Support meeting for aspergillosis patients with Paul Bowyer, Senior Scientist on recent advances in research on susceptibility to Chronic Pulmonary Aspergillosis

1. Support Meeting for
Aspergillosis Patients
LED BY GRAHAM ATHERTON
SUPPORTED BY
GEORGINA POWELL, DEBBIE KENNEDY & DEBORAH HAWKER
NAC CENTRE MANAGER CHRIS HARRIS
ADVANCES IN THE GENETICS OF SUSCEPTIBILTY TO CHRONIC PULMONARY
ASPERGILLOSIS BY DR PAUL BOWYER, RESEARCH GROUP LEADER
NATIONAL ASPERGILLOSIS CENTRE
UHSM
MANCHESTER
Fungal Research Trust

2. Programme
 1pm Light lunch, Tea Coffee
 1.30pm Paul Bowyer: Current research at the National Aspergillosis
Centre
 2pm Physiotherapy: Nebulisers
 2.20pm Break: Social time, chat to staff
 2.40pm NAC service information: Chris Harris
 3pm Your requests for future meetings
 3.10pm Meet the Team: Questions & Answers with Prof Denning
 3.30pm Close

3. Aspergillus Research
– What's New?
Paul Bowyer
University of Manchester

4. How does the immune system stop fungal disease?
The innate immune response is a complex multicellular process.
Meet the cells....
IMMUNE CELL: ROLE:
DETECTS PATHOGENS,
SNEAKS OFF AND
PROGRAMS THE
IMMUNE RESPONSE
DENDRITIC CELL

5. IMMUNE CELL: ROLE:
STOPS AND APPREHENDS
KNOWN PATHOGENS
MACROPHAGE
IMMUNE CELL: ROLE:
BRUTALLY ATTACKS THINGS
NEUTROPHIL

6. How the immune system stops fungal disease:
MACROPHAGE
EPITHELIUM
DENDRITIC CELL

7. How the immune system stops fungal disease:
WHATS ALL THIS
'ERE THEN?
MACROPHAGE
EPITHELIUM
I SAY CHAPS! DENDRITIC CELL

8. How the immune system stops fungal disease:
OI! NOW THEN
OI!!
MACROPHAGE
OI!!!
EPITHELIUM
DENDRITIC CELL
NEUTROPHILS

9. Adaptive Immunity – changes may lead to allergy

10. We recently used transcriptomics to look at
dendritic cells from individuals with ABPA and
chronic aspergillosis

11. Every cell in the body has the same DNA...
But every cell is not the same – or we would all be blobs...

12. There are 25000 genes in each cell
– but different cells use different sets of genes
Active genes make RNA
The transcriptome is the RNA produced by the cell
and tells us everything that the cell is doing

13. Transcriptomics tells us which genes
are active, and when...for ALL genes in the cell.
£££££....

14. We took blood from individuals with ABPA, CPA, no disease or asthma
From this we grew dendritic cells
Then we split the cells into two groups
- one was allowed to grow normally, the other had Aspergillus added.
Then we made RNA and looked at the transcriptomes
When we compare the difference between healthy cells and ABPA or CPA cells
OR when we look at how the cells respond to fungus
We can see everything the cells are doing and what makes the difference in disease

15. Individuals with ABPA or CPA:
Do not produce enough C-lectin proteins
from their C-lectin genes.
C-lectins bind to and sense the fungal cell.
Without C-lectins the immune system
cannot see the fungus

16. In conclusion:
You can't fight what you can't see...
Funded by:
Mike Bromley
Nicola Smith
David Denning

18. Nebulisers – what we use and why
Philip Langridge
Specialist Physiotherapist Aspergillosis

19. Overview
– What is a nebuliser?
– What’s the difference between an inhaler and
a nebuliser?
– What medication goes into a nebuliser?
– What sorts are there/ how do they work?
– Cleaning/ maintainance

20. What is a nebuliser?
• A device that converts liquids into a fine mist that
can be inhaled and thus deposit in the lungs
• A source of compressed gas (air or oxygen)
drives the nebuliser
• Can have mouthpiece or facemask (or through a
ventilator)

21. Compressors
–• Use compressedair as the Econoneb
Use compressed air as the
driving gas, at 6-8L/min.
driving gas, at 6-8L/min.
How it works: compressor as
• Consider the
– Air is“pump” that the the
the drawn into drives
compressor.
nebuliser
– It is driven through a filter
. and through tubing to the
nebuliser chamber. Portaneb
– When it enters the nebuliser
chamber it converts the
liquid drug into a fine
breathable mist, which the
patient inhales.

