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ALLERGIC BRONCHOPULMONARY
ASPERGILLOSIS
DR S . FAZLULLAH GUIDED BY
DR D.G. MHAISEKAR SIR
PULMONARY Aspergillosis
• Most common cause A . Fumigatus 80-90 %, then A.flavus, A.terreus, A.niger.
• Microscopic features = High-power photomicrograph can show the
conidiophores with the characteristic head appearance and minute spores.
Medium-power photomicrograph shows septate hyphae branching and angulations.
HYPERSENSITIVITY REACTIONS ALLERGIC BRONCHIAL ASTHMA ABPA BRONCHOCENTRIC GRANULOMATOSIS EXTRINSIC ALLERGIC ALVEOLITIS
SIMPLE COLONIZATION
SAPROPHYTIC GROWTH ASPERGILLOMA INVASIVVE INFECTION IBA CPA IPA
Spectrum of Pulmonary Aspergillosis
IT IS AN IDIOPATHIC INFLAMMATORY LUNG DISEASE CHARACTERIZED BY AN ALLERGIC INFLAMMATORY RESPONSE TO THE COLONIZATION OF ASPERGILLUS OR OTHER FUNGI IN THE LUNG.
ABPA complicates approximately 7 to 14 percent of cases of CHRONIC STEROID–DEPENDENT ASTHMA and 7 to 15 percent of cases of CYSTIC FIBROSIS.
ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS
ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS
ABPA is caused by a Complex Hypersensitivity Reaction to Aspergillus organisms. The fungi proliferate in the airway lumen , producing a constant supply of antigen. Type I hypersensitivity reaction with IgE and
IgG release occurs. TYPE 3 Immune complexes and inflammatory cells are then deposited in the bronchial mucosa. Eosinophilic infiltrates and Necrosis with bronchial wall damage and
bronchiectasis.
CRITERIA for the Diagnosis of ABPA
SEROPOSITIVE ABPA (ABPA-S)
• HISTORY OF Asthma .• ELEVATED TOTAL SERUM IgE • IMMEDIATE SKIN TEST REACTIVITY TO ASPERGILLUS FUMIGATUS• ELEVATED SPECIFIC SERUM IgE TO ASPERGILLUS FUMIGATUS• PRESENCE OF SERUM PRECIPITINS OR ELEVATED SPECIFIC SERUM IGG TO ASPERGILLUS FUMIGATUS
ABPA CENTRAL BRONCHIECTASIS (ABPA-CB)• ABOVE CRITERIA are positive• CENTRAL BRONCHIECTASIS BY HIGH RESOLUTION CT SCAN
CRITERIA for the Diagnosis of ABPA
Other supportive clinical findings• Peripheral Blood Eosinophilia .• CXR = Patchy, Fleeting Infiltrates .• Expectoration of Brown Mucuc
Plugs.• Sputum Culture Positive for
Aspergillus fumigatus.
STAGES OF ABPA
• STAGE 1 ACUTE
• STAGE 2 REMISSION
• STAGE 3 Exacerbation/recurrence
• STAGE 4 Steroid-dependent-asthma
• STAGE 5 Fibrotic lung disease
STAGES Stage I : Acute
• Acute ASTHMA Symptoms
• Elevated SERUM IgE (>1000 IU/ml)
• Peripheral BLOOD EOSINOPHILIA .
• FLEETING INFILTRATES on chest x-ray.
• Positive Specific IgE, IgG Skin Test reactivity, and precipitins to A. fumigatus.
• Responds to STEROIDS/ANTIFUNGAL.
Stage II: Remission• Resolution of symptoms• Resolution of pulmonary infiltrates• Improvement in eosinophilia and A. fumigatus specific blood
abnormalities.
• Recurrence / worsenning of clinical symptoms
• Recurrent pulmonary infiltrates• Rising IgE levels.
Stage III: Exacerbation/recurrence
Stage IV: Steroid-dependent-asthma
• Refractory steriod-dependent asthma.
• Persistently elevated serum IgE levels.
• Persistently elevated A. fumigatus–specific blood abnormalities.
