Respiratory Diseases Caused by Fungi

Respiratory Diseases Caused by Fungi

• Fungi are often harmless saprophytes, but some species can cause disease by infecting tissues, producing toxins, or inducing allergic responses.
• Mycosis is the term for fungal infections.
• Pulmonary fungal diseases are influenced by systemic and local factors.

Factors Predisposing to Pulmonary Fungal Disease

• Systemic factors:
  • Haematological malignancies
  • HIV
  • Diabetes mellitus
  • Chronic alcoholism
  • Radiotherapy
  • Glucocorticoids, cytotoxic chemotherapy, biologic therapies and other immunosuppressant medications
• Local factors:
  • Tissue damage from suppuration or necrosis
  • Alteration of normal bacterial flora by antibiotic therapy

Classification of Bronchopulmonary Aspergillosis

• Allergic bronchopulmonary aspergillosis (ABPA): a hypersensitivity reaction to germinating fungal spores in the airway, potentially complicating asthma and cystic fibrosis.
• Approximately 1-2% of asthmatics, and 5-10% of cystic fibrosis patients are affected.
• Genetic predisposition (various human leukocyte antigens) plays a significant role.

Allergic Bronchopulmonary Aspergillosis (ABPA)

• ABPA results from hypersensitivity to germinating fungal spores in the airway wall.
• It can complicate conditions such as asthma and cystic fibrosis.
• It's a recognised cause of pulmonary eosinophilia.

Clinical Features of ABPA

• Fever, breathlessness, cough (productive of bronchial casts), and worsening asthmatic symptoms are common early presentations.
• Early diagnosis can be challenging, as radiographic infiltrates may mimic pneumonia. Chest X-rays sometimes show segmental or lobar collapse in patients with stable asthma symptoms.
• Regular therapy with low-dose oral glucocorticoids (prednisolone 7.5-10 mg/day) is typically used to control the disease and prevent progressive tissue damage.

Features of Allergic Bronchopulmonary Aspergillosis (ABPA)

• Asthma (in most cases)
• Proximal bronchiectasis
• Positive skin test to extracts of Aspergillus fumigatus
• Elevated total serum IgE
• Elevated Aspergillus-specific IgE or IgG
• Peripheral blood eosinophilia
• Chest X-ray abnormalities
• Recovery of Aspergillus fumigatus from sputum

Chronic Pulmonary Aspergillosis (CPA)

• Includes various forms such as simple aspergilloma, chronic cavitary pulmonary aspergillosis, chronic fibrosing pulmonary aspergillosis, and Aspergillus nodules.
• These conditions are relatively uncommon and challenging to treat and diagnose.

Simple Aspergilloma

• Cavities formed by previous diseases (such as TB) or damaged bronchi offer favorable environments for inhaled Aspergillus to lodge and grow.
• CT scans often reveal irregular mucosal walls, which eventually collapse to form a fungal ball.

Invasive Pulmonary Aspergillosis (IPA)

• IPA is often a complication of profound neutropenia, frequently caused by immunosuppressive drugs and/or diseases.
• It can lead to severe necrotising pneumonia.
• Involvement of pulmonary vessels can cause thrombosis and infarction; systemic spread may occur to the brain, heart, and other organs.
• Tracheobronchial aspergillosis may result in fungal plaques and ulceration formation.

Risk Factors for Invasive Pulmonary Aspergillosis

• Neutropenia: duration and severity of the condition is crucial
• Solid organ or allogeneic stem cell transplant
• Long-term, high-dose glucocorticoid therapy
• Leukaemia and other haematological malignancies
• Cytotoxic chemotherapy
• Advanced HIV disease
• Severe chronic obstructive pulmonary disease
• Critically ill patients on intensive care units
• Chronic granulomatous disease

Diagnosing IPA

• HRCT scans often show characteristic macronodules which may have a 'halo' of reduced attenuation.
• Aspergillus detection in blood/BAL fluid or tissues, and culture or histology.
• Galactomannan, beta-1,3-D-glucan, and Aspergillus DNA blood tests help diagnosis.

Management of IPA

• Voriconazole is the drug of choice.
• Second-line agents include liposomal amphotericin, caspofungin, posaconazole, and isavuconazole.
• Early diagnosis and aggressive treatment are vital to reduce mortality risks.
• High-efficiency particulate air (HEPA) filter rooms, laminar air flow rooms, and personal protective equipment should be utilized to control the spread of Aspergillus.