2. COPD  Is a slowly progressive inflammatory disease of the airways and lung parenchyma.  Characterized by gradual loss of lung function with increasing obstruction to expiratory air flow.  obstruction is caused by inflammatory narrowing of the small airways (bronchiolitis) and proteolytic digestion of the lung tissue adjacent to these airways( emphesema).

3.  Chronic bronchitis is defined by a chronic productive cough for three months in each of two successive years in a patient in whom other causes of chronic cough have been excluded.

4.  Emphysema is defined by abnormal and permanent enlargement of the airspaces that are distal to the terminal bronchioles. This is accompanied by destruction of the airspace walls, without obvious fibrosis (ie, there is no fibrosis visible to the naked eye) Exclusion of obvious fibrosis was intended to distinguish the alveolar destruction due to emphysema from that due to the interstitial pneumonias.

5. Epidemiology  COPD is the third most common cause of death for both men & women worldwide.  evidence suggests that up to 50% of the population with COPD has not yet been diagnosed & that patient who smoke or have other risk factors for COPD may currently be asymptomatic.  COPD mortality increased 22% in the last decade.  worldwide COPD deaths in women which ave risen steadily since 1970 reached parity with COPD in men by 2000, and surpassed that of men in all racial groups in patients under 65 years of age.

6.  The substantial Increase in COPD mortality and morbidity is in part due to increased tobbaco use and changing global demographics that have enabeled a greater number of smokers to survive long enough to develop COPD.

7. Pathophysiology  Inflammation from COPD dameges and thickens small airways and disrubts normal repair mechanisms causing small airways fibrosis.  Proteases are released and dissolve some of the adjacent supporting lung tissue that tethers the small airways resulting in a decrease in the elastic recoil of the lungs that normally keeps airways open during exhalation.

8.  The decresed elasticity of the lung associated with emphysema causes static hyperinflation which has only modest impact on overall hyperinflation in most patients, in contrast dynamic hyperinflation occcurs when patients begin to inhale before full axhalation has been completed such that inspiratory air volume exceeds expiratory volume and air trapped within the lungs with each succesive breath.

9.  When the demand for greater minute ventilation increases the respiratory rate and tidal volume the available time for exhalation can become insufficient, & avicious circle of air trapping & progressive dynamic hyperinflation occurs.

10.  Hyperinflation flattens and reduces the effectiveness of the diaphragm, making use of accessory muscles of breathing more crucial while also markedly incresing the work of breathing as chest wall compliance decreses.

11.  Impaired gas diffusion as reflected by decresed Dlco on PFT,correlate with degree of emphysema as the capillary bed is reduced by loss of lung parenchyma.  Also the ability to increase minute ventilation is severly copmromised in patient with COPD.  As the disease progress the dynamic hyperinflation occur even during quiet breathing causing worsening dyspnea.

12. Risk factors All risk factors results from an interction between patient factors & enviromental factors These invlude:  Exposure to tobacco smoke(including 2 nd hand smoke)  Dust &chemicals( vapors, irritant & fumes)  Outdoor air pollution and enviromental(biomass) smoke.  Genetic factors such as alpha one antitrypsin deficiency.

13.  Hx of pulmonary TB  Hx of chronic asthma  Low educational attainment  poor nutrition  poor socioeconomic status  indoor( smoke from cunsumtion of( wood,coal charcoal) and outdoor air polution(carbon monoxide, nitrogen dioxide)  Most patients with COPD have a history of cigarette smoking or alternative inhalational exposure. However, some patients develop COPD without an obvious risk factor.

14. Pulmonary complications of COPD  pulmonary hypertension  cor pulmonale  pneumonia  pnrumothorax  Atelectasis  Lung cancer  bronchiectasis

15.  Patients who smoke have a higher prevalence of respiratory symptoms and lung function abnormalities a greater annual rate of decline in FEV1, and greater COPD mortality rate than non smokers.  the risk for COPD is dose related.  the age when the pt. started to smoke, total pack- years smoked and current smoker status are predictive of COPD mortality.  Smoking cessation is the single most clinically effective way to prevent COPD, slow progression of the established disease and improve survival

16.  20 % of all COPD cases occur in never – smoker.  20 of chronic heavy smoker develop COPD.  the best documented genetic influence is hereditary defociency of alpha 1 antitrypsine( acirculating inhibitor of serine protease)  Defeciency should be considered in patients diagnosed with COPD at ayoung age ( less than 45 years) in non smoker in patient with predominantly basal lung disease, and in patients with concurrent liver disease.

