12th January 2024

Fungal lung infections

Pneumocystis Pneumonia (PCP)

Background

Pneumocystis pneumonia (PCP) is a potentially life-threatening condition caused by the fungus Pneumocystis jirovecii (previously called Pneumocystis Carinii). PCP predominantly affects immunocompromised individuals, and it remains a leading AIDS-defining opportunistic infection in individuals infected with HIV.

Presentation

PCP usually occurs in individuals who are known to be immunocompromised, yet it may also be the first presentation of an underlying condition such as HIV.

Symptoms of PCP include:

• Progressive shortness of breath
• Cough, which is usually dry
• Fever
• Chest pain
• Decreasing exercise tolerance

Signs on respiratory examination are variable and can be normal. Patients may have fine crackles on auscultation. Measuring oxygen saturations during mobilisation can be very useful, as patients with PCP will classically demonstrate a drop in saturations on exertion.

Symptoms and signs of HIV should also be assessed if PCP is suspected; weight loss, lymphadenopathy or evidence of thrush or Kaposi’s sarcoma would all raise suspicion for underlying HIV.

Investigations

Patients with PCP usually have multiple tests performed before a diagnosis is confirmed. If PCP is suspected, blood tests to consider include:

• Inflammatory markers (WCC, CRP)
• HIV testing
• Lactate dehydrogenase – if elevated, this is indicative of PCP and can also be used to predict inpatient mortality in PCP patients
• β-D-Glucan – part of the fungal cell wall and therefore can be used in diagnosis (this should be discussed with the microbiology or respiratory team before requesting).

Chest X-rays in PCP can be normal but typically show diffuse bilateral peri-hilar interstitial infiltrates. A subsequent high resolution CT chest can be helpful.

Pneumocystis jirovecii cannot be routinely cultured but can be detected by staining the cyst wall using silver-based stains or by polymerase chain reactions. Repeated sputum samples may need to be taken to confirm the diagnosis. Bronchoalveolar lavage may be required to acquire samples if the patient is unable to expectorate or if their sputum is negative.

Image Source: Wikimedia Commons (2010). CT of infiltrates of pneumocystis pneumonia, Licensed under a creative commons licence. Available for free at: https://upload.wikimedia.org/wikipedia/commons/3/32/CT_of_infiltrates_of_pneumocystis_pneumonia.jpg (Accessed: 1 March 2022).

Management

High-dose co-trimoxazole is the first line management in PCP and can be given by mouth or as an intravenous infusion. In patients who cannot tolerate co-trimoxazole, alternatives in mild-to-moderate PCP include atovaquone, a combination of dapsone and trimethoprim, or a combination of clindamycin and primaquine; of these, only atovaquone is licensed for this indication in the United Kingdom.

In severe PCP, in which patients have breathlessness at rest or a PₐO₂ <8 kPa/SₐO₂ <91%, IV pentamidine isethionate is an alternative for patients who cannot tolerate co-trimoxazole or who have not responded to it.

Corticosteroids are given as an adjunct in patients with moderate or severe PCP associated with HIV and can be life-saving in severe PCP. Oral prednisolone or parenteral hydrocortisone can be used, and they are usually given in high dosage for 5 days before the dose is reduced to complete a 21-day course.

Prophylaxis against PCP should be given to all patients with a history of the infection and also for severely immunocompromised patients (in HIV-positive individuals, this is once their CD4 T-cell count falls below 200 cells/mm³). Oral co-trimoxazole is the drug of choice for prophylaxis.

Complications

Pneumothorax is a common complication seen in PCP, with a prevalence ranging from 13-61% in PCP patients in various studies.

Additional complications of PCP include:

• Respiratory failure
• Extra-pulmonary infection
• Acute respiratory distress syndrome (ARDS)

Pulmonary aspergillosis

Pulmonary aspergillosis is a collective term which incorporates a number of distinct conditions caused by infection with an Aspergillus species. Aspergillus are widely distributed fungal moulds, and Aspergillus fumigatus is the most common species to cause human disease. The types of pulmonary aspergillosis, which will be discussed in more detail below, include:

• Allergic bronchopulmonary aspergillosis (ABPA)
• Aspergilloma
• Invasive aspergillosis

Allergic bronchopulmonary aspergillosis (ABPA)

ABPA is a hypersensitivity reaction to the colonisation of the lungs with an Aspergillus species. The hypersensitivity initially causes IgE-mediated bronchospasm and oedema of the bronchial wall. Ultimately, damage to the bronchial wall results in bronchiectasis. ABPA predominantly affects patients with asthma and cystic fibrosis and usually presents with deterioration of their underlying respiratory disease.

Presenting symptoms can include:

• Wheeze
• Fever
• Cough which may be productive
• Malaise

The diagnosis of ABPA is usually made on the basis of an asthma/atopy history and the following findings on investigations:

• Eosinophilia
• Raised Aspergillus-specific IgE
• Raised total IgE
• Positive Aspergillus skin prick test
• New infiltrates/evidence of bronchiectasis on chest X-ray or CT scan

The mainstay of management of ABPA is corticosteroids, with a long course required that is tapered off over weeks/months. Itraconazole may be added for some patients, especially in those who rebound during or after steroid tapering.

