1. Support Meeting for
Aspergillosis Patients
LED BY GRAHAM ATHERTON
SUPPORTED BY
MARIE KIRWAN, GEORGINA POWELL & DEBBIE KENNEDY
NAC CENTRE MANAGER CHRIS HARRIS
ADVANCES FOR THE PREVENTION, DETECTION & TREATMENT OF ASPERGILLOSIS:
GRAHAM ATHERTON
NATIONAL ASPERGILLOSIS CENTRE
UHSM
MANCHESTER
Fungal Research Trust

2. Programme
 1pm Introduction
 1:05 Graham Atherton
 2:00 Tea & Coffee
 2.10 FRT becomes FIT
 2.30 New meeting location & format
 3:00 Close

3. Latest Advances- Aspergillosis
By Graham Atherton

4. Prevention
Identifying vulnerable people (Paul Bowyers Work)
Cleaning damp homes
Preventing contact with strain of aspergillus that are
already resistant to azole antifungals
(multidisciplinary) due to agricultural use.

5. Identifying the vulnerable
20 years ago researcher worked on one or two genes
at a time

6. Results (gene switched on)

7. Protein switched on

8. Time
1-2 genes – 3 years!!
Slow
Few genes tested
Results are isolated – we can’t see how other genes
are acting

9. Gene interaction - complexity
 One
pathway
 8 Genes
(proteins)
 Change in
one gene
affects all
others

11. How do we look at WHOLE picture?
Microchip
arrays
4000 genes
tested (10 000
in human
genome)

12. New technology
Thousands of genes tested
• Microchip arrays
• Genome sequencing – now very cheap and within a
short time will be available to everyone (Host
sequence)
• Has already been carried out on many Aspergillus
strains from clinic
LOTS OF INFORMATION!

14. Our Research (Paul Bowyer)
Carried out with your help!
Identifying
•How fungus fights antifungal drugs (so we can beat it)
•What makes people vulnerable to infection & allergy
We have detected several (>20-30?)genes that may be
important in all of these processes. Will now look at
how these change in vulnerable people.
Time needed to do all of this? – 12 months

15. Cleaning up damp homes
Damp homes are clearly bad for health – for our
patients even more so
‘Green’ groups push for houses that are sealed and
allow no fresh air in = damp
Just launched a big push to redress the balance with
a construction industry education program run by
ISSE (www.isse.org.uk)

16. Damp homes
Working on help & advice for
homeowners/landlords
 Reliable signs of the presence of mould & damp that indicate
problems for homeowner
 Work to establish guidelines for GP to recognise health
problems caused by damp homes

17. Resistant Aspergillus in the Environment
It has been discovered that there are many strains of
Aspergillus (including fumigatus) that are already
resistant to some antifungal drugs.
There are versions of azole antifungals used as
pesticides – work is underway internationally to
limit their use

18. Diagnosis
Existing techniques tend to be slow, both at identifying
species and testing it for resistance to antifungal drugs
•Genomics – Paul Bowyer’s work on discovering what
genes are important for resistance/infection/allergy
•Personalised medicine
•Computer programs (algorithms) to distinguish
invasive from colonised

19. Treatment
• New drugs
• Better use if drugs – personalising medicine
• Genotyping – cheap & available
• New types of delivery – Nanotechnology
• Vaccines
• New lungs??
– Advances in transplant
– Growing new lungs!!

20. New drugs
• Antifungals –
– micafungin (echinocandin IV – isolated from another fungus
(Coleophorma))
– Anidulafungin (echinocandin)
Both useful additions as they work differently to azoles.
But what else??

21. Future drugs
F2G (Manchester) have just received $30 million
funding for their new drug targets – several new
possible drugs, new targets, new mechanisms.
10 – 15 years away.

22. Future antifungal therapies
Vaccines. Recent papers have been published (by
our close colleagues in California - David Stevens)
showing that vaccines made from yeast work very
well to prevent Aspergillus infection in mice.
Immunity boosting. Antibody therapy for those
unable to produce their own
Nanotechnology

23. Nanotechnology
• A completely new way to get drugs into human tissue via
penetrating skin. Up until now we have had to use
solvents – these tend to be toxic, limiting use.
• We can now enclose drugs in extremely small
nanoparticles which can pass through cells & skin (and
importantly mucus) with no further help – already being
done for amphotericin B, silver & others (new lease of life
for older more toxic antifungals)
• Already used as a cream for nail infection but being
tested on CF patients to eradicate bacterial and fungal
lung colonisation with some success – improves
antifungal activity.
• Possible to target specific organs!