Stage V: Fibrotic lung disease
• Refractory Steriod-dependent asthma• Fibrotic lung disease ( Irreversible
obstructive and restrictive defects with impaired diffusing capacity )
• Chronic bronchiectasis symptoms ( Sputum production, frequent infections)
ABPA Clinical
• Asthma• Bronchial obstruction• Fever, malaise• Expectoration of brownish mucous
plugs• Eosinophilia• Hemoptysis• Wheezing +/-
AREA OF INVOLVEMENT Upper lobes predominate. ACTIVE STAGE - Perihilar ‘infiltrates’ (pseudohilar adenopathy). Massive homogeneous consolidation. Tramline shadows. Toothpaste shadows. Gloved-finger shadows. Air-fluid levels. CHRONIC STAGE - Proximal bronchiectasis manifested by: Parallel line shadows Ring shadows
Radiologic Manifestationsc
TRAMLINE SHADOW
TRAMLINE SHADOW
RING SHADOW
TOOTHPASTE SHADOW
PARALLAL LINE SHADOW
FINGER IN GLOVE Sign
FINGER IN GLOVE SIGN
GLOVED-FINGER SHADOWS
ABPA PFTs
• Airflow obstruction – reduced FEV1.
• Air trapping – increased RV.• Positive BD response in ½
cases.• Mixed Obst. And Rest. If bronchiectasis and fibrosis
present
BRONCHOSCOPY
Plug in airways Airway clear after removal
MUCOID IMPACTION
Without asthma, mucus plug lead to atelectasis. Usually presents with cough.
BRONCHOCENTRIC GRANULOMATOSIS.
Necrotizing granulomas, obstruct and destroy bronchiols . Eosinophilic inflamatory infiltrate and fibrosis with no tissue or vascular invasion.
Syndromes Related to ABPA
EOSINPHILIC PNEUMONITIS
Rarely caused by aspergillus. Cough dyspnea and fever with peripheral pulmonary infiltrate. Diagnosis made by biopsy. Good response to corticosteroids.
HYPERSESITIVITY PNEUMONITIS
Intense repeated inhalation of thermophilic bacteria, fungi, bird excreta, and chemical agents. Causes HYPERSENSITIVITY GRANULOMATOUS INFLAMATION of distal airway .
• ORAL CORTICOSTROIDS = Relief of Bronchospasm , Clearing of pulmonary
infiltrates and decrease IgE levels Dose = 0.5 mg/kg/d for 2 wks then taper. Most patients require prolonged low dose therapy.• ITRACONAZOLE = Low dose (200 mg bid for 16 weeks) can Help in 50% reduction of corticosteroid dose. With no
significant toxicity.
TREATMENT
Saprophytic Aspergillosis (Aspergilloma )
• Fungal hyphae mixed with mucus and cellular debris within a Preexistent Pulmonary Cavity .
• If peripheral, Pleural thickening is characteristic.• Mass is usually seperated from the cavity wall.• Review of 60.000 CXR indentified 0.01 %
Prevelance.• Infection without tissue invasion. • Solid rounded mass, some times mobile
• Clinical findings could be non-specific.• Some patients may remain asymptomatic.• Most frequent symptom is HEMOPTYSIS 75%.• Less commonly chest pain, dyspnea , malaise.• Wheezing and fever (could also be secondary to
underlying disease, or bacterial super infection of the cavity or aspergilloma itself).
Clinical feature
Risk factor Aspergilloma
• The most common predisposing factors are TUBERCULOSIS ( 11% & 17% ) and
SARCOIDOSIS. • Other conditions Bronchogenic Cyst.Pulmonary Sequestration. Pneumocystis Carinii Pneumonia In Patients
With (AIDS) .Bronchiectasis , Ankylosing Spondylitis,
Neoplasm.
Aspergilloma
• Approximately 10% of mycetomas resolve spontaneously.
• Reversibility of the pleural thickening upon resolution of intracavitary fungal material suggests that the thickening of the cavity wall and pleura is due to a Hypersensitivity Reaction.
FUNGUS BALL
MONOD’S SIGN
• Mobile aspergilloma within a pulmonary cystic cavity in a 43-year-old man. Chest CT scans obtained with the patient supine (a) and prone (b) show a change in the position of the aspergilloma. A fumigatus was discovered at bronchoscopy. (Courtesy of Josep M. Mata, MD, Unidad Diagnóstica de Alta Tecnología, Sabadell, Spain.)
