Asthma versus COPD


Published on

Published in: Health & Medicine
  • Be the first to comment

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide

Asthma versus COPD

  1. 1.  70 years old male with a history of dyspnea for 10 years  Presenting with dyspnea with white productive sputum, no fever or URI symptoms  Skin test +ve for house dust mites, pollens, and cockroaches  Nonsmoker  Prescribed drugs from clinic as follow  seretide (50/250) evohaler 1x2, Berodual MDI 1x4, Prednisolone (5) 1x2, Neulin 1x2  Refer for definite diagnosis:  Dyspnea R/O COPD or Asthma
  2. 2. Tinkelman et alวRespiration 2006;73:296–305
  3. 3. n = 417 Tinkelman et alวRespiration 2006;73:296–305
  4. 4. Tinkelman et alวRespiration 2006;73:296–305
  5. 5.  1961, Orie and colleagues from Groningen, the Netherlands,  “All airway diseases, including asthma, emphysema, and chronic bronchitis, should be considered a single disease with common genetic origins”
  6. 6. “chronic nonspecific lung disease”
  7. 7. P G Gibson; Thorax 2009
  8. 8. P G Gibson; Thorax 2009
  9. 9. P G Gibson; Thorax 2009
  10. 10. P G Gibson; Thorax 2009
  11. 11. Asthma as a Risk Factor for COPD in a Longitudinal Study  Study objective: To evaluate the association between physician-diagnosed asthma and the subsequent development of COPD in a cohort of 3,099 adult subjects from Tucson, AZ  Design and methods: A prospective observational study. Participants completed up to 12 standard respiratory questionnaires and 11 spirometry lung function measurements over a period of 20 years. Survival curves (with time to development of COPD as the dependent variable) were compared between subjects with asthma and subjects without asthma at the initial survey Graciela E. Silva;Chest 2004
  12. 12. P G Gibson; Thorax 2009
  13. 13. maximal expiratory flows at function residual capacity (VmaxFRC) 123 unselected subjects assessed at a mean age of 2 months by use of the chest compression technique, F/U 11, 16 and 22 yr Infants in the lowest quartile for VmaxFRC had the lowest mean FEV1/FVC ratios at all ages Stern DA; Lancet 2007;370:758–764
  14. 14. 10 % COPD have more reversibility 5% severe Asthma usually episodic in nature, does not progress, usually begins in early childhood, and shows a good response to bronchodilators and corticosteroids Peter J. Barnes; Am J Res and Crit Med: 2006 very slowly progressive onset and most patients are diagnosed in their 60s, there is little variability in symptoms, and patients show a poor response to bronchodilators and corticosteroids airflow limitation
  15. 15. Nobuyuki Hizawa; Allergology International. 2009
  16. 16.  Classical genetic predisposition is α1- antitrypsin deficiency, but this affects less than 1% of patients with COPD  Some novel asthma genes, including ADAM33, CCL5, and IL17F, have been associated with COPD Peter J. Barnes; Am J Res and Crit Med: 2006
  17. 17. ADAM33  A disintegrin and metalloproteinase 33 (ADAM33) is the first positionally cloned asthma gene  ADAM33 were shown to be significantly associated with the development of COPD and annual lung function decline in a general population Nobuyuki Hizawa; Allergology International. 2009
  18. 18. CCL5  CC chemokine ligand 5 gene (CCL5) was associated with susceptibility to late-onset asthma in patients who developed asthma at age >40 years  CCL5 has a genetic impact on the variable expression of emphysema in patients with COPD Nobuyuki Hizawa; Allergology International. 2009
  19. 19. IL17F  Genetic analyses of the association of asthma with the common variants of IL17F  IL-17F has provided evidence for its role in pulmonary neutrophilia through the induction of CXC chemokines  Increased infiltration of the airway with neutrophils characterizes lung inflammation in COPD and severe asthma Nobuyuki Hizawa; Allergology International. 2009
  20. 20. Peter J. Barnes; Am J Res and Crit Med: 2006 Infiltration of EO into the airway wall, with increased numbers of Th2 lymphocytes, and activated mast cells Predominant infiltrating inflammatory cells are PMN, macrophages, and cytotoxic T cells of the Tc1 subtype Histamine, cysteiny leukotrienes, and PGD2, IL5, IL13 PMN chemotactic mediators, LTB4 and IL-8
