Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre...
-
Upload
bryan-templeton -
Category
Documents
-
view
215 -
download
0
Transcript of Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre...
![Page 1: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/1.jpg)
Clinical and radiological presentation and diagnosis
David W. DenningNational Aspergillosis Centre
University Hospital South Manchester[Wythenshawe Hospital]University of Manchester
![Page 2: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/2.jpg)
The National Aspergillosis Centre
225-250 new patients with aspergillosis referred annually
![Page 3: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/3.jpg)
CLASSIFICATION OF ASPERGILLOSIS
Persistence without disease - colonisation of the airways or nose/sinuses
Airways/nasal exposure to airborne Aspergillus
Invasive aspergillosis• Acute (<1 month course)• Subacute/chronic necrotising (1-3 months)
Chronic aspergillosis (>3 months)• Chronic cavitary pulmonary• Aspergilloma of lung• Chronic fibrosing pulmonary• Chronic invasive sinusitis • Maxillary (sinus) aspergilloma
Allergic• Allergic bronchopulmonary (ABPA)• Extrinsic allergic (broncho)alveolitis (EAA)• Asthma with fungal sensitisation• Allergic Aspergillus sinusitis (eosinophilic fungal rhinosinusitis)
![Page 4: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/4.jpg)
Interaction of Aspergillus with the host
A unique microbial-host interaction
Immune dysfunction
Frequency
of a
sperg
illosis
Immune hyperactivity
Frequency
of
asp
erg
illosi
s
Acute IA
Subacute IA
AspergillomaChronic pulmonary
ABPASevere asthma with fungal sensitisation
Allergic sinusitis
. After Casadevall & Pirofski, Infect Immun 1999;67:3703
![Page 5: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/5.jpg)
Size of Aspergillus disease problem globally
1. Over 200,000 patients develop IA annually. Key groups include ~10% of acute leukaemia (30,000) and stem cell and other transplants (7,500) and 1.3% of COPD patients admitted to hospital (60,000 IA cases).
2. Chronic pulmonary aspergillosis after TB – 1.1M cases prevalence
3. Chronic pulmonary aspergillosis total - ~3M4. Asthma 197M in adults, of which ~10-20% severe,
UK and USA have very high prevalence rates
![Page 6: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/6.jpg)
How common is ABPA in asthma?
10/1390 (0.72%)
9/255 (3.5%)
6/264 (2.3%)
Donnelly, Irish J Med Sci 1991;160:288; Eaton, Chest 2000;118:66; Al-Mobeireek, Resp Med 2001;98:341
![Page 7: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/7.jpg)
Size of Aspergillus disease problem globally
1. Over 200,000 patients develop IA annually. Key groups include ~10% of acute leukaemia (30,000) and stem cell and other transplants (7,500) and 1.3% of COPD patients admitted to hospital (60,000 IA cases).
2. Chronic pulmonary aspergillosis after TB – 1.1M cases prevalence
3. Chronic pulmonary aspergillosis total - ~3M4. Asthma 197M in adults, of which ~10-20% severe,
UK and USA have very high prevalence rates5. Allergic bronchopulmonary aspergillosis in asthma -
~4M worldwide (2.1% of adults referred with asthma)
6. Severe asthma with fungal sensitisation - ~6M worldwide (33% of 10% (severe only))
![Page 8: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/8.jpg)
Interaction of Aspergillus with the host
A unique microbial-host interaction
Immune dysfunction
Frequency
of a
sperg
illosis
Immune hyperactivity
Frequency
of
asp
erg
illosi
s
Acute invasiveaspergillosis
Subacute invasiveaspergillosis
AspergillomaChronic pulmonaryaspergillosis
ABPASevere asthma with fungal sensitisationAllergic sinusitis
. After Casadevall & Pirofski, Infect Immun 1999;67:3703
Human genetic influence on disease
expression
![Page 9: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/9.jpg)
Chronic Pulmonary Aspergillosis
![Page 10: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/10.jpg)
Common symptomsCommon symptoms• Cough, usually productive• Shortness of breath• Weight loss• Tiredness• Coughing up blood• Chest ache / discomfort
Occasionally• Fever• Severe chest pain from rib fracture• Additional chest infections• Angina and heart attacks (chronic inflammation)
![Page 11: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/11.jpg)
Underlying diseases
