicotine, and body weight. 2011 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3195407/

Quote: “The release of hormones such as norepinephrine, dopamine, serotonin and γ-aminobutyric acid by the central nervous system influences brain chemicals that suppress eating and increase metabolic rate (such as pro-opiomelanocortin and cocaine-amphetamine-regulated transcript) as well as those that suppress eating and decrease metabolic rate (such as neuropeptide Y, Agouti-related peptide, melanin-concentrating hormone, and orexin).21”


#Benowitz NL. Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics. 2009

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946180/

Quote: “Stimulation of central nAChRs by nicotine results in the release of a variety of neurotransmitters in the brain, most importantly dopamine. Nicotine causes the release of dopamine in the mesolimbic area, the corpus striatum, and the frontal cortex. Of particular importance are the dopaminergic neurons in the ventral tegmental area of the midbrain, and the release of dopamine in the shell of the nucleus accumbens, as this pathway appears to be critical in drug-induced reward (12, 13). Other neurotransmitters, including norepinephrine, acetylcholine, serotonin, γ-aminobutyric acid (GABA), glutamate, and endorphins, are released as well, mediating various behaviors of nicotine.


Dopamine release signals a pleasurable experience, and is critical to the reinforcing effects of nicotine and other drugs of abuse (13). Chemically or anatomically lesioning dopamine neurons in the brain prevents nicotine self-administration in rats. When intracranial self-stimulation is used as a model for brain reward in rats, nicotine acutely lowers the threshold for self-stimulation (18). Thus, through its effects on dopamine release, acute nicotine administration increases brain reward function. Likewise, nicotine withdrawal is associated with significant increases in intracranial self-stimulation reward threshold, consistent with deficient dopamine release and reduced reward (19). The decrease in brain reward function experienced during nicotine withdrawal is an essential component of nicotine addiction and a key barrier to abstinence.”



– Beta-endorphins reduce pain and stress. 


#Gudehithlu et al. Nicotine-induced changes of brain β-endorphin. 2012. 

https://pubmed.ncbi.nlm.nih.gov/22483037

Quote: “In summary, we present evidence that acute and chronic nicotine treatment alters b-endorphin in the hypothalamus and the endorphinergic projections to striatum, namely nucleus accumbens, and hippocampus. b-Endorphin in prefrontal cortex responded in the same fashion to nicotine treatments. Together with the literature we propose that acute nicotine enhances the release of b-endorphin in the limbic brain; while, chronic nicotine reduces b-endorphin synthesis by suppressing the expression of the precursor peptide POMC at the genomic level.”



– Nicotine excites and calms you at the same time. You become more alert and able to focus. Your nerves become more sensitive to pleasant sensations, then your whole body relaxes. Together all of these effects just feel great. 


Nicotine triggers the release of a plethora of neurotransmitters in the brain with some causing excitement in the context of and some inducing more calming and relaxation. 


#Neal L. Benowitz. Neurobiology of Nicotine Addiction: Implications for Smoking Cessation Treatment. 2008.

https://www.amjmed.com/article/S0002-9343(08)00103-4/fulltext

Quote: “In humans, nicotine from tobacco induces stimulation and pleasure, and reduces stress and anxiety. Smokers come to use nicotine to modulate their level of arousal and for mood control in daily life. Smoking may improve concentration, reaction time, and performance of certain tasks. When a person stops smoking, nicotine withdrawal symptoms emerge. These include irritability, depressed mood, restlessness, anxiety, problems getting along with friends and family, difficulty concentrating, increased hunger and eating, insomnia, and craving for tobacco.11”

– But your brain immediately tries to return to normal and pushes back against the effects of nicotine. Which is fine as long as you have nicotine inside your blood. But once its effects wear off, your body is left overcompensating, creating a massive imbalance within itself. The more you smoke, the harder your body tries to push back, which is why nicotine is so addictive: You stop feeling like yourself without it. It is still great, but now you also need it just to feel normal. 


Nicotine competes with acetylcholine to bind to these receptors, and it wins over since there is more nicotine around your brain than acetylcholine after a smoke. Even though acetylcholine causes the right level of response, the flood of nicotine in your brain provokes a stronger response. And as you smoke more, the number of acetylcholine receptors in your brain increases which will need more acetylcholine. However, since your brain is not able to produce that much acetylcholine to bind the receptors, it will need nicotine to keep the receptors occupied and feel “normal”. 


#Rose et al. Kinetics of brain nicotine accumulation in dependent and nondependent smokers assessed with PET and cigarettes containing 11C-nicotine. 2009.

https://www.pnas.org/doi/full/10.1073/pnas.0909184107

Quote: “After acute administration of nicotinic agonists, the nAChR channel complex is activated and becomes permeable for sodium, potassium, and calcium ions. Nonetheless, prolonged exposure of nAChRs to nicotinic agonists leads to desensitization of the receptors. The desensitization diminishes channel permeability and the capability of the receptors to be activated in response to subsequent administration of agonist. For nAChRs to recover from desensitization, it is necessary to wash out the nicotinic agonists. Both the desensitization and the recovery from desensitization of nAChRs are dynamic processes that require from seconds to minutes, depending on the receptor subtypes. The sensitivities of nAChRs to nicotine and to other nicotinic agonists, both in processes to be activated and those to be desensitized, are also dependent on the receptor subtypes. It should be noted that prolonged exposure of nAChRs to subthreshold concentrations of nicotinic agonists can cause the receptor to desensitize without its significant activation (4). As a result, the measured in vitro EC50 values for activation (for nicotine, 0.5–100 μM) are in the range of at least one order of magnitude greater than the EC50 values for desensitization (5, 6). Finally, extended exposure of nAChRs to nicotine (from several hours to days) results in up-regulation of the receptors. The sensitivity to nicotine and the extent of this up-regulation are also dependent on receptor subtype (7).” 



– Nicotine comes with thousands of different chemical buddies. Cadmium, lead, arsenic and cyanide, hydrogen peroxide or nitrogen oxides cause damage wherever they end up. 


Tobacco smoke is a very complex mixture of chemicals, not only due to the chemicals inside the cigarettes but also chemicals produced by the combustion. It is not straightforward to analyze the smoke and not every cigarette has the same list of chemicals, therefore one finds varying numbers reported from a few hundred to 100,000. One of the most recent studies on the question reported a list of about 2500 components: 

 

#Brokl et al. Analysis of mainstream tobacco smoke particulate phase using comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry. 2014. 

https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/jssc.201200812

Quote: “The revised peak table contained nearly 1800 individual compounds for the DHS sample and over 900 for the solvent extracted sample. These methods of extraction were shown to be complementary, leading to only 11% of repeated analytes, and their combination gave rise to a list of almost 2500 individual compounds.”

Quote: “Tobacco smoke is an extremely complex and dynamic aerosol consisting of liquid/solid droplets, called the particulate phase, suspended in a mixture of gases and semivolatiles– the vapour phase. Its formation results from a series of complex processes including combustion, pyrolysis, pyrosyn-thesis, distillation, sublimation, condensation, filtration, andelution [1]. Smoke is emitted either from the filter-tip of a cigarette as the mainstream smoke (inhaled by a smoker or generated by a smoking machine), or emitted from the smol-dering tip of a cigarette in the form of sidestream smoke. Mainstream smoke consists of about 5600 identified com-pounds [2] and some reports claim the number of unidenti-fied compounds might reach up to 100 000 [3]. The analysis of such a complex sample is a very difficult task, especially when many of the analytes are present in very small concentrations.“


Another paper gives slightly different numbers: 


#Perfetti and Rodgman. The Complexity of Tobacco and Tobacco Smoke. 2011. 

https://www.researchgate.net/publication/279700594_The_Complexity_of_Tobacco_and_Tobacco_Smoke

Quote: “Tobacco and tobacco smoke are both complex mixtures.We previously reported 8430 unique chemical components identified in these complex mixtures but two years later our updated number was 8889. Addition of unlisted isomers raised these numbers to 8622 and 9081, respectively. Our previous number of 4994 identified tobacco components is now 5229; our previous number of 5315 identified tobacco smoke components is now 5685. An operational definition of a complex mixture is as follows: A complex mixture isa characterizable substance containing many chemical components (perhaps thousands) in inexact proportions.Detailed knowledge of the amount and type of each component within the substance is uncertain even with today's analytical technology. Although it has been esti-mated that as many as 100000 components are present in these complex mixtures, their analyses indicate that the vast majority of the mass of each of these complex mixtures accounts for the 8430 compounds reported previously.”


Following paper includes a shortened list of harmful ingredients by the FDA.   


#Morgan et al. How people think about the chemicals in cigarette smoke: A systematic review. 2017.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501992/pdf/nihms846863.pdf

Quote: “Metals and metalloids such as arsenic, cadmium, and lead are another group of carcinogens in cigarette smoke. These constituents are present in cigarette smoke because tobacco plants absorb them together with other elements from soil (International Agency for Research on Cancer, 2004). Arsenic and cadmium cause lung cancer and may also play a role in bladder and kidney cancers (International Agency for Research on Cancer, 2012a).