22. What’s the difference between a nebuliser
and an inhaler?
– “Nebulisers are useful when large doses of
inhaled drugs are needed when patients are
too ill or otherwise unable to use handheld
inhalers and when drugs are not available in
that format for example antibiotics” (B T S
1997)
– Salbutamol inhaler – 100mcg per puff
– Salbutamol nebuliser solution – 2.5mg or 5
mg in 2.5ml solution

23. Nebulised Medication – some examples
• Bronchodilators: • Mucolytics:
–Salbutamol (2.5mg/5mg) –Hypertonic saline
–Atrovent (250mcg/500mcg) ( 7% / 6%)
–Bricanyl (5mg) –Normal saline (0.9%)
• Antibiotics:
• Steroids
–Colistin (Colomycin) –Pulmicort & Flixotide
–Tobramycin • Rarely used
–Meropenem
–Gentamicin
–Vancomycin
–Amikacin
• Antifungals
–Amphotericin B
(Fungizone)

24. What sorts are there/ how do they work?
– Simple jet nebulisers
E.g. Microneb III
– Breath assisted
E.g. Pari Sprint
– (Etc)

25. Drug Delivery

26. Size (of particle) matters!
• Humungous in size are filtered in nose
– 100 microns (1 micron = 0.001 millimeter )
• Large in throat
– 10 - 20 microns
• Medium in small airways
– 2 - 5 microns
• Small in alveoli
– 1 - 3 microns
– (NB Aspergillus spores are very very small - 2-3 microns )

27. Nebulisation Time- (tell me when it’s over)
Nebulisation to dryness is difficult to define.
This maybe the time the nebuliser ‘spits’
intermittently or when no further aerosol has
been emitted. It has been shown 80% of
nebuliser drug is delivered in the first five
minutes (O’Callaghan 1989)

28. Nebuliser performance – judges
opinion
• When drug is delivered during respiratory
cycle
• Particle size/ where you want the drug to
deposit
• Respirable fraction….the percentage of
respirable particles within the aerosol output
(should be at least 50%)
• Residual volume
– Amount that never gets nebulised and
delivered to the user

29. Nebuliser performance – public opinion
• Cost of compressor, nebuliser
• Servicing
• Weight/ portability
• Nebulisation time
• Bottom line – does it do
what you want it to do?
• (does it help you more
than it hinders you)

30. Cleaning Recommendations
– Follow manufacturers instructions
– Don’t let your rolling boil run dry in the pan!!!

31. Any Questions/ comments?

32. Healthcare at Home
• Introduction
Why
Selection process
Who they are
Why we use them
What's on offer and who qualifies

33. Why
• Homecare was set up in November 2011
– Improve patient choice
– Improve patient service
– Improve ease of care by reducing hospital visits
and waiting in pharmacy
• to save VAT on high cost drugs
– V- £30,000 per annum
– P – £40,000 per annum
– There is a delivery charge but it is affordable

34. vFend

35. Posaconazole

36. Selection process
The decision to go forward and use a homecare
service was explored and agreed
This then went out to tender whereby companies
were allowed to apply to the Trust to be
considered in the process
This process took several months before a
decision was made

37. Requirements for applications
9 companies were selected from this
process and were invited to interview
where they were required to demonstrate
the following:
• Ability to deliver the service
• Safety and reliability with proven track
record
• Qualified staff

38. The Company - Healthcare at Home
• Who are they?
Healthcare at Home are a company who can
provide the following:
– Delivery of drugs
– Nursing care
– IV nursing care

39. Why Healthcare at Home
They have a vast amount of experience in drug
delivery
They have a team of nurses available in most
areas up and down the company
They have a large team of people at their
headquarters who can work closely with our
team and monitor this process

40. What’s on offer
Delivery of high cost drugs direct to patients
homes – entirely optional and at your
convenience
This applies to Voriconazole
Posaconazole
Itraconazole solution
Delivery is made to all patients under the care of
NAC providing funding is in place for the drugs

41. Who qualifies
• Patients who are under the care of NAC
• Patients who are on high cost drugs which are
paid for by NCG or PCT
It makes no difference if you live local or distant
the delivery can still be made
Deliveries are usually every two months
dependant on your prescription

42. Advantages/disadvantages
• Advantages:
– Reduces the amount of visits for patients
– Reduces travel for patients who live a long way
– Removed problem of patients running out of
medication
– Patient choice
– VAT savings

43. • Disadvantages:
– Not experienced many at present
– Some patients feel they would rather attend clinic
– Weather may cause problems if very severe but
again not experienced this yet.

44. Points to remember
• Patients are still very much under our care
• Should contact us with any concerns at any
time
• May require postal bloods in between visits
• Still need to attend clinic
• Can always attend in the interim if problems
arise
• Can withdraw from home delivery at any time

45. Going forward
• Nursing care- will be discussed separately
• IV’s at home – under discussion

46. Future meetings
Format is for several smaller talks each month:
1 invited speaker (external or internal)
2 – 3 slots for one each of:
Physiotherapist
Service management
Nurses
Diagnostics
Patient involvement in Research
Patient involvement in promoting awareness
Your feedback
Meet the Team

47. Future Meetings
Revisiting earlier subjects
 Damp homes & avoiding mould
 Nutrition
 Antifungal management
 Diagnostic services (tour of department?)
 NHS funding
 Genetic susceptibility to aspergillosis
 Lung function
 Clinical Q & A
 Allergens
 Physio

48. What else?
Is there anything you would like to suggest as a
subject? – remember it can be any part of the service
and only has to be enough to fill 10-15min
Leave suggestions (& criticisms) using forms provided
– anonymously if you prefer.
or
Email to admin@aspergillus.org.uk
or
Phone 0161 291 5866 – leave message if no answer

49. Manchester Museum Science Festival
October 31st till November 5th 2012
WE will be hosting an exhibition on fungal disease
including LIFE art winners.

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

51. 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.

52. 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

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