Camuset et al, Chest 2007:131:1435
9 patients with chronic cavitary pulmonary aspergillosis15 with chronic necrotising pulmonary aspergillosis
![Page 12: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/12.jpg)
Underlying diseases - CPA
Smith, ISHAM 2009
• Classical tuberculosis *• Atypical tuberculosis *• Allergic bronchopulmonary aspergillosis *• Lung cancer survivor *• Pneumothorax *• COPD/emphysema *• Sarcoidosis (stage II/III) *• Rheumatoid arthritis• Thoracic surgery• Asthma• Chest radiotherapy• None
* Common
![Page 13: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/13.jpg)
Chronic pulmonary aspergillosis – pre-existing disease
Prior pulmonary disease esp:
Atypical mycobacteria pulmonary infection
Sarcoidosis
Tuberculosis
Recurrent pneumothorax
Prior pulmonary surgery
ABPA
Denning DW et al, Clin Infect Dis 2003; 37:S265
![Page 14: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/14.jpg)
Frequency of chronic pulmonary aspergillosis after TB
Anonymous. Tubercle 1970;51:227
~10% of all cases of pulmonary TB get CPA
![Page 15: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/15.jpg)
Acute tuberculosis
Lee, Eur J Radiol 2008; 67:100;
Before After treatment
Cavities
Cavities
Cavities
No cavities
![Page 16: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/16.jpg)
Chronic pulmonary aspergillosis
Single fungal ball or aspergillomain a pre-existing
cavity
Infection of the lung by Aspergillus
![Page 17: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/17.jpg)
Simple (single) aspergilloma
Patient RK
Haempotysis, nil else
Positive Aspergillus antibodies in blood
Lobectomy
Wythenshawe Hospital
![Page 18: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/18.jpg)
Aspergillomas from 2 patients
Wythenshawe Hospital; Severo on www.aspergillus.org.uk
![Page 19: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/19.jpg)
Histology of an aspergillomaHistology of an aspergilloma
Severo on www.aspergillus.man.ac.uk
![Page 20: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/20.jpg)
Aspergillus fumigatus
![Page 21: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/21.jpg)
Aspergilloma due to Aspergilloma due to A. nigerA. niger and oxalosis and oxalosis
Oxalate crystals in wall of the aspergilloma
Severo on www.aspergillus.man.ac.uk
Renal oxalosis
![Page 22: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/22.jpg)
Early Aspergillus infection of a pulmonary Early Aspergillus infection of a pulmonary cavity – ‘pre-aspergilloma’cavity – ‘pre-aspergilloma’
Aspergillus growth on the surface of a pulmonary cavity
Severo on www.aspergillus.man.ac.uk
Orderly hyphal growth on the inside of the cavity
![Page 23: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/23.jpg)
‘Multicavity’ disease is the
hallmark of chronic cavitary pulmonary
aspergillosis (CCPA)
Wythenshawe Hospital
![Page 24: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/24.jpg)
Aspergilloma #3 – spatially ordered isolates from multiple cavities
Bowyer et al, unpublished
![Page 25: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/25.jpg)
Aspergillus precipitins (Aspergillus antibody (IgG) ) in blood
Severo on www.aspergillus.org.uk
Patient 1blood
Patient 2blood
Patient 3blood
Patient 4blood
Patient 5blood
Patient 6blood
Aspergillus extract
![Page 26: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/26.jpg)
Aspergillus IgG serology
Baxter, AAA 2010;Abstr 51
![Page 27: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/27.jpg)
Chronic pulmonary aspergillosis - serology
All 18 patients had positive Aspergillus precipitins (1+-4+)
All 18 patients had elevated inflammatory markers, CRP, PV and / or ESR
May have elevated total IgE and Aspergillus specific IgE (RAST)
Only 40% have a positive sputum culture
Denning DW et al, Clin Infect Dis 2003; 37:S265
![Page 28: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/28.jpg)
Chronic pulmonary aspergillosis
Single fungal ball or aspergillomain a pre-existing
cavity
Infection of the lung by Aspergillus
Chronic cavitary
pulmonary aspergillosis+/- fungal
ball
![Page 29: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/29.jpg)
Chronic cavitary pulmonary aspergillosis – CT reconstruction
Wythenshawe Hospital
