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Smoking
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In one pass Smoking does its harm not through one poison but because each puff delivers several kinds of things into the body at once, and each takes its own path.
Educational content, not medical advice — consult a clinician.
Story path
Chapter 1
What one puff carries in
Smoking does its harm not through one poison but because each puff delivers several kinds of things into the body at once, and each takes its own path.
Smoke has two parts: the gas that drifts, and tar, which condenses into fine particles. The particle part alone holds at least 3,500 compounds, many of them toxic, cancer-causing or able to mutate genes. The gas carries carbon monoxide and a large number of free radicals (reactive molecules missing an electron, which grab electrons from other molecules) — an estimated 10¹⁵ per puff, a million billion (Valavanidis review).
Once in the lungs, they split up:
Oxidants use up the body's antioxidant reserves, vitamin C first among them.Carbon monoxide takes over the places in the blood that carry oxygen.Nicotine is absorbed into the blood and acts on the brain and blood vessels.
This story follows those three lines. If you suddenly have chest pain that feels like pressure and can't get your breath, don't wait: call your local emergency number now. The chapter When to see a doctor lists all the warning signs.
Smoke has two parts: the gas that drifts, and tar, which condenses into fine particles. The particle part alone holds at least 3,500 compounds, many of them toxic, cancer-causing or able to mutate genes. The gas carries carbon monoxide and a large number of free radicals (reactive molecules missing an electron, which grab electrons from other molecules) — an estimated 10¹⁵ per puff, a million billion (Valavanidis review).
Once in the lungs, they split up:
Oxidants use up the body's antioxidant reserves, vitamin C first among them.Carbon monoxide takes over the places in the blood that carry oxygen.Nicotine is absorbed into the blood and acts on the brain and blood vessels.
This story follows those three lines. If you suddenly have chest pain that feels like pressure and can't get your breath, don't wait: call your local emergency number now. The chapter When to see a doctor lists all the warning signs.
Mechanism · Why the radicals in tar linger
Radicals in the gas phase are short-lived, but they sit in a steady state: constantly used up and constantly formed again, and the older the smoke, the higher their concentration (Valavanidis review).The radicals in tar are different. Each gram of tar carries about 10¹⁷ stable radicals. They come from a set of quinone compounds that can hand electrons to oxygen again and again, first making superoxide, then hydrogen peroxide and the most reactive of all, the hydroxyl radical (Pryor review). The system can turn over round after round, so tar settled in the airways becomes a small workshop that keeps making oxidants.
Lab work has shown a few more things:
Tar extracts made DNA form a marker of oxidative damage (8-OHdG).The tar radical can get into living cells, bind to DNA and nick the DNA strand.Ordinary filters did not substantially reduce the radicals in smoke.
Know how much weight these carry: they are chemistry and cell experiments. They show how the damage can happen, not how much damage has been measured in any one person.
Chapter 2
Carbon monoxide takes oxygen's seat
Hemoglobin in red blood cells loads oxygen in the lungs and carries it around the body. Carbon monoxide can bind at the same site, and hemoglobin's affinity for it is about 250 times its affinity for oxygen (Rose review). The carbon monoxide breathed in with smoke takes over some of the seats meant for oxygen this way.
There is a second problem: once carbon monoxide binds, the remaining sites on the same hemoglobin hold oxygen more tightly and are less willing to let go of it in the tissues. So the blood carries less oxygen and hands less of it to the tissues. Carbon monoxide can also bind myoglobin, the oxygen store in heart and skeletal muscle.
When doctors look at the share of hemoglobin occupied by carbon monoxide, they use different lines for two groups: in nonsmokers, 2% or more is abnormal; in smokers, only 10% or more. That the two lines differ shows in itself that smokers normally carry more carbon monoxide in their blood.
The good news is that it leaves quickly too: breathing ordinary air, carbon monoxide has a half-life of about 320 minutes.
There is a second problem: once carbon monoxide binds, the remaining sites on the same hemoglobin hold oxygen more tightly and are less willing to let go of it in the tissues. So the blood carries less oxygen and hands less of it to the tissues. Carbon monoxide can also bind myoglobin, the oxygen store in heart and skeletal muscle.
When doctors look at the share of hemoglobin occupied by carbon monoxide, they use different lines for two groups: in nonsmokers, 2% or more is abnormal; in smokers, only 10% or more. That the two lines differ shows in itself that smokers normally carry more carbon monoxide in their blood.
The good news is that it leaves quickly too: breathing ordinary air, carbon monoxide has a half-life of about 320 minutes.
