ABPA
ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS
Dr.Veerendra SinghMD (Medicine)Fellow UPDA
Allergic Bronchopulmonary Aspergillosis: An Unusual Complication
of Bronchial AsthmaPages with reference to book, From329To331S.
Fayyaz Hussain, Javaid A. Khan(Department of Medicine, The Aga Khan
University Hospital, Karachi.)M. Ata Khan(Department of Medicine,
The Aga Khan University Hospital. Karachi.)
Case 1.A 19 year old male, asthmatic from childhood. developed
fever, cough, hemoptysis and pulmonary infiltrate in 1987. He was
treated for TB for nine months. In 1992, he again presented with
fever, anorexia, cough, hemoptysis S. Fayyaz Hussain, Javaid A.
Khan(Department of Medicine, The Aga Khan University Hospital,
Karachi.)M. Ata Khan(Department of Medicine, The Aga Khan
University Hospital. Karachi.)
Sputum was negative for AFB but on clinical suspicion, he was
restarted on quadruple anti-TB therapy in adequate doses. In
addition, he continued to receive bronchodilators, inhaled steroids
and intermittent courses of oral prednisolone.
Six months later, while still on anti-TB drugs, he developed
recurrence of symptoms with right pleuritic chest pain, fever,
cough, wheeze and hemoptysis. Repeat chest x-ray showed infiltrates
in right lung (Figure ib).S. Fayyaz Hussain, Javaid A.
Khan(Department of Medicine, The Aga Khan University Hospital,
Karachi.)M. Ata Khan(Department of Medicine, The Aga Khan
University Hospital. Karachi.)
S. Fayyaz Hussain, Javaid A. Khan(Department of Medicine, The
Aga Khan University Hospital, Karachi.)M. Ata Khan(Department of
Medicine, The Aga Khan University Hospital. Karachi.)
Sputum for AFB was negative. He had eosinophilia of 12% (WBC
count 12600/dI) and 2grossly elevated serum IgE (>1000 iu/ml).
Aspergillus antibodies were negative.
Diagnosis of ABPA was made and prednisolone 30 mg daily was
started. This resulted in rapid resolution of clinical and
radiological features. Patient remains well on maintenance
prednisolone at a dose of 7.5 mg daily.S. Fayyaz Hussain, Javaid A.
Khan(Department of Medicine, The Aga Khan University Hospital,
Karachi.)M. Ata Khan(Department of Medicine, The Aga Khan
University Hospital. Karachi.)
Case 2:A 24 year old male, asthmatic for four years, presented
with high grade fever, cough with purulent sputum and right sided
chest pain. He had two similar episodes during the last one year.
Bilateral widespread rhonchi and crepitation were found on chest
examination. Chest x-ray showed bilateral interstitial infiltrates
and bronchiectatic changes. White cell count was 12700/dl with 33%
eosinophils. Sputum for AFB were negative. Serum IgE was elevated
above 1700 lU/mi.
S. Fayyaz Hussain, Javaid A. Khan(Department of Medicine, The
Aga Khan University Hospital, Karachi.)M. Ata Khan(Department of
Medicine, The Aga Khan University Hospital. Karachi.)
S. Fayyaz Hussain, Javaid A. Khan(Department of Medicine, The
Aga Khan University Hospital, Karachi.)M. Ata Khan(Department of
Medicine, The Aga Khan University Hospital. Karachi.)Diagnosis of
ABPA was made and prednisolone 1mg/kg/day was started. Patient
improved
Allergic Bronchopulmonary Aspergillosis: An Unusual Complication
of Bronchial AsthmaPages with reference to book, From329To331S.
Fayyaz Hussain, Javaid A. Khan(Department of Medicine, The Aga Khan
University Hospital, Karachi.)M. Ata Khan(Department of Medicine,
The Aga Khan University Hospital. Karachi.)
The clinical features of ABPA (cough, fever, hemoptysis and lung
infiltrates) are usually mistaken for pulmonary tuberculosis
Chest.2006;130(2):442-448. doi:10.1378/chest.130.2.442 Allergic
Bronchopulmonary Aspergillosis*:Lessons From 126 Patients Attending
a Chest Clinic in North India.Ritesh Agarwal, MD, DM, FCCP; Dheeraj
Gupta, MD, DM, FCCP; Ashutosh N. Aggarwal, MD, DM; Digamber Behera,
MD, FCCP; Surinder K. Jindal, MD, FCCPFive hundred sixty-four
patients were screened using an Aspergillus skin test; 223 patients
(39.5%) were found to be positive, and ABPA was diagnosed in 126
patients (27.2%). There were 34 patients (27%) with ABPA-S, 42
patients with ABPA-CB, and 50 patients with ABPA-CB-ORF. Fifty-nine
patients (46.8%) had received antitubercular therapy in the past.