![Page 30: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/30.jpg)
Chronic cavitary pulmonary aspergillosis (CCPA) – sputum production
Wythenshawe Hospital
Aspergillus cultures positive in CCPA in 10-40% of cases only
![Page 31: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/31.jpg)
‘Multicavity’ disease is the hallmark of chronic cavitary pulmonary aspergillosis
(CCPA)
Wythenshawe Hospital
![Page 32: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/32.jpg)
Chronic cavitary pulmonary aspergillosis (CCPA) – haemoptysis
Wythenshawe Hospital
![Page 33: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/33.jpg)
Chronic Cavitary Pulmonary Aspergillosis
Normal 30 year female smoker
Patient JAJan 2001
![Page 34: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/34.jpg)
Chronic Cavitary Pulmonary Aspergillosis
Patient JAApril 2003
![Page 35: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/35.jpg)
Multifocal cavities with aspergillomas – unrecognised phenotype
Wythenshawe Hospital
![Page 36: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/36.jpg)
18F-FDG PET positive pulmonary nodules in aspergillosis – a differential diagnosis of lung
cancer
Baxter, Thorax 2011
10 patients
Presentations like lung cancer
1 subacute IPA1 ABPA1 aspergilloma7 CPA
Aspergillus IgG 28 ->200 mg/L
All positive on histology
![Page 37: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/37.jpg)
CLASSIFICATION OF ASPERGILLOSIS
Persistence without disease - colonisation of the airways or nose/sinuses
Airways/nasal exposure to airborne Aspergillus
Invasive aspergillosis• Acute (<1 month course)• Subacute/chronic necrotising (1-3 months)
Chronic aspergillosis (>3 months)• Chronic cavitary pulmonary• Aspergilloma of lung• Chronic fibrosing pulmonary• Chronic invasive sinusitis • Maxillary (sinus) aspergilloma
Allergic• Allergic bronchopulmonary (ABPA)• Extrinsic allergic (broncho)alveolitis (EAA)• Asthma with fungal sensitisation• Allergic Aspergillus sinusitis (eosinophilic fungal rhinosinusitis)
![Page 38: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/38.jpg)
Allergic Bronchopulmonary Aspergillosis
![Page 39: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/39.jpg)
ABPA – Diagnostic clues
• Asthma/CF not well controlled• History of ‘pneumonia’• History of coughing up plugs, or paroxysms of
coughing that clear when chest clears• Central bronchiectasis on CT scan, or mucoid
impaction• Eosinophilia
Rare cases in non-asthmatics, non-CF patients
![Page 40: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/40.jpg)
Asthma – variable airflow obstruction
Patient SY, Aspergillus Website
Inhaled steroids
![Page 41: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/41.jpg)
Proposed new criteria for ABPA
1. Serum IgE >1000 IU/mL2. Asthma OR CF 3. Airway obstruction (ie CT scan/bronchoscopy) by or production of mucus plugs containing hyphae
Which fungus?1. Fungal sensitisation (IgE or SPT) and/or fungus detected in respiratory secretions
Knutsen et al, AAAAI Task Force on Fungus and Asthma
![Page 42: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/42.jpg)
ABPA - March – doing well
FEV1 = 3.00
Aspergillus IgE = 31
IgE = 1900.
No treatment
![Page 43: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/43.jpg)
September – episode of pneumonia
FEV1 = 1.6.
IgE = 3000
Aspergillus IgE = 52.5.
Exacerbation of ABPA
![Page 44: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/44.jpg)
Exacerbation of ABPAPatient AL
www.aspergillus.org.uk
May 2010 January 2011 June 2011
![Page 45: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/45.jpg)
Exacerbation of ABPAPatient AL
www.aspergillus.org.uk
September 2011
![Page 46: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/46.jpg)
Mucoid impaction due to ABPA
www.aspergillus.org.uk
![Page 47: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/47.jpg)
Mucoid impaction due to ABPA
www.aspergillus.org.uk
![Page 48: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/48.jpg)
Sputum in ABPA
www.aspergillus.org.uk
![Page 49: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/49.jpg)
ABPA – bronchoscopy views showing mucous plugging
www.aspergillus.org.uk
![Page 50: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/50.jpg)
A. fumigatus in BAL and in bronchial tissue in ABPA