Mechanism · How fast it clears after you stop
A half-life is the time it takes for the amount left to halve. At about 320 minutes per halving, five half-lives come to about 27 hours, and by then only about one thirtieth of the extra carbon monoxide is left. So a day or so after you stop smoking, this part of your blood is essentially back to a nonsmoker's level.Read that number carefully: the 320-minute half-life comes from studies of carbon monoxide poisoning. The day or so above is calculated from it; it is not an hour-by-hour timeline measured in people who quit.
The same review has two more points that help explain why carbon monoxide does more than carry a little less oxygen:
Breathing pure oxygen cuts the half-life to about 74 minutes; this is the basic hospital treatment for carbon monoxide poisoning.Myoglobin's affinity for carbon monoxide is about 60 times its affinity for oxygen; in people who are poisoned, carbon monoxide bound in heart muscle damages heart function.
The carbon monoxide level from smoking is far lower than in poisoning. These two points show where it can reach and what it can do; they do not mean smoking is the same as poisoning.
Chapter 3
Smoke uses up vitamin C faster
Vitamin C is one of the first antioxidants to act in blood and tissue: when an oxidant arrives, vitamin C gives up an electron and is used up in the process. The steady stream of oxidants in smoke keeps that drain running.
A small study that tracked vitamin C with an isotope label (Kallner 1981) found that in men smoking more than 20 cigarettes a day, vitamin C turned over faster than in nonsmokers. For the same intake, smokers keep less of it.
On that basis, the US Institute of Medicine (IOM) dietary reference intakes add 35 mg a day for smokers on top of the recommended amount, because smoking raises oxidative stress and the metabolic turnover of vitamin C.
That gap can be covered from food, with fresh vegetables and fruit as the main sources; the Vitamin C story lists how much common foods contain. Remember that this only settles one account: by the mechanism, eating more vitamin C can make up for what smoke uses up, but it cannot block anything else in the smoke.
A small study that tracked vitamin C with an isotope label (Kallner 1981) found that in men smoking more than 20 cigarettes a day, vitamin C turned over faster than in nonsmokers. For the same intake, smokers keep less of it.
On that basis, the US Institute of Medicine (IOM) dietary reference intakes add 35 mg a day for smokers on top of the recommended amount, because smoking raises oxidative stress and the metabolic turnover of vitamin C.
That gap can be covered from food, with fresh vegetables and fruit as the main sources; the Vitamin C story lists how much common foods contain. Remember that this only settles one account: by the mechanism, eating more vitamin C can make up for what smoke uses up, but it cannot block anything else in the smoke.
Evidence · Does secondhand smoke lower it too
Yes, at least in one study. Tribble 1993 compared three groups in the US: 44 nonsmokers regularly exposed to secondhand smoke, 47 smokers, and 50 people with no tobacco exposure.In the secondhand-smoke group, blood vitamin C fell right between the other two: higher than in smokers, lower than in the unexposed, even though all three groups took in similar amounts of vitamin C from their diets.Low blood vitamin C (below 23 μmol/L) was found in 24% of smokers, 12% of those exposed to secondhand smoke, and none of the unexposed.Only in the two smoke-exposed groups were low intakes clearly linked to low blood levels.
The authors concluded that long-term smoke exposure, especially combined with low vitamin C intake, may lower vitamin C stores in both active and passive smokers.
Read it carefully: this is a small cross-sectional study, which can only show how these groups differed at one point in time. The IOM did not set a separate amount for people exposed to secondhand smoke. If someone in your home smokes, two things follow: eat enough vegetables and fruit every day, and, more fundamentally, keep smoke out of the house.
Chapter 4
Why beta-carotene pills hurt smokers
In observational studies, people who eat more vegetables and fruit, and have more beta-carotene in their blood, get less lung cancer. So researchers gave smokers high-dose beta-carotene pills to see whether it would lower lung cancer. The result went the other way:
In Finland's ATBC trial, of 29,133 male smokers, those given beta-carotene had 18% more lung cancer and 8% higher total mortality.In the US CARET trial, of 18,314 smokers, former smokers and asbestos workers, beta-carotene plus vitamin A raised the of lung cancer to 1.28, and the trial was stopped 21 months early because of it.
On that basis, the US Preventive Services Task Force (USPSTF) recommends against beta-carotene supplements to prevent cardiovascular disease or cancer.
This does not mean carrots and leafy greens are a problem. The trials gave a single ingredient as a high-dose pill, which is not the same as eating it whole in vegetables and fruit. If you smoke, don't take extra high-dose beta-carotene pills, and check whether a multivitamin's formula contains it. Multivitamin · #1 supplement worldwide covers these trials in full.
In Finland's ATBC trial, of 29,133 male smokers, those given beta-carotene had 18% more lung cancer and 8% higher total mortality.In the US CARET trial, of 18,314 smokers, former smokers and asbestos workers, beta-carotene plus vitamin A raised the of lung cancer to 1.28, and the trial was stopped 21 months early because of it.
