“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

www.aspergillus.man.ac.uk
 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

www.aspergillus.man.ac.uk
ABPA - CT showing central bronchiectasis

www.aspergillus.man.ac.uk
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.