Hypersensitivity pneumonitis


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Hypersensitivity pneumonitis

  1. 1. Interesting case<br />January 26, 2011<br />
  2. 2. A Thai 71 years-old female pt., married, Ex-govern teacher, Buddhism, Bangkok<br />CC: Acute dyspnea 1d<br />PI: 3 week PTA develop progressive dyspnea with low grade fever and dry cough within 2 d , then go to clinic and found abnormal CXR=>go to private hospital for admission<br />Dx:atypical pneumonia and Receive iv Levofloxacin for 1 day  clinical worsening<br />CXR progress=>on BiPAP, add tazocin and tamiflu<br />Information data<br />
  3. 3. Day 3 : start dexa 5 mg iv q 6 hrs.=>clinical improved within 12 hrs.<br />Day 4: CXR improved switch to oral pred and levofloxacin about 3d then D/C with HM 1 wk<br />1 week PTA develop fever with chill then return to same hospital Dx: sepsis Rx: cefazolin+maxipime *3d=>no fever (H/C:NG) HM : invanz IV OD<br />1d develop fever and dyspnea then go to KCMH<br />At KCMH SpO2 room air 89-90%<br />Information data<br />
  4. 4. U/D : HT and DLP for 2 yr<br />No Hx of atopy, autoimmune or drug allergy<br />No FH of autoimmune or CA<br />No smoking<br />She has many types of bird at home and farming quail for 6 months<br />Information data<br />
  5. 5. Physical examination<br />Vital signs : BT 38.5 C, RR 24/min, PR 108 bpm, BP 100/60 mmHg<br />GA : An old Thai female, normal consciousness, sick<br />HEENT : not pale, no jaundice<br />Neck : LN cannot be palpated, no neck vein engorged<br />Heart : Tachycardia without significant murmur<br />Lungs : bilateral basilar crackles<br />Abdomen : no hepatosplenomegaly<br />Extremities : no lesion, no edema<br />Neuro : grossly intact<br />Information data<br />
  6. 6. Lab :<br />Hct 35% wbc 9840 N90 L6 E0 Plt 256,000<br />BUN 14 Cr 0.6 TB 1.6 DB1.3 ALP 366 AST 574 ALT 373<br />ABG pH 7.4 pO2 84 pCO2 33 (canula 5LPM)<br />Information data<br />
  7. 7. Chest X rayday1<br />
  8. 8. HRCT<br />Diffuse heterogeneous ground glass opacities with interlobular septal thickening scattering in both lungs<br />More pronounce in both upper lobes and RML <br />
  9. 9. HRCT<br />Minimal amount of Rt. Pleural effusion<br />
  10. 10. BAL<br />Wbc 410 PMN 71% Mono 29%<br />Small amount of cell composed ciliated cell, alveolar macrophage mixed with some mixed inflammatory cell predominate mononuclear cells<br />TransbronchialBx<br />Alveolar septa are mildly thickening and increase fibroblastic stroma and mild lymphocyte inf.,mildpneumocyteproliferate,focal accumulation of alveolar macrophage, no neoplasm,nogranuloma, or identified organism<br />Bronchoscope <br />
  11. 11. After steroid Rx<br />12 Jan 2011<br />19 Jan 2011<br />
  12. 12. Hypersensitivity pneumonitis<br />Boonthorn<br />26 January 2011<br />
  13. 13. Introdution<br />Definition<br />Epidemiology<br />Diagnotic criteria<br />Classification<br />Investigation<br />Pathology and pathophysiology<br />Treatment<br />Outline <br />
  14. 14. extrinsic allergic alveolitis<br />occurs upon exposure to organic dust<br />associated with farming (moldy grain or hay handling) term “farmers lung”<br />other most common settings<br />contacts with birds (pigeons, parakeets)<br />humidifiers, moldy wood<br />chemical compounds (e.g. isocyanates, zinc)<br />Introduction<br />Allergy 2009: 64: 322–334<br />
  15. 15. Pulmonary disease with symptoms of dyspnea and cough resulting from inhalation of Ag to which patient has been previously sensitized ( HP study group )<br />An inappropriate immune response to inhaled Ag that causes shortness of breath, restrictive lung defect, interstitial infiltrates seen on lung imaging caused by accumulation of large numbers of activated T lymphocytes in the lungs, characterized by episodic bouts of fever a few hours after exposure ( Cormier and Schuyler )<br />Definition <br />Allergy 2009: 64: 322–334<br />Asthma and the workplace. New York: Marcel Dekker, 2006<br />Am J RespirCrit Care Med 2003;168: 952–958. <br />
  16. 16. Population-based study (in New Mexico), estimated annual incidence of ILD = 30 per 100,000 ( HP<2% )<br />prevalence of farmers lung in exposed farmers from 0.5% to 3% ( complicated by geographical variables, climatic conditions and, farming practices )<br />Epidemiology <br />Allergy 2009: 64: 322–334<br />