On that basis, the US Preventive Services Task Force (USPSTF) recommends against beta-carotene supplements to prevent cardiovascular disease or cancer.
This does not mean carrots and leafy greens are a problem. The trials gave a single ingredient as a high-dose pill, which is not the same as eating it whole in vegetables and fruit. If you smoke, don't take extra high-dose beta-carotene pills, and check whether a multivitamin's formula contains it. Multivitamin · #1 supplement worldwide covers these trials in full.
Mechanism · What smoke plus a high dose did
The human trials answered whether harm happens, not why. A ferret experiment (Wang 1999) offers one possible explanation.Researchers split ferrets into groups and, over 6 months, gave them a high dose of beta-carotene, exposed them to cigarette smoke, or both:
Every ferret given beta-carotene showed marked cell growth in lung tissue and squamous metaplasia (the airway lining switching to a tougher, flatter cell type), and smoke made the change worse.All three treated groups had low retinoic acid in the lungs (the form in which vitamin A acts inside cells), and expression of one retinoic acid receptor (RAR-beta) was 18% to 73% lower.In the group given the pill plus smoke, two genes that drive cell growth (c-Jun and c-Fos) were expressed 3 to 4 times more.
From this the authors proposed that weakening the vitamin A signal that keeps cells maturing normally could be one mechanism that makes tumors more likely in the lung.
Read it carefully: this is an animal study and has not been confirmed directly in people. Another explanation often given is that high-dose beta-carotene, oxidized in a smoky, oxygen-rich lung, turns around and generates free radicals; that step has not been measured in people either.
Chapter 5
Why weight goes up after quitting
Nicotine holds weight down from two sides: it makes the body burn about 10% more energy a day, and it acts on the brain's appetite signals so you eat less (Audrain-McGovern review). So on average, adult smokers weigh 4 to 5 kg less than nonsmokers.
Quit, and both sides let go at once: the metabolic rate falls and appetite rises. In one study, people who quit ate on average about 227 kcal more a day, which explained about 69% of the weight gained 3 months after quitting.
A pooling 62 studies (Aubin 2012) gives the shape in detail: people who quit without medication had gained on average about 4.67 kg at 12 months, most of it in the first 3 months. But people differ widely: about 16% actually lost weight, and about 13% gained more than 10 kg.
Weight gain is no reason to keep smoking: in the US Framingham cohort, people whose weight went up after quitting still had a clearly lower risk of cardiovascular disease (Clair 2013, an observational study).
Quit, and both sides let go at once: the metabolic rate falls and appetite rises. In one study, people who quit ate on average about 227 kcal more a day, which explained about 69% of the weight gained 3 months after quitting.
A pooling 62 studies (Aubin 2012) gives the shape in detail: people who quit without medication had gained on average about 4.67 kg at 12 months, most of it in the first 3 months. But people differ widely: about 16% actually lost weight, and about 13% gained more than 10 kg.
Weight gain is no reason to keep smoking: in the US Framingham cohort, people whose weight went up after quitting still had a clearly lower risk of cardiovascular disease (Clair 2013, an observational study).
In practice · Getting through the first three months
Once you know the mechanism, the approach follows: most of the weight comes in the first 3 months and comes mainly from eating more, so plan what you will eat during that stretch ahead of time.Fill the appetite gap in advance: eat meals at regular times, and when you want a snack, have bulky, low-calorie things like vegetables and fruit at hand. This follows from the mechanism; it is not a plan tested in trials.Move more: activity can make up some of the drop in metabolic rate. Weight Management · Foundations explains how the energy balance works.Don't expect the medication to manage your weight too: the review notes that most drugs that help people quit only delay the weight gain, and weight rises once the drug stops; in the , people who quit with different drugs had gained about the same at 12 months.
On the heart, Clair 2013 reports these numbers: among people without diabetes, the median weight gain in the 4 years after quitting was 2.7 kg; compared with continuing smokers, recent quitters had a for cardiovascular disease of 0.47, almost unchanged once weight change was taken into account. In people with diabetes the direction was the same, but it did not reach statistical significance.
One counterintuitive finding is worth knowing too: in some studies, the heaviest smokers weighed more than lighter smokers. Nicotine's push on weight does not outweigh the other habits that tend to come along with it.
