12th January 2024

Respiratory Infections

Pneumonia

Background

Pneumonia is inflammation of the lung parenchyma caused by infection, which results in alveoli of the affected areas becoming filled with pus or fluid. In hospital, the diagnosis is made based on symptoms and signs of an acute lower respiratory tract infection and chest X‑ray findings of new shadowing that is not due to another cause. Pneumonia can be classified in multiple ways, including:

• The causative organism which can be bacterial, viral, fungal or parasitic
• The severity of infection, most commonly using the CURB-65 score
• The pattern of consolidation on the chest X-ray. Pneumonia can be split into lobar pneumonia, where inflammation is confined to one lobe, and bronchopneumonia, where there are patchy foci of consolidation with no lobar localisation
• The place where infection occurred, e.g. community-acquired vs hospital-acquired. Pneumonia is defined as hospital-acquired if it occurs >48 hours after hospital admission

Epidemiology

Between 0.5-1% of adults in the United Kingdom (UK) develop community-acquired pneumonia (CAP) every year, with the condition particularly common in the elderly population. Pneumonia carries significant morbidity and mortality; over 100,000 patients per year are admitted to an NHS hospital in England with a primary diagnosis of pneumonia, and approximately 30,000 deaths per year in the UK are due to pneumonia.

Causative organisms

Pneumonia is most commonly caused by bacterial infection. Streptococcus pneumoniae is the most common cause of CAP, accounting for approximately 80% of cases. Other common organisms include Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus, which is classically seen after influenza infection. Klebsiella pneumoniae is a less common cause of pneumonia except in alcoholics and can present with cavitating lesions. “Atypical” causes of pneumonia are those which are challenging to detect through standard bacterial methods and include Legionella pneumophila, Mycoplasma pneumoniae, Chlamydia pneumoniae and Chlamydia psittaci, which is commonly seen in bird owners. 

The pathogens typically associated with hospital-acquired pneumonia (HAP) differ from those in CAP, with Gram-negative enterobacteria (e.g. Enterobacter spp, Escherichia coli and Proteus spp) and Staphylococcus aureus being considered the ‘core’ pathogens. Pseudomonas aeruginosa is a cause of severe HAP and is classically seen in patients on mechanical ventilation. Aspiration pneumonia, typically seen in individuals with swallowing difficulties, often has a mixed picture with anaerobic species involved. 

Presentation

Pneumonia typically presents with a relatively short history of symptoms over hours to days. Common symptoms include:

• Fever
• Shortness of breath
• Productive cough
• Pleuritic chest pain
• Malaise

Risk factors for pneumonia are smoking, immunosuppression, impaired swallowing, and concurrent lung conditions such as bronchiectasis. 

Atypical pneumonias typically present with a slightly longer history of flu-like symptoms, including headache, diarrhoea, and malaise. Mycoplasma pneumoniae infection is commonly associated with dermatological manifestations, such as erythema multiforme or Stevens-Johnson syndrome. Legionella can colonise building water systems and classically occurs in outbreaks in hotels. 

Signs on examination can include: 

• Pyrexia
• Tachycardia
• Tachypnoea
• Hypoxia
• Reduced chest expansion on the affected side
• Dull percussion note over the area of consolidation
• Coarse crackles and bronchial breathing on auscultation over the area of consolidation
• Increased vocal resonance over the area of consolidation

Investigations

Investigations in suspected pneumonia aim to confirm the diagnosis, establish the causative pathogen and determine the severity. 

Investigations to consider include:

• Blood tests
  • Full blood count – to assess the white cell count and differential. Mycoplasma infection can also cause cold autoimmune haemolytic anaemia. If this is suspected, the full blood count should be followed up with a blood film showing spherocytes and reticulocytosis and direct antiglobulin test (DAT). 
  • Urea & electrolytes – urea is included as part of the CURB-65 score. Legionella pneumonia is typically associated with hyponatraemia. 
  • Liver function tests – Legionella can cause deranged liver function tests
  • C-reactive protein
  • Blood cultures
  • Venous blood gas for lactate
  • Serology for atypical organisms, e.g. Mycoplasma
• Arterial blood gas – if hypoxic
• Chest X-ray to assess for consolidation
• Sputum culture
• Urine for Legionella and Pneumococcal antigens

Image Source: Wikimedia Commons (2017).  X-ray_of_lobar_pneumonia, Licensed under a creative commons licence. Available for free at: https://upload.wikimedia.org/wikipedia/commons/5/51/X-ray_of_lobar_pneumonia.jpg (Accessed: 22 February 2022).

