1. Eosinophilic and Hypersensitivity Pneumonias
Wyatt E. Rousseau, MD

2. Hypersensitivity Pneumonias
Wyatt E. Rousseau, MD
May 10, 2007

3. Eosinophilic Lung Disease
Peripheral blood eosinophilia with radiographic abnormalities
Lung tissue eosinophilia on TBBx or OLBx
Increased eosinophils in BAL

4. Pulmonary Eosinophilia - Causes
Drug and Toxin Induced
Helminthic and Fungal Infection
Acute Eosinophilic Pneumonia
Chronic Eosinophilic Pneumonia
Churg – Strauss Syndrome
Others

5. Drug and Toxin Induced Eosinophilic Lung Disease
Nitrofurantoin, Ampicillin, NSAIDs, Pentamidine
Phenytoin, L-Tryptophan, Ranitidine, Trazadone
Metals, Scorpion stings, Heroin, Cocaine, Dust, Smoke, Scotchguard, Sulfite exposure, Organic chemicals

6. Helminthic/Fungal Infection related
Transpulmonary larvae migration-Loffler’s
Ascaris lumbricoides
Hookworm
Strongyloides stercoralis
Pulmonary Parenchymal Invasion
Helminths, e.g. Paragonimiasis
Heavy hematogenous seeding-Trichinosis, Strongyloidiasis, Schistosomiasis, Cutaneous and visceral larva migrans

7. Helminthic/Fungal Infection related
Tropical Pulmonary Eosinophilia
Wuchereria bancrofti
Brugia malayi
Allergic Broncho-Pulmonary Aspergillosis

8. Allergic Bronchopulmonary Aspergillosis
ABPA
Allergic Bronchopulmonary Aspergillosis

9. ABPA
Complex hypersensitivity reaction in patients with asthma that occurs when bronchi become colonized by Aspergillus
Repeated episodes of bronchial obstruction, inflammation, and mucoid impaction can lead to Bronchiectasis, Fibrosis, and respiratory compromise

10. ABPA Pathology
Mucoid impaction of bronchi, eosinophilic pneumonia, bronchocentric granulomatosis
Asthma
Septated hyphae with dichotomous branching may be seen in mucous, but do not invade the mucosa
Culture + in 2/3 of patients

11. ABPA Clinical Asthma Bronchial obstruction Fever, malaise
Expectoration of brownish mucous plugs
Eosinophilia
Hemoptysis
Wheezing +/-

12. ABPA Radiologic features
Upper lobe infiltrates
Atelectasis
“Tram lines”
“Parallel lines”
Ring shadows
“Toothpaste shadows”
“Gloved finger shadows”
Perihilar infiltrates may simulate adenopathy
Cylindrical bronchiectasis

15. ABPA PFTs Airflow obstruction – reduced FEV1
Air trapping – increased RV
Positive BD response in ½
Mixed obst. and rest. if bronchiectasis and fibrosis present
Reduced DLCO if bronchiectasis present

16. ABPA Diagnosis Hx Asthma Skin test reactivity to Aspergillus
Ppt. serum antibodies to A. fumigatus
Serum IgE > 1000 ng/ml
Peripheral blood eosinophilia >500/mm3
Pulmonary infiltrates
Central bronchiectasis
Elevated IgE and IgG to A. fumigatus

17. ABPA Treatment Corticosteroids
Inhaled steroids may help control symptoms of asthma but do not have documented efficacy in preventing acute episodes of ABPA
Itraconazole

18. Acute Eosinophilic Pneumonia
Acute, febrile, hypoxic, RF often, mechanical ventilation
Bx - DAD, hyaline membranes
Blood eosinophilia absent
HIV often

19. Chronic Eosinophilic Pneumonia
Subacute, cough, fever, dyspnea, wheeze, sweats
Asthma precedes/accompanies in 50%
CXR –”photographic negative” of CHF in less than 1/3. Occasional pleural effusion, cavitations
Bx - Giant cells, BOOP often

