Airborne fungi infections Dr David W Denning FRCPath
Airborne fungi infections Dr David W. Denning 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 Aspergillus niger Aspergillus fumigatus www. aspergillus. man. ac. uk
Aspergillus spore head Spores 3 u. M across (i. e. easily are drawn into the lungs)
The supporting cast Alternaria Cladosporium Penicillium
Airborne fungi and their ‘diseases’ Aspergillus Alternaria Cladosporium Penicillium Others Invasive (lifethreatening) infection Chronic infection Allergy/asthma
Where 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 type No pillows Mean cfu/g pillow Predominant species * Synthetic 3 8. 6 x 102 - 2 x 103 A. fumigatus R. rubra Feather 3 1. 8 x 102 - 1. 8 x 103 A. 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 aspergillosis Chronic pulmonary aspergillosis Allergic aspergillosis ABPA Severe asthma association
Invasive aspergillosis Chronic pulmonary aspergillosis Allergic aspergillosis ABPA Severe 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 Actual cases 793 8. 10% 2. 8 -15. 1% 64 ? 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 ? 127, 766 1. 86% 1. 3 -2. 2% 2, 376 ? ~200, 000 3. 62% 2. 7 -3. 7% 7, 240 ? <400 0. 60% 0. 02 -4. 0% 2 ? 10, 992 ? Bone marrow Tx Solid organ Tx Advanced cancer ICU AIDS Total
Invasive aspergillosis Chronic pulmonary aspergillosis Allergic aspergillosis ABPA Severe asthma association
Chronic pulmonary aspergillosis January 2001 30 year old smoker with no immune defect
Chronic pulmonary aspergillosis April 2003 30 year old smoker with no immune defect
Predicted numbers of chronic lung Aspergillus infections in the UK Those at risk Prior TB (? 5%) Sarcoidosis with cavitation (12% of all) Lung damage (pneumothorax etc) Prevalence rate in the UK Incurable currently ? ? 200 -1000 cases (require life-long treatment)
Invasive aspergillosis Chronic pulmonary aspergillosis Allergic aspergillosis ABPA Severe 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 risk Adults with asthma Cystic fibrosis = 4, 100, 000 on treatment = 2, 700 adults Prevalence rate in the UK ~ 1% of asthmatics ~15% adult CF patients = 41, 000 patients = 405 patients
Invasive aspergillosis Chronic pulmonary aspergillosis Allergic aspergillosis ABPA Severe asthma association
Severe asthma with fungal sensitisation
Aspergillus fumigatus Negative Control Alternaria Histamine Candida Cladosporium House dust mite Penicillium Grass Cat Dog
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
Hospital admission with asthmatic attacks and mould allergy 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% O’Driscoll et al, BMC Pulm Med 2005; 18: 4
Severe asthma and moulds Severe asthma – 235 (21%) of all asthmatics Odds ratio Increasing frequency of fungal skin test positivity in severe asthma Zureik et al, Br Med J 2002; 325: 411
Predicted numbers of severe asthmatics with fungal sensitisation in the UK Those at risk Adults with asthma Severe asthma Mould allergic = 4, 100, 000 on treatment = 5 -21% = 35 -50% Prevalence rate in the UK Lower number Upper number = 71, 750 patients = 430, 500 patients ~40, 000 adults admitted to hospital in the UK each year with asthma Admissions 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
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