Chapter 6
What recovers after quitting, and when
The benefits of quitting don't arrive all at once; each part of the body comes back at its own pace:
Carbon monoxide: with a half-life of about 320 minutes, by that rate the extra amount is essentially gone a day or so after your last cigarette.Wound healing: oxygen supply to the tissues recovers soon after stopping; the inflammatory cells that clear debris and fight infection recover in part within about 4 weeks; the fibroblasts that do the repair are slower (Sørensen review).Lungs: in a large quit-smoking trial, smokers with mild-to-moderate airflow limitation who actually quit gained an average of 47 mL of lung function in the first year, and afterwards lost it each year at half the rate of continuing smokers, about the same as people who never smoked (Lung Health Study).Heart and blood vessels: among heavy smokers in the US Framingham study, within 5 years of quitting the rate of cardiovascular disease was already clearly lower than in those who kept smoking; only after 10 to 15 years could it no longer be told apart from never smokers (an observational study).
In the first month after quitting, a cough may temporarily get worse; Chronic cough explains why. If you want help, see a doctor or a stop-smoking clinic: the US Preventive Services Task Force (USPSTF) recommends, with high certainty, offering nonpregnant adults who smoke both behavioral support and stop-smoking medication; which medicine to use is your doctor's call. The evidence on these medicines in pregnancy is insufficient, so if you are pregnant, ask your doctor first.
Carbon monoxide: with a half-life of about 320 minutes, by that rate the extra amount is essentially gone a day or so after your last cigarette.Wound healing: oxygen supply to the tissues recovers soon after stopping; the inflammatory cells that clear debris and fight infection recover in part within about 4 weeks; the fibroblasts that do the repair are slower (Sørensen review).Lungs: in a large quit-smoking trial, smokers with mild-to-moderate airflow limitation who actually quit gained an average of 47 mL of lung function in the first year, and afterwards lost it each year at half the rate of continuing smokers, about the same as people who never smoked (Lung Health Study).Heart and blood vessels: among heavy smokers in the US Framingham study, within 5 years of quitting the rate of cardiovascular disease was already clearly lower than in those who kept smoking; only after 10 to 15 years could it no longer be told apart from never smokers (an observational study).
In the first month after quitting, a cough may temporarily get worse; Chronic cough explains why. If you want help, see a doctor or a stop-smoking clinic: the US Preventive Services Task Force (USPSTF) recommends, with high certainty, offering nonpregnant adults who smoke both behavioral support and stop-smoking medication; which medicine to use is your doctor's call. The evidence on these medicines in pregnancy is insufficient, so if you are pregnant, ask your doctor first.
Safety · Quit early before an operation
Surgical wounds show most clearly what smoke does to repair. In a pooling 140 cohort studies and more than 470,000 patients (Sørensen 2012), smokers compared with nonsmokers had, after surgery:an of about 3.60 for tissue death in the woundabout 2.07 for delayed healing or the wound opening upabout 1.79 for surgical site infectionabout 2.44 for bone or a fistula failing to heal
Former smokers still had somewhat more healing problems than people who never smoked (odds ratio 1.30), but fewer than current smokers (0.69). In 4 randomized trials, helping patients quit around the time of surgery clearly reduced surgical site infections (odds ratio 0.43), while other healing problems were not clearly reduced.
A companion review on mechanisms explains why: smoking temporarily starves tissue of oxygen, weakens the inflammatory cells' ability to reach a wound and kill bacteria, and holds back the fibroblasts and collagen that do the repair. After quitting, oxygen supply returns quickly, inflammatory cells recover in part within about 4 weeks, and the repair step recovers most slowly.
So if you have an operation planned, tell your surgeon that you smoke and start quitting as early as you can.
sorensen-2012-smoking-wound-meta
Numbers · Your bones keep this account too
In a of 10 prospective cohorts and 59,232 people (Kanis 2005), current smokers compared with nonsmokers had:a of about 1.25 for any fractureabout 1.84 for hip fracture
Interestingly, explained only a small part of this: with bone density taken into account, the relative risk of hip fracture was still 1.60, and low bone density accounted for only 23% of the smoking-related risk of hip fracture. In other words, a reassuring bone density scan does not mean the full effect of smoking on your bones has been seen.
Former smokers still had a higher risk than never smokers, but a lower one than current smokers. These are all results from observational studies. How bone is broken down and rebuilt is covered in Osteoporosis.
kanis-2005-smoking-fracture
Chapter 7
When to see a doctor
If you smoke, or someone in your home does, don't wait at home with any of these:
Chest pain that feels like pressure or squeezing, or pain spreading to the arm, neck or jaw, with sweating or breathlessness: this may be a heart attack, so call your local emergency number now.So breathless you can't speak, or pain in your chest or upper back: go to the emergency department now.Coughing up blood, or seeing blood on a tissue you coughed into: see a doctor soon.A cough lasting more than 3 weeks, or unexplained weight loss, loss of appetite, constant tiredness or repeated chest infections: see a doctor.
Most of the time these symptoms are not cancer, but they are a reason to have a doctor examine you in person, the sooner the better; if you are over 40, especially don't put it off.
If you want to quit but can't, that alone is worth a visit to a doctor or a stop-smoking clinic.
