Chronic Pulmonary Aspergillosis (CPA)

Chronic Pulmonary Aspergillosis (CPA) is a long-term Aspergillus infection of the lung, usually but not exclusively caused by Aspergillus fumigatus. Unlike acute forms of aspergillosis, CPA affects immunocompetent people for reasons that are not yet fully understood, and fungal growth is consequently slow. CPA commonly causes cavities in lung tissue containing balls of fungal growth (aspergilloma). Patients commonly have pre-existing or co-existing lung disease, e.g. asthma, sarcoidosis, Chronic Obstructive Pulmonary Disease (COPD), tuberculosis, cystic fibrosis, Chronic Granulomatous Disorder (CGD) and other pre-existing lung damage.

The diagnosis of CPA requires a combination of characteristics: one or more cavities with or without a fungal ball present or nodules on thoracic imaging, direct evidence of Aspergillus infection (microscopy or culture from biopsy) or immunological response to Aspergillus spp. and exclusion of alternative diagnoses, all present for at least 3 months. Aspergillus antibody (precipitins) is elevated in over 90% of patients.

Invasive aspergillosis (probably better referred to as Acute Invasive Aspergillosis AIA) is a distinct illness primarily affecting highly immunocompromised patients e.g. prolonged neutropenia, allogeneic hematopoietic stem cell transplant, solid organ transplant, inherited or acquired immunodeficiencies, corticosteroid use, and more.

Chronic Pulmonary Aspergillosis consists of five current consensus definitions:

Chronic Cavitary Pulmonary Aspergillosis (CCPA) is the most common form, defined by one or more cavities, with or without a fungal ball present.
Simple Aspergilloma (single fungal ball growing in a cavity).
Aspergillus Nodules – an unusual form of CPA, no cavity forming, mimicking carcinoma of the lung, metastases, cryptococcal nodule, coccidioidomycosis or other rare pathogens and can only be definitively diagnosed using histology.
Chronic Fibrosing Pulmonary Aspergillosis (CFPA) is late stage CCPA.
Subacute invasive aspergillosis (SAIA) is very similar to CCPA but occurs in mildly immunocompromised or debilitated patients (e.g. diabetes mellitus, malnutrition, alcoholism, advanced age, prolonged corticosteroid administration or other modest immunocompromising agents, chronic obstructive lung disease, connective tissue disorders, radiation therapy, non-tuberculous mycobacterial (NTM) infection or HIV infection. Histology can often show tissue invasion. Progression is more rapid than with CCPA.

CT scans from patients with various forms of chronic pulmonary aspergillosis. (A) Simple aspergilloma; (B) Chronic cavitary pulmonary aspergillosis; (C) Chronic fibrosing pulmonary aspergillosis; (D) Aspergillus nodule. Figure taken from Kosmidis C, Denning DW, The clinical spectrum of pulmonary aspergillosis, Thorax 2015;70:270-277 — CT scans from patients with various forms of chronic pulmonary aspergillosis. (A) Simple aspergilloma; (B) Chronic cavitary pulmonary aspergillosis; (C) Chronic fibrosing pulmonary aspergillosis; (D) Aspergillus nodule. Figure taken from Kosmidis C, Denning DW, The clinical spectrum of pulmonary aspergillosis, *Thorax* 2015;**70:**270-277

Symptoms

Patients with aspergillomas often have few specific symptoms, but 50-90% experience some coughing up of blood.
For other types of CPA, symptoms may include weight loss, fatigue, cough, haemoptysis and breathlessness, usually for a period longer than 3 months.

Diagnosis

Most patients with CPA have an underlying lung disease. These include TB, previous treatment for lung cancer, sarcoidosis, emphysema and COPD. Chest X-rays or CT scans may show one or more lung cavities, and blood tests may be positive for Aspergillus antibodies. A galactomannan assay is a more reliable test for Aspergillus exposure. A sample of sputum may be cultured in an attempt to see if Aspergillus grows. Occasionally a biopsy is taken & tested.

Diagnosis is difficult and often requires specialist experience, consequently, NHS Commissioning: Highly Specialised Services have provided funding for the UK Chronic Pulmonary Aspergillosis Service, which is part of the National Aspergillosis Centre in Manchester, UK, where advice and referral can be sought.

Treatment

Patients with single aspergillomas generally do well with surgery and are best given pre-and post-operative antifungals to prevent other complications. For more complex cases (CCPA), lifelong use of antifungals is normal, along with regular X-rays to observe progress. It is important to monitor the blood levels of antifungals to ensure optimal dosing, as individuals vary in how their bodies process these drugs.

If bleeding is occurring and surgery is not possible, other treatments can limit blood loss. For example, tranexamic acid can be given to encourage clotting. If that fails and bleeding becomes excessive, blood vessel embolisation should be carried out.

Prognosis

For most patients, CPA will be a lifelong illness. 84% of patients do well post-surgery if that is an option. In less than 10% of cases, the disease spontaneously disappears. The vast majority of patients with CPA require chronic disease management. In most, the key aims of therapy are to reduce symptoms and prevent disease progression.

Occasionally patients are both asymptomatic and do not progress even without therapy. At the other end of the spectrum are highly symptomatic patients whose disease appears to progress despite high-intensity antifungal therapy, sometimes with combined immunotherapy. Arresting progression, and in particular minimising loss of lung function, is a key goal of therapy, unfortunately not always achieved; likewise, weight gain, reduction in fatigability, reduced cough, sputum production, haemoptysis and breathlessness are all valuable benefits of long-term antifungal therapy, also not always achieved.