  21. 21. Fold increases in inflammatory cells of subjects with atopic asthma and smokers' (chronic) bronchitis (CB) with/without COPD versus healthy controls Asthma CB CB and COPD CD45 2 2.2 2.3 CD3 2 2.3 4.0 CD4 2.5 ± 2.8 CD8 2 3 8.4 CD4/CD8 ratio 3:1 1:4 1:2 Neutrophil 1.5↓ ± 2.2 Eosinophil 93 1.7 3.5 Macrophage ± 4.5 8.6 Peter Jeffery; Middleton 2008
  22. 22. P J Barnes;nature reviews immunology 2008 Epithelial cells release stem-cell factor maintaining mucosal mast cells at the airway surface
  23. 23. P J Barnes;nature reviews immunology 2008 elastin degradation
  24. 24. P J Barnes;nature reviews immunology 2008
  25. 25. Epithelial fragility and deposition of collagen under the airway Epithelial “subepithelial fibrosis” Airway smooth muscle hypertrophy and hyperplasia and increased bronchial vascularity Central airways, although inflammatory changes are also seen in small airwaysin patients with more severe disease; parenchymal involvement is not seen Airway epithelium may show squamous metaplasia Small airways and lung parenchyma, with fibrosis of bronchioles and parenchymal destruction, mucous gland hyperplasia Peter J. Barnes; Am J Res and Crit Med: 2006
  26. 26. Healthy Severe asthma Ravi S. Aysola; Chest 2008 Lamina Reticularis ;collagen I, collagen III, collagen V, fibronectin, and tenascin
  27. 27. Sutherland and Martin; J ALLERGY CLIN IMMUNOL2003
  28. 28. P J Barnes;nature reviews immunology 2008
  29. 29. Contraction of airway smooth muscle as a result of multiple bronchoconstrictor mediators Structural changes of small airways and closure of small airways as a result of disrupted alveolar attachments, resulting in air trapping and dyspnea Peter J. Barnes; Am J Res and Crit Med: 2006 airway narrowing
  30. 30. Asthma COPD Airflow obstruction Variable (± irreversible component) Progressive deterioration of lung function (? reversible component) Postmortem Hyperinflation: airway plugs (exudate and mucus); no emphysema Excessive mucus (mucoid/purulent); small airway disease; emphysema Sputum Eosinophilia, metachromatic cells, Creola bodies Macrophage; neutrophil (infective exacerbation) Surface epithelium Fragility/loss Fragility undetermined Bronchiolar mucous cells Mucous metaplasia (debated) Metaplasia/hyperplasia Reticular basement membrane Homogeneously thickened and hyaline Variable or normal Congestion/edema Present Variable/fibrotic Bronchial smooth muscle Enlarged mass (large airways) Enlarged (small airways) Bronchial glands Enlarged mass (no change in mucin histochemistry) Enlarged (increased acidic glycoprotein) Cellular infiltrate Predominantly CD3, CD4, CD25 (IL-2R) positive; marked eosinophilia (EG2 positive, degranulated); mast cell increase (decrease in severe/fatal cases) Predominantly CD3, CD8, CD68, CD25, VLA-1, and HLA-DR positive; mild eosinophilia (not degranulated?); mast cell increase Cytokines IL-4 and IL-5 gene expression (Th2 profile) GM-CSF protein; ±IL-4 but not IL-5 Peter Jeffery; Middleton 2008
  31. 31. Response to β2-agonists Modest response to anticholinergic drugs Good response to corticosteroids Respond to anticholinergics to a similar extent as β2-agonists Poor response to steroid (macrophage and reduction histone deacetylase2) Impressive antiinflammatory effect of a combination therapy with a corticosteroid and LABA Peter J. Barnes; Am J Res and Crit Med: 2006 greater number of EO and higher levels of exhaled NO
  32. 32. Sutherland; J ALLERGY CLIN IMMUNOL2004
  33. 33. Take Home message  COPD and asthma involve chronic inflammation of the respiratory tract, the pattern of inflammation is markedly different between these two diseases  Mild asthma is characterized by eosinophilic inflammation driven by TH2 cells and DCs, and is associated with mast-cell sensitization by IgE, and by the release of multiple bronchoconstrictors
  34. 34.  COPD is characterized by neutrophilic inflammation that can be driven by a marked increase in the number of lung- resident macrophages, which also attract CD4+ and CD8+ T cells to the lungs  However, these distinctions between asthma and COPD may not be as clear, overlap syndrome