[...]

Cardiovascular toxicants damage the heart and circulatory systems. Constituents that are important cardiovascular toxicants in cigarette smoke include carbon monoxide, nicotine, oxidants (such as nitrogen oxides and free radicals), hydrogen cyanide, arsenic, and acrolein (Benowitz, 2003; U.S. Department of Health and Human Services, 2010; U.S. Food Drug Administration, 2012). Both carbon monoxide and hydrogen cyanide interfere with the blood's capacity to carry oxygen (National Research Council of the National Academies, 2008; U.S. Department of Health and Human Services, 2014).”

#Takanami et al. Analysis of Hydrogen Peroxide in an Aqueous Extract of Cigarette Smoke and Effect of pH on the Yield. 2009. 

https://www.tandfonline.com/doi/pdf/10.1271/bbb.90324

Quote: “Such reactive oxygen species as superoxide anion radicals, hydrogen peroxide, and hydroxyl radicals have been detected in an aqueous extract of cigarette smoke.1,2 These species have been associated with the biological activities of cigarette smoke.3 Hydrogen peroxide, among these species, is relatively stable under physiological conditions and has been considered to be a source of hydroxyl radicals inside cells.4 Hydrogen peroxide has been mainly detected in aqueous extracts of cigarette smoke.5–7 The quantitative results reported are in the order of 10 micrograms per cigarette, but the yield strongly depended on the conditions for the sample preparation.5”


There is quite a lot of research regarding all the different mechanisms and processes that these chemicals interfere with and create damage. However, it would take pages to explain them all and it is well beyond what we can cover here. However, as an example, increased cadmium levels in the lungs of smokers decrease the functionality of macrophages through reducing their production of reactive oxygen species which is fundamental to the ability of macrophages to kill invaders.  


#Lugg ST, Scott A, Parekh D, Naidu B, Thickett DR. Cigarette smoke exposure and alveolar macrophages: mechanisms for lung disease. 2022. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8685655/

Quote: “Cadmium is a heavy metal of considerable toxicity found in CS (cigarette smoke), which has been shown to influence the phagocytic and microbiocidal capacity of murine AMs.74 Cadmium levels were significantly elevated (ninefold) in BAL from human smokers, which correlated with loss of membrane Rac2 and p67 phox localisation and NOX2-derived ROS synthesis.75 In the same study, in CS exposed mice, cadmium inhibited Rac2 activation needed for the generation of ROS in lung macrophages, recovery of Rac2 function reduced Streptococcus pneumoniae bacterial burden and increased survival. This may explain, in part, a mechanism for lower respiratory tract infection susceptibility in smokers.” 


It goes without saying that secondhand smoke also contains these toxic constituents. 


#CDC. Secondhand Smoke Is Toxic and Poisonous. 2006.

https://www.cdc.gov/tobacco/sgr/2006/pdfs/shs-toxic.pdf

Quote: “The National Toxicology Program estimates that at least 250 chemicals in second-hand smoke are known to be toxic or carcinogenic (cancer causing).

• Secondhand smoke contains a number of poisonous gases and chemicals, including hydrogen cyanide (used in chemical weapons), carbon monoxide (found in car exhaust), butane (used in lighter fluid), ammonia (used in household cleaners), and toluene (found in paint thinners).

• Some of the toxic metals contained in secondhand smoke include arsenic (used in pesticides), lead (formerly found in paint), chromium (used to make steel), and cadmium (used to make batteries). “



– Carbon monoxide reduces how much oxygen your blood can carry.


Carbon monoxide is much more eager than oxygen to bind your oxygen-carrier molecule in your red blood cells. so when it is around, your cells prefer to give them a ride rather than the oxygen molecules. 


 #CDC. Carbon Monoxide. Retrieved December 2023. 

https://www.cdc.gov/niosh/topics/co-comp/default.html

Quote: “Exposure to carbon monoxide impedes the blood’s ability to carry oxygen to body tissues and vital organs. When carbon monoxide is inhaled, it combines with hemoglobin (an iron-protein component of red blood cells), producing carboxyhemoglobin (COHb), which greatly diminishes hemoglobin’s oxygen-carrying capacity. Hemoglobin’s binding affinity for carbon monoxide is 300 times greater than its affinity for oxygen. As a result, small amounts of carbon monoxide can dramatically reduce hemoglobin’s ability to transport oxygen.”



– In your lungs your cilia cells struggle. It is hard to push mucous clocked up with tar and some of your cilia cells die. 


Smoking makes the cilia beat slower and causes their erosion from the lung cells.   


 #Mehta H, Nazzal K, Sadikot RT. Cigarette smoking and innate immunity. 2008. 

https://pubmed.ncbi.nlm.nih.gov/19109742/

Quote: “There are typical histologic changes in the airways of cigarette smokers consisting of varying degrees of denudation of ciliary epithelium, an increase in the number of goblet cells, submucosal gland hypertrophy and squamous cell metaplasia [23–24]. Chronic exposure to cigarette smoke decreases ciliary beating and interferes with proper airway clearance. A decrease in ciliary beat frequency has been found in the airways of hamsters exposed to cigarette smoke for a year. However, this effect appears to be species dependent as in rats exposed to cigarette smoke for a similar period demonstrated increased ciliary beat [25]. ”



– Your alveoli are super sensitive and can’t handle this sort of stress. A few of your tiny air sacs pop like balloons, causing irreparable damage. 


The rupture of alveolar walls happens as part of the condition called pulmonary emphysema. It is a form of chronic obstructive pulmonary disease (COPD). Emphysema is caused by chronic exposure to toxic gases and currently cigarette smoking is the most common reason. It creates holes in the lung tissue and decreases the alveolar and capillary surface area, which means a decrease in the gas exchange area required for breathing. Alveolar sacs are ruptured by the enzymes whose activities are normally inhibited by secretions of macrophages.    


#Johns Hopkins Medicine. Pulmonary Emphysema. Retrieved December 2023. 

https://www.hopkinsmedicine.org/health/conditions-and-diseases/pulmonary-emphysema

Quote: “What is pulmonary emphysema?

Emphysema is a chronic lung condition in which the air sacs (alveoli) may be:

Overinflation of the air sacs is a result of a breakdown of the alveoli walls. It causes a decrease in respiratory function and breathlessness. Damage to the air sacs can't be fixed. It causes permanent holes in the lower lung tissue.


Pulmonary emphysema is part of a group of lung diseases called COPD (chronic obstructive pulmonary disease). COPD lung diseases cause airflow blockage and breathing problems. The 2 most common conditions of COPD are chronic bronchitis and emphysema.”


#Pahal P, Avula A, Sharma S. Emphysema. 2023.

https://www.ncbi.nlm.nih.gov/books/NBK482217/

Quote: “Elastin is an important component of the extracellular matrix that is required to maintain the integrity of the lung parenchyma and small airways. Elastase/anti-elastase imbalance increases the susceptibility to lung destruction leading to airspace enlargement. Cathepsins and neutrophil-derived proteases (i.e., elastase and proteinase) act against elastin and destroy the connective tissue of the parenchyma of the lung. Cytotoxic T cells release TNF-a and perforins, which destroy the epithelial cells of the alveolar wall.


Cigarette smoking not only causes mucus hypersecretion and release of neutrophilic proteolytic enzymes, but it also inhibits anti-proteolytic enzymes and alveolar macrophages. Genetic polymorphisms have a role in inadequate antiprotease production in smokers. All of these contribute to the development of emphysema.”



– Your body needs to get rid of all of this tar immediately! Goblet cells pump out extra mucus to compensate, which makes breathing harder, so you start coughing to get the tar and mucous out.


Goblet cells are the main producers of mucus in your airways. Smokers have increased levels of transcription factors that normally control goblet cell production and mucus secretion.  


#Jordan D. Davis & Tomasz P. Wypych. Cellular and functional heterogeneity of the airway epithelium. 2012.

https://www.nature.com/articles/s41385-020-00370-7

Quote: “Goblet cells, named for their goblet-like appearance, are the chief mucus producing cells of the airways, which together with ciliated cells facilitate effective MCC. Mucus contains an assortment of products, namely electrolytes, metabolites, fluids, antimicrobial products, and mucins, further subdivided into cell-associated mucins, secreted mucins, and gel-forming mucins (principal examples being MUC5AC and MUC5B).56”

[...]