This story is education and does not replace a diagnosis.
Chest pain that feels like pressure or squeezing, or pain spreading to the arm, neck or jaw, with sweating or breathlessness: this may be a heart attack, so call your local emergency number now.So breathless you can't speak, or pain in your chest or upper back: go to the emergency department now.Coughing up blood, or seeing blood on a tissue you coughed into: see a doctor soon.A cough lasting more than 3 weeks, or unexplained weight loss, loss of appetite, constant tiredness or repeated chest infections: see a doctor.
Most of the time these symptoms are not cancer, but they are a reason to have a doctor examine you in person, the sooner the better; if you are over 40, especially don't put it off.
If you want to quit but can't, that alone is worth a visit to a doctor or a stop-smoking clinic.
This story is education and does not replace a diagnosis.
References · 21
- Valavanidis, A., Vlachogianni, T., & Fiotakis, K. (2009). Tobacco smoke: involvement of reactive oxygen species and stable free radicals in mechanisms of oxidative damage, carcinogenesis and synergistic effects with other respirable particles. International Journal of Environmental Research and Public Health, 6(2), 445-462. Review plus the authors' EPR and spin-trapping lab work. The particulate phase contains at least 3,500 compounds, many toxic, carcinogenic or mutagenic; the gas phase holds an estimated ~10^15 free radicals per puff (after Pryor), formed and destroyed in a steady state and rising as smoke ages; tar holds ~10^17 stable radicals per gram. The tar semiquinone system can redox-cycle; aqueous tar extracts formed the DNA lesion 8-OHdG; hydroxyl-radical generation was synergistic with asbestos, PM2.5 and diesel particles; conventional and haemoglobin 'bio-filters' did not substantially alter the radical content of smoke. Chemistry and cell findings, not measured harm in people (abstract and full text, PMID 19440393). 10.3390/ijerph6020445
- Pryor, W. A. (1997). Cigarette smoke radicals and the role of free radicals in chemical carcinogenicity. Environmental Health Perspectives, 105(Suppl 4), 875-882. Review. Radicals are probably involved in a substantial number, though probably not a majority, of cancer initiation reactions; promotion always involves radicals to some extent. Aqueous cigarette tar extracts contain a quinone-hydroquinone-semiquinone system that reduces oxygen to superoxide and hence hydrogen peroxide and the hydroxyl radical; the tar radical can penetrate viable cells, bind to DNA and cause nicks. Laboratory chemistry and cell work (abstract, PMID 9255574). 10.1289/ehp.97105s4875
- Rose, J. J., Wang, L., Xu, Q., McTiernan, C. F., Shiva, S., Tejero, J., & Gladwin, M. T. (2017). Carbon monoxide poisoning: pathogenesis, management, and future directions of therapy. American Journal of Respiratory and Critical Care Medicine, 195(5), 596-606. Review of CO poisoning. Hemoglobin has a 250-fold greater affinity for CO than for oxygen; CO binding stabilizes the high-affinity R-state, so the remaining sites hold oxygen tighter and release less to tissues; CO also binds myoglobin (60-fold greater affinity than oxygen) and cytochrome c oxidase. COHb of 2% or more in nonsmokers and 10% or more in smokers is considered abnormal. Normobaric oxygen cuts the CO elimination half-life from 320 minutes on room air to 74 minutes; hyperbaric oxygen to about 20 minutes. It is about poisoning, not about smoking-level exposure (full text, PMID 27753502; erratum 2017). 10.1164/rccm.201606-1275CI
- Kallner, A. B., Hartmann, D., & Hornig, D. H. (1981). On the requirements of ascorbic acid in man: steady-state turnover and body pool in smokers. American Journal of Clinical Nutrition, 34(7), 1347-1355. Healthy male volunteers smoking more than 20 cigarettes a day, given a single oral dose of 14C-labelled ascorbic acid at steady-state intakes of about 30-180 mg/day. Smokers had a higher metabolic turnover than nonsmokers; the authors concluded smokers need at least 140 mg/day to reach steady-state concentrations and body pools comparable to nonsmokers, for whom about 100 mg/day had been reported appropriate. Small isotope-tracer study; the later IOM increment for smokers (+35 mg/day) rests on it (abstract, PMID 7258125). 10.1093/ajcn/34.7.1347
- Institute of Medicine. (2000). Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academies Press. www.ncbi.nlm.nih.gov/books/NBK225483