22. Churg – Strauss Syndrome Allergic granulomatosis and angiitis
Vasculitis
Sinusitis, asthma, blood eosinophilia
Lung, skin, cardiovascular, GI, nervous systems
Patchy opacities
Bx-eosinophilic infiltrates, eosinophilic vasculitis, necrotizing granulomas, and necrosis

23. Other Causes of Pulmonary Eosinophilia
Idiopathic Hypereosinophilic Syndrome
Idiopathic Lung Diseases
Neoplasms
Nonhelminthic Infections – Cocci and rarely Tuberculosis

24. Hypersensitivity Pneumonitis Extrinsic Allergic Alveolitis
A syndrome characterized by diffuse inflammation of lung parenchyma and airways in response to inhalation of antigens to which the patient has been previously sensitized

25. HP – Incidence and Mortality
General population based cohort study from a UK primary care database: 271 cases from , approx. 0.9 per 100,000 person years. Mean age at diagnosis 57; male=female
Increased risk of dying (hazard ratio 2.98)
Less likely to smoke (OR 0.56)
Solaymani-Dodaran M, West J, Smith C, Hubbard R. Extrinsic allergic alveolitis: incidence and mortality in the general population. QJM 2007; 100:

26. Case Report
BH, 50 y.o. WF NS, described three episodes in three weeks of SOB, chest tightness, and hemoptysis. Initial episode lasted 2 hours, asso. with fever and chills, T. to 101F. , and tsp. of bloody phlegm.
PMH: hysterx 1984, on Premarin, Lexapro, Neurontin, trazadone, calcium, Fosamax. Parents both smoked, F d. lung CA, M d. emphysema and bronchiectasis, D with asthma. Pt. had had severe complications of arthroscopy-6 surgeries, 3 ½ years of immobilization until TKR in 12/02, with

27. lymphedema, but had become quite physically
fit with resting pulse usually 47. On PE, macular, papular rash over abdomen, chest, and neck. No nodes, clear chest, and left leg was not more swollen than right.
She had had chest CT 2/10/04 considered normal, and Lung scan 2/12/04 suggesting airways disease with inhomogeneous perfusion and prolonged washout.
I recommended some lab work including D-dimer, CRP, and a venous doppler. She declined; so I asked her to take a sputum cup to bring in if she coughed and I planned a

28. CTA if another episode. She called the next day after a worse episode of tightness, SOB, and hemoptysis.
CTA 2/17/04 “tree in bud bilateral and diffuse” suggesting infection or inflammation. Bronchoscopy 2/18/07 appeared normal, with biopsies revealing “mild chronic inflammation.” March 4 received report of outpatient sputum growing an AFB, and I assumed MAC, and discussed Abx therapy. She then decided on VATS OLBx. (Bronch and OLBx cultures were both negative ultimately.)

29. Lung biopsy revealed chronic bronchiolitis/
hypersensitivity pneumonitis (extrinsic allergic alveolitis) with opinion from Mayo Clinic path arriving on 3/30/04. “Hot tub lung due to MAC”. I recommended Prednisone 20 mg. daily, but she had major psychiatric complications for which Seroquel was added and prednisone reduced. X-ray, spirometry, and symptoms resolved. Prednisone tapered and stopped in late May. Recurrence of symptoms and rash in August/September.

30. HP -CT Findings Ground glass opacities
Poorly defined centrilobular nodules
Mosaic attenuation on inspiration
Air trapping on expiration
Reticulation (fibrosis) when chronic
Silva CI, Churg A, Muller NL. Hypersensitivity pneumonitis: spectrum of high-resolution CT and pathologic findings. Am J Roentgenol 2007; 188:

33. Patchy ground glass with air trapping

41. Classification of HP Acute HP Subacute or Intermittent HP
Chronic progressive HP

42. Acute HP Clinical-Abrupt
Lab-ESR,IGG,RA,CRP,LDH, BAL lymphocytosis, restrictive physiology
CXR-micronodular interstitial, but freq. normal-HRCT needed, but not absolute
Histopathology-poorly formed, noncaseating interstitial granulomas, monos, giant cells

