“Allergic Bronchopulmonary Aspergilosis”
Tamsil Syafiuddinn
FK UISU-Medan
“ASPERGILLOSIS”
AN OVERVIEW
DIAGNOSIS AND CLASSIFICATION
Aspergillus Life-cycle
Spores inhaled Germination
Mass of hyphae Hyphal elongation
(plateau phase) and branching
[Link]
Immunosuppression and infection
• Inhalation of aspergillus spores is a
common daily occurrence. A healthy
immune system would normally remove
the spores and no symptoms or
infection would occur.
• In individuals whose immune system
may be suppressed either because of
illness eg AIDS, cancer patients or
drugs, spores may germinate and
resulting tissue or systemic aspergillus
invasion can result.
• Individuals with allergies such as
asthma, can also be vulnerable to
aspergillus disease.
CLASSIFICATION OF ASPERGILLOSIS
Invasive aspergillosis
• Acute (<1 month course)
Airways/nasal • Subacute/chronic necrotising (1-3 months)
exposure to
airborne Chronic aspergillosis (>3 months)
Aspergillus
• Chronic cavitary pulmonary
• Aspergilloma of lung
• Chronic fibrosing pulmonary
• Chronic invasive sinusitis
Persistence • Maxillary (sinus) aspergilloma
without disease
- colonisation
of the airways Allergic
or nose/sinuses • “Allergic bronchopulmonary (ABPA)”
• Extrinsic allergic (broncho)alveolitis (EAA)
• Asthma with fungal sensitisation
• Allergic Aspergillus sinusitis (eosinophilic
fungal rhinosinusitis)
Size of fungal disease problem globally
1. Invasive aspergillosis - ? 70,000 cases/year in EU, >5M at
risk; new problems COPD, ICU etc - ~50% mortality
2. Candidaemia in UK – 2,000 cases, rising, many more at risk,
~40% mortality
3. Cryptococcal meningitis - ~1M worldwide annually
4. Chronic pulmonary aspergillosis after TB – 1.1M cases
prevalence
5. Chronic pulmonary aspergillosis total - ~3M
6. Asthma 197M in adults, of which ~10-20% severe, UK and
USA have very high prevalence rates
7. Allergic bronchopulmonary aspergillosis in asthma -
~3M worldwide (2.1% of adults with asthma)
8. Severe asthma with fungal sensitisation - ~13M worldwide
(33% of 20% (severe only))
Where in the hospital does invasive
aspergillosis occur?
Cornillet et al, Clin Infect Dis 2006;43:577
Risk of acquisition (and pace of progression) Examples of at-risk patients and pace of progression
25%
20%
15%
10%
5%
Degree of immunocompromise
Interaction of Aspergillus with the host
A unique microbial-host interaction
Frequency of aspergillosis
“ABPA”
Frequency of aspergillosis
Acute IA
Severe asthma with
fungal sensitisation
Subacute IA Allergic sinusitis
Aspergilloma
Chronic pulmonary
Immune dysfunction Immune hyperactivity
.
After Casadevall & Pirofski, Infect Immun 1999;67:3703
Aspergillus, IPA and COPD
~ 22% of
Aspergillus in
COPD = invasive
aspergillosis
Guinea et al, Clin Microbiol Infect 2010;16:870
Invasive aspergillosis in COPD
Bulpa, Clin Infect Dis 2007;30:782
Risk factors for invasive aspergillosis in ICU
Meersseman, Clin Infect Dis 2007;45:205
ALLERGIC BRONCHOPULMONARY
ASPERGILLOSIS – Key diagnostic criteria
ABPA possible
• Asthma
ABPA possible
• Blood eosinophilia (>1,000 / cu mm)
ABPA probable
• History of pulmonary infiltrates
ABPA almost certain
• Central bronchiectasis
• Precipitins against A. fumigatus positive
If 3 tests +ve, then
• Aspergillus IgE antibody >2x asthma control ABPA very likely,
• Aspergillus IgG antibody >2x asthma control If all 4 +ve the
• Total serum IgE concentration, >1000 iu/mL diagnosis established
Rickett et al. Arch Intern Med 1983; 143: 1553; Patterson, Chest 2000;118:7
ABPA
After bronchoscopy
Before bronchoscopy
[Link]
ABPA - CT showing central bronchiectasis
[Link]
Stages of ABPA (not necessarily progressive)
Stage I = Acute flare
Infiltrates, markedly elev’d IgE
Stage II = Remisson
No infiltrates, off steroids > 6 mos, elev’d or NL IgE
Stage III = Recurrent exacerbations
Infiltrates, markedly elev’d IgE
Stage IV = Glucocorticoid-dependent asthma
Infiltrates present intermittently or not at all, elev’d or NL IgE
Stage V = Fibrotic (end stage) lung dz
Fibrotic, bullous, cavitary lung lesions, IgE may be normal
Tx - Goals
• 1) Early control of immunologic activity /
inflammation to try to prevent progression to
bronchiectasis and fibrosis
• 2) Monitoring for response and early
detection of relapses
• 3) ?? Dec fungal burden in airways
Tx - Steroids
Doses vary depending on stage and prescriber preference. Higher
dosages for longer durations may be more effective for tx’g flares.
Stages 1 & 3 – Prednisone 0.5-1.0 mg/kg Qday x 14 days, then QOD x 6-8
wks, then taper by 5-10 mg q 2 weeks until d/c’d
Should see resolution of infiltrates and 35-50% dec in serum total IgE (measured q1-2
months during acute treatment)
Stage 2 – Steroids not needed. Monitor IgE q6 months x 1 year then q 1-2
years. Doubling of baseline IgE indicates relapse (stage 3)
Stage 4 – Steroid dependent. Aim for lowest possible dose
Stage 5 – Steroids not helpful
Steroid “prophylaxis” – Ca, Vit D, bisphosphonate
Tx - Itraconazole
• Dec’s antigenic stimulus for bronchial
inflammation, possibly by dec;g specific
Aspergillus IgG
• Dec’d metabolism of steroids, so may be able
to use lower dosages
• 16 week course + steroids significant
increased likelihood of clinical response (46 vs
19%)
– 200 TID x 3 days, then 200 BID x 16 wks, +/- Qday
x 16 wks
Sitou Timou Tumou Tou
(Sam Ratulangi , 1890 -1949)
Conclusions and Sugestions
The spectrum of disease is broad and can be severe and
debilitating, requiring lung transplantation, however if
recognized early and managed aggressively, ABPA is
treatable can remit indefinitely and progressive lung
damage can be avoided.
Conclusions and Sugestions
Teaching Hospital must have “Lung Mycosis Institute”
Institutes are often physician-led and collaborative:
Care would also be more patient-centric, bridging the gap
between medical and procedural specialists, like a “lung
mycosis institute” with pulmologists ,thoracic surgeons,
radiologist, clinical pharmacologist, pathologist ,microbiologist
Institutes can leverage physician leadership to set minimum
standards for physician participation in the institute and can
establish incentives to standardize care across employed,
integrated, and loyal physicians.