Aspergilloma

Aspergillomas are mass-like balls of the fungus, which typically arise in pre-existing pulmonary cavities. Classically, aspergillomas occur in the cavities of post-primary pulmonary tuberculosis (and therefore occur in the upper lobes). Other causes of pulmonary cavities, in which aspergillomas can form, include pulmonary sarcoidosis and PCP.

Usually, aspergillomas are asymptomatic, although cough and fever may be present. Haemoptysis can also be a presenting feature, which in some cases can be life-threatening if there is erosion of the aspergilloma into a bronchial artery.

The diagnosis of aspergilloma is usually made with a combination of radiological findings, on chest X-ray and CT, of a mass within a cavity and elevated serum precipitin (IgG) levels to Aspergillus species. The ‘air-crescent’ and Monod signs are often discussed in aspergilloma chest X-rays, which describe air surrounding an aspergilloma.

Asymptomatic patients usually do not require any treatment, although long-term itraconazole is sometimes used. Patients with symptomatic aspergillomas should be considered for surgical resection, yet this is often not possible due to insufficient respiratory reserve. In the setting of large-volume haemoptysis, selective bronchial artery embolism can be life-saving.

Image Source: Wikimedia Commons (2011). Aspergilloma_X-ray, Licensed under a creative commons licence. Available for free at: https://upload.wikimedia.org/wikipedia/commons/3/3a/Aspergilloma_X-ray_%285390379081%29.jpg (Accessed: 1 March 2022).

Invasive aspergillosis

Invasive aspergillosis is extremely rare in immunocompetent individuals and is most commonly seen in patients undergoing intensive chemotherapy or organ transplantation or those with advanced AIDS. The condition is rapidly progressive and carries a high morbidity and mortality. Angioinvasion is commonly seen, which leads to fungus spreading haematogenously and affecting extra-pulmonary organs, including the kidneys, brain and heart.

The diagnosis of invasive aspergillosis is challenging, and the diagnostic process can involve the following investigations:

• Chest X-ray and CT scanning which may show nodules, cavities or pulmonary infiltrates
• Sputum samples or samples from bronchoalveolar lavage can undergo culture or PCR. Galactomannan, which is a component of the cell wall of Aspergillus species, can also be assessed for in respiratory samples or in the serum
• Serum β-D-Glucan
• Aspergillus IgG levels

Voriconazole is the treatment of choice for invasive aspergillosis.

References

• Choi JS, Kwak SH, Kim MC, Seol CH, Kim SR, Park BH, et al. Clinical impact of pneumothorax in patients with Pneumocystis jirovecii pneumonia and respiratory failure in an HIV-negative cohort. BMC Pulm Med [Internet]. 2022 Dec 1 [cited 2022 Mar 1];22(1):1–9. Available from: https://bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-021-01812-z
• Pneumocystis Jirovecii Pneumonia – StatPearls – NCBI Bookshelf [Internet]. [cited 2022 Mar 1]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482370/
• Pneumocystis Jirovecii Pneumonia. PCP information | Patient [Internet]. [cited 2022 Mar 1]. Available from: https://patient.info/doctor/pneumocystis-jirovecii-pneumonia
• Tasaka S. Recent Advances in the Diagnosis and Management of Pneumocystis Pneumonia. Tuberc Respir Dis (Seoul) [Internet]. 2020 Apr 1 [cited 2022 Mar 1];83(2):132. Available from: /pmc/articles/PMC7105429/
• Pneumocystis Pneumonia – NORD (National Organization for Rare Disorders) [Internet]. [cited 2022 Mar 1]. Available from: https://rarediseases.org/rare-diseases/pneumocystis-pneumonia/
• Pneumocystis pneumonia | Treatment summary | BNF content published by NICE [Internet]. [cited 2022 Mar 1]. Available from: https://bnf.nice.org.uk/treatment-summary/pneumocystis-pneumonia.html
• Symptomatic HIV infection | Diagnosis | HIV infection and AIDS | CKS | NICE [Internet]. [cited 2022 Mar 1]. Available from: https://cks.nice.org.uk/topics/hiv-infection-aids/diagnosis/symptomatic-hiv-infection/#longstanding-hiv-infection
• Aspergillosis | Types of Fungal Diseases | Fungal Diseases | CDC [Internet]. [cited 2022 Mar 1]. Available from: https://www.cdc.gov/fungal/diseases/aspergillosis/index.html
• Jones J, Gaillard F. Pulmonary aspergillosis. Radiopaedia.org [Internet]. 2008 May 2 [cited 2022 Mar 1]; Available from: http://radiopaedia.org/articles/937
• Aspergillosis | Asthma + Lung UK [Internet]. [cited 2022 Mar 1]. Available from: https://www.blf.org.uk/support-for-you/aspergillosis
• Kosmidis C, Denning DW. The clinical spectrum of pulmonary aspergillosis. Thorax [Internet]. 2015 Mar 1 [cited 2022 Mar 1];70(3):270–7. Available from: https://thorax.bmj.com/content/70/3/270
• Aspergillosis. What is aspergillosis? Symptoms and treatment. | Patient [Internet]. [cited 2022 Mar 1]. Available from: https://patient.info/doctor/aspergillosis