The vast majority of patients had bronchiectasis at presentation to
our hospital. High-attenuation mucous impaction was noted in 21
patients (16.7%). There was no significant difference between the
stages of ABPA and the duration of illness, the severity of asthma,
and the serologic findings (ie, absolute eosinophil count, IgE
levels [total] and IgE levels [forAspergillus fumigatus]).
Conclusions:There is a high prevalence of ABPA in asthmatic
patients presenting at our hospital. The disease entity is still
underrecognized in India; the vast majority of patients have
bronchiectasis at presentation, and almost half are initially
misdiagnosed as having pulmonary tuberculosis. There is a need to
redefine the definitions of ABPA and the optimal dose/duration of
glucocorticoid therapy. This study reinforces the need for the
routine screening of asthmatic patients with an Aspergillus skin
test.
Fifty-nine patients (46.8%) had received antitubercular therapy
in the past
Respiratory Medicine CMEVolume 4, Issue 4, Pages 149-200
(2011)Case ReportAllergic bronchopulmonary aspergillosis presenting
with cough variant asthma with spontaneous remissionHirofumi
Matsuoka,Towa Uzu,Midori Koyama,Yasuko Koma,Kensuke
Fukumitsu,Yoshitaka Kasai,Daiki Masuya,Harukazu Yoshimatsu,Yujiro
SuzukiA 60-year-old woman presented with a dry cough without
dyspnea or wheezing. Chest CT showed an image of mucoid impactions,
which were identified as mucoid impactions by
bronchofiberscopy.
Fig. 1. Chest radiograph showing bilateral infiltrates.
Fig. 2.
a: Chest CT image during the acute phase shows an image of
mucoid impactions in the right middle lung lobe and the left
lingular bronchus.
b: Chest CT image during the remission stage shows
bronchiectasis in the lingula of the left lung. The image of
m...
Fig. 3. Bronchofiberscopy findings. Mucoid impaction in the
right middle lung lobe bronchus Respiratory Medicine CME, Volume 4,
Issue 4, 2011, 175177A 60-year-old woman presented with a dry cough
without dyspnea or wheezing.
Aspergillus nigerwas cultured from her mucus. Her serum total
IgE was 5150IU/ml. Precipitins and IgE specific forAspergilluswere
positive. She had no history of asthma and no evidence of
bronchoconstriction by pulmonary function tests. Thus, a diagnosis
was made of allergic bronchopulmonary aspergillosis without
asthma.
Natural history of aspergilllus infection in Indian population
isa course of anti TB, bronchial asthma with frequent steroid
intake
17. DUrzo,Mclvor A.R. Allergic bronchopulmonary aspergillosis in
asthma.Can Fam Physician. 2000 Apr; 46: 882884.
18.Shah A, Panchal N, Agarwal AK. Concomitant allergic
bronchopulmonary aspergillosis and allergic aspergillus sinusitis:
a review of an uncommon association.Clin Exp
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case of allergic bronchopulmonary aspergillosis following active
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Uncommon associations of allergic bronchpulmonary
aspergillosis
Sources of Infection?
Aspergillus species are found in :
Soil, Compost and decaying vegetationAir; spores may be
inhaledWater / storage tanks in hospitals etcFoodFire proofing
materialsBedding, pillowsVentilation and air conditioning
systemsComputer fans
Aspergillus spores
17Objective: Aspergillus spores are widespread and are readily
inhaled.
The life cycle of Aspergillus
Spores inhaled
Germination
Mass of hyphae (plateau phase)
Hyphal elongation and branching
18Short movie clips showing germination of spores and growth of
hyphae can be viewed on this website at the following link:
http://www.aspergillus.man.ac.uk/secure/educationsection/movies/af65hyphae.html
Patients whose immune system is already weakened are most
susceptible. Those most at risk include some cancer and leukaemia
patients, those on chemotherapy and transplant patients.
Immune malfunction
Frequency of aspergillosis
Immune hyper-reactivity
Frequency of aspergillosis
Acute invasiveaspergillosisAspergilloma
Allergic aspergillosisAllergic sinusitis
Normal immune function
Relative risk of Aspergillus infection
19Objective: The risk of developing invasive aspergillosis
increases with increasing levels of immune deficiency. In contrast
the risk of allergic aspergillosis is enhanced in individuals whose
immune system is hyper-reactive. The two chest X-rays show examples
of acute invasive and allergic pulmonary aspergillosis.Aspergilloma
- This is a very different disease also caused by the Aspergillus
mould where the fungus exploits an existing weakness. The fungus
grows within a cavity of the lung, which was previously damaged
during an illness such as tuberculosis or sarcoidosis. Any lung
disease which causes cavities can leave a person open to developing
an aspergilloma. The spores penetrate the cavity and germinate,
forming a fungal ball within the cavity. The fungus secretes toxic
and allergic products which may make the person feel ill. The
picture shows the fungal ball (aspergilloma) which was removed from
a lung and measures about 6cm diameter.