- Tribble, D. L., Giuliano, L. J., & Fortmann, S. P. (1993). Reduced plasma ascorbic acid concentrations in nonsmokers regularly exposed to environmental tobacco smoke. American Journal of Clinical Nutrition, 58(6), 886-890. Cross-sectional: 44 passive smokers, 47 active smokers, 50 unexposed nonsmokers. Plasma ascorbic acid in passive smokers was intermediate between active smokers and unexposed nonsmokers despite similar dietary vitamin C intakes; hypovitaminosis C (< 23 umol/L) in 24% of active and 12% of passive smokers, none of the unexposed. Low plasma levels were associated with low intake only in the smoke-exposed groups. Conclusion: chronic smoke exposure, particularly with low vitamin C intake, may reduce ascorbate pools in both active and passive smokers (abstract, PMID 8249873). 10.1093/ajcn/58.6.886
- The ATBC Cancer Prevention Study Group. (1994). The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. NEJM, 330(15), 1029–1035. 29,133 male smokers aged 50-69 in south-western Finland; alpha-tocopherol 50 mg/day, beta-carotene 20 mg/day, both, or placebo; follow-up 5-8 years. Lung cancer: alpha-tocopherol -2% (-14 to 12%), beta-carotene +18% (3 to 36%). Fewer prostate cancers with alpha-tocopherol, more deaths from haemorrhagic stroke; total mortality 8% higher with beta-carotene (abstract, PMID 8127329). 10.1056/NEJM199404143301501
- Omenn, G. S., et al. (1996). Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease (CARET). NEJM, 334(18), 1150–1155. 10.1056/NEJM199605023341802
- US Preventive Services Task Force. (2022). Vitamin, mineral, and multivitamin supplementation to prevent cardiovascular disease and cancer: recommendation statement. JAMA, 327(23), 2326–2333. 10.1001/jama.2022.8970
- Wang, X.-D., Liu, C., Bronson, R. T., Smith, D. E., Krinsky, N. I., & Russell, M. (1999). Retinoid signaling and activator protein-1 expression in ferrets given beta-carotene supplements and exposed to tobacco smoke. Journal of the National Cancer Institute, 91(1), 60-66. Ferrets given a high-dose beta-carotene supplement, cigarette smoke, or both for 6 months. All supplemented animals showed a strong proliferative response and squamous metaplasia in the lung, enhanced by smoke; all three treatment groups had lower lung retinoic acid and 18%-73% lower RAR-beta expression; the combined group had threefold to fourfold higher c-Jun and c-Fos expression. Authors propose diminished retinoid signaling as a mechanism that could enhance lung tumorigenesis after high-dose beta-carotene plus smoke. The other half: their background notes people who eat more fruit and vegetables or have high serum beta-carotene have lower lung cancer risk. Animal study (abstract, PMID 9890171). 10.1093/jnci/91.1.60
- Audrain-McGovern, J., & Benowitz, N. L. (2011). Cigarette smoking, nicotine, and body weight. Clinical Pharmacology & Therapeutics, 90(1), 164-168. Narrative review. Adult smokers weigh on average 4-5 kg less than nonsmokers; smoking increases 24-h energy expenditure by about 10% (about 200 kcal/day); nicotine acts through central neurotransmitters on appetite-suppressing and metabolism-raising pathways (pro-opiomelanocortin, CART). Post-cessation weight gain comes from a fall in metabolic rate and a rise in intake: in one study quitters ate on average 227 kcal/day more, explaining 69% of the weight gained at 3 months. The other half: the heaviest smokers weigh more than lighter smokers in some studies, and cessation drugs delay rather than prevent the weight gain (full text, PMID 21633341). 10.1038/clpt.2011.105
- Aubin, H.-J., Farley, A., Lycett, D., Lahmek, P., & Aveyard, P. (2012). Weight gain in smokers after quitting cigarettes: meta-analysis. BMJ, 345, e4439. Meta-analysis of 62 studies (cessation trial arms). In untreated quitters mean weight gain was 1.12 kg at 1 month, 2.26 kg at 2, 2.85 kg at 3, 4.23 kg at 6 and 4.67 kg (95% CI 3.96 to 5.38) at 12 months; most gain occurs within 3 months. Variation is large: at 12 months about 16% lost weight, 37% gained under 5 kg, 34% gained 5-10 kg and 13% gained more than 10 kg. Estimates were similar with different pharmacotherapies and between people concerned and not concerned about weight (abstract, PMID 22782848). 10.1136/bmj.e4439
- Clair, C., Rigotti, N. A., Porneala, B., Fox, C. S., D'Agostino, R. B., Pencina, M. J., & Meigs, J. B. (2013). Association of smoking cessation and weight change with cardiovascular disease among adults with and without diabetes. JAMA, 309(10), 1014-1021. Framingham Offspring cohort, 3,251 participants, 631 CVD events. Median 4-year weight gain in recent quitters without diabetes was 2.7 kg. Versus smokers, recent quitters had HR 0.47 (0.23-0.94) and long-term quitters 0.46 (0.34-0.63) for CVD, barely changed by adjusting for weight change: a net cardiovascular benefit despite weight gain. The other half: among people with diabetes the point estimates were similar but not statistically significant; observational (abstract, PMID 23483176). 10.1001/jama.2013.1644
