LED BY GRAHAM ATHERTON SUPPORTED BY NAC CENTRE MANAGER CHRIS HARRIS CPA AND THE USE OF ITRACONAZOLE DAVID DENNING- DIRECTOR OF THE NATIONAL ASPERGILLOSIS CENTRE NATIONAL ASPERGILLOSIS CENTRE UHSM MANCHESTER Support Meeting for Aspergillosis Patients & Carers Fungal Research Trust
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Management of Chronic Pulmonary Aspergillosis and IgE for the Layperson
Professor Denning summarises how we manage CPA at the National Aspergillosis Centre, what we have learned, what we are still learning. Graham Atherton describes IgE and how it affects Aspergillosis
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LED BY GRAHAM ATHERTONSUPPORTED BY
NAC CENTRE MANAGER CHRIS HARRIS
CPA AND THE USE OF ITRACONAZOLEDAVID DENNING- DIRECTOR OF THE NATIONAL ASPERGILLOSIS
CENTRE
NATIONAL ASPERGILLOSIS CENTREUHSM
MANCHESTER
Support Meeting for Aspergillosis Patients &
Carers
Fungal Research Trust
Programme
1.30 David Denning – NAC Director 2.00 Graham Atherton – Your subject (IgE) 2.30 Patients Discussion (Break) 3.00 Group discussion/Requests for information
Genomics Research – the first major breakthroughs Manchester Fungal Infection Group (MFIG) Patients survey
3.20 Q & A from the floor or online
Treating chronic pulmonary aspergillosis – how do assess
response and what confuses us
David W. DenningNational Aspergillosis Centre, University Hospital of South
ManchesterThe University of Manchester
Different patterns of CPA
Radiological response varies by subtype of CPA
Chronic cavitary pulmonary aspergillosis
National Aspergillosis Centre
Chronic fibrosing pulmonary aspergillosis
Different patterns of CPA
Aspergillus nodule Simple aspergilloma
Simple (single) aspergilloma
Patient RK
Haempotysis, nil else
Positive Aspergillus antibodies in blood
Lobectomy and cured
Howard et al. Mycoses 2013;56:434
Aspergillus nodule
Patient BJ
Incidental discovery, thought to be carcinoma
Positive Aspergillus antibodies in blood
Biopsy showed Aspergillus
Treated with itraconazole
Farid et al, J Cardiothorac Surg 2013;8:180
Objectives of antifungal therapy
Very ill patients:Save their lives with (usually) IV and then oral therapy
Quite ill patients:Improve quality of life by minimising symptomsPrevent further haemoptysis (coughing blood)Stop progression of scarring in the lungPrevent the emergence of antifungal resistanceAvoid antifungal toxicity
Patients with few symptomsStop progression of scarring in the lungPrevent the emergence of antifungal resistanceAvoid antifungal toxicity
Randomised controlled open comparison of micafungin and voriconazole for chronic
pulmonary aspergillosis
Kohno et al. J Infect Dis 2010;61:410
Micafungin 150-300mg/d versus voriconazole 12 ➞ 8mg/Kg/d107 patients with CPA 2-4 weeks treatment
Felton, Clin Infect Dis 2010; 51:1383.
CPA and voriconazole Rx
Camuset et al, Chest 2007:131:1435
9 patients with chronic cavitary pulmonary aspergillosis15 with chronic necrotising pulmonary aspergillosis
13/24 (54%) primary therapy with voriconazole3 intolerant of voriconazoleMedian duration of Rx 6.4 mos (4-36)
Time to initial response with posaconazole therapy
6 months 12 months
Mean
95% confidence interval
Felton et al. Clin Infect Dis 2010; 51:1383
Oral itraconazole
35%
41%Stable
Improved Standard care No antifungal
23%
7%
29%
64%Deterioration
Impact of oral itraconazole therapy for chronic pulmonary aspergillosis after TB over 6 months
Agarwal R, et al, Mycoses. 2013 Mar 18. doi: 10.1111/myc.12075.
Chronic pulmonary aspergillosis – quality of life improvement to azole therapy using SGRQ over 12 months
Al-shair et al, Clin Infect Dis 2013, Online
All patients
n= 71 66 36
Posaconazole Voriconazole Itraconazole
n= 25 23 7 n= 24 24 15n= 19 16 12
ImprovedStableDeteriorated
Progression of CCPA
1992 1994 on no Rx 1997 still on no Rx
April 2003, untreated
July 2001, untreated
Chronic cavitary pulmonary aspergillosis transforming to fibrosing
aspergillosis
Patient JP, June 1999
Denning DW et al, Clin Infect Dis 2003; 37(Suppl 3):S265-80
CPA treatment - principles• Important defects in innate immunity so long term (i.e. life-long) antifungal treatment, if possible• Some patients appear not to progress, but should to be kept under observation, as progression may be subclinical• Minimise other causes of lung infection with immunisation and antibiotics
• Itraconazole, voriconazole and posaconazole all effective, but adverse events – check levels
• Amphotericin B and micafungin IV useful for failure of oral azole therapy
Scientists are reporting a significant milestone for cancer research after charting 21 major mutations behind the vast majority of tumours.
The disruptive changes to the genetic code, account for 97% of the 30 most common cancers.
Finding out what causes the mutations could lead to new treatments. Some, such as smoking are known, but more than half are still a mystery.
Consequences
Genomic sequencing of a person or family could tell us a lot about what their risk of which cancers is, what caused it and what we should do about it!
The same will be possible for aspergillosis – we just need a bit more time!
Manchester Fungal Infection Group (MFIG)
The University of Manchester has invested in building a world-leading research group to tackle a problem that is largely unrecognised yet affects millions of people each year.
Globally and annually, over 300 million people suffer from serious fungal infections, resulting in 1,350,000 deaths – many of which are unavoidable.
Most serious fungal infections are hidden, occurring as a consequence of other health problems such as asthma, AIDS, cancer or organ transplants. Delays or missed diagnosis often lead to death, serious chronic illness or blindness.
Manchester Fungal Infection Group (MFIG)
Now, the newly formed multidisciplinary Manchester Fungal Infection Group (MFIG) hopes to make a difference with the recruitment of three leading experts from Edinburgh and London.
Professor Nick Read has moved from Edinburgh University and leads the group, while Dr Elaine Bignell from Imperial College, London, has been appointed as a Reader, and Dr Mike Bromley as a lecturer. Manchester senior lecturers, Dr Paul Bowyer and Peter Warn will also join the MFIG and will work alongside the already thriving research and teaching teams of Professors David Denning and Malcolm Richardson, and Dr Riina Richardson, to form this pioneering Group.
Suggest a subject
Can be on any relevant subject you would like to hear our opinion or get our help with
Send suggestions to [email protected] notes to me at clinic or at the meetingPhone them in (24 hrs) at 0161 291 5866
Subjects
Mike Leach is there a half life to the aspergillus. if the anti fungal is working should there be a patterned reduction in IgE
Does aspergillus have a halflife?
Mike Leach is there a half life to the aspergillus? If the
anti fungal is working should there be a patterned reduction in IgE
I will assume Mike is talking about ABPA
Immune system
Our immune system has many parts that can correspond to several different waves of attack against infection Physical barriers (skin, mucus) Immediate non-specific (no memory) Adaptive (specific – provides immunity)