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OBSTRUCTIVE DISEASES. Causes of airway narrowing Loss of tethering Airway smooth muscle constriction Airway plugging (mucous, foreign body) Airway edema.

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Presentation on theme: "OBSTRUCTIVE DISEASES. Causes of airway narrowing Loss of tethering Airway smooth muscle constriction Airway plugging (mucous, foreign body) Airway edema."— Presentation transcript:

1 OBSTRUCTIVE DISEASES

2 Causes of airway narrowing Loss of tethering Airway smooth muscle constriction Airway plugging (mucous, foreign body) Airway edema

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4 Normal Emphysema

5 Causes of airway narrowing Loss of tethering Airway smooth muscle constriction Airway plugging (mucous, foreign body) Airway edema

6 Air Smooth Muscle Cell Epithelial Cell

7 Causes of airway narrowing Loss of tethering Airway smooth muscle constriction Airway plugging (mucous, foreign body) Airway edema

8 Mucus filling the airway lumen in asthma

9 Causes of airway narrowing Loss of tethering Airway smooth muscle constriction Airway plugging (mucous, foreign body) Airway edema

10 Normal Airway Edema

11 Measuring airway obstruction

12 AIRWAY OBSTRUCTION: FEV1/FVC < 80%

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14 Normal values for lung volume depend on: Age Sex Height Race Weight (for some subdivisions of lung volume)

15 DEFINITION OF ASTHMA 1. Reversible Airway Narrowing 2. Increased Airway Responsiveness 3. Airway Inflammation (History of Allergy)

16 Air Smooth Muscle Cell Epithelial Cell

17 Jeffrey et al, Am. J. Respir. Crit. Care Med : 28S-38S MUCOUS HYPERSECRETION IN ASTHMA

18 DEFINITION OF ASTHMA 1. Reversible Airway Narrowing 2. Increased Airway Responsiveness 3. Airway Inflammation (History of Allergy)

19 AIRWAY HYPERRESPONSIVENESS

20 DEFINITION OF ASTHMA 1. Reversible Airway Narrowing 2. Increased Airway Responsiveness 3. Airway Inflammation (History of Allergy)

21 Th2-lymphocytes promotes IgE formation (IL-4, IL-13) promotes eosinophil migration (IL-5) promotes contraction of smooth muscle promotes recruitment of more eosinophils Eosinophil

22 van den Toorn et al, Am. J. Respir. Crit. Care Med : Normal Asthma Major Basic Protein Staining (eosinophils)

23 Symptoms of Asthma : cough shortness of breath chest tightness wheezing

24 HISTOLOGICAL FEATURES OF ASTHMA Subepithelial fibrosis Mucous cell hyperplasia Smooth muscle hypertrophy Increased vascularity

25 Jeffrey et al, Am. J. Respir. Crit. Care Med : 28S-38S BASEMENT MEMBRANE THICKENING IN ASTHMA

26 Ordonez et al, Am. J. Respir. Crit. Care Med : INCREASED MUCOUS PRODUCING CELLS (blue purple stain) Normal Asthma

27 Jeffrey et al, Am. J. Respir. Crit. Care Med : 28S-38S MUCOUS HYPERSECRETION IN ASTHMA

28 Jeffrey et al, Am. J. Respir. Crit. Care Med : 28S-38S AIRWAY SMOOTH MUSCLE HYPERTROPHY IN ASTHMA

29 Jeffrey et al, Am. J. Respir. Crit. Care Med : 28S-38S INCREASED AIRWAY VASCULARITY IN ASTHMA

30 Pulmonary Function Total lung capacity is usually normal, but the FRC is elevated and RV is increased Decreased FEV1/FVC ratio Lung stiffness is usually normal or low Airway obstruction is due to smooth muscle constriction and mucus hypersecretion

31 AIRWAY OBSTRUCTION: FEV1/FVC < 80%

32 asthma

33 Blood gases PaO 2 - low because of mismatch of ventilation and perfusion PaCO 2 often low (hyperventilation due to anxiety) if PaCO 2 increases it’s usually a sign that respiratory failure is approaching (patient needs to be ventilated)