- Sørensen, L. T. (2012). Wound healing and infection in surgery: the pathophysiological impact of smoking, smoking cessation, and nicotine replacement therapy: a systematic review. Annals of Surgery, 255(6), 1069-1079. 177 pathophysiological studies. Smoking temporarily lowers tissue oxygenation and aerobic metabolism; it blunts inflammatory-cell chemotaxis, migration and oxidative bacterial killing, unbalances proteolytic enzymes, and slows fibroblast migration and proliferation and collagen synthesis. Cessation restores tissue oxygenation and metabolism rapidly and inflammatory-cell function in part within 4 weeks, but the proliferative response remains impaired. Nicotine does not affect the tissue microenvironment; nicotine replacement effects appear marginal (abstract, PMID 22566015). 10.1097/SLA.0b013e31824f632d
- Scanlon, P. D., Connett, J. E., Waller, L. A., Altose, M. D., Bailey, W. C., Buist, A. S., & Tashkin, D. P. (2000). Smoking cessation and lung function in mild-to-moderate chronic obstructive pulmonary disease: the Lung Health Study. American Journal of Respiratory and Critical Care Medicine, 161(2), 381-390. 3,926 smokers with mild-to-moderate airway obstruction (mean age 48.5) randomized to two cessation programs or no intervention; lung function measured yearly for 5 years. Quitters' FEV1 improved by an average of 47 mL (2%) in the year after quitting; afterwards sustained quitters declined 31 mL/year versus 62 mL/year in continuing smokers, comparable to never-smokers. The quitter-versus-smoker comparison is by actual smoking status, not by randomized arm; benefit held despite heavy past smoking, older age or poor baseline function (abstract, PMID 10673175). 10.1164/ajrccm.161.2.9901044
- Duncan, M. S., Freiberg, M. S., Greevy, R. A., Jr., Kundu, S., Vasan, R. S., & Tindle, H. A. (2019). Association of smoking cessation with subsequent risk of cardiovascular disease. JAMA, 322(7), 642-650. Framingham original and offspring cohorts, 8,770 people, median follow-up 26.4 years; primary analysis in heavy ever smokers (20+ pack-years). Versus current smoking, quitting within 5 years was associated with a lower CVD rate (6.94 vs 11.56 per 1,000 person-years; HR 0.61, 0.49-0.76). The other half: versus never smokers, former smokers' risk stayed significantly elevated beyond 5 years and ceased to be significant only 10 to 15 years after quitting. Observational (abstract, PMID 31429895). 10.1001/jama.2019.10298
- Morice, A. H., Millqvist, E., Bieksiene, K., Birring, S. S., Dicpinigaitis, P., Domingo Ribas, C., Hilton Boon, M., Kantar, A., Lai, K., McGarvey, L., Rigau, D., Satia, I., Smith, J., Song, W.-J., Tonia, T., van den Berg, J. W. K., van Manen, M. J. G., & Zacharasiewicz, A. (2020). ERS guidelines on the diagnosis and treatment of chronic cough in adults and children. European Respiratory Journal, 55(1), 1901136. Chronic cough: over 8 weeks in adults, 4 weeks in children; global adult prevalence about 10% (meta-analysis). Cough is a vagal reflex; a poor cough reflex leads to recurrent aspiration; polymodal receptors such as TRPV1, TRPA1 and P2X3 on airway nerve endings respond to gastric fluid, acid, smoke, particulates and hyper- or hypotonicity, and ATP from stressed cells is an important stimulus; receptive fields also in lung parenchyma, pharynx, oesophagus and the ear canal (Arnold's reflex); cortical influences modulate the reflex and women have a greater somatosensory cortical area devoted to cough; the system shows redundancy, plasticity and adaptation; most patients show cough reflex hypersensitivity, triggered by low-level stimuli such as cold air, perfumes, smoke and bleach; specialist-clinic patients two-thirds female, most often in their sixth decade. T2 (eosinophilic) inflammation in about a quarter (cough variant asthma, eosinophilic bronchitis). Non-acid and gaseous reflux may contribute and oesophageal dysmotility is highly prevalent in chronic cough. ACE inhibitor cough in about 15%; ACE inhibitors reset the reflex so timing may not match; angiotensin II antagonists do not affect the cough reflex; no patient with cough should be given an ACE inhibitor; bisphosphonates and calcium channel antagonists may worsen reflux and cough; prostanoid eye drops such as latanoprost may descend the lacrimal duct and irritate the pharynx. Smoking is the major remediable cause; smokers have suppressed capsaicin cough sensitivity and cough may transiently increase in the first month after quitting. Stress urinary incontinence, interference with speech and depression are the most impactful complications; women with cough and incontinence have worse quality of life, and incontinence is rarely discussed, so it