  17. 17. RadioGraphics 2009; 29:1921–1938<br />
  18. 18. Diagnostic criteria<br />Allergy 2009: 64: 322–334<br />
  19. 19. Diagnostic criteria<br />Allergy 2009: 64: 322–334<br />J Allergy ClinImmunol1989;84:839–844<br />Most widely used are those from Richerson et al.<br />History and physical findings and pulmonary function tests indicate an interstitial lung disease<br />X-ray film is consistent<br />There is exposure to a recognized cause<br />There is antibody to that antigen<br />
  20. 20. Diagnostic criteria<br />HP study<br />Allergy 2009: 64: 322–334<br />Am J RespirCrit Care Med 2003;168: 952–958<br />
  21. 21. Diagnostic criteria<br />Allergy 2009: 64: 322–334<br />Am J RespirCrit Care Med 2003;168: 952–958<br />
  22. 22. Classification of HP<br />Richerson’s classification of HP<br />Allergy 2009: 64: 322–334<br />J Allergy ClinImmunol1989;84:839–844<br />
  23. 23. Chest X-ray<br />to rule out other diseases <br />In acute HP<br />ground-glass infiltrates, nodular and/or striated patchy opacities<br />Up to 20% have normal chest X-rays<br />In subacute HP<br />Distribution is usually diffuse but often sparing the bases.<br />None of these findings is specific of HP<br />Investigation <br />Allergy 2009: 64: 322–334<br />
  24. 24. patchy airspace disease and multiple ill-defined lung nodules with minimal upper lung volume loss<br />RadioGraphics 2009; 29:1921–1938<br />
  25. 25. Investigation <br />High-resolution CT<br />patterns are not specific but suggest that HP be considered in the differential diagnosis when present<br />Allergy 2009: 64: 322–334<br />
  26. 26. Insidious hypersensitivity pneumonitis in a 39-year-old woman with history of exposure to parakeets and cockatiels. (a) HRCT demonstrates extensive ground-glass opacity with a centrilobularconcentration. (b) Axial CT image obtained after therapy and removal from exposure shows complete resolution<br />RadioGraphics 2009; 29:1921–1938<br />
  27. 27. Insidious hypersensitivity pneumonitis. Axial high-resolution CTimages depict ill-defined centrilobular ground-glass opacities<br />RadioGraphics 2009; 29:1921–1938<br />
  28. 28. Pulmonary function tests<br />No discriminative properties in differentiating HP from other interstitial lung diseases<br />Acute HP<br />restrictive pattern with low DLCO<br />Chronic HP<br />most frequent profile is obstructive defect resulting from emphysema <br />In HP study<br />39 of 177 patients (22%) DLCO could be normal results at the time of diagnosis<br />Investigation <br />Allergy 2009: 64: 322–334<br />
  29. 29. Specific antibodies<br />only 1–15% of people exposed to HP antigen develop disease while in some cases the majority of exposed individuals have high titre of serum precipitating Ab but they remain asymptomatic <br />10% of people exposed to Saccharopolysporarectivirgula, main agent for Farmer’s lung,developAb while only 0.3% => disease<br />can be useful as supportive evidence<br />Investigation <br />Allergy 2009: 64: 322–334<br />
  30. 30. Specific antibodies<br />Antigens available for testing in most centres<br />pigeon and parakeet sera, dove feather antigen, Aspergillus sp., Penicillium, S. rectivirgula and Thermoactinomycesviridans ( pigeon breeder’s disease, bird fancier’s lung, farmer’s lung and humidifier lung )<br />Trichosporoncutaneum (summer-type HP)<br />determination of precipitins or total IgGAb ( ELISA technique lacks standardization )<br />Investigation <br />Allergy 2009: 64: 322–334<br />
  31. 31. Serum precipitin Negative predictive value 81-88% and positive predictive value 71-75% for prevalence of HP 20-35%<br />EurRespir J 2007; 29: 706–712<br />
  32. 32. Sera were collected in Sweden and South Africa and levels of IgG antibodies specific to pigeon, budgerigar and parrot antigens were quantified using the UniCAP system<br />Comparison of the two methods resulted in a good concordance<br />with a level of agreement of 94.1% (kappa statistic = 0.83)<br />Int Arch Allergy Immunol 2004;134:173–178<br />
  33. 33. Inhalation challenge<br />lack standardization both in inhalation protocols and criteria defining positive response<br />Bronchoalveolarlavage<br />normal number of lymphocytes rules out all but residual disease<br />alveolar lymphocytosis<br />HP, sarcoidosis, interstitial pneumonia associated with collagen vascular disease, silicosis, BOOP , HIV-associated pneumonitis and drug-induced pneumonitis<br />Investigation <br />Allergy 2009: 64: 322–334<br />