17. Extrapulmonary effect and comorbid conditions  weight loss  muscle wasting  and weakness are common in sever COPD as aresult of deconditioning and malnutrition.

18. Assesment &disease progression  Dyspnea  Chronic cough.  Intermittent wheezing  Sputum production  Decrease exercise tolerance  Hx of significant exposure to tobbaco smoke  Hx of other risk factors for the disease.

19. Physical examination  May be normal  Early in the disease, the physical examination may be normal, or may show only prolonged expiration and wheezes on forced exhalation  In more advanced disease there may be evidnce of dynamic hyperinflation characterized by hyperresonance and distant breath sounds.

20.  Rapidly tapering vascular shadows  increased radiolucency of the lung  flat diaphragm, and a long, narrow heart shadow on a frontal radiograph accompanied by a flat diaphragmatic contour and an increased retrosternal airspace on a lateral radiograph. These findings are due to hyperinflation

21.  Bullae, defined as radiolucent areas larger than one centimeter in diameter and surrounded by arcuate hairline shadows.  CT can determine whether the emphysema is centriacinar or panacinar. Centriacinar emphysema occurs preferentially in the upper lobes and produces holes in the center of secondary pulmonary lobules. In contrast, panacinar emphysema more commonly involves the lung bases and involves the entire secondary pulmonary lobule Panacinar emphysema can cause a generalized paucity of vascular structures

22.  Arterial blood gases  mild or moderate hypoxemia without hypercapnia in patients with mild COPD  As the disease progresses, the hypoxemia becomes more severe and hypercapnia develops

23. Spirometry  The most important values measured are the forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC).  An FEV1/FVC ratio less than 0.70 generally indicates airway obstruction.  ACP &GOLD define airflow obstrucyion as apost bronchodilator FEV1/ FVC ratio less than 70%.  Diagnostic spirometry should be performed after administration of inhaled bronchodilator to improve the accuracy of the study results.

24. GOLD guidelines classify COPD based on the level of airflow obstruction. I: Mild COPD FEV1/FVC <70 percent, FEV1 ≥80 percent predicted II: Moderate COPD FEV1/FVC <70 percent, 50 percent ≤FEV1 <80 percent predicted III: Severe COPD FEV1/FVC <70 percent, 30 percent ≤FEV1 <50 percent predicted

25. IV: Very Severe COPD FEV1/FVC <70 percent FEV1 <30 percent predicted or FEV1 <50 percent predicted plus chronic respiratory failur….. GOLD 2011.

26. Modefied medical research council questionnair for assesing severity of dyspnea (MMRC). Severity score level of breathlessness(BRLN) none 0 not troubled with BRLN except with sternous exercise. Mild 1 troubled by shortness of breath when hurrying or walking up aslight hill. Moderate 2 walks slower than people of the same age owing to BRLN or has to stop for breath when walking at own pace on level ground. Severe 3 stops for breath after walking approx. 100 M. or after afew minute on level ground.

27. Very severe 4 too BRLN to leave the house or breathless when dressing or undressing

28. Ongoing monitoring Monitoring to adjust COPD therapy should focus on dose of medication, adherance to the regimen, inhaler technique, effectivness of symptom control,&the side effects of Rx.

29. GOLD classification system for COPD severity Patient group severity definition A low risk/fewer symptoms mild or moderate airflow limitation(previously GOLD I OR II)& or equal or less than 1 exacerbation per year and MMRC scor less then 2. B low rik/more symptoms same as above but MMRC score is equal or more than 2

30. c high risk/ fewer symptoms sever or very sever A.F limitation( previously GOLD 3 or 4)& or equal and more than2 exacerbation per year &MMRC score less than 2. D high risk /more symptoms same as above but wiyh 2or more exacerbation per year & MMRC score equal or more than 2. Note: A.F( AIRFLOW).

31. BODE INDEX A compsite disease marker that takes in account the systmic nature of the disease.  The index incorprates spirometry, MMRC scores, and other parameters and is useful in evaluating the risk of hospitalization and estimating the long term prognosis of the disease.  Ahigher scvore is associated with a worse outcomes  Patients with Abode score of 7 or higher will have a4 year survival rate of 20% or lower.

