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