Management

The management of pneumonia depends on the severity of the condition and the causative organism. The CURB-65 score is a predictive score of mortality from CAP, which is commonly used to guide treatment. The score is as follows:

• Confusion (AMTS ≤ 8) – 1 point
• Urea ＞7mmol/L – 1 point
• Respiratory rate ≥ 30 breaths per minute – 1 point
• Blood pressure: systolic ＜90mmHg or diastolic ≤ 60mmHg – 1 point
• Age ≥ 65 years – 1 point

Patients with a score of 0 or 1 are categorised as low severity (less than 3% mortality risk), and these individuals can often be managed as outpatients. A score of 2 is moderate severity (3‑15% mortality risk), which often requires hospital admission, while a score of 3 or above is categorised as severe (more than 15% mortality risk), which should prompt a consideration of discussion with the intensive care team.

Antibiotics are the mainstay of treatment for bacterial pneumonia. If possible, low-severity CAP should be managed with oral amoxicillin, with doxycycline or clarithromycin being alternatives if amoxicillin is unsuitable. Moderate severity CAP is typically treated with amoxicillin and clarithromycin, while severe CAP is managed with a combination of co-amoxiclav (typically IV initially) and clarithromycin. 

If specific causative organisms for the pneumonia are identified, the treatment may be modified following discussion with the microbiology team. For instance, the first-line treatment for Legionella pneumophila would typically be a fluoroquinolone such as levofloxacin or a macrolide such as clarithromycin, while Mycoplasma is often managed with a macrolide. 

Antibiotic guidelines differ for HAP, with NICE recommending oral co-amoxiclav for patients with non‑severe symptoms or signs and not at higher risk of resistance or a choice of either piperacillin with tazobactam (Tazocin), ceftazidime, ceftriaxone, cefuroxime, meropenem or ceftazidime with avibactam IV for patients with severe symptoms or signs (for example, symptoms or signs of sepsis) or at higher risk of resistance. In patients with aspiration pneumonia, metronidazole is typically added to provide anaerobic cover, and a referral to Speech and Language Therapy should be strongly considered to assess the safety of the swallow. 

A follow-up chest X-ray should be arranged after 6 weeks to ensure resolution of consolidation (if it has not resolved, this should raise suspicion for an underlying abnormality, such as a lung tumour) for adults with either symptoms and signs that persist despite treatment, and/or who are at higher risk of underlying malignancy (particularly smokers and people aged more than 50 years). It is important to advise patients that symptoms may persist long beyond the end of their antibiotic course. For instance, it is expected that by three months, most of their symptoms should have resolved, yet fatigue may still be present. 

Complications

A number of complications can result from pneumonia. Type 1 respiratory failure, with a PₐO₂ < 8, is common due to the impedance of oxygen diffusion across pus/fluid in the alveolar spaces. Inflammation of the pleura due to the infection can cause an exudative pleural effusion to develop. Small pleural effusions may be of no consequence; however, drainage may be required if the effusion becomes large and leads to symptoms. Additionally, if the effusion becomes infected with pus in the pleural space (empyema), this must also be drained. An empyema should be suspected in patients with evidence of pleural effusion on a chest X-ray and recurrent fevers despite treatment of their pneumonia. Aspirated pleural fluid is classically yellow and turbid, with a pH < 7.2 being diagnostic of empyema. Additional complications of pneumonia include sepsis and the development of lung abscesses, which typically cause a swinging fever. 

Image Source: Wikimedia Commons (2017). Left-sided Pleural Effusion, Licensed under a creative commons licence. Available for free at :https://upload.wikimedia.org/wikipedia/commons/5/57/Left-sided_Pleural_Effusion.jpg (Accessed: 22 February  2022).

