CHRONIC OBSTRUCIVE PULMONARY DISEASE and ASTHMA: Treatment Options

1. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com CHRONIC OBSTRUCIVE PULMONARY DISEASE and ASTHMA: Treatment Options PETER KRUMPE MD PULMONARY and CRITICAL CARE MEDICINE VA Sierra Nevada Health Care System University of Nevada SOM, Reno, NV

2. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Peter Krumpe, MD Boehringer-Ingelheim Support Speaker�s bureau Research grants Other support Altana, Pfizer, Lilly, Chiron, Bayer, Cubist

3. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Objectives: Discuss Major Symptoms of Lung Disease Cough* Sputum (volume, color, cohesiveness) Noisy breathing (wheezes, ronchi, crackles) Shortness of breath (rest, exercise, position); tachypnea Cyanosis

4. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Cough Productive versus dry Duration acute: viral tracheitis, bronchitis, pneumonia chronic: Post-nasal drip, GERD, asthma, irritant exposures (smoking), lung cancer, TB, CHF, foreign body Irwin, R , et al. Diagnosis and Management of Cough: ACCP Evidence-Based Clinical Practice Guidelines. 2006. Chest 129: Supplement 1.

5. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Objectives- COPD Epidemiology: Understand changing population at risk for COPD Know relation of smoking, airway inflammation to COPD progression Know the consequences of exacerbations of COPD

6. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Traditional Prognostic Factors for COPD Age FEV1 Hypoxemia Hypercapnea

7. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Mortality in COPD FEV1 <35% normal predicts of COPD mortality Oga, T et al. Am J Respir Crit Care Med 2003. 167:54

8. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Changing Ideas About COPD Women Age Pathophysiology Role of inflammation Causes other than smoking ???

9. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com New COPD Prognostic Factors Fat-free body mass loss Symptoms score (SGQL) Hospitalizations for exacerbations Frequency, Severity

10. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com




14. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Objectives- COPD Pathophysiology: Know causes of airway obstruction Understand environmental and genetic causes of emphysema Understand the damaging cycle of dyspnea, deconditioning and disability

15. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Pathophysiology of COPD: Smoking induces airway inflammation� TNF alpha is central to smoke induced airway inflammation Macrophages and PMNs recruited to respiratory bronchioles amplify inflammation, burp elastase Elastolytic damage causes loss of lung recoil and supporting structures




19. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Dynamic Airway Collapse: Inspiration vs. Expiration

20. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Airway epithelium in Emphysema Scanning Electron Micrograph of the Lining of the Bronchus of a Lung Affected by Emphysema. David Gregory and Debbie Marshall/Wellcome Photo Library.Scanning Electron Micrograph of the Lining of the Bronchus of a Lung Affected by Emphysema. David Gregory and Debbie Marshall/Wellcome Photo Library.




24. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Causes of COPD in Non-smokers Alpha 1 AT Deficiency Primary Ciliary Dysknesia Beta receptor heterogeneity Dietary deficiency: Retinoic acid, Beta-carotene Strong family history in absence of these� other genetic factors?

25. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Why do only 20% of Smokers Develop COPD? Actually about 80% will, if followed with spirometry to age 75 and older They die of heart disease or cancer first?


27. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Markers of inflammation and oxidative stress in exacerbated COPD H2O2 in breath condensate increased Serum IL-8, soluble ICAM in serum increased Both decreased with treatment� decreased inflammation and oxygen free radical stress

28. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Histone Deacetylase in COPD

29. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Why Does COPD Progress in Ex-smokers? Chronic or Latent Viral Infection Causing Enhanced Lung Inflammation? Adenovirus E1A DNA in airway cells of COPD Inflammation continues after the smoke stops! Enhanced transcription of IL-8 and ICAM-1





34. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Time Spend Inside the House Being house-bound increases after exacerbations Frequent exacerbations were most severely impacted On any day, number who never went outside increased from 34% to 44% after exacerbation

35. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Objectives- COPD Treatment: Understand the evidence supporting treatments that changes in natural history of COPD Smoking cessation, Vaccines, Home Oxygen, Long acting bronchodilators (LABAs, Anticholinergics), Inhaled corticosteroids Symptomatic relief Short acting bronchodilators, antibiotics, rehab


37. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Pulmonary Vaccines Polyvalent pneumococcal vaccine every 6 years. 23 strains. Influenza vaccine annually

38. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Oxygen Therapy Prevents Cor Pulmonalle Tune up patients PaO2 less than 55 mm Hg (RA) Sat less than 86% RA Concentrators are cost effective E-tanks/ cart or pulse dose delivery systems for mobility

39. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Frequent Flyers! Multiple exacerbations Major cost of careProgressive loss of function, disability�leading to death

40. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Treatments Directed To Prevention of Exacerbations Ipratropium and Tiotropium Bromide Beta Agonists- long and short of it Xanthines, PDE4 inhibitors Inhaled and systemic steroids Oxygen Rehab, VRLS, transplantation


42. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Cholinergic Innervation of Proximal Airways Acetycholine mediates bronchial constriction Atropine, ipratropium bromide, tiotropium bromide block constriction Particle deposition easiest to achieve in central airways




46. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Tiotropium Reduces COPD Exacerbations VA Patients Six month placebo controlled trial 26 VA Medical Centers Exacerbations defined: �new respiratory sx, > 3 days, requiring rx with steroids, antibiotics or hospitalization�

47. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Tiotropium Reduced COPD Exacerbation in VA Patients Tio reduced exacerbations vs. placebo (27% vs. 33%) Tio reduced hospitalizations (7% vs. 9%) Tio delayed time to first exacerbation and number of treatment days

48. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Tiotropium in COPD- 4 Year Trial UPLIFT, a randomized double-blind trial Tiotropium vs. Placebo; 5993 patients. Measured rate of decline FEV1 and FEV1/FVC% post-bronchodilator� Tio not different from placebo Tio improved rates of COPD exacerbation, hospitalization and quality of life scores


50. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Beta 2 Agonists- Side Effects The �twitchies� Tachycardia Low K Tachyphylaxsis

51. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Levalbuterol (Xopenex) R-isomer � less side effects than racemic albuterol Nebulized solution HFA-MDI

52. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com LABAs Salmeterol, Formoterol Anti-inflammatory? Abrupt withdrawal may cause airway hyperactivity (FDA alert) Combination fluticasone-salmeterol Calverley P, Pauwels R, Vestbo J, Jones P, Pride N, Gulisvik A et al. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease : a randomized controlled trial. Lancet 2003;361:449-56


54. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Corticosteroids Some COPD patients may have �asthmatic � component. About 10% of COPD patients have an increase in FEV1 after Prednisone trial. Exacerbations: high dose IV steroids x 3 days, switch to PO prednisone in a two week tapering dose. (eventually re institute MDI steroids)

55. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Inhaled corticosteroid/LABA- Fluticasone/Salmeterol Combination inhaler(Seritide; Advair) is at least equivalent to its components administered separately Combination therapy reduced exacerbation rates, Salmeterol has been shown to be an effective first-line bronchodilator in COPD and fluticasone has been shown to reduce the frequency and or severity of exacerbations in COPD patients in two key trials.

56. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com ICS plus Salmeterol vs. Salmeterol alone: Survival in COPD Mortality 12.6% in combination vs. 15.2% for salmeterol alone (p =0.052) Combination decreased exacerbation rates but increased pneumonia rates (19.6% vs. 12.3%; p= 0.001) Torch study Calverley, P, et al. N Engl J Med 2007: 775-89.

57. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Theophylline: non-selective PDF Inhibitor Sustained release Bed time �Chicken dosing� Avoid escalation of dose as patient becomes more symptomatic Roflumilast- selective PDE4 inhibitor

58. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Acute Exacerbations of COPD Over 50% are viral About 10% are Chalmydia Pneumoniae or Mycoplasma Legionella uncommon in NV Bacteria: Strep, Haemophilus (non-typable), Moroxella, Pseudomonas, Staph� often new strains

59. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Managing Acute Exacerbations Industrial strength bronchodilators Systemic corticosteroids Consider antibiotics (increased cough, yellow sputum, thick sputum) Controlled Oxygen CPAP/BIPAP Intubation for fatigue, somnolence

60. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Systemic Corticosteroids Treatment of an exacerbation of COPD with oral or parenteral corticosteroids significantly reduces treatment failure and the need for additional medical treatment . It increases the rate of improvement in lung function and dyspnoea over the first 72 hours, but at a significantly increased risk of an adverse drug reaction

61. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Bacterial vs. Non-bacterial Bacterial: potential pathological microorganism isolated in 19% of 116 COPD exacerbations Non-bacterial: negative result of a sputum Gram stain, absence of a decrease in lung function and occurrence of <2 exacerbations in the previous year ��.100% predictive of a nonbacterial origin of the exacerbation. The presence of all 3 of these clinical characteristics yielded a positive predictive value of 67% for a bacterial exacerbation. Save $$$?

62. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com AECB: Antibiotics Co-Trimoxazole Doxycycline Azithromycin or Clarythromycin Levofloxacin, Gatifloxacin, Moxifloxacin Risk for pseudomonas? CIPROFLOXACIN 750 mg BID

63. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Objectives: Rehabilitation for COPD

64. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Pulmonary Rehabilitation Deconditioning from dyspnea Range of Motion Upper body weight training Endorphins reduce depression Socialization Panic Training; pursed lips resp. End of life decision making.


66. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Volume Reduction Lung Surgery: the NETT Trial Selection: moderately severe COPD with apical bullae, low exercise capacity Improves diaphragm mechanics by decreasing hyperinflation Timed walk increases from about 900 to 1200 feet. FEV1 increases about 20% Some come off Oxygen therapy Costs about $50K


68. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Resect Apical Bullae

69. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Lung Transplantation for Emphysema Ex-smokers x 1 year, age <65, CO2 <55, diffuse air trapping, STRONG support network, no transfusion hx. Exclusions: CAD, CRF, HIV, colon CA or other malignancies, Hep C, +RPR or +PPD, Psych dx, substance abuse. Donor availability (ironically, CMV + increases donor availability)

70. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Lung Volume Reduction by Bronchoscopic Obstruction of Apical Airways Occlusive balloons left in situ Airway to bullus stints (like a TIPS) Major Problems: collateral ventilation prevents apical collapse, so thwarts the intended advantage of improved diaphragm mechanics Retained secretions, pneumonitis?

71. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Asthma Its hard to define but I know it when I see it � Stuart Potter, Supreme Court Justice

72. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Objectives- COPD or Asthma? Contrast COPD with asthma: symptoms, lab tests, responses to inhaled challenges Recognize asthma syndromes Understand asthma prevention Understand unique therapeutic opportunities to treat asthma

73. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Contrasts COPD sputum at awakening normal IgE smoking hx less atopy less reversible PMNs; IL8 Asthma 4AM wheezing increased IgE less smoking triggers, atopic hx more reversible Eosinophiles IL5, IL10, IL13 Seasonal Fall, winter

74. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Asthma Triggers Pollens Dust mites* Cockroaches* Cat saliva Molds, fungi, helmenths* Chemicals (SO2, TDI) Chitin exoskeletons

75. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Genetics and Environment in Asthma


77. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Airway Smooth Muscle Constriction

78. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Airways without and with Asthma

79. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Treatment for Asthma Allergen avoidance Inhaled corticosteriods Leukotriene receptor antagonists Rescue plan (prednisone rescue) Desensitization (induce blocking antibodies�. IgG)

80. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Omalizumab prevents IgE from binding to cell-surface receptors

81. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Dry Powder Inhalers Salmeterol in combination with Fluticasone (Diskus) Rapid inhalation from RV, breath hold

82. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Inhaled Corticosteroids Not of benefit in COPD morality Decreased hospitalization Assists on titration of patients off of systemic corticosteroids. Mainstay of Asthma therapy!!! Must use a spacer with MDI, slow inhale �Swish and spit�

83. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Steroid Resistant Asthma Methotrexate Anti- IgE MAB (Xolair) Anti-TNFa (Etanercept)


85. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Omalizumab prevents IgE from binding to cell-surface receptors

86. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com TNFa Contributions to Asthma

87. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Anti TNFa in Steroid Resistant Asthma

88. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Additional Ideas Diet, vitamins A,C, E Alpha 1 AT replacement Secretion management Check for immunoglobulin deficiency Look for causes non-asthmatic wheezing

89. January 2009 Treating COPD and Asthma Mucusdoc@hotmail.com Summary: Prevent COPD Exacerbations! Smoking cessation*** Viral and bacterial vaccines LABAs; corticosteroids; tiotropium Theophylline at bedtime Antibiotics for potential bacterial AECB Oxygen prevents cor pulmonalle *** Corticosteroid trial? Rehabilitation; VRLS for selected patients


CHRONIC OBSTRUCIVE PULMONARY DISEASE and ASTHMA: Treatment Options

CHRONIC OBSTRUCIVE PULMONARY DISEASE and ASTHMA: Treatment Options

Presentation Transcript

Chronic obstructive pulmonary disease

CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Chronic Obstructive Pulmonary Disease and Asthma Update

ASTHMA AND THE CHRONIC PULMONARY DISEASE COPD MANAGEMENT.

CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Chronic Obstructive Pulmonary Disease

Chronic Pulmonary Diseases Asthma and COPD

Chronic Obstructive Pulmonary Disease

CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Chronic Obstructive Pulmonary Disease

Pathophysiology of asthma and chronic obstructive pulmonary disease

CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Chronic obstructive pulmonary disease

ASTHMA AND THE CHRONIC PULMONARY DISEASE (COPD) MANAGEMENT.

Chronic Obstructive Pulmonary Disease

Pathophysiology of asthma and chronic obstructive pulmonary disease

Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease (COPD) Treatment Market

Asthma and Chronic Obstructive Pulmonary Disease Inhalers

Chronic Obstructive Pulmonary Disease (COPD) Treatment Market