Increased mucus production by goblet cells is a common feature of asthma, COPD, PCD, and CF.5,56 SPDEF and Foxa3 levels are elevated in patients suffering from asthma, COPD and CF, as well as in chronic smokers.56,66,68 Overexpression of SPDEF resulted in elevated levels of various inflammatory markers at baseline (e.g., IL-13, IL-25, IL-33, CCL17, CCL20, CCL24, and granulocyte-macrophage colony-stimulating factor (GM-CSF), likely contributing to enhanced recruitment of eosinophils, type 2 innate lymphoid cells and T cells in response to HDM.64”

– Your immune system activates and macrophages begin eating up tar particles. Smokers have way more of these clean up cells here because their lungs are literally full of dirt. 


Under normal conditions, macrophages are the most common immune cells in the lungs. They are specifically called alveolar macrophages and protect the lungs through various mechanisms like phagocytosis, producing cytokines, and anti-inflammatory molecules. Macrophages are much more numerous in smokers lungs. But their functions are greatly impaired. 


#Wallace WA, Gillooly M, Lamb D. Intra-alveolar macrophage numbers in current smokers and non-smokers: a morphometric study of tissue sections. 1992

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC463808

Quote: “RESULTS: The smokers had a significantly increased number of alveolar macrophages per unit lung volume and per unit surface area, through the relative increase was less than has appeared from bronchoalveolar lavage studies. When smokers and non-smokers with similar lung structure were compared the smokers had more alveolar macrophages, indicating that smoking and not loss of lung structure is responsible for the increase.”


#Karimi R, Tornling G, Grunewald J, Eklund A, Sköld CM. Cell recovery in bronchoalveolar lavage fluid in smokers is dependent on cumulative smoking history. 2012.

https://pubmed.ncbi.nlm.nih.gov/22479573/

Quote: “In the present study, we retrospectively analyzed the effects of cigarette smoking on cellular components in BAL fluid in a large number of asymptomatic smoking volunteers. There was a reduction in the percentage of recovered fluid with increasing age. The total cell count and cell concentration were positively correlated to cumulative smoking history with considerable intra-individual variability. Compared to healthy never smokers, the cell concentration were four-fold increased with an increased concentration of all inflammatory cells, in particular macrophages.”



– But the nicotine makes the macrophages sluggish and inefficient. 


Phagocytosis is the main mechanism that macrophages eat and eliminate foreign particles. Smoking reduces this function, making the body more susceptible to infection with various microbes. It disturbs the chemicals of which macrophages are involved in production and regulation which creates further damage. However, these are only two of the ways that smoking disrupts the normal working of macrophages. The following paper provides a good summary of the mechanisms involved in how smoking makes macrophages inefficient.   

 

#Lugg ST, Scott A, Parekh D, Naidu B, Thickett DR. Cigarette smoke exposure and alveolar macrophages: mechanisms for lung disease. 2022 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8685655/

Quote: “AMs from smokers have been shown to have defective autophagy,59 a cellular function that removes unnecessary or dysfunctional cellular components and required to eliminate intracellular Mycobacterium tuberculosis.60 In addition, nicotine in CS extract has been shown to impair AM M. tuberculosis killing,61 which may play a role in the increased risk of M. tuberculosis infection in smokers.

[...]
Cathepsin S is another potent elastase, with expression and activity found to be increased in current smokers.70 Cystatin C (CysC) is a major constitutive secretory product of AMs and is the most important inhibitor to cysteine proteinases which are also produced by the cells. CysC forms complexes with cathepsins and regulates proteinase secretion or leakage from dying or diseased cells. CysC release has been shown to be downregulated in response to CS.71 Thus, CS tips the balance of proteinase/anti-proteinase release from AMs, contributing to cell death alongside inadequate repair, with elastolysis and connective tissue destruction, all of which are involved in the pathology of emphysema.”  



#Arnson et al. Effects of tobacco smoke on immunity, inflammation and autoimmunity. 2010. 

https://www.sciencedirect.com/science/article/abs/pii/S0896841109001620

Quote: “Macrophages are the main lung cell population which serves as the first line of cellular defense against pollutants due to their antigen-presenting function and phagocytic properties. Cigarette smoke particles (the main component of particles is kaolinit) are visible in a light microscope in the cytoplasm of alveolar macrophages, even after a short period of tobacco use and they persist up to 2 years following smoking cessation [18]. Chronic smoke exposure causes an influx of alveolar macrophages into the airways lumen of smokers [19]. Apart from changes in the morphology and the number of alveolar macrophages, impaired function of these cells has been observed in smokers. In general, macrophages obtained from tobacco smokers are less mature, have elevated expression of CD14 (monocyte marker), have a condense cytoplasm, and are hyperdense. Macrophages from the lungs of smokers have a greater inhibitory effect on lymphocyte proliferation and natural killer (NK) cells than macrophages from the lungs of non-smokers. They also express a selective functional deficiency in their ability to kill intracellular bacteria [20].”


The overall effects of smoking on macrophages are summarized in the following figure: 


#Lugg ST, Scott A, Parekh D, Naidu B, Thickett DR. Cigarette smoke exposure and alveolar macrophages: mechanisms for lung disease. 2022 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8685655/

– Worse, they vomit chemicals that dissolve your lung tissue and cause tiny wounds that turn into scar tissues. Scars in your lungs are bad if you like breathing. 


There are numerous ways in which smoking damages the lung tissue. One of them involves the proteases, which are enzymes that break down proteins. Alveolar macrophages can secrete molecules that can inhibit the function of the proteases under normal conditions. However, in smokers lungs, alveolar macrophages produce much less of these inhibitors, which causes tissue destruction.  


#Lugg ST, Scott A, Parekh D, Naidu B, Thickett DR. Cigarette smoke exposure and alveolar macrophages: mechanisms for lung disease. 2022 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8685655/

Quote: “AMs also produce elastolytic cysteine proteinases that have the capacity to cause significant lung destruction, particularly in an acidic environment.69 Cathepsin S is another potent elastase, with expression and activity found to be increased in current smokers.70 Cystatin C (CysC) is a major constitutive secretory product of AMs and is the most important inhibitor to cysteine proteinases which are also produced by the cells. CysC forms complexes with cathepsins and regulates proteinase secretion or leakage from dying or diseased cells. CysC release has been shown to be downregulated in response to CS.71 Thus, CS tips the balance of proteinase/anti-proteinase release from AMs, contributing to cell death alongside inadequate repair, with elastolysis and connective tissue destruction, all of which are involved in the pathology of emphysema.”



– Nicotine raises your heart rate while ordering your blood vessels all over your body to constrict. 


#Benowitz NL, Burbank AD. Cardiovascular toxicity of nicotine: Implications for electronic cigarette use. 2016 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4958544

Quote: “Cigarette smoking causes a >150% increase in plasma epinephrine and acutely increases cardiac work by stimulating heart rate (as much as 10-15 bpm acutely and on average 7 bpm throughout the day), myocardial contractility, and blood pressure (acute increase 5-10 mm Hg) (3). Heart rate and blood pressure increase regardless of whether the route of administration is tobacco-smoke or nicotine (intravenous, intranasal, chewing gum or smokeless tobacco).

Cardiac output increases as a result of increased heart rate, enhanced cardiac contractility and enhanced cardiac filling, the latter due to systemic venoconstriction. Nicotine constricts blood vessels, including those in the skin and coronary blood vessels, but dilates blood vessels in skeletal muscle. Vasoconstriction of the skin results in reduced skin blood flow and reduced fingertip skin temperature. Actions of nicotine that reduce blood flow in microvascular beds may contribute to impaired wound healing, macular degeneration, progressive renal disease and placental dysfunction during pregnancy.” 



– Meanwhile toxic chemicals get stuck all over them, causing countless tiny wounds all over your body that will turn into scars. Those scars leak proteins that create random blood clots making your blood vessel even narrower. Constricted and narrow vessels put a lot of stress on your heart muscle that has to work much harder to keep blood flowing. 


#Pittilo. Cigarette smoking, endothelial injury and cardiovascular disease. 2000.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2517732/

Quote: “Despite the strong epidemiological evidence that exists linking cigarette smoking and cardiovascular disease, the mechanisms by which cigarette smoking causes disease and the components of smoke responsible remain poorly understood. Endothelial injury is considered to be a key initiating event in the pathogenesis of atherosclerosis (Ross 1986,1993) and it has therefore seemed reasonable to hypothesize that cigarette smoke, or some components of it, may exert its effects by damaging the endothelium. Components of smoke that gain access to the circulation will come in contact with blood and with the vascular endothelial cells that form a monolayer lining the vessels. These cells are now known to have a crucial role in controlling the blood circulation and to be highly active metabolically (Gryglewski et al. 1988; Vane & Botting 1995). Even minor disturbances to their normal functioning could have significant implications for the initiation and development of atherosclerosis. Endothelial functions, including an increase in permeability and decreased nitric oxide (NO) production along with increased expression of adhesion molecules and adherence of leukocytes to the vessel wall, have been shown to be impaired by risk factors for cardiovascular disease such as hypertension, hyperlipidaemia and hyperglycaemia (Haller 1997). This review examines the evidence that cigarette smoking can bring about vessel wall damage with particular reference to the vascular endothelium.”



