tobacco smoking and the lung

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TOBACCO SMOKING AND THE LUNGS BY Mahmoud M. Alsalahy, MD Banha Faculty of Medicine Egypt

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What is tobacco ? ■ Dried leaves of Nicotiana glauca, Nightshade or Potato Family ( Solanaceae ) , Tree Tobacco. ■ Origin : Arizona and parts of New Mexico ■ Contains nicotine and anabasine & MAOI ■ Types : Black and Brown ■ How consumed: smoking, chewing, buccal, snuff ■ Why consumed ? Pharmacologic actions of nicotine

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DANGEROUS !!!!!!!!! Burnet tobacco smoke contains more than 6000 toxic substances including oxides, aldheydes, heavy metals, oxygen radicals, radioactive intermediates, ….

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IMPORTANT FACTS Nicotine in tobacco is highly addicting so quitting is difficult Tobacco consumption peaked in 60s of 2o th century In late 90s, marked drop in western world and marked rise in 3 rd world (2%/yr) 90 % of smokers are between 14 and 25 yrs old Race : above 40 is more in blacks & below 25 is more in whites

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Tobacco smoking among adults in USA

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● Most pts with SID are above 40 ● In western world : ● an average smoker has 30% risk of having fatal disease and 30% risk of non fatal disease ● 20% of all deaths are related to SID ● Expected that : more than 10% of 6 billions now in the world will die due to SID ● By 2010 the world burns 500 billion $ /yr, in KSA, 2.3 billion riyals/yr importation and 4 billions for SID costs

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EFFECTS OF TOBACCO SMOKING ON THE LUNGS □ Early: causes physiologic Derangements □ Later causes disease □ Finally causes death

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EFFECTS OF TOBACCO SMOKING ON LUNG PHYSIOLOGY ₪ Lung volumes and capacities

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₪ Gas transfer

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₪ On m atching ventilation and perfusion

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Fig. 2.13 Distribution of ventilation–perfusion ratios measured by the multiple inert gas technique in a normal subject (a) and in a patient with chronic bronchitis and emphysema (b).

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₪ Hb oxygen delivery

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₪ Tracheobronchial escalator Smoking impairs tracheobronchial clearance: = Impaired ciliary function = Viscid secretions Mucus transfer rate and cilia beating frequency before and after 2 cigarettes p < 0.05 p < 0.01

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Normal bronchial mucosa Bronchial mucosa in smokers

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₪ Lung elasticity

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₪ Lung surfactant Tobacco smoking causes poor surfactant function (abnormal apoprotein)

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₪ On lung immunity Tobacco smoking impairs all immune functions of the lung Impairs mucociliary function Impairs monocytes & macrophages function Increase CD8 + and decrease CD4 + T-lymphocytes Decrease IgA secretion

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Fig. 1.16 Electron micrograph of human alveolar macrophages obtained at broncho -alveolar lavage showing phagolysosomes containing inclusions derived from cigarette smoke and occasional lamellar bodies (¥ 2025). The relatively smooth membranes are associated with cigarette smoke exposure. (Courtesy of Dr R. Agius .)

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₪ Lung repair In humans, the lung continues to develop for up to 8 years after birth. Animal studies have shown that developing lungs are particularly susceptible to injury by toxic compounds that are present in large abundance in tobacco smoke. These studies have also shown that once the developing lung is injured, it takes longer to repair than an adult lung and, in some regions, does not repair at all. Tobacco smoke affects all cellular and humoral factors and cellular signaling needed for repair especially macrophages and fibroblasts

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₪ Lung drug delivery and metabolism ● Reduced ACE activity ● Improper drug delivery by inhalation

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LUNG DISEASES DUE TO TOBACCO © PATHOGENETIC MECHANISMS: Inflammation : Direct irritation Auto-immunity Vasculopathy (ischemia) b. Carcinogenesis: 1. Impaired immunological surveillance 2. Oncogene mutations 3. Direct irritation c. Vasculopathy: Atherosclerosis: endothelial injury, dyslipidaemia(↑LDL) Thrombogenesis: raised fibrinogen, plt activation, atheroma

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© DISEASES CAUSED BY TOBACCO USE: □ Tobacco worker's lung □ Tobacco smoking Chronic bronchitis and COPD Lung cancer Asthma Pneumothorax Thromboembolic disease Pulmonary infections Tuberculosis Collagen vascular and autoimmune disorders Respiratory failure and ARDS Indirect: GERD, cardiogenic pulmonary edema

