1. 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

2. 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

3. Introductions

4. Aspergillus – 38 species have caused disease Common in the environment www.aspergillus.man.ac.uk Aspergillus niger Aspergillus fumigatus

5. Aspergillus spore head Spores 3uM across (i.e. easily are drawn into the lungs)

6. The supporting cast Alternaria Penicillium Cladosporium

7. Airborne fungi and their ‘diseases’ Aspergillus Alternaria Cladosporium Penicillium Others Invasive (life- threatening) infection Chronic infection Allergy/asthma

8. Where are airborne fungi found? Outside air Home Hospital

9. Aspergillus and compost

10. Airborne fungi and pillows

11. Feather pillowSynthetic pillow

12. Fungus in the bedroom We have been examining pillows for fungi: Pillow type No pillows Mean cfu/g pillow Predominant species * Synthetic38.6 x 10 2 - 2 x10 3 A. fumigatus R. rubra Feather31.8 x10 2 - 1.8 x10 3 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

13. Airborne fungi on clothes and fabrics

14. 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

15. Airborne fungi

16. Airborne fungi and hospital construction

17. Airborne fungi and hospital computers

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

19. Airborne fungi in hospital

20. Outside room Inside room

21. Airborne fungi in hospital

22. Airborne fungi in hospital after continous air filtration Outside room Inside room

23. Invasive aspergillosis Chronic pulmonary aspergillosis Allergic aspergillosis ABPA Severe asthma association

24. Invasive aspergillosis Chronic pulmonary aspergillosis Allergic aspergillosis ABPA Severe asthma association

25. Life-threatening aspergillosis 24 year old with genetic immune defect

26. Predicted numbers of invasive Aspergillus infections in the UK PatientNumber (2002) % invasive aspergillosis RangeExpected cases invasive aspergillosis Bone marrow Tx7938.10%2.8-15.1%64 Solid organ Tx2,6972.2-2.8%0.8-16(lung)%62-78 Leukaemia15,8026.50%2.0-9.6%1,027 Solid tumour (neutropenic) 27,8241%1 study only278 Advanced cancer127,7661.86%1.3-2.2%2,376 ICU~200,0003.62%2.7-3.7%7,240 AIDS<4000.60%0.02-4.0%2 Total10,992 Actual cases ?

27. Invasive aspergillosis Chronic pulmonary aspergillosis Allergic aspergillosis ABPA Severe asthma association

28. Chronic pulmonary aspergillosis 30 year old smoker with no immune defect January 2001

29. Chronic pulmonary aspergillosis 30 year old smoker with no immune defect April 2003

30. 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 ???? 200-1000 cases Incurable currently (require life-long treatment)

31. Invasive aspergillosis Chronic pulmonary aspergillosis Allergic aspergillosis ABPA Severe asthma association

32. ABPA Plug in airways Airway clear after removal

33. ABPA with airway obstruction Mild asthma with shortness of breath

34. Predicted numbers of ABPA patients in the UK Those at risk Adults with asthma = 4,100,000 on treatment Cystic fibrosis = 2,700 adults Prevalence rate in the UK ~ 1% of asthmatics= 41,000 patients ~15% adult CF patients= 405 patients

35. Invasive aspergillosis Chronic pulmonary aspergillosis Allergic aspergillosis ABPA Severe asthma association

36. Severe asthma with fungal sensitisation

37. Histamine House dust mite Cat Cladosporium Dog Grass Negative Control Aspergillus fumigatus Alternaria CandidaPenicillium

38. 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)

39. 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

40. Airborne fungal fragments Fungal fragment Diffusing allergen leeching out of fungus in contact with liquid

41. Hospital admission with asthmatic attacks and mould allergy AllergenAsthma, no admission (n=82) Asthma, 2+ admission (n=46) House dust mite56 % 67 % Grass pollen46 % 63 % Cat37 % 59 % Dog18 % 48 % Any non fungal allergen70% 74% O’Driscoll et al, BMC Pulm Med 2005;18:4

42. AllergenAsthma, no admission (n=82) Asthma, 2+ admission (n=46) Aspergillus 7 % 37 % Alternaria 5 % 26 % Cladosporium 1 % 41 % Penicillium 2 % 30 % Candida10 % 33 % Any fungal allergen16% 76% Hospital admission with asthmatic attacks and mould allergy O’Driscoll et al, BMC Pulm Med 2005;18:4

43. 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

44. Predicted numbers of severe asthmatics with fungal sensitisation in the UK Those at risk Adults with asthma = 4,100,000 on treatment Severe asthma = 5-21% Mould allergic= 35-50% Prevalence rate in the UK Lower number= 71,750 patients Upper number= 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)

45. 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