– Inside your skin, the chemicals trigger enzymes that break down collagen, the protein that makes your skin elastic and smooth. This creates folds and wrinkles. Your skin ages much quicker and you look older sooner.


#Arisa Ortiz and Sergei A. Grando. Smoking and the skin. 2012.

https://onlinelibrary.wiley.com/doi/10.1111/j.1365-4632.2011.05205.x

Quote: “Cigarette smoke is an important accelerator of the aging process through the formation of free radicals and induction of related pathologies (Fig. 4).16 Smoking may exhaust cellular defense and repair functions, resulting in an accumulation of damage due to mutations and malfunctioning proteins. Smoking also alters extracellular matrix turnover in the skin,17 leading to an imbalance between biosynthesis and degradation of dermal connective tissue proteins. While smoking downregulates synthesis of type I and type III collagens, a major factor for accelerated skin aging,18 it also elevates tropoelastin and increases collagen degradation.19 Smoking is an independent risk factor for the increase of elastic fibers in the reticular dermis of non-exposed skin. This increase results from degradation of elastic material in an additive manner, as in solar elastosis.20”


#Francès C. Smoker's wrinkles: epidemiological and pathogenic considerations. 1998. 

https://pubmed.ncbi.nlm.nih.gov/9787966/

Quote: ”In conclusion, although a specific cigarette skin, characterized by a sallow complexion, periorbital, and perioral wrinkles, was evoked in early reports, the specificity of this smoker’s appearance had not yet been demonstrated scientifically. In contrast, the more recent epidemiological studies confirmed that cigarette smoking is a risk factor for premature wrinkling. Figure 1A, B shows the similar periorbital wrinkles of a female smoker and nonsmoker, both of whom where about 60 years old.”



– But maybe the worst thing is what happens to your immune system: All over our body it reacts to tiny wounds and activates, fighting an invisible enemy, damaging healthy cells in the process. 


Explaining all the different ways in which smoking creates a burden on the immune system  would take pages, since it virtually interferes over your whole immune landscape. Several examples are decreased ability of dendritic cells in migrating to lymph nodes, impaired macrophages, unbalanced T Cell ratios. The following review paper summarizes many points from chronic inflammation to autoimmunity.


#Arnson et al. Effects of tobacco smoke on immunity, inflammation and autoimmunity. 2010. 

https://www.sciencedirect.com/science/article/abs/pii/S0896841109001620

Quote: “Smoking is associated with both release and inhibition of proinflammatory and anti-inflammatory mediators. A large network of pulmonary and systemic cytokines is involved in chronic inflammation of smokers. Cigarette smoke induces the release of TNF-a, TNFa receptors, interleukin (IL)-1, IL-6, IL-8 and granulocyte-macrophage colony-stimulating factor (GM-CSF) [4,5]. On the other hand, smoking has also been associated with decreased IL-6 production through Toll-like receptors (TLR)-2 and 9, decreased IL-10 production via TLR-2 activation and also decreased IL-1b, IL-2, TNF-a, and IFN-g production by mononuclear cells [6].”

#Yamaguchi. Smoking, immunity, and DNA damage. 2019.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546629/

Quote: “As mentioned before, one of the first impacts on immunity caused by smoking is to trigger an inflammatory chronic response in the lungs, which increases over the years due to repeated exposure to smoke and the addition of new field-mutations across the pulmonary epithelia. Macrophages are considered the main players of chronic inflammation, which results in tissue destruction due to the increased release of high levels of pro-inflammatory cytokines and matrix metalloproteinases, as compared to non-smokers (13,14).”


The following review covers the effects of smoking specifically on the innate immune system.


#Mehta H, Nazzal K, Sadikot RT. Cigarette smoking and innate immunity. 2008 

https://pubmed.ncbi.nlm.nih.gov/19109742/

Quote: “Here we review the immunosuppressive effects of cigarette smoke and the mechanisms by which smoking affects host innate immunity including structural and functional changes in the respiratory ciliary epithelium, lung surfactant protein, and immune cells such as alveolar macrophages, neutrophils, lymphocytes and natural killer (NK) cells. Thus smoking cessation should be emphasized not only for prevention of cancer and coronary artery disease but also for patients with recurrent infections and immunosuppressive states.”


The following study for example shows how smoking impairs neutrophils as they accumulate in smokers lungs. 


#Guzik et al. Cigarette smoke-exposed neutrophils die unconventionally but are rapidly phagocytosed by macrophages. 2011 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101810/

Quote: “Pulmonary accumulation of neutrophils is typical for active smokers who are also predisposed to multiple inflammatory and infectious lung diseases. We show that human neutrophil exposure to cigarette smoke extract (CSE) leads to an atypical cell death sharing features of apoptosis, autophagy and necrosis.
[...]
Furthermore, CSE-exposed neutrophils exhibited a compromised ability to ingest the respiratory pathogen, Staphylococcus aureus, which likely contributes to bacterial persistence in the lungs of smokers and is likely to promote further pulmonary recruitment of neutrophils. These data provide mechanistic insight into the lack of accumulation of apoptotic neutrophil populations in the lungs of smokers and their increased susceptibility to degradative pulmonary diseases and bacterial infections.”



– While at the same time the nicotine makes it slow and sluggish. Worse at fighting actual diseases. 


#Nise H. Yamaguchi. Smoking, immunity, and DNA damage. 2019. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546629/pdf/tlcr-08-S1-S3.pdf

Quote: “Tar and nicotine have immunosuppressive effects on the innate immune response and tobacco products containing high concentrations of tar and nicotine cause the greatest immunologic changes. For instance, cigarette smoke altogether suppresses or decreases neutrophils phagocytic activity and affects chemotaxis, kinesis, and cell signaling. It also inhibits the release of reactive oxygen species (ROS), thus compromising pathogen killing by neutrophils and other cells of the innate immunity (1).”



– Over time fats get stuck in the scars inside blood vessels, which get narrower and narrower, until they start to suffocate your organs. Your overworked heart beats even harder to push blood through the extra resistance and your blood pressure rises. 


Deposition of fat in the arteries arises as part of the disease atherosclerosis. 


#NIH. National Hearth, Lung and Blood Institute. What Is Atherosclerosis?. 2022. 

https://www.nhlbi.nih.gov/health/atherosclerosis
Quote: ”Atherosclerosis develops slowly as cholesterol, fat, blood cells and other substances in your blood form plaque. When the plaque builds up, it causes your arteries to narrow. This reduces the supply of oxygen-rich blood to tissues of vital organs in the body.” 

Deposition of fat alters the surface of the arteries which can result in clot formation and sudden blockage of blood flow.


#Rafieian-Kopaei et al. Atherosclerosis: process, indicators, risk factors and new hopes. 2014

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4258672

Quote: “Currently, atherosclerosis is a common disease in which fatty deposits called atheromatous plaques appear in the inner layers of arteries. Formation of these plaques starts with the deposition of small cholesterol crystals in the intima and its underlying smooth muscle. Then the plaques grow with the proliferation of fibrous tissues and the surrounding smooth muscle and bulge inside the arteries and consequently reduce the blood flow. Connective tissue production by fibroblasts and deposition of calcium in the lesion cause sclerosis or hardening of the arteries. Finally, the uneven surface of the arteries results in clot formation and thrombosis, which leads to the sudden obstruction of blood flow.[5]”


Atherosclerosis puts extra strain on the heart and makes it less effective at pumping blood. 


#Yeragani et al. Increased pulse-wave velocity in patients with anxiety: implications for autonomic dysfunction. 2006. 

https://www.sciencedirect.com/science/article/abs/pii/S0022399905004551

Quote: “Thickening of arterial walls occurs with aging, and risk factors such as smoking, obesity, high fatty-food intake, and several genetic factors influence this process. Atherosclerosis increases blood pressure (BP) and makes the heart a less effective “pump,” eventually leading to ventricular enlargement. This will lead to an increased load on the heart leading to an abnormality of cardiac electrical conduction, which may result in cardiac repolarization lability leading to serious cardiac arrhythmias. Thus, identifying these changes in the vessel walls is of paramount importance.”


Smoking is established as a risk factor for atherosclerosis by a substantial amount of research. 


#Wang Z, Wang D, Wang Y. Cigarette Smoking and Adipose Tissue: The Emerging Role in Progression of Atherosclerosis. 2017.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5763059/

Quote: “Smoking is an established risk factor for atherosclerosis through several underlying pathways. Moreover, in the development of atherosclerotic plaque formation, obesity, defined as excess fat mass accumulation, also plays a vital role in dyslipidemia and insulin resistance. Substantial evidence shows that cigarette smoking induces multiple pathological effects in adipose tissue, such as differentiation of adipocytes, lipolysis, and secretion properties in adipose tissue. Therefore, there is an emerging speculation in which adipose tissue abnormality induced by smoking or nicotine is likely to accelerate the progression of atherosclerosis. Herein, this review aims to investigate the possible interplay between smoking and adipose tissue dysfunction in the development of atherosclerosis.”