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1. CHRONIC BRONCHITIS & COPD Chronic irreversible airway obstruction 90 % due to tobacco smoking Direct relation between No. of cigarettes and severity In both active and passive smokers Progression stops on quitting Irritants in smoke cause chronic mucosal inflammation with marked hypertrophy mucus secreting elements Progresses to emphysema and respiratory failure Core pulmonale finally occurs

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Management plan for chronic bronchitis & COPD

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2. Lung cancer: ● Tobacco smoking is responsible for about 90 % of lung cancers ● Cigarette smokers are 8–20 times more likely to develop lung cancer than lifelong non-smokers ● All types of lung cancers are now known to be related ● Risk is markedly reduced in ex-smokers ● All forms of smoking as well as passive smoking are responsible ● Lung cancer is declining in developed world and increasing in 3 rd world ● Increasing among females due to increasing smoking

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3. Tobacco smoking and bronchial asthma ● Increased bronchial responsiveness ● Frequent bronchial irritation symptoms ● Increased sensitization to occupational agents ● Aggravation of acute episodes ● Association with asthma severity ● Risk factor for asthma ? ● Exaggerated decline in lung functions ● Role in development of fixed airway obstruction and COPD ?

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4. Pneumothorax. Increased risk of primary and secondary types

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5. Thromboembolic disease Smoking is a risk factor for DVT especially in women 6. Pulmonary infections: ● Increased incidence: impaired defense ● More severe forms : impaired defense ● Recurrence: colonization ● Delayed response to treatment: resistance ● Overwhelm lung functions ● Patients are more liable to ARDS

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7. Impact on TB: ● ↑ mycobacterium tuberculosis infection ● ↑ risk of progression from infection to disease ● ↑ risk of death among TB patients (61%) ● Passive smoking ↑development of active TB among contacts ● Prevalence of TB infection is more among current or ex-smokers than never smoked. ● The risk of TB is more with the duration of smoking ● Smoking influences the clinical progress of TB lesions.

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8. Collagen vascular and autoimmune disorders: ● Lungs are commonly affected in autoimmune diseases ● Tobacco smoking worsens autoimmunity by: = Citrullination of peptides = Hydrocarbons : cytokine response (IL-1 & TNF ἁ ) ● Collagen vascular disorders and idiopathic fibrosis are the most common disorders

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9. Respiratory failure and ARDS In smokers respiratory failure and ARDS are: ● Easy to develop ● More worse ● Difficult to treat ● In survivors : residual lung damage is more 10. Indirectly induced : ● GERD: repeated aspiration ● Cardiogenic pulmonary edema: LV dysfunction

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TOBACCO WORKER̕S LUNG ● Tobacco dust exposure ↓ lung volumes ● Allergic alveolitis ● Cell mediated and immune complex reaction ● Hay fever like manifestation ● Leads to lung fibrosis

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DUE TO THE REAL DANGERS TO THE LUNGS, SMOKERS MUST QUIT

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How to quit Tom?

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■ Helping a smoker to quit : ■ Explain all to the patient ■ Let the patient set a specific quit date ■ Multiple approaches better than single approach Non pharmacologic : ● Group counseling and education ● Gradual reduction: ▪ Cold turkey ▪ Tapering of ● Helping measures: ▪ Hypnosis ▪ Exercises ▪ Acupuncture

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2. Pharmacologic : ■ NICOTINE REPLACEMENT THERAPY : ■ At least 3-4 weeks of therapy ■ Some need 3 months therapy 1. Polacrilex Resins: ■ Gums ■ Lozenges 2. Transdermal patches: 3. Nicotine inhalers 4. Nasal spray ■ DOPAMINERGIC STIMULANTS : Bupropion : - Antidepressant - Potentiate dopaminergic and nor-adrenergic signaling - 150 mg starting dose > twice daily

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2. Varenicline : - An ἁ 4 β 2 receptor partial agonist - Has a nicotine antagonist action - Very appointing - Dose: 0.5mg/d for3 days then twice/d for 4 days then 1mg twice daily for 12 wks

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■ OTHER DRUGS : 1. CB1 blockers : Rimonabant - Decrease cravings - Decrease weight gain - Still under investigation 2. Clonidine : an alpha adrenergic agonist 3. Nortriptyline: a tricyclic antidepressant 4. Topimerate: an antiseizure drug 5. Selegiline : antiparkinsonian drug ■ NICOTINE VACCINES ■ HARM REDUCTION

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■ SMOKING PREVENTION : Public health campaigns against tobacco consumption School teaching about smoking hazards Tobacco sales restrictions - Limit sale sites - Increase taxes

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Please keep my air clean

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THANK YOU