24. Nanoparticles
These are up to 250 times smaller than width of human hair

25. Nanoparticles
Next step could be to try similar on deeper
infections: ABPA, SAFS, CPA and so on

26. New lungs – is it possible?

27. Lung – highly complex
Blood vessels
Airways
Dozens of different cell types
Highly organised – absolutely no good if we get it
slightly wrong
How can we possibly replicate that structure

28. Stem cells
We are made up of billions of individual cells but we
all started off as a single cell – the fertilised egg.
We now know that a small number of highly
specialised cells are the seeds for entire organs once
developmental growth has completed in the womb –
these are referred to as stem cells

29. Current Research
Stem cells are extremely hard to find and very rare –
only recently has this been possible (2011)
Lung cell research – Boston University Center for
Regenerative Medicine
June 2012 report
http://www.bu.edu/today/2012/from-stem-cells-to-
lung-cells/

30. From stem cells to lung cells - 1
Stem cell will grow and divide to reproduce itself just
as any other cell will – until it is given the signal to
start producing lung tissue
Boston Team created a stem cell that glowed green
once it has been activated to produce lung tissue

31. From stem cells to lung cells - 2
Take mouse lungs and remove all cells to leave a
bare ‘scaffold’
Add lung stem cells, activate and grow

32. From stem cells to lung cells – 3
Does it function as a lung?
Rat lung grown for 1 week
Transplanted into a rat where it worked for 2 hours!
Structurally these are real, working lungs

33. Repairing lung – stem cells
Repairing lung tissue (alveoli) damaged by ‘flu
virus

34. Repairing lung – reconditioning
4 out of 5 lungs received for transplant are of
insufficient condition to use as much damage is
often done prior to removal
Newcastle University Hospital (2012) are
developing a way to ‘recondition’ unsuitable lungs
by keeping them functioning ‘ex vivo’ for several
days after donation, treating them with antibiotics
(antifungals?)
Lungs become usable!!

35. The future for stem cells
Human research?
Intriguingly research shows stem cells repairing
lungs as a completely natural process after damage
(small structures) – perhaps we can harness this?
Boost it by adding new stem cells or stimulating
those already there?
Host of possibilities!

36. Summing up
Modern genetic research progresses much faster
than 20 years ago
Tools are now much more powerful
Stem cell & genomics research is in its infancy –
imagine where we will be in 10 - 20 years time??
Rate limiting factor – availability of patient data &
individuals prepared to help e.g. before the NAC it
would have been very difficult to collect data on as
many CPA patients as we can now.

37. Patient Information – future improvements
NHS IT records database – should include every
record of every patient & will allow researchers to
browse cases & collect research information very
efficiently – to come in 2015
Cost, privacy worries & politics may prevent this
happening or reduce its impact – another moral
dilemma.

38. Changes at FRT
Fungal Research Trust
=
Fungal Infection Trust

39. FRT is changing its name to FIT
Why?
•FIT will continue to fund research exactly as FRT was
always very successful at doing
•FIT will also carry out a number of projects abroad to
attempt to reach the many millions of infected people
in countries like Africa & India via their governments.
This is subject to quite separate funding from
different sources.
•Every £ raised for research in the UK for FIT will still
go towards the same research funded by FRT.

40. When will FIT start?
Within weeks FIT will become active and NEW
initiatives will be carried out under that new name
From January 2013 FRT will have effectively
transferred completely to FIT

41. Student competitions
Aim: Building awareness amongst younger people & parents
 UPDATE: 3-400 entries – Has now been judged and winners chosen
Winners will be announced at the Manchester Science Festival, where
we will also hold a 4 day education and awareness exhibition using the
winning images to help illustrate various types of fungal infection
www.manchestersciencefestival.com/

42. Annual Survey of Patients
105 patients asked
10% had been to a Support Meeting
9% viewed online
26% viewed recordings
47% do not use Aspergillus Website
Approximately 50% do not use the internet
WE NEED TO SUPPORT THOSE PEOPLE NOT
USING INTERNET BETTER

43. Annual Survey of Patients
Why don’t you attend the Aspergillosis Support Meeting?

44. Time and Place
Most attend clinic on Friday
Closer to Clinic the better
Meeting now to be held in Friday afternoons at 1.30pm
Hope to move the meeting to a room in the North
West Lung Centre
Provide tea & coffee (possibly even sandwiches) from
1pm – there is a small socialising area

45. Format & content
Numbers attending smaller
Some comments that content is less relevant to all
and a return to talks on aspergillosis would be
welcome
Suggestions:
More involvement from centre staff
More, shorter sessions in specific areas every month

46. Format changes – 20 min sessions

47. Other suggestions
Doctor present for 20 min at every meeting
We have a session held by a patient – once per
month (volunteers?)
Your choice of subject
Patient leader(s)
Comment sheet to be available at each meeting for
anonymous constructive criticism

48. New Patient Meeting
First new meeting is on the third Friday of October –
the 19th
It will take place in the Altounyan Suite, a short walk
from the Chest clinic

49. Altounyan Suite
NO access from outside ONLY via Chest Clinic

50. Directions to Altounyan
• From main entrance: follow hospital corridor and turn
into Chest Clinic corridor. Through double doors and
reception is in front of you. *Altounyan Suite is
signposted from here.
• Pass reception on the right and continue down corridor
passing Lung Function room on the left and go through
double doors at the end.
• There is another set of double doors in front of you which
is locked. Push intercom button and ask for access.
• Carry straight on following signs, though the door in
front of you passing the stairwell on your right. Go
through final single door and enter the small atrium.
• The Altounyan suite is the room on your right.

51. Thank You
“The best chance we have of beating this illness is to
work together”
Living with it, Working with it, Treating it
Fungal Research Trust