– So hard fluids seep out of blood vessels into your lungs, which makes breathing even harder. 


#PennMedicine. About Pleural Effusion. Retrieved 2024

https://www.pennmedicine.org/for-patients-and-visitors/patient-information/conditions-treated-a-to-z/pleural-effusion

Quote: “The body produces pleural fluid in small amounts to lubricate the surfaces of the pleura. This is the thin tissue that lines the chest cavity and surrounds the lungs. Pleural effusion is an abnormal, excessive collection of this fluid.


There are two types of pleural effusion:


Risk factors for pleural effusion may include:



–The likelihood of a blood clot to blocking a critical passage in the body rises enormously, which can eventually cause a heart attack or a stroke. 


#Barua and Ambrose. Mechanisms of Coronary Thrombosis in Cigarette Smoke Exposure. 2013.

https://www.ahajournals.org/doi/epub/10.1161/ATVBAHA.112.300154

Quote: “Cigarette smoking (CS) is a major risk factor for acute coronary thrombosis leading to myocardial infarction and sudden cardiac death.7 Cigarette smoke exposure (CSE) seems to alter the balance of antithrombotic/prothrombotic factors and profibrinolytic/antifibrinolytic factors by affecting the functions of ECs, platelets, fibrinogen, and coagulation factors.7 A meta-analysis of 20 studies showed a 36% reduction in the crude relative risk of mortality for patients with coronary heart disease who quit smoking compared with those who continued smoking. Smoking cessation also leads to an exponential reduction in acute cardiovascular events, particularly in the first year after quitting.8 Furthermore, public smoking bans in Helena, Montana and Boulder, Colorado, as well as in Scotland and France, were associated with significant reductions in thrombotic cardiovascular events.9–12”

– Almost all smokers eventually get Chronic Obstructive Pulmonary Disease – so much of your alveoli are irreversibly destroyed that you are always short of breath, never able to breathe freely. Once you have it, it can only get worse, never better again.


Chronic Obstructive Pulmonary Disease (COPD) is caused by damage to the airways or other parts of the lung that blocks airflow. COPD generally covers two conditions: emphysema, where the walls of air sacs are damaged, and chronic bronchitis, in which the lining of airways is inflamed. Symptoms include but are not restricted to coughing with excess mucus, shortness of breath during daily activities, excess phlegm production, and wheezing. COPD is a progressive disease, meaning that  the symptoms develop slowly and get worse and worse. Even though it is sometimes referred to as smokers cough, COPD is way more serious than just coughing. It can reach serious levels that the patient can not carry out the basic daily activities. Unfortunately, there is no cure and the damage is irreversible. 


#NIH. A Quick Guide On COPD. 2022.

https://www.nhlbi.nih.gov/resources/quick-guide-copd

Quote: “In COPD, less air flows in and out of the airways because of one or more of the following:

• The airways and air sacs lose their elastic quality.

• The walls between many of the air sacs are destroyed.

• The walls of the airways become thick and inflamed.

• The airways make more mucus than usual, which can clog them.”


COPD is a disease with a high burden. It kills around 3 million people every year and though smoking is not the only cause of COPD, it is the number one risk factor, especially in the high income countries. Regarding the prevalence of COPD among smokers, there have been different numbers due to different COPD definitions and measurement methods used, but we stick to the statement in the following publication, though we list references with different values as well. 


#Rennard SI, Vestbo J. COPD: the dangerous underestimate of 15%. 2006 

https://pubmed.ncbi.nlm.nih.gov/16631861/

Quote: ”People are often heard to puzzle over a seeming paradox: why do most smokers not get COPD? In fact, almost all of them probably do. They might not develop disabling respiratory symptoms but if they smoke long enough, they will fulfill diagnostic criteria for the disease and could be at risk for morbidity and potentially benefit from treatment. In this context, Burrows and coworkers showed that the distribution of FEV1 shifts as a function of smoking dose.4 A similar analysis of data for 14 000 participants from the Copenhagen City Heart Study5 replicates these findings almost exactly (figure). The crucial implication is that, with enough smoking, almost all smokers will have measurably reduced function; some will be severely affected. Furthermore, a few nonsmokers will also develop airflow limitation.”  (FEV1: forced expiratory volume in 1 s)


#Safiri et al. Burden of chronic obstructive pulmonary disease and its attributable risk factors in 204 countries and territories, 1990-2019: results from the Global Burden of Disease Study 2019. 2022. 

https://www.bmj.com/content/bmj/378/bmj-2021-069679.full.pdf

Quote: “The proportion of DALYs due to COPD that were attributable to individual risk factors differed across the Global Burden of Disease regions. Globally, smoking (46.0%), pollution from ambient particulate matter (20.7%), and occupational exposure to particulate matter, gases, and fumes (15.6%) had the highest contributions to DALYs due to COPD (fig 5). The proportion of DALYs due to COPD that were attributable to these three risk factors were higher in men (figs S11 and S12).
[...]

Smoking is the most common risk factor for all chronic respiratory conditions5  and, apart from being the leading risk factor for COPD, nearly half of smokers eventually develop the disease.48 49 Therefore, preventing exposure to tobacco smoke would be the most effective long term strategy for reducing the burden of COPD.47”


#Lopez et al. Chronic obstructive pulmonary disease: current burden and future projections. 2006.

https://erj.ersjournals.com/content/erj/27/2/397.full.pdf

Quote: “Three major risk factors have been identified for COPD, namely: 1) cigarette smoking; 2) heavy exposure to occupational and indoor air pollution; and 3) a1-antitrypsin deficiency [9, 12, 13, 20]. While cigarette smoking accounts for 80–90% of COPD risks in developed countries, smoking behaviour alone is not sufficient to explain the geographical difference in prevalence rate of symptoms [9, 21]. Studies have suggested that the prevalence rate for symptoms increases with increasing levels of air pollution, independent of cigarette consumption, indicating that outdoor and indoor air pollution may account for the geographical differences.”


#Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2023. 

https://goldcopd.org/wp-content/uploads/2023/12/GOLD-2024_v1.1-1Dec2023_WMV.pdf

Quote: “With these caveats in mind, it can be estimated that globally there are around three million deaths annually due to COPD. It is estimated that the increased prevalence of smoking in LMICs coupled with aging populations in high income countries will result in over 5.4 million deaths from COPD and related conditions by 2060. ”


There are several mechanisms that COPD can arise through, from chronic inflammation to epithelial lung cells just dying. 


#Demedts, I.K., Demoor, T., Bracke, K.R. et al. Role of apoptosis in the pathogenesis of COPD and pulmonary emphysema. 2006. 

https://doi.org/10.1186/1465-9921-7-53
Quote: “Chronic obstructive pulmonary disease (COPD) is characterised by chronic inflammation of the airways and progressive destruction of lung parenchyma, a process that in most cases is initiated by cigarette smoking. Several mechanisms are involved in the development of the disease: influx of inflammatory cells into the lung (leading to chronic inflammation of the airways), imbalance between proteolytic and anti-proteolytic activity (resulting in the destruction of healthy lung tissue) and oxidative stress. Recently, an increasing number of data suggest a fourth important mechanism involved in the development of COPD: apoptosis of structural cells in the lung might possibly be an important upstream event in the pathogenesis of COPD.”



– Finally there is cancer. You get a sort of double whammy. On the one hand you flood your whole system and especially your lungs with at least 70 highly cancer-causing chemicals. 


Since there are many different carcinogens flooding into the body with smoking, there is not a single way that it induces cancer. The figure below demonstrates a simple overview. 


#Centers for Disease Control and Prevention (US); National Center for Chronic Disease Prevention and Health Promotion (US); Office on Smoking and Health (US). How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General. 2010. 

https://www.ncbi.nlm.nih.gov/books/NBK53010/

Quote: “Cigarette smoke alters a range of immunological functions including innate and adaptive immune responses (Sopori 2002). These effects, acting as tumor- promoting or cocarcinogenic stimuli, could affect tobacco-related carcinogenesis. Cigarette smoking increases the number of alveolar macrophages in the lung, possibly leading to higher levels of oxygen radicals and MPO activity, which are hypothesized to be important in tumor promotion. Investigators examined the effects of smoking on the function of natural killer (NK) cells—a lymphoid cell type involved in surveillance of tumor growth (Lu et al. 2007). They obtained strong evidence that suppression of NK cell activation was related to increased lung metastases in mice exposed to cigarette smoke. Other studies demonstrated that nicotine is immunosuppressive and thus might be responsible for some of the effects of cigarette smoke (Sopori 2002).”