![Page 51: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/51.jpg)
Severe Asthma and Fungal Sensitisation
www.emphysema-copd.co.uk
![Page 52: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/52.jpg)
Fungal exposure in asthmatics is related to:
• Life-threatening asthmatic attacks (ie thunderstorm asthma)
• Severe asthma and hospital admission
• Increased wheezing and symptoms
• Loss of medication control
• Allergic bronchopulmonary mycosis
• Eosinophilic fungal rhinosinusitis
O'Hollaren, N Engl J Med 1991; 324: 359; and many others
![Page 53: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/53.jpg)
Green et al, J Allergy Clin Immunol 2005;115:1043
Airborne fungal fragments
Fungal fragment
Diffusing allergen leeching out of fungus in contact with liquid
![Page 54: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/54.jpg)
Bowyer et al, BMC Genomics 2006;7:251
Genomic analysis of allergens
![Page 55: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/55.jpg)
Severe asthma and mould senstivity –
Alternaria and Cladosporium
Mild asthma – 564 (50%)
Moderate asthma – 333 (29%)
Severe asthma – 235 (21%)
Zureik et al, Br Med J 2002;325:411
![Page 56: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/56.jpg)
0.0
2.5
5.0
7.5
10.0
12.5
15.0
17.5
20.0M
ea
n s
en
siti
zati
on
sc
ore
(m
m)
(Mea
n a
nd
95
% C
I)
Non-Mould allergens
NoHospitalAdmission
SingleAdmission
MultipleAdmissions
O’Driscoll et al, BMC Pulmonary Medicine 2005;5:4
Mould allergens
NoHospitalAdmission
SingleAdmission
MultipleAdmissions
P= <0.0001
![Page 57: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/57.jpg)
Colonisation in ‘normal’ lungs
Lass-Florl et al, Br J Haematol 1999;104:745
22 of 30 (73%) grew a fungus in both lung
samples taken
10/30 (33%) grew >1 species
![Page 58: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/58.jpg)
Asthma and Aspergillus
Fairs et al, Am J Respir Crit Care Med 2010; July 16
79 adult asthmatics and 14 controls
Patients sensitised to A. fumigatus compared with non-sensitised asthmatics had:lower lung function (% pred. FEV1 68% vs 88% p < 0.05), more bronchiectasis (68% versus 35% p < 0.05) and more sputum neutrophils (80.9% vs 49.5% p < 0.01).
![Page 59: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/59.jpg)
Severe asthma and aspergillosis in ICU
57 of 357 (16%) admitted ICU with acute asthma
Compared with 755 outpatients with asthma
Aspergillus skin prick test used to screen for aspergillus hypersensitivity, if positive IgE etc for ABPA checked
Aspergillus positive ABPA
Asthma in ICU 29/57 (51%) 22/57 (39%)
Outpatient asthma 90/755 (39%) 155/755 (21%)
P value 0.010.001
Agarwal et al, Mycoses 2009 Jan 24th
![Page 60: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/60.jpg)
Severe asthma with invasive aspergillosis
Felton et al Chest 2010;137:724
![Page 61: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/61.jpg)
Severe asthma with fungal sensitisation (SAFS)
Denning et al, Eur Resp J 2006; 27;27:615
Criteria for diagnosis• Severe asthma (BTS step 4 or 5)
AND• RAST (IgE) positive for any fungus
OR• Skin prick test positive for any fungus
AND• Exclude ABPA (ie total IgE <1,000 iu/mL)
![Page 62: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/62.jpg)
Comparison of ABPA and SAFS serology
ABPA results normal range date 1 date 2
SAFS results
Patient1
2
![Page 63: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/63.jpg)
O’Driscoll, unpublished
Skin prick testing – example of SAFS result
Cladosporium +ve
![Page 64: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/64.jpg)
Fungal sensitisation in severe asthma – skin prick test or RAST for
diagnosis?N= 121 patients screened
O’Driscoll et al, Clin Exp Allergy. In press
SPT + RAST both positive
100%
50%
4310 13
34
SPT positiveRAST negative
SPT negativeRAST positive
SPT negativeRAST negative
}>23%
discordant results
![Page 65: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/65.jpg)
Fungal sensitisation in severe asthma – number sensitised to one or more
fungi
O’Driscoll et al, Clin Exp Allergy. In press
1 2 3 4 5 6 7
N = 40
N = 20
29 11 11 123
77
Sensitisation to one or more fungi
13 sensitised to only Aspergillus 8 to Candida 3 to Trichophyton 3 to Penicillium 1 to Alternaria 1 to Cladosporium
