Airborne fungi infections Dr David W. Denning FRCP FRCPath Scientific Advisor to the Fungal Research Trust Clinician, Wythenshawe Hospital Head, Antifungal.

Airborne fungi infections

Dr David W. Denning FRCP FRCPath

Scientific Advisor to the Fungal Research Trust

Clinician, Wythenshawe Hospital

Head, Antifungal Testing Laboratory

Faculty, University of Manchester

WWW.aspergillus.man.ac.uk

Airborne fungal infections

Fungi are all around us in the air and yeasts (ie Candida) live in our guts

Exposure to fungi is one of life’s certainties

Introductions

Aspergillus –

38 species have caused disease

Common in the environment

www.aspergillus.man.ac.uk

Aspergillus niger Aspergillus fumigatus

Aspergillus spore head

Spores 3uM across (i.e. easily are drawn into the lungs)

The supporting cast

Alternaria

Penicillium

Cladosporium

Airborne fungi and their ‘diseases’

Aspergillus

Alternaria

Cladosporium

Penicillium

Others

Invasive (life- threatening) infection

Chronic infection

Allergy/asthma

Where are airborne fungi found?

• Outside air

• Home

• Hospital

Aspergillus and compost

Airborne fungi and pillows

Airborne fungi and pillows

Feather pillow Synthetic pillow

Fungus in the bedroom

We have been examining pillows for fungi:

Pillow typeNo pillows

Mean cfu/g pillowPredominant species *

Synthetic 3 8.6 x 102 - 2 x103A. fumigatus

R. rubra

Feather 3 1.8 x102 - 1.8 x103A. fumigatus

R. rubra*Other common species were other Aspergillus spp., Penicillium spp., Cladosporium spp.

What this means is that each ‘old’ pillow contains ~1 million fungal spores

Woodcock et al, Allergy 2005 In press

Airborne fungi on clothes and fabrics

Airborne fungi

Common sources of airborne fungi

Outside air – especially Cladosporium

After thunderstorms – esp Alternaria

In homes – esp Aspergillus and outdoor fungi

In hospitals – esp Aspergillus

Airborne fungi

Airborne fungi and hospital construction

Airborne fungi and hospital computers

Airborne fungi on air conditioning systems in hospital (intake ducts)

Airborne fungi in hospital

Airborne fungi in hospital

Outside room Inside room

Airborne fungi in hospital

Airborne fungi in hospital after continous air filtration

Outside room Inside room

Invasive aspergillosisChronic pulmonary aspergillosisAllergic aspergillosis

ABPASevere asthma association

Invasive aspergillosisChronic pulmonary aspergillosisAllergic aspergillosis

ABPASevere asthma association

Life-threatening aspergillosis

24 year old with genetic immune defect

Predicted numbers of invasive Aspergillus infections in the UK

Patient Number (2002)

% invasive aspergillosis

Range Expected cases invasive aspergillosis

Bone marrow Tx 793 8.10% 2.8-15.1% 64

Solid organ Tx 2,697 2.2-2.8% 0.8-16(lung)% 62-78

Leukaemia 15,802 6.50% 2.0-9.6% 1,027

Solid tumour (neutropenic)

27,824 1% 1 study only 278

Advanced cancer 127,766 1.86% 1.3-2.2% 2,376

ICU ~200,000 3.62% 2.7-3.7% 7,240

AIDS <400 0.60% 0.02-4.0% 2

Total 10,992

Actual cases

?

?

?

?

?

?

?

?

Invasive aspergillosisChronic pulmonary aspergillosisAllergic aspergillosis

ABPASevere asthma association

Chronic pulmonary aspergillosis

30 year old smoker with no immune defect

January 2001

Chronic pulmonary aspergillosis

30 year old smoker with no immune defect

April 2003

Predicted numbers of chronic lung Aspergillus infections in the UK

Those at riskPrior TB (?5%)Sarcoidosis with cavitation (12% of all) Lung damage (pneumothorax etc)

Prevalence rate in the UK ???? 200-1000 cases

Incurable currently (require life-long treatment)

Invasive aspergillosisChronic pulmonary aspergillosisAllergic aspergillosis

ABPASevere asthma association

ABPA

Plug in airways Airway clear after removal

ABPA with airway obstruction

Mild asthma with shortness of breath

Predicted numbers of ABPA patients in the UK

Those at riskAdults with asthma = 4,100,000 on treatmentCystic fibrosis = 2,700 adults

Prevalence rate in the UK~ 1% of asthmatics = 41,000 patients~15% adult CF patients = 405 patients

Invasive aspergillosisChronic pulmonary aspergillosisAllergic aspergillosis

ABPASevere asthma association

Severe asthma with fungal sensitisation

Histamine House dust mite Cat

Cladosporium

Dog

GrassNegativeControl

Aspergillusfumigatus

AlternariaCandida Penicillium

Spore counts and asthma attacks and admission to hospital

All circumstantial evidence

• Thunderstorm asthma – linked to Alternaria

• Asthma deaths (Chicago) linked to high ambient spores counts and season (summer autumn) when spore counts highest

• Asthma hospital admission linked to high ambient spore counts (Derby, New Orleans, Ottawa)

• Asthma hospital attendance linked to high spore counts, but not pollen counts (Canada)

• Asthma symptoms increased on days of high spore counts (California, Pennsylvania)

Fungus at home

Environmental data

• Mouldy housing associated with worse asthma

• Wheezing in children associated with damp housing

• Mouldy and damp school associated with asthma symptoms and emergency room visits

• Highest concentration of Aspergillus fumigatus is at home

Airborne fungal fragments

Fungal fragment

Diffusing allergen leeching out of fungus in contact with liquid

Hospital admission with asthmatic attacks and mould allergy

Allergen Asthma, no admission (n=82) Asthma, 2+ admission (n=46)

House dust mite 56 % 67 %

Grass pollen 46 % 63 %

Cat 37 % 59 %

Dog 18 % 48 %

Any non fungal allergen 70% 74%

O’Driscoll et al, BMC Pulm Med 2005;18:4

Allergen Asthma, no admission (n=82) Asthma, 2+ admission (n=46)

Aspergillus 7 % 37 %

Alternaria 5 % 26 %

Cladosporium 1 % 41 %

Penicillium 2 % 30 %

Candida 10 % 33 %

Any fungal allergen 16% 76%

Hospital admission with asthmatic attacks and mould allergy

O’Driscoll et al, BMC Pulm Med 2005;18:4

Severe asthma and moulds

Severe asthma – 235 (21%) of all asthmatics

Zureik et al, Br Med J 2002;325:411

Increasing frequency of fungal skin test positivity in severe asthma

Odds ratio

Predicted numbers of severe asthmatics with fungal sensitisation in the UK

Those at riskAdults with asthma = 4,100,000 on treatmentSevere asthma = 5-21%Mould allergic = 35-50%

Prevalence rate in the UKLower number = 71,750 patientsUpper number = 430,500 patients

~40,000 adults admitted to hospital in the UK each year with asthmaAdmissions reduced to 25% with antifungal therapy in 14 patients (pre antifungal - 1.63 admissions per year, post antifungal 0.4)

Conclusions

Fungi are all around us in the air

Exposure to airborne fungi is one of life’s certainties

Many people in the UK have infection or allergy due to fungi, and additional research and care is required for these patients.

Ascertainment of national caseload would be useful