References

• Regunath H, Oba Y. Community-Acquired Pneumonia. StatPearls. 2021 Aug 11; [accessed 21 Feb 2022] Available from: https://www.ncbi.nlm.nih.gov/books/NBK430749/
• Prince SE, Dominger KA, Cunha BA, Klein NC. Klebsiella pneumoniae pneumonia. Heart & Lung. 1997 Sep 1;26(5):413–7. doi: 10.1016/S0147-9563(97)90028-5
• Pneumonia in adults Quality standard. 2016; [accessed 21 Feb 2022] Available from: www.nice.org.uk/guidance/qs110
• Pneumonia statistics | British Lung Foundation. [accessed 21 Feb 2022] Available from: https://statistics.blf.org.uk/pneumonia#statistic175
• Mackenzie G. The definition and classification of pneumonia. Pneumonia (Nathan Qld). 2016 Dec;8(1). [accessed 21 Feb 2022] Available from: https://pubmed.ncbi.nlm.nih.gov/28702293/
• Recommendations | Pneumonia (hospital-acquired): antimicrobial prescribing | Guidance | NICE. [accessed 21 Feb 2022] Available from: https://www.nice.org.uk/guidance/ng139/chapter/Recommendations#treatment-for-adults-young-people-and-children
• Recommendations | Pneumonia (community-acquired): antimicrobial prescribing | Guidance | NICE. [accessed 21 Feb 2022] Available from: https://www.nice.org.uk/guidance/ng138/chapter/Recommendations
• Atypical Pneumonia | CDC. [accessed 21 Feb 2022] Available from: https://www.cdc.gov/pneumonia/atypical/index.html
• Abdulhadi B, Kiel J. Mycoplasma Pneumonia. PCR for Clinical Microbiology: An Australian and International Perspective. 2021 Jul 25;179–82. [accessed 21 Feb 2022] Available from: https://www.ncbi.nlm.nih.gov/books/NBK430780/
• Trotter CL, Stuart JM, George R, Miller E. Increasing Hospital Admissions for Pneumonia, England – Volume 14, Number 5—May 2008 – Emerging Infectious Diseases journal – CDC. Emerging Infectious Diseases. 2008;14(5):727–33. [accessed 21 Feb 2022] Available from: https://wwwnc.cdc.gov/eid/article/14/5/07-1011_article
• Chahin A, Opal SM. Severe Pneumonia Caused by Legionella pneumophila: Differential Diagnosis and Therapeutic Considerations. Infectious Disease Clinics of North America. 2017 Mar 1;31(1):111. [accessed 21 Feb 2022] Available from: /pmc/articles/PMC7135102/
• McEachern R, Campbell J. HOSPITAL-ACQUIRED PNEUMONIA: EPIDEMIOLOGY, ETIOLOGY, AND TREATMENT. Infectious Disease Clinics of North America. 1998 Sep 1;12(3):761–79. doi: 10.1016/S0891-5520(05)70209-9

Tuberculosis

Background

Tuberculosis (TB) globally represents a leading cause of death by an infectious agent. TB is caused by Mycobacterium tuberculosis (MtB), an aerobic bacillus transmitted by the respiratory route. From the point of deposition of aerosols containing MtB onto lung alveolar surfaces, the progression of disease can have several outcomes, from patients who are able to clear the initial infection to those who have haematogenous spread of the infection throughout the body. TB is a notifiable disease in the UK. 

Epidemiology

Globally, it is estimated that 1.5 million deaths per year are caused by TB, with approximately 10 million incident cases per year. In the UK, the incidence of TB has been slowly reducing over recent years, currently standing between 4000-5000 cases per year. Approximately 300 deaths per year in the UK are caused or contributed to by TB.