43. Subacute or Intermittent HP
Clinical-gradual cough, dyspnea, fatigue, anorexia, wt. loss, malaise; tachypnea and rales
Lab-BAL lymphocytosis, hypoxemia. Restrictive or mixed spiro, decreased DLCO
CXR-nml, micronodular, reticular. HRCT micronodules, ground glass, emphysema, fibrosis
Histopathology- noncaseating granulomas, bronchiolitis with or w/o organizing pneumonia

44. Chronic Progressive HP
Clinical-insidious cough, dyspnea, fatigue, weight loss, clubbing
Lab-not very helpful-BAL lymphocytosis but not crisp; restrictive, but usually mixed DL always reduced, and exertional hypoxemia
CXR-may be normal, but usually progressive fibrosis; emphysema often
Histopathology-granulomatous pneumonia, BO with or w/o OP, fibrosis

45. HP Diagnosis
Known exposure to antigen-History, environmental investigation, IgG antibodies
Compatible clinical, radiographic,and physiology
BAL lymphocytosis
Positive inhalation challenge
Histopathology

46. Clinical Prediction Exposure to known antigen
Positive precipitating antibodies to that antigen
Recurrent symptoms
Inspiratory crackles
Sx occurring 4-8 hours after exposure
Weight loss
Lacasse Y, for the HP Study Group. Clinical Diagnosis of Hypersensitivity Pneumonitis. Am J Respir Crit Care Med 2003; 168:

47. Helpful Clues to Recognize HP
Hx recurring pneumonias, esp. if some regularity
Sx after moving to new house or job
Pets, esp. birds, with patient or family
Hx water damage to home or office
Use of hot tub, sauna, or pool
Others with similar sx or have left work for illness
Pt feels better when away from home or office

48. HP Associated with Farming
Moldy hay, grain, silage-Farmer’s lung
Mold on pressed sugar cane-Bagassosis
Tobacco plants
Mushroom workers
Potato riddlers
Cheese washers

49. HP Associated with Ventilation and Water-Related Contamination
Humidifier fever
Unventilated shower
Hot tub lung
Sauna taker’s lung
Lifeguard lung

50. HP Associated with Birds/Poultry
Bird fancier’s lung
Poultry worker’s lung
Turkey handling disease
Canary fancier’s lung
Duck fever

51. HP Associated with Veterinary Work and Animal Handling
Laboratory worker’s lung
Pituitary snuff taker’s disease
Furrier’s lung
Bat lung
Coptic lung (mummy handlers)
Pearl oyster shell pneumonitis

52. HP Associated with Grain and Flour Processing
Grain measurer’s lung
Miller’s lung
Malt worker’s disease

53. HP Associated with Milling and Construction
Wood dust pneumonitis
Sequoisis
Maple bark disease
Wood trimmer’s disease
Suberosis (moldy cork)
Composter’s lung
Thatched-roof lung

54. HP Associated with Plastics, Painting, Electronics, Etc.
Chemical HP – Toluene diisocyanate
Detergent worker’s lung
Pauli’s reagent alveolitis
Vineyard sprayer’s lung
Bible printer’s lung
Epoxy resin lung

55. HP in Textile Workers Byssinosis (brown lung) – cotton
“Velvet” worker’s lung
Upholstery fabric workers
Lycoperdonosis (lycoperdon puffballs)

56. HP Treatment Antigen avoidance Corticosteroids – 0.5-1 mg/kg daily
Alternatives…

57. HP Prevention/Avoidance
Reduction of antigen burden
Design of facilities-moisture control
Preventative maintenance, esp. HVAC
Protective devices-filters, respirators

58. HP Prognosis
Farmer’s lung – most recover; 50% have chronic lung dis, but minor, usually emphysematous changes
Bird fancier’s lung – prognosis usually worse. Duration of exposure, older age, greater exposure, all tend toward worsened severity