  34. 34. Bronchoalveolarlavage<br />CD4+/CD8+ ratio depends on <br />Stage of disease<br />type and dose of inhaled antigen <br />duration of antigenic exposure<br />CD4+/CD8+ ratio < 1 => HP (chronic)<br />high CD4+/CD8+ ratio related to sarcoidosis<br />Transbronchial biopsy<br />limited usefulness for diagnosis of farmer’slung<br />Investigation <br />Allergy 2009: 64: 322–334<br />
  35. 35. Lung biopsy<br />In acute stages<br />interstitial lymphocytes infiltrates and fibrosis, edema, noncaseatinggranulomas, and bronchiolitisobliterans<br />Macrophages with foamy cytoplasm in alveolar space<br />In chronic stages<br />widespread fibrotic reaction (prominent feature)<br />often without predominant involvement of upper lobes with contraction<br />Emphysema <br />Investigation <br />Allergy 2009: 64: 322–334<br />
  36. 36. 2 most common and most characteristic histopathologic featuresof HP: lymphocytic infiltrates within the interstitium, sometimes referred to as cellular interstitial pneumonitis (arrowheads), and a poorly formed granuloma (arrow).<br />RadioGraphics 2009; 29:1921–1938<br />
  37. 37. Current Opinion in Pulmonary Medicine 2008, 14:440–454<br />
  38. 38. Current Opinion in Pulmonary Medicine 2008, 14:440–454<br />
  39. 39. Current Opinion in Pulmonary Medicine 2008, 14:440–454<br />
  40. 40. Current Opinion in Pulmonary Medicine 2008, 14:440–454<br />
  41. 41. Type III and IV hypersensitivity<br />High titres of antigen-specific precipitating serum IgG that can fix complement<br />Ab specific to offending agent are increased in both serum and BAL<br />resulting C5 induces macrophages activation<br />cells infiltration, particularly lymphocytes, and formation of granuloma in lung<br />Pathology and pathophysiology<br />Allergy 2009: 64: 322–334<br />
  42. 42. Important actors in HP: inflammatory cells<br />Lymphocytes<br />main cells involved in pathophysiology of HP <br />60–90% of BAL-recovered cells<br />CD8+ lymphocytes, CD45 RO T lymphocytes, B lymphocytes<br />Neutrophils<br />Elastase break down of elastic fibres promote emphysema<br />production of oxygen-free radicals and trigger development of fibrosis <br />Pathology and pathophysiology<br />Allergy 2009: 64: 322–334<br />
  43. 43. Important actors in HP: inflammatory cells<br />Macrophages<br /><ul><li>C5 fraction activates alveolar macrophages which release inflammatory and chemotactic factors eg. IL-8, RANTES, CCL18, MCP-1 and MIP-1α to recruitment of other cells eg. Neutrophils and macrophages</li></ul>Soluble factors<br />Th1 cytokine (IL-12)<br />IL-1, IL-8, TNF, IL-6, MCP-1 and MIP-1α<br />Surfactant<br />Increased concentrations of phosphatidylanolamine and phosphatidylinositol<br />Pathology and pathophysiology<br />Allergy 2009: 64: 322–334<br />
  44. 44. Promoting and protective factors<br />Aetiological agents<br />Small slowly degradable particles<br />adjuvant effect causes release of ROS,PGs,LTs and proteolytic compounds<br />Viral infection<br />could enhance HP by increasing expression of CD86 co-stimulatory molecule on APC<br />Genetic predispositions<br />polymorphism in TNF-α-308 promoter associated with high production of TNF in patients with bird-fancier’s lung<br />Pathology and pathophysiology<br />Allergy 2009: 64: 322–334<br />
  45. 45. Promoting and protective factors<br />Nicotine<br />HP and specific antibodies are more frequent in nonsmokers <br />smoking habits affect alveolar macrophages phagocytosis and decrease capacity to produce IL-1 and TNF<br />decrease total BAL cells like lymphocytes ,B7 co-stimulatory molecules on macrophages <br />In smokers, viral infection not increase CD86 molecules expression on macrophages <br />Suppressive cells<br />tolerogenic DC able to drive differentiation of Treg cells<br />Pathology and pathophysiology<br />Allergy 2009: 64: 322–334<br />
  46. 46. ideal treatment for any form of HP is contact avoidance with offending Ag<br />only drugs currently used for HP are oral corticosteroids<br />Dose is unclear<br />Recommend 50 mg of oral prednisolone daily<br />others suggest 20 mg would be sufficient<br />Low-dose steroids seem as effective as contact avoidance<br />Treatment <br />Allergy 2009: 64: 322–334<br />