Stages of TB disease

TB has human-to-human transmission by the respiratory route. Individuals with active respiratory TB produce aerosol droplets containing MtB when coughing, sneezing or speaking. If others inhale these infectious droplets, they lodge in the lung alveoli and bacilli are taken up by resident macrophages. From this point the progression of disease can have several outcomes, largely determined by the host immune response. An unknown proportion of individuals appear able to completely clear the infection, suggesting they are protected by as-of-yet-unknown immune mechanisms. For some individuals, primary infection leads to active TB (primary progressive tuberculosis), when the replication of bacilli cannot be effectively suppressed by the innate immune system. In most healthy individuals, MtB infection causes little or no symptoms as the immune system acts to wall off the bacteria in granulomas, which limit further replication and spread and form latent TB infection. Most individuals will remain with their infection in latency lifelong; however, for some, the infection can later become active (reactivation). Miliary TB occurs when there is massive lymphohematogenous dissemination of the bacilli to the lungs and other organs, which results in the formation of millet seed-sized tuberculous foci.

Risk factors

There are a number of factors which increase an individual’s risk of TB infection. These include:

• Being born in a high prevalence area, such as India, Pakistan, Romania, Bangladesh etc. 
• Being in close contact with someone with active respiratory TB, e.g. living in the same household or working in close proximity.
• Having a comorbid condition, such as HIV, diabetes mellitus or occupational lung disease
• Taking immunosuppressive drugs
• Having a history of excessive alcohol, injecting drug users, and smokers
• Having a low socioeconomic status, with individuals using homeless hostels and shelters and people living in prison, particularly at risk.

Given the above, anyone with confirmed or suspected TB should be offered testing for HIV. Furthermore, as anti-tumour necrosis factor (TNF)-alpha biologic therapies have been shown to increase risk of reactivation of latent TB, any patient being offered these medications should be tested for TB before their commencement. 

Presentation

Patients with latent TB are usually asymptomatic. 

Active pulmonary TB can present with the following symptoms: 

• Fever
• Weight loss
• Night sweats
• Productive cough
• Haemoptysis
• Lymphadenopathy

Active extra-pulmonary TB can affect any organ, and therefore, the presentation varies depending on the system(s) affected. 

Diagnosis

Latent TB can be diagnosed by Mantoux testing (tuberculin skin testing) or interferon-ɣ release assays (IGRA). In the Mantoux test, TB antigen is injected intradermally, and the area is assessed 48-72 hours later to look for evidence of a delayed-type hypersensitivity reaction occurring, which indicates previous exposure to the antigen. This test can provide a false positive result if the patient has previously had the BCG vaccine and false negative results in individuals who are immunosuppressed (e.g. HIV-positive patients). IGRA testing involves exposing T-lymphocytes of individuals to MtB antigens and measuring interferon-ɣ to detect for previous infection. IGRA tests are not affected by prior BCG vaccination. 

For suspected active pulmonary TB, a chest X-ray should be performed, with further diagnostic investigations carried out if the radiological appearance is suggestive of TB. While there are no radiographic features that are alone diagnostic of TB, a number of features are typical. Mediastinal and hilar lymphadenopathy is a common chest X-ray finding, consolidation, and cavitation, which has a predilection for the upper lobes. If appearances suggest TB, multiple respiratory samples should be sent for microscopy and culture for acid-fast bacilli (bacilli which resist acid on Ziehl-Neelsen staining). If possible, these should be three deep cough sputum samples, including an early morning sample. Bronchoscopy and lavage may be required to acquire samples. Rapid diagnostic nucleic acid amplification tests should be performed on these specimens if there is clinical suspicion of TB disease, and the person has HIV or rapid information about mycobacterial species would alter the person’s care. 

In patients with suspected extra-pulmonary TB, samples should be collected again, allowing for microscopy and culture. For instance, in suspected TB meningitis cerebrospinal fluid should be taken for TB microscopy and culture; in suspected pleural TB, pleural fluid should be sent; in suspected TB lymphadenitis, a lymph node biopsy should be sent, and so on. 

Image Source: Wikimedia Commons (2010). Tuberculosis image 1, Licensed under a creative commons licence. Available for free at: https://upload.wikimedia.org/wikipedia/commons/9/9a/Tuberculosis_image1.jpg (Accessed: 22 March 2021).