32. BODE INDEX FOR SEVERITY OF COPD variable points 0 1 2 3 >or equal to 50-64 36-49 <orequal to 35 65 FEV1(%of predicted) 6 minute walking >orequai to350. 250-349. 150-249. <orequai to149 Distance(meters) MMRC 0-1 2 3 4 BMI >21 <or equal to 21

33. Management  Reduce symptoms  Prevent exacerbation  enhance quality of life  And reduce the disease morbidity and mortality.

34.  Inhaled medications are the mainstay of therapy in COPD.  Pharmacologic intervention may reduce symptoms, diminish the frequency & severity of exacerbatios, reduce the frequency of hospitalization & improve exercise tolerance &health status.  Short acting as needed bronchdilators either alone or in combination are usually the 1 st Rx intervention implemented for mild COPD.  Short acting bronchodilator is appropriate for alleviation of intermittent symptoms for all levels of COPD, ( breakthrough symptoms that may occur on daily maintainace therapy and for treatment of acute exacerbations)

35. Drug treatment for COPD

36. NOTESSIDE EFFECTAGENT BRONCHODILATORS Generally used as needed for mild disease with few symptoms Sympathomimatic symptoms such as andtremor &tachycardia Inhaled short acting beta 2 agonist(albuterol,fenot erol,levalbuterol,metap roterenol,pirbuterol,ter butaline) Not to be used with tiotropium, used as neededfor mild disease with few sympyoms, avoid using both short and long acting anticholenergics. Dry mouth,mydriasis on contact with eye, tachycardia, tremor,rarely acute norrow angle glucoma. Inhaled short acting anticholenergic agents(ipratropium) Not to be used with tiotropium,use when short acting bronchodilator provid insufficient control if symptoms for patients with FEV1Less than 60% Dry mouth,mydriasis on contact with eye, tachycardia, tremor,rarely acute norrow angle glucoma Inhaled long acting anticholenergic agents(tiotropium,acli dinium) Use as maintainace therapy when shrot acting bronchodilators provide insufficient control of symptomsfor pt. with an FEV1 less than 60%, not intenede to be used for treatment of exacerbations of COPD or acute bronchospasm. Sympathomimatic symptoms such as andtremor &tachycardia Overdose can be fatal Inhaled long acting beta agonist( salmetrol, formetrol,arformetrol,i ndacaterol) Use as maintainace therapy, generally use only after long acting bronchodilators Rx.tp provide additional symptoms relief of exacerbation, may improve respiratory muscle function. Tachycardia, nausea, vomiting disturbed pulmonary function and sleep narrow therapeutic range over dose can be fatal with seizure and arrythmia Methylxanthines( theophylline,aminophu lline; sustained and short acting) NOTESSIDE EFFECTAGENT BRONCHODILATORS Generally used as needed for mild disease with few symptoms Sympathomimatic symptoms such as andtremor &tachycardia Inhaled short acting beta 2 agonist(albuterol,fenoterol,levalbuterol,m etaproterenol,pirbuterol,terbutaline) Not to be used with tiotropium, used as neededfor mild disease with few sympyoms, avoid using both short and long acting anticholenergics. Dry mouth,mydriasis on contact with eye, tachycardia, tremor,rarely acute norrow angle glucoma. Inhaled short acting anticholenergic agents(ipratropium) Not to be used with tiotropium,use when short acting bronchodilator provid insufficient control if symptoms for patients with FEV1Less than 60% Dry mouth,mydriasis on contact with eye, tachycardia, tremor,rarely acute norrow angle glucoma Inhaled long acting anticholenergic agents(tiotropium,aclidinium) Use as maintainace therapy when shrot acting bronchodilators provide insufficient control of symptomsfor pt. with an FEV1 less than 60%, not intenede to be used for treatment of exacerbations of COPD or acute bronchospasm. Sympathomimatic symptoms such as andtremor &tachycardia Overdose can be fatal Inhaled long acting beta agonist( salmetrol, formetrol,arformetrol,indacaterol) used as maintainance therapy rarely used because of side effect but may be benefecial tp patients who cant use inhaler. Sympathomimatic symptoms such as andtremor &tachycardia Oral beata agonist( albuterol,metaproteernol,terbutaline)

