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Hypersensitivity Pneumonitis
REVIEW
호흡기 내과 R4 노태준
HISTORICAL BACKGROUND

Grain sifters and measurers, Ramazzini, 18th century.
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Farmer’s lung, decay, weevils, and mold in the grain, 1932 England.
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Hypersensitivity lung diseases caused by a variety of antigens.
• bagassosis, mushroom worker’s lung, pigeon breeder’s disease
INTRODUCTION
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Hypersensitivity pneumonitis (HP)
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Immune mediated lung disease.
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Uncommon disease is caused by inhalation and sensitisation to antigens
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Protozoa, molds, animals, insects, bacteria, chemicals, and other organic
materials
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Exposure to antigens, host susceptibility : pathogenesis of HP.
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Acute, subacute or chronic forms.
There are over 200 antigens known : various forms of HP.
J Chest Dis Allied Sci 2006; 48: 115-128
PATHOGENESIS
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Sequential induction of type III and type IV immune responses
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Type-3 response
• Immune complex mediated immune response / involving Blymphocytes
• acute inflammatory lung reaction – 4-6 hrs
• constitutional effects -- mild fever, chills, flu-like symptoms
Type-4 response
• cell-mediated immune response / involving CD8+ cytotoxic Tlymphocytes
• delayed hypersensitivity
• chronic inflammatory lung reaction -- occurs over days to weeks
PATHOGENESIS
antigen
Industrial Health 2001, 39, 269–279
acute form
chronic form
J Chest Dis Allied Sci 2006; 48: 115-128
CLINICAL PRESENTATION
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Acute Form
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High-level of exposure over a short period of time.
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Symptoms within 4 to 8 hours, similar to acute viral infection.
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High fever up to 40`C, chills, myalgia, fatigue, dyspnea, non-productive
cough
Usually recover in about 18 to 24 hours, if removed from the environment.
CLINICAL PRESENTATION

Subacute Form
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Repeated low-level exposure.
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Progressive respiratory symptoms over weeks-to-months : cough, dyspnea
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Without acute systemic symptoms as the acute form.
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Hypoxemia especially with exertion.
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Removal offending environment : improves symptoms.
CLINICAL PRESENTATION
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Chronic Form
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Prolonged and continuous exposure to low-levels of antigens
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Irreversible pulmonary damage without major acute attacks.
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Progressive dyspnea, cough, malaise, weakness, anorexia, and weight loss
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Interstitial fibrosis is prominent.
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Avoidance of the offending antigen : not complete resolution of symptoms.
DIAGNOSIS
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No available single clinical or unique diagnostic laboratory test
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A combination of several evaluation procedures : conclusive diagnosis.
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Blood tests
Radiologic findings
PFT
Histopathogy
BAL finding
Precipitin Antibodies Against Sensitizing Antigens
BLOOD TESTS
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Marked blood neutrophilia and lymphopenia with the acute form
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Not peripheral blood eosinophilia
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Elevation of CRP, ESR, LDH
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Enhanced rheumatoid factor in over 50%
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An increase in serum IgA, IgG, and IgM levels, but not IgE.
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The presence of precipitating antibodies.
RADIOLOGIC FINDINGS
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Radiologic findings in HP correlate with the stage of disease.
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Acute HP
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CXR : nodular infiltrates, patchy ground-glass opacities
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HRCT : ground glass opacities
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either centrally or peripherally
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predominantly in the lower lung zones with sparing of the apices
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Subacute HP
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CXR : reticulonodular appearance with small nodules.
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HRCT : centrilobular nodules with larger areas of ground-glass opacity
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Air trapping d/t obstructive bronchiolitis
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Mosaic perfusion d/t blood flow redistribution
Chronic HP
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CXR : diffuse reticulonodular infiltrates, volume loss, coarse linear opacities
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HRCT : fibrotic changes, honeycombing, and traction bronchiectasis.
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More severe in mid to upper zones of the lung.
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Rare : Pleural effusions, hilar adenopathy, calcification, atelectesis
Journal of Thoracic Imaging 17:261–272
Journal of Thoracic Imaging 17:261–272
Journal of Thoracic Imaging 17:261–272
PULMONARY FUNCTION TEST
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Restrictive pattern with a reduction in lung volumes.
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Decrease in diffusion capacity (DLCO).
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Reduced DLCO reflect a filling of the alveolar space with fluid and
inflammatory cells.
BAL FINDINGS
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Acute exposure within 48 hours : predominance of neutrophils
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Characteristic increase in the number of CD8+ T cells
• decrease in the ratio of CD4+/CD8+ T cells to less than one.
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An elevation of specific IgG, IgA, and IgM antibodies.
HISTOPATHOLOGY
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Lung biopsy is not usually required for diagnosis, not pathognomonic.
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Acute HP : acute bronchiolitis with a neutrophilic infiltrate
Subacute HP : diffuse interstitial lymphocytic infiltrate, scattered small
poorly formed non-caseating granulomas with foamy alveolar macrophages
Chronic HP :Interstitial fibrosis with lymphocyte and plasma cells
Pathologic findings from patients with chronic HP reveal luminal and mural alveolitis, granulomas, intra-alveolar
buds, and interstitial fibrosis. The major cell type found is lymphocyte, but intra-alveolar macrophages with a
"foamy" appearance are characteristic
Skin Hypersensitivity Tests
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Conflicting reports on the usefulness of skin testing in HP.
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A number of studies : presence of immediate skin test reactivity
• diluted bird serum and fecal extracts in bird fancier’s disease.
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Other report : much lower reactivity in exposed normal subjects
• hay extract in farmer’s lung patients
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Skin testing currently has limited value in the diagnosis of HP.
Chest 1997; 111: 534-6
MANAGEMENT
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As with other allergic lung diseases, the most important aspect of management
is identification of the inciting antigen so that avoidance measures can be
implemented.
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Frequently, avoidance alone is sufficient intervention.

In occupational diseases this may include changing professions and job
retraining, changing working materials, instituting personal respiratory
protection.
Pharmacologic Therapy
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For acute symptoms, oral prednisolone at 40-80 mg daily for 1-2 weeks
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Subacute and chronic HP may require 40-80 mg daily with a taper over several
months depending on the response to improvement in symptoms and functional
abnormalities.
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Pharmacologic therapy with supplemental oxygen and parenteral
corticosteroids is indicated for ill patients with abnormalities on lung function
testing, radiographs or with hypoxemia
PROGNOSIS
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Early treatment of acute or subacute disease results in a complete recovery for
most patients
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chronic form : permanent sequelae such as progressive interstitial fibrosis,
emphysema or even asthma-like symptoms.
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Treatment with oral steroids has been demonstrated to improve symptoms and
resolve hypoxemia, but has not been shown to affect the long-term prognosis.
CONCLUSIONS
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Hypersensitivity pneumonitis is a complex immune-mediated reaction to
various environmental antigens.
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Despite the varied nature of the antigens, the presentation is similar with acute,
subacute or chronic forms
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if not identified and left untreated, may progress to irreversible lung disease
with fibrosis.
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However, with early recognition, treatment with avoidance and systemic
steroids, the prognosis is excellent.