34 Epidemiology of Asthma currently affects 5-10% of US population incidence and severity are increasing mortality has plateaued Still relatively rare highest in industrialized countries Higher in urban than rural areas

35 Asthma Prevalence United States, Source: National Health Interview Survey; National Center for Health Statistics 12-Month Lifetime Attack Current

36 IgE Allergen Chemicals released: Mast cell histamine leukotrienes proteases cytokines (IL-4, IL-5)

37 Smooth Muscle Cell Mast Cell (releases chemicals) (contracts)

38 Time (hours) Allergen FEV 1.0 (% baseline) Early Response Late Response

39 Mast Cell White blood cells

40 Mast Cell Smooth Muscle Cell

41 Time (hours) Allergen FEV 1.0 (% baseline) Early Response Late Response

42 Allergen avoidance

43 Allergy skin testing team.zobel.dlsu.edu.ph/sites/students/G6/List...

44 MOST IMPORTANT ALLERGENS IN THE US Cat House dust Cockroach Mold

45 Cat washing itself aerosolizes allergen

46 Cat being washed – helps reduce allergen exposure (recommended 2X/week)

47 100  m House Dust Mite - Dermatophagoides sp. The average pillow is home to 10,000 of these!

48 Avoiding exposure to dust mite allergens Encase pillows and mattresses Use HOT (>130 o C) water to wash bedding and clothes Reduce carpeting (in particular wall to wall carpeting, which cannot be adequately cleaned) Reduce humidity (mites are dependent on water in the air for their water supply) Avoid fabric coverings on furniture and windows Platts-Mills et al, J Allergy Clin Immunol Nov;106(5):

49 The American cockroach A particular problem in low income housing Insects move from one apartment to another

50 Mold

51 TRIGGERS FOR ASTHMA allergen exposure exercise breathing cold dry air viral infections irritants (ex: ozone) occupational exposure to dust or fumes

52 PREVENTION AND TREATMENT OF ASTHMA Medications Education Allergen Avoidance

53 ASTHMA THERAPY  -agonists 2.Corticosteroids 3.Leukotriene antagonists and inhibitors 4.Anti-IgE

54  -agonists Mimic adrenalin Relax smooth muscle Effects are immediate but not sustained Provide symptom relief, but do not remove the underlying causes

55 before after High resolution CT scans of airways before and after a  -agonist New England Journal of Medicine 352:15, 2005 FEV 1 Before: 1.27 L After: 1.76 L

56 Corticosteroids: Reduce inflammation Improve lung function and symptoms Decrease airway hyperresponsiveness Reduce exacerbations Must be taken regularly regardless of symptoms Not immediately effective

57 cme.med.harvard.edu/syl/fanta.html

58 Actions of Leukotrienes Very potent constrictors of airway smooth muscle Mucus hypersecretion Edema formation Eosinophil chemoattraction Leukotriene synthesis inhibitors and receptor antagonists Prevent synthesis or effects of leukotrienes

59 cme.med.harvard.edu/syl/fanta.html

60 Reduces corticosteroid requirements Reduces symptom scores Reduces rescue medication use Improves lung function Reduces exacerbations Anti-IgE therapy also: Fahy et al. AJRCCM :1828

61 Genes Environment Asthma WHAT CAUSES ASTHMA?

62 - exposure to allergens -pollution -cigarette smoke -viruses Genes Environment Asthma - cytokines - genes that regulate IgE levels - others

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65 From: Camargo et al, Arch Intern Med 159: , 1999

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68 Evidence for the hygiene hypothesis Less asthma in individuals who grow up on farms Less asthma in individuals with older siblings Less asthma in children in daycare

69 New Engl J Med 343:

70 Gold and Wright, Ann Rev Public Health, 26:89-113, 2005 Asthma is more common in the developed than the developing world

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72 COPD – chronic obstructive pulmonary disease 4 th leading cause of death in the US 2 nd leading cause of disability Smokers disease Consists of 2 diseases (many have both) - emphysema - chronic bronchitis