should be asked about. Initial assessment excludes malignancy, infection, foreign body and ACE inhibitor use; spirometry and chest X-ray; routine chest CT not suggested when X-ray and examination are normal (conditional, very low). Treatment is by sequential therapeutic trials, one agent at a time, stopped if no response; morphine responds within a week, ICS may take a month; if successful continue several months to let neuronal hypersensitivity resolve, then withdraw to test for remission. Short ICS trial 2-4 weeks (conditional, low): of ten RCTs, two in unselected chronic cough found benefit, while in non-asthmatic cough (negative methacholine) ICS was not superior to placebo. Short anti-leukotriene trial 2-4 weeks, particularly in asthmatic cough (conditional, low). Anti-acid drugs not routinely (conditional, low): no benefit over placebo without acid reflux, modest at most with it; high-dose esomeprazole for 12 weeks in patients with rare or no heartburn gave no benefit. Low-dose morphine in refractory cough (strong, moderate); gabapentin or pregabalin (conditional, low), limited by side effects such as dizziness, fatigue, cognitive changes, nausea and blurred vision; cough control therapy (physiotherapy, speech and language therapy) suggested (conditional, moderate). Children: differences in airway morphology, vulnerability, cough-reflex control and immune maturation make cough a symptom of an underlying disease; sudden cough in a healthy preschool child may be foreign-body aspiration requiring bronchoscopy; protracted bacterial bronchitis, a previously unrecognised common cause of wet cough, is defined by continuous wet cough over 4 weeks, no other pointers, and resolution after 2-4 weeks of an appropriate oral antibiotic, and may precede bronchiectasis; neuromodulators not used in children (full text PMC6942543; PMID 31515408). 10.1183/13993003.01136-2019
- US Preventive Services Task Force (Krist, A. H., Davidson, K. W., Mangione, C. M., et al.). (2021). Interventions for tobacco smoking cessation in adults, including pregnant persons: US Preventive Services Task Force recommendation statement. JAMA, 325(3), 265-279. High certainty that behavioral interventions and FDA-approved pharmacotherapy, alone or combined, give a substantial net benefit for smoking cessation in nonpregnant adults (A recommendation: ask all adults about tobacco use, advise them to stop, provide behavioral interventions and FDA-approved pharmacotherapy). Pregnant persons: behavioral interventions (A); pharmacotherapy evidence insufficient (I). E-cigarettes for cessation: evidence insufficient (I). 14.0% of US adults smoked cigarettes (abstract, PMID 33464343). 10.1001/jama.2020.25019
- NHS. (2026). Heart attack: symptoms. Symptoms can include chest pain that may feel like crushing or squeezing on the chest and may spread to the arm, neck and jaw; feeling short of breath; feeling or being sick; feeling like indigestion; sweating; and pale, blue or grey skin. Call 999 for chest pain that feels tight or like squeezing, or that spreads to the arms, neck or jaw, with severe difficulty breathing, or if someone becomes unresponsive. A heart attack needs emergency treatment in hospital (page last reviewed 31 March 2026). www.nhs.uk/conditions/heart-attack/symptoms
- NHS. (2026). Lung cancer: symptoms. Main symptoms include a cough that is not going away, shortness of breath, coughing up blood, chest or shoulder pain, repeated chest infections, unexplained weight loss, loss of appetite and tiredness. See a GP if you've had a cough for longer than 3 weeks or have any other symptoms; ask for an urgent GP appointment or contact NHS 111 if you've coughed up blood or noticed blood on a tissue you've coughed into; call 999 or go to A&E if you're struggling to breathe or have pain in your chest or upper back. These symptoms are often caused by other conditions (page last reviewed 20 August 2026). www.nhs.uk/conditions/lung-cancer/symptoms
- Hamilton, W., Peters, T. J., Round, A., & Sharp, D. (2005). What are the clinical features of lung cancer before the diagnosis is made? A population based case-control study. Thorax, 60(12), 1059-1065. 247 lung cancers in people over 40 and 1,235 controls matched by age, sex and practice in all 21 Exeter general practices; the whole primary care record for 2 years before diagnosis was coded. Haemoptysis, weight loss, loss of appetite, dyspnoea, chest pain, fatigue and cough, finger clubbing, thrombocytosis and abnormal spirometry were independently associated with lung cancer, as was smoking; excluding the final 180 days before diagnosis, haemoptysis, dyspnoea and abnormal spirometry remained associated (abstract, PMID 16227326). 10.1136/thx.2005.045880