Treatment In asymptomatic patients, No therapy needed Surgical Resection = Severe life-threatening hemoptysis Preserved lung funtion. ANTIFUNGAL AGENT = 1. LOCAL Intracavitary
Instillation
AMPHOTERICINE 2. SYSTEMIC ITRACONOZOLE 200 to 400 mg/day
CAVERNOSTOMY.
Selective Bronchial Artery Embolization can be performed in those with
poor lung function.
Semi-invasive (Chronic Necrotizing) Aspergillosis
No vascular invasion. Tissue necrosis and destruction. Granulomatous inflammation similar to that seen in
reactivation tuberculosis. Usually no previous cavity, vs presence of cavity in
non-invasive form. May occur with mild immunosuppression.
Predisposing factors • Chronic debilitating illness, Advanced age. • Alcoholism, Malnutrition.• DM, CF, COPD.• Prolonged steroid therapy, Radiation therapy.• Inactive TB.• Pneumoconiosis.• Sarcoidosis.
Semi-invasive (Chronic Necrotizing) Aspergillosis
SYMPTOMS Often insidious and include chronic cough, sputum
production, fever, and constitutional symptoms. Hemoptysis has been reported in 15% of
affected patients . May manifest with chronic bronchitis and
recurrent episodes of mild hemoptysis.
Invasive Pulmonary Aspergillosis (IPA)
Major risk factors.• Prolonged neutropenia >3 wks or
neutrophil dysfunction.• Corticosteroid therapy .• Transplantation ie BM .• Hematologic malignancy( leukemia)• Cytotoxic therapy.• AIDS.
Airway- Invasive Aspergillosis
• The presence of Aspergillus organisms deep to the airway basement membrane.
• It occurs most commonly in Immunocompromised Neutropenic Patients and In Patients With AIDS.
• Clinical manifestations include acute tracheobronchitis, bronchiolitis, and bronchopneumonia.
• Patients with acute tracheobronchitis usually have normal radiologic findings.
• Occasionally, tracheal or bronchial wall thickening may be seen.
• Bronchiolitis is characterized at HRCT by the presence of Centrilobular Nodules and branching linear or nodular areas of increased attenuation having a "tree-in-bud“ appearance.
Airway- Invasive Aspergillosis
Tree in bud appearance
Characteristic CT findings • Nodules surrounded by a halo of ground-
glass attenuation "HALO SIGN“ or pleura-based, wedge-shaped areas of consolidation.
• These findings correspond to hemorrhagic infarcts.
• In severely neutropenic patients, the halo sign is highly suggestive of angioinvasive aspergillosis.
Angioinvasive Aspergillosis
"HALO SIGN“
Air Crescent sign
• The clinical diagnosis is difficult, and the mortality rate is high.
• Positive culture Methanamine silver, PAS.• BAL 97% specific. But less sensitive.• Chest CT findings = Halo sign, Cresent
sign.• Open or thoracoscopic lung biopsy is
the gold standard.
Diagnosis
Galactomannan Antigen Polysaccharide cell wall component. ELISA test. It has 67-100 % sensitivity and 86-98.8 % specificity. Can precede the clinical diagnosis by 6-14 day.
Diagnosis
Most commonly used medicine - Ampho B 0.6 – 1.2 mg/kg/d , In severly immunocomromized 1 -1.5 mg/kg Response 20-83%.
TREATMENT
Other treatment optionsItraconazol = 200-400 mg/d 39% response. Caspofungin = 50 -70 mg ivVoriconazole, Posaconazole.
TREATMENT
• Voriconazole vs Ampho B, (391 pt randomized ). Succesfull response rate 49.7% for Voriconazole arm, 27.8% for Ampho B. Herbrecht et al, NEM 347: 408 (2002).
• Caspofungin, 70% favorable response in pulmonry disease for salvage therapy, daily dose.
• Vori + Caspo, combination better out come.
TREATMENT
SURGICAL RESECTIONMassive hemoptysis.Localized lesion.
TREATMENT