37. notesSide effectsOral phosphodiesterase- 4 inhibitor Used to decrease risk of exacerbation in patient with sever COPD with chronic bronchitis and hx of exacerbations, should not be used with methylxanthines owing to potential toxicity, very expensive&should be used in selected patients. Diarrhea, nausea,bachache,decreased appetite dizziness. roflumilast

38. notesSide effectsAnti inflamatory agents Most effective ib patients with hx of frequent exacerbations & when used in conjunction with long acting bronchodilators Dysphonia, skin bruising,oral candidiasis, rarely side effects of oral corticosteroids) Inhaled cirticosteroids( fluticasone, budesonide, beclomethasone,cicles onide) Use for significant exacerbations of COPDWith taper, avoid if possible in stableCOPD,to to limit corticosteroids toxicity, consider inhaled corticosteroids to facilitate weaning of systemic corticosteroids. Skin bruising, adrenal supression, glucoma, osteoporosis, DM,Systemic HTN,pneumonia,catara cts,opportunistic infections,insomnia,m ood disturbance. oral corticosteroids( prednisone, prednisolone)

39. notesSide effectsCombination agents Fluticasone/ salmetrol is approved as maintainance therapy &for prevention of exacerbations, budesonide /formetrol as maintainance therapy, combinations are not to be used for treatment of acute bronchospasm. Same combined effects of both drug classes. Combined inhaled long acting beta2 agonist &inhaled corticosteroidsin asingle inhaler(fluticasone/salmetrol,b udesinide / formetrol) note to be used with tiotropium, generally used as needed for mild disease with few symptoms, avoid using both short &long acting anticholenergic, this combinationtherapy may be used for maintainance therapy only if patients have well controlled disease on this combination Rx and don’t require rescue therapy if when expense is determining factor. Same combined effects of both drug classes Combination short actingbeta2 agonists plus anticholenergic in asingle inhaler (Slbutamol/ipratropium)

40. Step therapy for patients with COPD. Confirm diagnosis(FEV1less than 70%)  Respiratory symptoms and FEV1 60%-80% of predicted  Consider PRN bronchodilator Rx with a short acting anticholenergic, short acting beta2 agonist or combination of both.  respiratory symptoms & FEV1< 60% of predicted Bronchodilator monotherapy with either along acting inhaled beta 2 agonist or anticholenergic agent with short acting bronchodilater PRN for rescue or exacerbation.

41.  Limited benefit ? no Verify adherance and review inhaler yes technique. alternate class or combine classes of long acting bronchodilateor with or without inhaled corticosteroid. Limited benefit? Side effects.. No yes consider add-on therapy( such as methylxanthine or phosphodiesterase -4 inhibitor).

42.  Other agents:  Alpha one antitrypsin replacement therapy may be used in the rare patient whose COPD is related to alpha one antitrypsine deficiency  mucolytic agents may provide minor benefit to few patients with viscous sputum.

43.  antibiotic agents  Most benefecial in treatment of infectious exacerbations of COPD.  also indicated in patients with sever exacerbations of COPD who require mechanical ventilation whether invasive or non invasive.  usually flouroquinolone such as levofloxacin or third generation cephalosporine plus macrolide, usually cover the most common pathogens( H.INFLUENZA,STREPTOCOCCUS PNEUMONIA,AND MAROXILLA CATARRHALIS)as will as causes of atypical pneumonia.

44. non pharmacological agents Oxygen : long-term oxygen therapy improves survival and quality of life in hypoxemic patients with COPD Long-term oxygen therapy should be prescribed for all patients with COPD who have chronic hypoxemia (PaO2 ≤55 mmHg or SpO2 ≤88 percent

45. smoking cessation smoking cessation can reduce the rate of FEV1 decline that exists in smokers with COPD. As an example, the Lung Health Study reported a decline in postbronchodilator FEV1 of 54.2 and 66.1 mL in women and men, respectively, who continued to smoke over an 11 year period. Women and men who were sustained quitters of smoking had an FEV1decline of only 21.5 and 30.2 mL per year, respectively

46.  Smoking cessation and O2 therapy are the only interventions demonestrated to reduce COPD risk and positively affect decline in pulmonary function  Smoking cessation is the most important goal in the management of COPD in patients who smoke

47. Pulmonary rehabilitation: primary goals of rehabilitation — lower and upper extremity exercise conditioning, breathing retraining, education, and psychosocial support Other important therapeutic modalities that are stressed in many rehabilitation programs, including smoking cessation, oxygen therapy, bronchodilators, antibiotics, nutritional support, and respiratory muscle training and resting.