![Page 66: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/66.jpg)
Distinguishing different forms of aspergillosisDisease group
CCPA ABPA + CCPA ABPA SAFS SAFS
n 116 16 98 52 52
Median serum IgE level (IQR)
99.8 (26.4-350)
(n=107)
2739(1100-7500)
(n=16)
2300(1100-4550)
(n=97)
370(140-750)
(n=52)
Aspergillus specific IgG
93.6% (103/110)
81.3% (13/16) 65.4% (53/81) 35.9% (14/39)
Positive fungal culture
25% (29/116) 25.0% (4/16) 23.5% (23/98) 21.2% (11/52)
Positive specific IgE
Positive SPT
Mixed mould N/T N/T 88.9% (8/9) 90.9% (20/30) 100% (2/2)
A. fumigatus 37.7% (40/106)
93.8% (15/16) 96.9% (94/97) 78.8% (41/52) 90.9% (20/30)
Alternaria alternata
10.0% (1/10) 100% (10/10) 77.5% (55/71) 32.5% (13/40) 47.4% (9/19)
C. albicans 33.3% (3/9) 90.0% (9/10) 81.4% (57/70) 37.5% (15/25) 52.6% (10/19)
Cladosporium herbarum
20.0% (2/10) 80.0% (8/10) 70.4% (50/71) 24.4% (10/41) 35.5% (6/17)
Penicillium chrysogenum
27.3% (3/11) 100% (10/10) 85.3% (58/68) 30.0% (12/40) 43.8% (7/16)
Trichophyton mentagrophyt
e
33.3% (2/6) 100% (3/3) 65.2% (30/46) 25.0% (9/36) 23.1% (3/13)
![Page 67: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/67.jpg)
Disease group
CCPA ABPA + CCPA ABPA SAFS SAFS
n 116 16 98 52 52
Median serum IgE level (IQR)
99.8 (26.4-350)
(n=107)
2739(1100-7500)
(n=16)
2300(1100-4550)
(n=97)
370(140-750)
(n=52)
Aspergillus specific IgG
93.6% (103/110)
81.3% (13/16) 65.4% (53/81) 35.9% (14/39)
Positive fungal culture
25% (29/116) 25.0% (4/16) 23.5% (23/98) 21.2% (11/52)
Positive specific IgE
Positive SPT
Mixed mould N/T N/T 88.9% (8/9) 90.9% (20/30) 100% (2/2)
A. fumigatus 37.7% (40/106)
93.8% (15/16) 96.9% (94/97) 78.8% (41/52) 90.9% (20/30)
Alternaria alternata
10.0% (1/10) 100% (10/10) 77.5% (55/71) 32.5% (13/40) 47.4% (9/19)
C. albicans 33.3% (3/9) 90.0% (9/10) 81.4% (57/70) 37.5% (15/25) 52.6% (10/19)
Cladosporium herbarum
20.0% (2/10) 80.0% (8/10) 70.4% (50/71) 24.4% (10/41) 35.5% (6/17)
Penicillium chrysogenum
27.3% (3/11) 100% (10/10) 85.3% (58/68) 30.0% (12/40) 43.8% (7/16)
Trichophyton mentagrophyt
e
33.3% (2/6) 100% (3/3) 65.2% (30/46) 25.0% (9/36) 23.1% (3/13)
Distinguishing different forms of aspergillosis
![Page 68: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/68.jpg)
Conceptual framework for CPA and Conceptual framework for CPA and IAIA
www.aspergillus.org.uk
Aspergilloma - CCPA - CNPA/subacute IPA - acute IPA
Imm
une
func
tion
Hyphal load in tissue
Normal
Massive
Vascular invasion, necrosis,
disseminationGranulomas, acute
inflammation, central necrosis
Chronic inflammation and fibrosis
![Page 69: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/69.jpg)
Alternative Aspergillus diagnoses
• Aspergillus bronchitis• Obstructing bronchial aspergillosis• Invasive Aspergillus tracheobronchitis• Community acquired Aspergillus pneumonia• Sub-acute invasive pulmonary aspergillosis
(often called chronic necrotising pulmonary aspergillosis or CNPA)
• Extrinsic allergic (bronchiol)alveolitis (EAA)• Aspergillus empyema
![Page 70: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/70.jpg)
Arendrup, Scand J Infect Dis 2006:38:945
6th Jan 24th Feb
![Page 71: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/71.jpg)
Obstructing bronchial aspergillosis
Patient ML Pre-bronchscopy
Denning et al, New Engl J Med 1991;324: 654
Patient ML After bronchoscopy
![Page 72: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/72.jpg)
Subacute invasive pulmonary aspergillosis in AIDS
Patient HB Day +14, CD4 cells 84/uL
Biopsy positive for Aspergillus
Sambatakou, Eur J Clin Microbiol Infect Dis 2005;24:628
![Page 73: Clinical and radiological presentation and diagnosis David W. Denning National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital]](https://reader036.fdocuments.in/reader036/viewer/2022062511/5515c3be55034693758b476d/html5/thumbnails/73.jpg)
Conclusions
• CPA = 3 months of pulmonary cavitation or nodule +/- aspergilloma, with symptoms + Aspergillus IgG or precipitins positive
• CPA patients almost all have an underlying diagnosis
• ABPA = asthma (any severity) or cystic fibrosis + total IgE >1,000 + SPT or Aspergillus IgE positive.
• SAFS = severe asthma + fungal SPT or IgE positive + total IgE <1,000
• Some patients have overlap syndromes and more than 1 Aspergillus diagnosis