Nicotine, even without the other accompanying carcinogens in cigarettes, can also promote tumor angiogenesis and tumor growth. 


#Cooke JP. Angiogenesis and the role of the endothelial nicotinic acetylcholine receptor. 2007 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1941778/

Quote: “An endothelial nicotinic acetycholine receptor (nAChR) mediates endothelial proliferation, survival, migration and tube formation in vitro, and angiogenesis in vivo. Exogenous nicotine stimulates this angiogenic pathway. This action of nicotine may contribute to tumor angiogenesis and tumor growth; atherosclerotic plaque neovascularization and progression; and other tobacco-related diseases. The endothelial nAChR mediates an angiogenic pathway that is interdependent with growth factor mediated pathways, as shown by pharmacological and molecular studies. The characterization of this new angiogenic pathway may provide a new therapeutic avenue for disorders of insufficient or pathological angiogenesis.”


The number of carcinogenic substances is likely to change product to product. We report an average number based on the information we could find. 


#Centers for Disease Control and Prevention (US); National Center for Chronic Disease Prevention and Health Promotion (US); Office on Smoking and Health (US). How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General. 2010. 

https://www.ncbi.nlm.nih.gov/books/NBK53010/

Quote: “Each puff of each cigarette contains a mixture of thousands of compounds, including more than 60 well-established carcinogens. The carcinogens in cigarette smoke belong to multiple chemical classes, including polycyclic aromatic hydrocarbons (PAHs), N-nitrosamines, aromatic amines, aldehydes, volatile organic hydrocarbons, and metals. In addition to these well-established carcinogens, others have been less thoroughly investigated. These include alkylated PAHs, oxidants, free radicals, and ethylating agents. Considerable evidence indicates that in human cancers caused by cigarette smoking, PAHs, N-nitrosamines, aromatic amines, and certain volatile organic agents play a major role. Extensive data in the literature demonstrate the uptake of these carcinogens by smokers. The data confirm the expected presence of metabolites of these substances in the urine of smokers at higher levels than those in nonsmokers.”


#Li and Hecht. Carcinogenic components of tobacco and tobacco smoke: A 2022 update. 2022 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9616535/

Quote: “Tobacco and tobacco smoke contain a complex mixture of over 9500 chemical compounds, many of which have been recognized as hazardous to human health by regulatory agencies. In 2012, the U.S. Food and Drug Administration established a list of harmful and potentially harmful constituents in unburned tobacco and tobacco smoke, 79 of which are considered as carcinogens.”



– The average smoker loses 10 years of life. Which means that some lose like 5 years and others more like 25. You don’t know which one will be you. But it cuts into your health span even more – making a much larger part of your life spent being chronically sick.


It is not possible to come up with a single number regarding the lifespan since there are also many confounding parameters. However, there is one thing certain regardless: all studies found a large enough risk of losing years of healthy life. 


For example, the following study found that smokers die on average 10 years younger than nonsmokers within a group of male British doctors born 1900-1930. 

#Doll R, Peto R, Boreham J, Sutherland I. Mortality in relation to smoking: 50 years' observations on male British doctors. 2004

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC437139/

Quote: “The excess mortality associated with smoking chiefly involved vascular, neoplastic, and respiratory diseases that can be caused by smoking. Men born in 1900-1930 who smoked only cigarettes and continued smoking died on average about 10 years younger than lifelong non-smokers. Cessation at age 60, 50, 40, or 30 years gained, respectively, about 3, 6, 9, or 10 years of life expectancy. The excess mortality associated with cigarette smoking was less for men born in the 19th century and was greatest for men born in the 1920s. The cigarette smoker versus non-smoker probabilities of dying in middle age (35-69) were 42% ν 24% (a twofold death rate ratio) for those born in 1900-1909, but were 43% ν 15% (a threefold death rate ratio) for those born in the 1920s. At older ages, the cigarette smoker versus non-smoker probabilities of surviving from age 70 to 90 were 10% ν 12% at the death rates of the 1950s (that is, among men born around the 1870s) but were 7% ν 33% (again a threefold death rate ratio) at the death rates of the 1990s (that is, among men born around the 1910s).”

#Banks, E., Joshy, G., Weber, M.F. et al. Tobacco smoking and all-cause mortality in a large Australian cohort study: findings from a mature epidemic with current low smoking prevalence. 2015
https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-015-0281-z

Quote: “In Australia, up to two-thirds of deaths in current smokers can be attributed to smoking. Cessation reduces mortality compared with continuing to smoke, with cessation earlier in life resulting in greater reductions.”


#Martin Dockrell and Mark Cook. Smoking attributable deaths in England: When the information changes. 2021.

https://ukhsa.blog.gov.uk/2021/07/06/smoking-attributable-deaths-in-england-when-the-information-changes/

Quote: “The number of smokers aren’t affected, nor is the likelihood that a smoker will die as a result of smoking. About 1 in 7 adults smoke and around 2 in 3 lifelong smokers will die of smoking related deaths.”


#Jha and Peto. Global Effects of Smoking, of Quitting, and of Taxing Tobacco. 2014.

https://www.nejm.org/doi/10.1056/NEJMra1308383

Quote: “First, the risk is big. Large studies in the United Kingdom, the United States, Japan, and India have examined the eventual effects on mortality in populations of men and of women in which many began to smoke in early adult life and did not quit.11-16 All these studies showed that in middle age (about 30 to 69 years of age), mortality among cigarette smokers was two to three times the mortality among otherwise similar persons who had never smoked, leading to a reduction in lifespan by an average of about 10 years (Figure 1). This average reduction combines zero loss for those not killed by tobacco with an average loss of well over a decade for those who are killed by it.”

#Streppel MT, Boshuizen HC, Ocké MC, Kok FJ, Kromhout D. Mortality and life expectancy in relation to long-term cigarette, cigar and pipe smoking: the Zutphen Study. 2007 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2598467/

Quote: ”Duration of cigarette smoking was strongly associated with mortality from cardiovascular disease, lung cancer and chronic obstructive pulmonary disease, whereas both the number of cigarettes smoked as well as duration of cigarette smoking were strongly associated with all‐cause mortality. Average cigarette smoking reduced the total life expectancy by 6.8 years, whereas heavy cigarette smoking reduced the total life expectancy by 8.8 years. The number of total life‐years lost due to cigar or pipe smoking was 4.7 years. Moreover, cigarette smoking reduced the number of disease‐free life‐years by 5.8 years, and cigar or pipe smoking by 5.2 years. Stopping cigarette smoking at age 40 increased the life expectancy by 4.6 years, while the number of disease‐free life‐years was increased by 3.0 years.”



– Smokers are often seen as unhinged or without discipline which is unfair.  


There are not any large-scale studies on the perception of nonsmokers regarding smokers but the following study found out that nonsmokers have a more negative judgment of smokers compared to smokers. 


#Dillard et al. Perceptions of smokers influence nonsmoker attitudes and preferences for interactions. 2013.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3668795/

Quote: “In the present studies, we asked a novel set of questions about perceptions of smokers. Unlike previous studies that have emphasized perceptions of smokers’ personality (Brosh et al., 2003; Tokheim et al., 1990), we focused on perceptions of their smoking characteristics. Findings of Study 1 showed that compared to smokers’ self-reports, nonsmokers estimated that smoking played a larger role in smokers’ self-concepts, they were more addicted to smoking, and less motivated to quit. In Study 2, we found that the discrepant view between nonsmokers and smokers mattered: Compared to a smoker who was described in terms of smokers’ self-reports (from Study 1), a smoker who was described in terms of nonsmokers’ views was judged more negatively by nonsmokers and less preferred for interactions.”



– The physical addiction lasts around 3 days – but the psychological addiction is much harder to overcome because you form strong habits and it is connected to many social cues like hanging out with friends or winding down from work.


Withdrawal symptoms peak around the third day though the timeframe can vary from person to person depending on the daily consumption, duration and any many other factors. Experiencing withdrawal symptoms is a manifestation of physical addiction. Behavioral conditioning is maybe the strongest obstacle for quitting. On top of the pharmacological dependence, there is also association of smoking to different contextual cues, moods or environmental factors that become strong behavioral triggers over many rounds of repetition. 


#Ian McLaughlin. Nicotine Withdrawal. 2015. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4542051/

Quote: “An aversive abstinence syndrome manifests 4–24 h following cessation of chronic use of nicotine-containing products. Symptoms peak on approximately the 3rd day and taper off over the course of the following 3–4 weeks.

[...]

The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) reports 7 primary symptoms associated with nicotine withdrawal: irritability/anger/frustration, anxiety, depressed mood, difficulty concentrating, increased appetite, insomnia, and restlessness (American Psychiatric Association 2013). The syndrome might also include constipation, dizziness, nightmares, nausea, and sore throat. For practical purposes, nicotine withdrawal symptoms are classified as affective, somatic, and cognitive. Affective symptoms include anxiety, anhedonia, depression, dysphoria, hyperalgesia, and irritability. Somatic manifestations include tremors, bradycardia, gastrointestinal discomfort, and increased appetite. Cognitive symptoms manifest as difficulty concentrating and impaired memory (Heishman et al. 2010).” 


