17th February 2025

Fungal respiratory infections

Overview of fungal respiratory infections

Fungal diseases of the lung are mostly associated with the immunosuppressed or those with complications from tuberculosis. History is fundamental due to the subset of patients most susceptible.

In the laboratory, beta-d-glucan is a useful fungal-specific marker which may aid in diagnosis.

Pneumocystis pneumonia (PCP)

PCP is an opportunistic fungal infection of the lung which causes an idiosyncratic pneumonia. It is strongly associated with HIV but may also be seen in immunosuppressed transplant patients, those on corticosteroids, following chemotherapy or in patients with cancer.

Classically, the infection causes a cough with severe desaturation on exertion.

Chest X-ray often shows bilateral hilar infiltrates; however, chest examination is often normal. Microscopy is the diagnostic tool in PCP, with bronchoalveolar lavage being the gold standard.

First-line treatment is co-trimoxazole (trimethoprim and sulfamethoxazole). In patients at particular risk of PCP, co-trimoxazole may be given prophylactically. Continuous positive airway pressure (CPAP) may be used to assist with oxygenation in PCP and intubation may be needed. For patients with an oxygen requirement, corticosteroids should be given.

Histoplasmosis

Histoplasma is a fungus found in animal droppings in the Midwest and South-East USA, with particular prevalence around the Mississippi River. The disease is also prevalent in Mexico and Central America. 

In immunocompetent individuals, the disease is often asymptomatic, although 1-3 weeks after acquisition, patients may develop a self-limiting flu-like illness with bilateral alveolar shadowing and hilar/mediastinal lymphadenopathy on chest X-ray. Some cases may turn into chronic, cavitating disease. Disseminated disease can occur in the immunosuppressed. Adrenal insufficiency is a rare, life-threatening complication.

Gold-standard diagnosis involves Histoplasma seen either on microscopy or histopathology from biopsied tissue. Alternatively, diagnosis can be obtained via antigen testing. Oral itraconazole is the treatment.

Aspergillus

Aspergillus moulds, especially Aspergillus fumigatus, can produce a variety of respiratory diseases.

Allergic bronchopulmonary aspergillosis (ABPA)

Asthma precipitated by Aspergillus and ABPA are IgE- and IgG-mediated reactions which are responsive to steroids. Signs and symptoms are typical of asthma and include reduced exercise tolerance and wheeze.

Patients with ABPA have a chronic inflammatory IgE and IgG response to Aspergillus, which causes damage to bronchi and eventually bronchiectasis. Diagnosis is mainly based on a history of asthma (particularly with recurrent exacerbations), IgG precipitins to Aspergillus, central bronchiectasis and a positive skin prick test. Patients benefit from itraconazole alongside steroids and conventional asthma treatment. 

Invasive aspergillosis 

This is when Aspergillus hyphae invade body tissue. Invasive aspergillosis occurs nearly exclusively in cases of immunosuppression. Isolating Aspergillus hyphae from the respiratory tract via sputum or a bronchoalveolar lavage provides a diagnosis.

Invasive disease can cause fever, haemoptysis and dyspnoea when afflicting the lungs; other pathologies, such as endocarditis, depend on the site of dissemination. The lungs are the most common mechanism of entry to the body.

Raised circulating levels of galactomannan, a component of the Aspergillus cell wall, provides evidence of aspergillosis. Management is with a prolonged course of an IV antifungal.

Aspergilloma

Aspergillomas are balls of fungal hyphae that exist within a cavity in the lung, usually secondary to previous tuberculosis infection. Haemoptysis is the most common symptom, but many aspergillomas are asymptomatic. CT thorax may show the halo sign.

Treatment is dependent on symptoms; surgery or antifungals may be required.

Candidal pneumonia

Candidal pneumonia, caused by Candida, may occur in the immunosuppressed, especially in transplant patients. Due to the neutropenia required for bone marrow transplantation, these patients are particularly susceptible. Pulmonary involvement with candidal infection is non specific but carries a high mortality and the patient may be severely unwell.

A T2 magnetic resonance (T2MR) assay will be positive but a transbronchial or surgical lung biopsy is required for a definitive diagnosis. Treatment is with an antifungal such as fluconazole or amphotericin B.

Cryptococcus

Cryptococcal lung disease, caused by Cryptococcus neoformans, is rare but possible in the immunosuppressed. Pulmonary involvement will necessitate a CT head and lumbar puncture due to the strong association with CNS involvement. Serum cryptococcal antigen will help make a diagnosis. Treatment is with several weeks of IV antifungals. 

Blastomycosis

Blastomycosis is caused by Blastomyces dermatitidis, a fungus found in contaminated soil mostly in the United States but also in South Asia and the Middle East. It is uncommon and mostly asymptomatic but can cause a severe pneumonia with ARDS as a rare but serious complication. Treatment is with itraconazole.

References

• Tasaka S. Recent Advances in the Diagnosis and Management of Pneumocystis Pneumonia. Tuberculosis and Respiratory Diseases. 2020;83
• Linder KA, Kauffman CA. Histoplasmosis: Epidemiology, Diagnosis, and Clinical Manifestations. Current Fungal Infection Reports. 2019 May 7;13(3):120–8
• Chapman S. Oxford handbook of respiratory medicine. Oxford, United Kingdom: Oxford University Press; 2014
• Akuthota P. Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis [Internet]. Kauffman CA, Barnes PJ, Finlay G, editors. UptoDate. 2022 [cited 2022 Apr 27]. Available from: https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-allergic-bronchopulmonary-aspergillosis
• National Institute for Health and Care Excellence. Antifungals, systemic use [Internet] [accessed 17/08/2022]. NICE. Available from: https://bnf.nice.org.uk/treatment-summary/antifungals-systemic-use.html
• McBride JA, Gauthier GM, Klein BS. Clinical Manifestations and Treatment of Blastomycosis. Clinics in Chest Medicine. 2017 Sep;38(3):435–49