Fungal Lung Disease

What patients are most at risk of developing fungal disease?

• those with underlying health conditions

  • TB, HIV, cancer

• immunocompromised individuals

• people who’ve had organ transplant

What causes aspergillosis?

What kind of pathogen is it (think other fungal infections)?

What is the mortality rate of aspergillosis?

• aspergillus fumigatus - an environmental mould that can infect humans

• is an opportunistic pathogen

• 40-90%

Why is aspergillosis a growing concern?

• lots of drug-resistant aspergillosis species due to fungicides and pesticides being used in agriculture (the fungus got used to them…)

Why is aspergillosis more common now than in the past?

• is an opportunistic infection

• patients are now immunocompromised more than before

  • think, people are surviving AIDS, cancer, TB

    • these people used to die

  • but now aspergillosis can get them

What are the types of aspergillosis?

• allergic bronchopulmonary aspergillosis (ABPA)

• chronic pulmonary aspergillosis (CPA)

• aspergilloma - linked with CPA

• invasive pulmonary aspergillosis (IPA)

What is allergic bronchopulmonary aspergillosis (ABPA)?

• allergic to aspergillus mould

What is chronic pulmonary aspergillosis (CPA)?

• long term lung infection

What is aspergilloma?

• a ball of mould in the lungs - linked with CPA (chronic pulmonary aspergillosis)

What is invasive pulmonary aspergillosis (IPA)?

• life-threatening infection in individuals with weakened immune system

If patient is immunodeficient, what kind of aspergillosis is likely to affect them?

• IPA (invasive pulmonary aspergillosis) - most severe

If asthmatic patients get aspergillosis what is it considered?

• hypersensitivity-allergy

• severe asthma with fungal sensitisation (SAFS)

If patients with COPD get aspergillosis disease what type is it and why?

• CPA (chronic pulmonary aspergillosis)

• due to these patients having damage to the lungs and inflammation

What T helper lineage is SAFS (severe asthma with fungal sensitisation) typically?

• Th2 lineage

  • eosinophil predominantly

  • elevated IgE levels

  • mucus hypersecretion and airway remodelling

What percentage of adults w/ severe asthma have fungal sensitisation?

• 50%

What is the difference between ABPA and SAFS?

• SAFS has an absence of fungal growth in the lungs (ABPS does have fungal growth)

What percentage of patients with CF end up with ABPA?

Why?

What do the fungal spores secrete and what do they cause?

• 5-10%

• in CF patients, uptake and killing of aspergillosis is reduced

• secrete exoproteases and other fungal products which further affect mucocilliary clearance - and affect epithelial barrier (cause pro-inflammation)

Is ABPA common in asthmatics?

• no, rare (only 1%)

What cells and interleukins are involved in ABPA?

• aspergillosis triggers release of IgE → binds to mast cells = release of histamine and Th2 cytokines (IL-4, 5 AND 13)

• local and systemic eosinophil

• local neutrophil

• elevated levels of IgG, IgA and IgE antibodies

What is aspergilloma?

• fungal ball which consists of hyphae, dead cells and extracellular matrix

What are symptoms of CPA?

• chronic inflammation, productive cough, weight loss, dyspnoea, fatigue and mild hemoptysis (coughing up blood)

What is hemoptysis?

• coughing up blood

What antibody is increased in CPA?

• IgG

What occurs in IPA that causes such a high mortality rate?

What organs are affected?

• invasive aspergillosis (affects immunocomp)

• aspergillus hyphae invade arterioles and lung parenchyma = ischemic necrosis

• aspergillus pierce through alveolar = disseminate into blood = thrombosis

• kidneys, liver, spleen, sinuses and CNS

What are treatment options for aspergillosis?

• voriconazole (1st line)

  • amphotericin B (1st line if voriconazole cannot be used)

• caspofungin or itraconazole

• posaconazole

What is azole moa?

• inhibits ergosterol biosynthesis by binding to sterol 14alpha demethylase (causing inhibition)

What is most severe S/E of liposomal amphotericin B?

• nephrotoxicity

What is echinocandin MOA?

Does echinocandin kill aspegillus?

• interferes with fungal wall synthesis by non-competitively inhibiting B1-3D-glucan synthase

• at the Fks1p extracellular domain

• no, it is a fungistatic, not a fungicide