#Neal L. Benowitz. Neurobiology of Nicotine Addiction: Implications for Smoking Cessation Treatment. 2008.

https://www.amjmed.com/article/S0002-9343(08)00103-4/fulltext

Quote: “Cigarette smoking is maintained, in part, by such conditioning. People habitually smoke cigarettes in specific situations, such as after a meal, with a cup of coffee or an alcoholic drink, or with friends who smoke. The association between smoking and these other events repeated many times causes the environmental situations to become powerful cues for the urge to smoke. Likewise, aspects of the drug-taking process, such as the manipulation of smoking materials, or the taste, smell, or feel of smoke in the throat, become associated with the pleasurable effects of smoking. Even unpleasant moods can become conditioned cues for smoking. For example, a smoker may learn that not having a cigarette provokes irritability (a common symptom of the nicotine abstinence syndrome) and smoking a cigarette provides relief. After repeated experiences of this sort, a smoker may come to regard irritability from any source, such as stress or frustration, as a cue for smoking.”


#DiFranza, Sanouri and Ursprung. The latency to the onset of nicotine withdrawal: A test of the sensitization-homeostasis theory. 2008.

https://www.sciencedirect.com/science/article/abs/pii/S0306460308001184

Quote: “The latency to withdrawal (LTW) is the expired time between the last cigarette and when the smoker feels the need to smoke again. The sensitization-homeostasis theory predicts that the LTW is inversely related to the frequency and duration of smoking such that more frequent cigarette consumption and a longer history of tobacco use will be associated with a shorter LTW. An anonymous cross-sectional survey of 1055 10th and 11th grade students of mixed ethnicity was conducted in two schools using self-completed questionnaires. Participants were asked “After you have smoked a cigarette, how long can you go before you feel you need to smoke again?” Of 162 current smokers, 73.5% reported a regular need to smoke and a LTW. Reported values for the LTW ranged from .05 h to “3 weeks or more.” Monthly cigarette consumption ranged from 1 to 895. The LTW correlated inversely with monthly cigarette consumption (Kendall’s tau b = − .53, P < .001) and the duration of smoking (Kendall’s tau b = − .25, P < .001) as predicted by the sensitization-homeostasis theory.”



– The perverse thing is that almost everybody who starts smoking starts smoking as a teenager.

According to the 2021 Global Burden of Disease report, the majority of smokers start between ages 14-25. 


#IHME and Lancet Public Health. 2021. 

https://www.thelancet.com/infographics-do/tobacco

Quote: “In 2019, there were an estimated 155 million smokers aged between 15 and 24 years – equivalent to 20.1% of young men and 5.0% of young women, globally.”

#CDC. Youth and Tobacco Use. Retrieved November 2023. 

https://www.cdc.gov/tobacco/data_statistics/fact_sheets/youth_data/tobacco_use/index.htm

Quote: “Tobacco product use is started and established primarily during adolescence.1,2 Nearly 9 out of 10 adults who smoke cigarettes daily first try smoking by age 18. Flavorings in tobacco products can make them more appealing to youth.4,5 In 2021, 80.2% of high school students and 74.6% of middle school students who used tobacco products in the past 30 days reported using a flavored tobacco product during that time.6 In 2023, 90.3% of high school students and 87.1% of middle school students who used e-cigarettes in the past 30 days reported using a flavored e-cigarette during that time.7”



– Today about a billion people will light a cigarette, which is a lot but at least the trends are looking good.


Even though the global prevalence has decreased, there are two main points to keep in mind: First, the absolute number has increased due to population increase. Second, there are large regional differences. Although there are countries in which the prevalence has been steadily decreasing, there are also countries which have not peaked yet and are predicted to increase in the coming years. 


The most recent data on global prevalence of smoking is from the Global Burden of Disease study from 2019. 


#Lancet. The global burden of tobacco. 2021.

https://www.thelancet.com/infographics-do/tobacco

Quote: “The most comprehensive data on global trends in smoking highlights its enormous global health toll. The number of smokers worldwide has increased to 1.1 billion in 2019, with tobacco smoking causing 7.7 million deaths – including 1 in 5 deaths in males worldwide.”

Even though the global prevalence is decreasing, the number of people is still increasing due to the increase in the global population. 

#GBD 2019 Tobacco Collaborators. Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and attributable disease burden in 204 countries and territories, 1990–2019: a systematic analysis from the Global Burden of Disease Study 2019. 2021. 

https://www.thelancet.com/action/showPdf?pii=S0140-6736%2821%2901169-7

Quote: “Since 1990, global age-standardised prevalence of smoking tobacco use among males aged 15 years and older decreased by 27.5% (95% UI 26.5–28.5) and among females decreased by 37.7% (35.4–39.9), with variable progress across countries (table). Prevalence of smoking tobacco use among males aged 15 years and older decreased significantly between 1990 and 2019 in 135 countries (66%), but decreased significantly among females in only 68 countries (33%). The largest decreases were observed in Brazil, where prevalence decreased by 72.5% (70.1–74.7) among males and by 74.7% (71.2–78.0) among females. Among individuals aged 15 years and older, prevalence of smoking tobacco use increased significantly over the past 30 years in 20 countries for males”


Following chart shows the change in prevalence and population of smokers per region. 

#GBD 2019 Tobacco Collaborators. Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and attributable disease burden in 204 countries and territories, 1990–2019: a systematic analysis from the Global Burden of Disease Study 2019. 2021. 

https://www.thelancet.com/action/showPdf?pii=S0140-6736%2821%2901169-7

Quote: “In many countries, reductions in prevalence have not kept pace with population growth (figure 1; appendix 2 pp 94–102). As a result, the number of smokers globally

has increased steadily each year since 1990, when there were 0·99 billion (95% UI 0·98–1·00) smokers globally, with the exception of the period between 2011 and 2017, during which no significant change in the number of smokers occurred (figure 1). Of 204 countries and territories included in our analysis, 113 (55%) had a significant increase in the number of current smokers between 1990 and 2019 and 111 (54%) had a significant increase between 2005 and 2019. Among both males and females, the super-regions with the largest relative increases in the number of smokers since 1990 were north Africa and the Middle East (104·1% [98·1–111] increase) and sub-Saharan Africa (74·6% [69·9–79·1] increase; appendix 2 pp 94–102). The largest relative decreases in the number of smokers were observed in the Latin America and the Caribbean (19·8% [16·9–22·5] decrease) and high-income (17·6% [16·2–18·9] decrease) super-regions.”



#WHO global report on trends in prevalence of tobacco use 2000–2025 Fourth edition. 2021. 

https://iris.who.int/bitstream/handle/10665/348537/9789240039322-eng.pdf?sequence=1

Quote: “The global number of tobacco smokers aged 15 years and older in 2000 was estimated at 1.13 billion and is projected to decline to around 0.96 billion by 2025, based on countries’ current prevalence and trends in population size. While the global number of smokers aged 15 years and older is in decline, only three WHO regions have a consistent decline in smoker numbers since 2000: the Region of the Americas, the European Region, and the South-East Asia Region. The number of smokers in the Western Pacific Region is

estimated to have peaked in 2015 and is now declining. Numbers of smokers are continuing to grow in the African Region and the Eastern Mediterranean Region.”

– In 2000 34% of adults were smoking, in 2020 it was only 23%. 


The following chart shows the percentage of population 15 years old and older that use any tobacco product (including cigarettes, pipes, cigars, cigarillos, waterpipes, bidis, kretek, heated tobacco products, and all forms of smokeless tobacco)  on a daily or non-daily basis. Tobacco products exclude e-cigarettes (which do not contain tobacco), “e-cigars”, “e-hookahs”, JUUL and “e-pipes”. 


#World Bank. Retrieved December 2023. 

https://genderdata.worldbank.org/indicators/sh-prv-smok/?view=trend

#GBD 2019 Tobacco Collaborators. Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and attributable disease burden in 204 countries and territories, 1990–2019: a systematic analysis from the Global Burden of Disease Study 2019. 2021. 

https://www.thelancet.com/action/showPdf?pii=S0140-6736%2821%2901169-7

Quote: “Globally, there were 1.14 billion (95% UI 1.13–1.16) current smokers in 2019. Age-standardised prevalence of current use of smoking tobacco among individuals aged 15 years and older was 32.7% (32.3–33.0) among males and 6.62% (6.43–6.83) among females.”


#Lancet. The global burden of tobacco. 2021.

https://www.thelancet.com/infographics-do/tobacco

– Still, in 2023 about 8 million people died from it.