48. VACCINATIONS Pneumococcal polysaccharide vaccinePneumococcal polysaccharide vaccine should be offered to patients with COPD who are ≥65 years old, or who are younger than 65 years with a forced expiratory volume in one second (FEV1) less than 40 percent An annual influenza vaccine should be given to all patients.

49. Noninvasive positive pressure ventilation Noninvasive ventilatory support is sometimes useful in the treatment of acute or severe chronic respiratory failure Endotrachial intubation with mechanical ventilation.

50.   Lung volume reduction surgery The efficacy of LVRS varied among patient groups, but there was an overall survival advantage that was most marked in patients with upper lobe emphysema and low exercise capacity. On the other hand, safety monitoring detected a marked increase in early mortality in patients with an FEV1 <20 percent predicted and either a DLCO <20 percent predicted or homogeneous changes on chest CT.

51.  Lungs transplantation.

52.  Acute exacerbations of COPD  criteria and classification of acute COPD exacerbation. Major criteria  increase in sputum volune  increase in sputum purulence ( yellow or green)  worsening of baseline dyspnea additional criteria  upper respiratory infection in the past 5 days  Fever of no apparent cause  Increase in wheezing and cough  Increase in respiratory rate or heart rate20% above baseline  fatique,insomnia,depression and confusion degree of exacerbation: mild=1major+1 or more addetional criteria Moderate=2 major criteria sever=all 3 major criteria

53. Indications for immediate admission to the ICU for COPD exacerbations:  Sever dyspnea that respond inadequately to initial emergency therapy.  changes in mental status.  despite supplemental o2 therapy & non invasive ventilation the pt. has persist or worsening hypoxemia (arterial po2 60mmhg) and or sever worsening respiratory acidosis ( ph <7.25) & require endotracheal intubation with mechanical ventilation  Need for vassopressors.

54. Patient with COPD exacerbation should be hospitalized in the presence of:  Underlying sever COPD  Advanced pt age  significant comorbidities  Marked increase in intensity of symptoms  Newly occuring arrythmia  Insufficient home support  onset of new physical signs  Failure to respond adequately to initial medical Rx.

55. Home management:  for mild to moderate COPD as will as for pt. with end stage disease  oral corticosteroid should be added if the pt. baseline FEV1 is less than 50% of predicted when a pt. experience a COPD that dosnt require hospitaliztion Rx with lower dose oral corticosteroids tapered more quickly than be done in a more critically pt.

56. Hospital management  Addition or adjument of bronchodilator  Inhaled or systemic corticosteroids  Antibiotic therapy  Possible mechanichal ventilation.  chest physiotherapy  O2 Therapy.

57. Discharge and follow up:  No longer require short acting inhaled beta 2 agonist more frequently than Q 4 hours  Clinically stable and have demonstrated stable ABGS level for the last 12- 24 hours and can understand the correct use of medication  follow up visit 2-4 weeks after discharge or sooner if clinically necessary and subsequent Rx is same as for stable COPD.

58. Thank you

60. BRONCHODILATORS Bronchodilators are the therapeutic mainstay for patients with COPD. They include beta agonists, anticholinergics, and theophylline, which is used less often. Bronchodilators have been consistently shown to induce long-term improvements in symptoms, exercise capacity, and airflow limitation.theophylline

61.  Short-acting beta agonists include albuterol, levalbuterol, and pirbuterol. with either agent is acceptablealbuterol levalbuterolpirbuterol

62.  Short-acting anticholinergic medications improve lung function and symptoms ipratropium, ipratropium improve lung function,decrease coug, increas exercise capacity, and decreased dyspnea ipratropium

63. Beta agonists — The long-acting beta agonists (LABAs):include salmeterol arformoteroand formoterolarformoteroformoterol IndacaterolIndacaterol is a once-daily LABA that is approved for the treatment of COPD. It has both a rapid onset and a long duration of action

64. The long-acting anticholinergic medication: tiotropium, improves lung function and decreases dynamic hyperinflation, while also decreasing dyspnea and exacerbations. In addition, it improves trough airflow (ie, 24 hours after the last dose) and reduces hyperinflation, indicating that its effects are long-lasting. tiotropium Tiotropium may slow the rate of decline in FEV1