Image Source: Wikimedia Commons (2018). Chest radiograph of miliary tuberculosis. 2, Licensed under a creative commons licence. Available for free at: https://upload.wikimedia.org/wikipedia/commons/7/70/Chest_radiograph_of_miliary_tuberculosis_2.jpg (Accessed: 22 February 2022).

Management

Adults aged under 65 years old with latent TB are treated with either:

• 3 months of isoniazid (with pyridoxine) and rifampicin or
• 6 months of isoniazid (with pyridoxine).

The risk of hepatotoxicity from these medications has been shown to significantly increase in patients aged over 65 years, and therefore, the decision to treat latent TB infection in elderly patients requires careful consideration of risks and benefits.

Patients with active TB without central nervous system (CNS) involvement should be offered: 

• isoniazid (with pyridoxine), rifampicin, pyrazinamide and ethambutol for 2 months then
• isoniazid (with pyridoxine) and rifampicin for a further 4 months.

For patients with CNS involvement, isoniazid (with pyridoxine) and rifampicin are continued for 10 months (rather than four) after the initial two months of quadruple therapy. 

Patients with active TB admitted to hospital should be cared for in a single room until they have completed two weeks of the standard treatment regimen. If the patient is suspected or confirmed to have multi-drug resistant TB, whereby the organism is resistant to isoniazid and rifampicin (+/- other anti-tuberculous treatments), the patient should be managed in a negative pressure room. 

Adverse effects of TB medications

Patients starting on a TB treatment regime must have their liver and renal function assessed before commencing treatment. Visual acuity should be tested by Snellen chart before treatment with ethambutol.

Table 1: adverse effects of medications used to treat tuberculosis. Adapted from: Antitubercular Medications – StatPearls – NCBI Bookshelf [Internet]. [cited 2022 Mar 11]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557666/

References

• Seung KJ, Keshavjee S, Rich ML. Multidrug-Resistant Tuberculosis and Extensively Drug-Resistant Tuberculosis. Cold Spring Harb Perspect Med [Internet]. 2015 Sep 1 [cited 2022 Feb 22];5(9). Available from: /pmc/articles/PMC4561400/
• Smith BM, Schwartzman K, Bartlett G, Menzies D. Adverse events associated with treatment of latent tuberculosis in the general population. C Can Med Assoc J [Internet]. 2011 Feb 22 [cited 2022 Feb 22];183(3):E173. Available from: /pmc/articles/PMC3042475/
• Bhalla AS, Goyal A, Guleria R, Gupta AK. Chest tuberculosis: Radiological review and imaging recommendations. Indian J Radiol Imaging [Internet]. 2015 Aug 1 [cited 2022 Feb 22];25(3):213. Available from: /pmc/articles/PMC4531444/
• Recommendations | Tuberculosis | Guidance | NICE [Internet]. [cited 2022 Feb 22]. Available from: https://www.nice.org.uk/guidance/ng33/chapter/Recommendations#active-tb
• Recommendations | Tuberculosis | Guidance | NICE [Internet]. [cited 2022 Feb 22]. Available from: https://www.nice.org.uk/guidance/ng33/chapter/Recommendations#latent-tb
• Miliary Tuberculosis – StatPearls – NCBI Bookshelf [Internet]. [cited 2022 Feb 22]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK562300/
• Kiazyk S, Ball T. Tuberculosis (TB): Latent tuberculosis infection: An overview. Canada Commun Dis Rep [Internet]. 2017 Mar 2 [cited 2022 Feb 22];43(3–4):62. Available from: /pmc/articles/PMC5764738/
• Active Tuberculosis – StatPearls – NCBI Bookshelf [Internet]. [cited 2022 Feb 22]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK513246/
• Clinical Manifestations – Tuberculosis in Adults and Children – NCBI Bookshelf [Internet]. [cited 2022 Feb 22]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK344404/
• Global Health – Newsroom – Tuberculosis [Internet]. [cited 2022 Feb 22]. Available from: https://www.cdc.gov/globalhealth/newsroom/topics/tb/index.html
• Tuberculosis [Internet]. [cited 2022 Feb 22]. Available from: https://www.who.int/news-room/fact-sheets/detail/tuberculosis

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