The most recent update from WHO reports around 8 million total deaths which also includes secondhand smoke. Another study, GBD 2019, reports 7.69 million deaths but excludes the health effects of secondhand smoke. 


#WHO. Tobacco. 2023. 

https://www.who.int/news-room/fact-sheets/detail/tobacco

Quote: “The tobacco epidemic is one of the biggest public health threats the world has ever faced, killing over 8 million people a year around the world. More than 7 million of those deaths are the result of direct tobacco use while around 1.3 million are the result of non-smokers being exposed to second-hand smoke (4).”


#GBD 2019 Tobacco Collaborators. Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and attributable disease burden in 204 countries and territories, 1990–2019: a systematic analysis from the Global Burden of Disease Study 2019. 2021. 

https://www.thelancet.com/action/showPdf?pii=S0140-6736%2821%2901169-7

Quote: “Globally in 2019, smoking tobacco use accounted for 7.69 million (7.16–8.20) deaths and 200 million (185–214) disability-adjusted life-years, and was the leading risk factor for death among males (20.2% [19.3–21.1] of male deaths). 6.68 million [86.9%] of 7.69 million deaths attributable to smoking tobacco use were among current smokers.”


#He H, Pan Z, Wu J, Hu C, Bai L, Lyu J. Health Effects of Tobacco at the Global, Regional, and National Levels: Results From the 2019 Global Burden of Disease Study. 2022.

https://www.researchgate.net/publication/357203786_Health_Effects_of_Tobacco_at_the_Global_Regional_and_National_Levels_Results_From_the_2019_Global_Burden_of_Disease_Study

– But it’s not all doom and gloom. There are many successful strategies for quitting, we've put some links to some in the video description. 


One of our experts for this script, Katharina Starnberg (Tabakambulanz, LMU, Munich), kindly provided sources for strategies for quitting and treatment.

 The current standard treatment that provides the best outcome for successful quitting is cognitive behavioral therapy supported by nicotine replacement or medications like bupropion and varenicline. The behavioral therapy is generally done in groups or individually by certified smoke-free coaches. There are also commonly referred practices like acupuncture and hypnosis. Even though some people found them useful, there is no good scientific evidence for their success in lasting cessation. 


#Wu et al. Effectiveness of smoking cessation therapies: a systematic review and meta-analysis. 2006. 

https://bmcpublichealth.biomedcentral.com/articles/10.1186/1471-2458-6-300

Quote: “The findings of this review point the direction for future studies. It is interesting that the three modalities examined have distinct biological mechanisms of action. NRT presumably works by reducing symptoms of nicotine withdrawal, thereby increasing the likelihood of smoking cessation. Bupropion is a weak dopamine and nor-epinephrine reuptake inhibitor. One of the primary symptoms of smoking cessation has been depressive symptoms and it has been hypothesized that smokers may be increasing central dopamine levels by reducing monoamine oxidase inhibitor activity[116]. The mechanism of action of bupropion, therefore, may be to maintain central levels of dopamine through the process of cessation, although its effectiveness has been identified to be independent of symptoms of depression[102]. Varenicline is a nicotinic acetylcholine receptor partial agonist. The authors of one the studies demonstrating its efficacy comment that "Partial agonists at this (receptor) could stimulate the release of sufficient dopamine to reduce craving and withdrawal while simultaneously acting as a partial antagonist by blocking the binding and consequent reinforcing effects of smoked nicotine[5]." Regardless of the exact mechanism of action of the three modalities, it is clear they are distinct and suggest the possibility of combination therapy or therapy targeted on the particular type of symptoms experienced during cessation. Future studies could examine these options, given that despite the effectiveness of these therapies rates of smoking remain high at one year in the treatment groups [82]. Furthermore, given the benefits described of smoking cessation as secondary prevention, the use of these cessation modalities in patients with active smoking related disease warrants further study [117]. Future studies should further examine the safety and effectiveness in reducing morbidity and mortality of all three of these modalities in patients with active smoking related disease.”


NHS has a good website and they also provide a smartphone app for helping people with quitting:
 https://www.nhs.uk/better-health/quit-smoking/


One can also find information on the website of Centers for Disease Control and Prevention:

https://www.cdc.gov/tobacco/data_statistics/fact_sheets/cessation/smoking-cessation-fast-facts/index.html

Even though smartphone applications would not be effective on their own, several reviews and research papers found them useful when used together with behavioral therapy and pharmacotherapy.  


#Guo et al. The Effectiveness of Smartphone App–Based Interventions for Assisting Smoking Cessation: Systematic Review and Meta-analysis. 2023.

https://www.jmir.org/2023/1/e43242

Quote: “Results: A total of 9 randomized controlled trials involving 12,967 adults were selected for the final analysis. The selected studies from 6 countries (the United States, Spain, France, Switzerland, Canada, and Japan) were included in the meta-analysis between 2018 and 2022. Pooled effect sizes (across all follow-up time points) revealed no difference between the smartphone app group and the comparators (standard care, SMS text messaging intervention, web-based intervention, smoking cessation counseling, or apps as placebos without real function; odds ratio [OR] 1.25, 95% CI 0.99-1.56, P=.06, I2=73.6%). Based on the subanalyses, 6 trials comparing smartphone app interventions to comparator interventions reported no significant differences in effectiveness (OR 1.03, 95% CI 0.85-1.26, P=.74, I2=57.1%). However, the 3 trials that evaluated the combination of smartphone interventions combined with pharmacotherapy compared to pharmacotherapy alone found higher smoking abstinence rates in the combined intervention (OR 1.79, 95% CI 1.38-2.33, P=.74, I2=7.4%). All SASC interventions with higher levels of adherence were significantly more effective (OR 1.48, 95% CI 1.20-1.84, P<.001, I2=24.5%).”

On the other hand, not all of the many cessation apps have proven helpful, so it is of prime importance to find the certified and suitable one for one’s personal need which keeps one to use it daily and use it along with other treatments. 


#Bold et al. Smartphone Apps for Smoking Cessation: Systematic Framework for App Review and Analysis. 2023. 

https://pubmed.ncbi.nlm.nih.gov/37440305/

Quote: “Results: We initially identified 389 apps, excluded 161 due to irrelevance and nonfunctioning, and rated 228, including 152 available for Android platforms and 120 available for iOS platforms. Some of the top-returned apps (71/228, 31%) in 2021 were no longer functioning in 2022. Our analysis of rated apps revealed limitations in accessibility and features. While most apps (179/228, 78%) were free to download, over half had costs associated with in-app purchases or full use. Less than 65% (149/228) had a privacy policy addressing the data collected in the app. In terms of intervention features, more than 56% (128/228) of apps allowed the user to set and check in on goals, and more than 46% (106/228) of them provided psychoeducation, although few apps provided evidence-based support for smoking cessation, such as peer support or skill training, including mindfulness and deep breathing, and even fewer provided evidence-based interventions, such as acceptance and commitment therapy or cognitive behavioral therapy. Only 12 apps in 2021 and 11 in 2022 had published studies supporting the feasibility or efficacy for smoking cessation.


Conclusions: Numerous smoking cessation apps were identified, but analysis revealed limitations, including high rates of irrelevant and nonfunctioning apps, high rates of turnover, and few apps providing evidence-based support for smoking cessation. Thus, it may be challenging for consumers to identify relevant, evidence-based apps to support smoking cessation in the app store, and a comprehensive evaluation system of mental health apps is critically important.”


– People who stop smoking by the age of 35 on average don’t die earlier than non-smokers. If you are older than that, even quitting late can add years to your life! It's a bit like with climate change – every bit counts even if damage is already done. 


In the following study, data from the US National Health Interview Survey collected through 1997-2018 from more than half a million people aged 25 to 84 years showed that mortality rates of smokers who quit at age 35 were similar to never smokers. Moreover, quitting before age 45 was associated with reductions of approximately 90% of the excess mortality risk associated with continued smoking. But this does not mean that one can smoke until 35 for 20 years and all is fine. Never smokers are always better off and the earlier one quits the better it is, no need to wait until 35. 


#Thomson et al. Association Between Smoking, Smoking Cessation, and Mortality by Race, Ethnicity, and Sex Among US Adults. 2022.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9593233/
Quote: “In this nationally representative, prospective cohort study in the US, among men and women from diverse racial and ethnic groups, cigarette smoking was associated with substantial excess mortality, but smoking cessation was associated with a substantial reversal of risk. Compared with never smokers, current smokers had 3 times the overall mortality rate among White individuals and approximately twice the mortality rate among Black, Hispanic, and other non-Hispanic individuals, with similar relative excess mortality by sex within each racial and ethnic group after adjusting for age, educational level, and alcohol consumption. However, quitting smoking before age 45 years was associated with reductions of approximately 90% of the excess mortality risk associated with continued smoking, and quitting at ages 45 to 64 years was associated with reductions of approximately 66% of this excess risk irrespective of race and ethnicity (Figure 2).”