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74 Other consequences of smoking Heart disease Stroke Cancer* *In 2000, cancer due to cigarette smoking accounted for 20% of all cancer deaths worldwide in 200

75 Consequences of passive smoking in children Lower birth weight in children of mothers who smoke Lower lung size in children of parents who smoke Increased incidence of asthma, bronchitis, and pneumonia in children of parents who smoke

76 From the US Department of Health and Human Services, 2003 Smoking is the leading cause of preventable death in the US

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79 Thun et al, Carcinogenesis 31:100, 2010 Global burden of smoking 1.3 billion people smoke

80 Jeffrey et al, Am. J. Respir. Crit. Care Med : 28S-38S EMPHYSEMA

81 Jeffrey et al, Am. J. Respir. Crit. Care Med : 28S-38S

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83 Emphysema Normal male lung

84 Mucous gland hypertrophy in chronic bronchitis

85 Pressure Volume Healthy Lung Pressure Volume Curves Emphysema

86 ETIOLOGY Cigarette smoke (particles and chemicals) Inflammation Influx of activation of neutrophils and macrophages release of proteases release of oxygen radicals release of inflammatory mediators Destruction of lung tissue Production of mucous Airway remodeling

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88 Signs and Symptoms Emphysema Dyspnea at rest Thin Barrel chest Wheeze on expiration Chronic Bronchitis Cough Sputum No dyspnea at rest but does occur with exertion Cyanosis Frequent respiratory infections Pops and rales

89 FEV1 (% of value at age 25) Age (years) Never smoked or Not susceptible Smoked regularly And susceptible Stopped at 45 Stopped at 65 disability death

90 Evidence for genetic susceptibility for COPD Familial association of low FEV 1.0 Linkage analysis studies Genes associated with COPD susceptibility  1-antitrypsin (anti-protease) 2.microsomal epoxide hydrolase (degradation of chemicals in smoke) 3.glutathione-S-transferases (degradation of chemicals in smoke) 4.Hemeoxygenase 1 (antioxidant) 5.TNF  (inflammation)

91 Blood gases Emphysema PaO 2 is low but not very low cause: V/Q mismatch “pink puffers” - increase ventilation to keep blood gases normal PaCO 2 is normal Chronic Bronchitis PaO 2 usually very low cause: V/Q mismatch and hypoventilation “blue bloaters” – do not increase ventilation to keep blood gases normal PaCO 2 is high

92 Chronic bronchitis Normal

93 Consequences of low PaO 2 1) Polycythemia – increased numbers of red blood cells (RBC’s) Low PaO 2 Increased erythropoetin release from kidney Acts of bone marrow to increased production of RBC’s 2) Right heart hypertrophy (cor pulmonale) Due to pulmonary hypertension (hypoxic vasocontriction and loss of capillary bed) Can lead to right heart failure and death

94 Cyanosis Occurs when deoxygenated hemoglobin exceeds 5 g/100 ml typical total hemoglobin is 15 g/100 ml Low PaO 2 and increased numbers of red blood cells both contribute to cyanosis in chronic bronchitis

95 Treatment Smoking cessation – prevents further loss of lung function Bronchodilators, particularly anticholinergics Increasing use of corticosteroids – data are not yet in regarding efficacy Lung reduction surgery – not usually recommended

96 Indoor air pollution – biomass fuels Fullerton D et al Occup Env Med 66:777, 2009

97 Smith KR et al Thorax 55:518, 2000

98 US EPA 24 hour standard not to be exceeded more than once/year: 260 ug/m 3

99 Indoor air pollution Responsible for 1.6 million deaths/year Disease burden worldwide exceeds outdoor air pollution 5-fold Most lethal killer worldwide after malnutrition, unsafe sex, lack of safe drinking water and sanitation Increases risk of COPD in women about 3-fold Responsible for 0.7 of the 2.7 million COPD deaths worldwide/year Burden is mostly on women and children Source: World Health Organization

100 Hours per day near stove Smith KR et al Thorax 55:518, 2000 Acute respiratory tract infection and exposure to biomass fuels

101 Smith KR et al Thorax 55:518, 2000


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