Spectrum of pulmonary disorders caused by Aspergillus
species
Invasive pulmonary aspergillosis (IPA) is a severe disease, and
can be found not only in severely immunocompromised patients, but
also in critically ill patients and those with chronic obstructive
pulmonary disease (COPD). Aspergilloma is a fungus ball that
develops in a pre-existing cavity within the lung parenchyma
ABPA is a hypersensitivity manifestation in the lungs that
almost always affects patients with asthma or cystic fibrosis .
allergic pulmonary disorder caused by hypersensitivity to
Aspergillus fumigatus 1Occurs in asthma or cystic fibrosis2result
of immune response to Aspergillus colonization of airway and poor
clearance of mucus secretionssubsequent bronchiectasis, pulmonary
fibrosis, and compromise of pulmonary functionfirst described by
Hinson et al in 1952 in UK1.CHEST 2009; 135:805826.2. Middletons
Allergy, Principle&Practice 7th edition.Allergic
Bronchopulmonary Aspergillosis
Clinical featureSymptom occasionally be asymptomatic low-grade
fever, wheezing, bronchial hyperreactivity,hemoptysis, or
productive coughExpectoration of brownish black mucus plugs (31 to
69%)Physical examination normal or polyphonic wheezeClubbing (16%
)coarse crackles (15%)localized findings of consolidation and
atelectasis during exacerbationComplications eg. pulmonary HT
and/or respiratory failure
CHEST 2009; 135:805826.
Laboratory FindingsAspergillus Skin TestType I and III
reactionSPT and intradermal test (if SPT negative )
Total Serum IgE Levelsmost useful test for diagnosis and
follow-up of ABPAExclude ABPA ( if not steroid used)35 to 50%
decrease : criteria for remissionDoubling of baseline IgE levels :
relapse of ABPA
CHEST 2009; 135:805826
Laboratory FindingsSerum IgE and IgG Antibodies Specific to A.
fumigatusHallmark of ABPAcutoff value of IgG/IgE > twice pooled
serum samplesSerum Precipitins Against A. fumigatusPrecipitating
IgG Ab using double gel diffusion techniquePeripheral
EosinophiliaAEC >1,000 cells/L (major criteria)low eosinophil
count not exclude ABPACHEST 2009; 135:805826
Laboratory FindingsSputum Cultures for A fumigatussupportive
,but not diagnosticrarely perform for diagnosis of ABPAPulmonary
Function TestsCategorize severity, no diagnostic valueusual finding
is obstructive defectRole of Specific Aspergillus AntigensFurther
studies are requiredCHEST 2009; 135:805826
Radiologic InvestigationsChest radiographic findingsTransient
changesPatchy areas of consolidationRadiologic infiltrates:
toothpaste and gloved finger shadows due to mucoid impaction in
dilated bronchiCollapse: lobar or segmentalPerihilar infiltrates
may simulate adenopathyPermanent changesParallel-line shadows
representing bronchial wideningRing-shadows 12 cm in diameter
representing dilated bronchi en facePulmonary fibrosis: fibrotic
scarred upper lobes with cavitationCHEST 2009; 135:805826
Fig. Chest X-Ray of ABPA patient with right middle zone
infiltrate
28
Fig. Chest X-Ray of ABPA patient with Consolidation and Finger
like shadow
29There are bilateral perihilar areas of shadowing with
bronchial wall thickening and dilatation, indicating central
bronchiectasis. In addition there is a large thick walled cavity in
the periphery of the left mid zone, which also contains an
irregular soft tissue density. This appearance is typical of a
mycetoma in a cavity
Chest x-ray in a patient with ABPA: ring shadows (long arrows)
represent bronchiectatic airways seen in cross-section; tram lines
(short arrow) seen longitudinally
Radiologic Investigations
CHEST 2009; 135:805826
Radiologic InvestigationsHRCT findingsCentral
bronchiectasisMucus plugging with
bronchocelesConsolidationCentrilobular nodules with tree-in-bud
opacitiesBronchial wall thickeningAreas of atelectasisMosaic
perfusion with air trapping on expirationCHEST 2009; 135:805826
Fig. CT chest of ABPA patient with Mucoid impaction of central
bronchiectasis and Atelectasis
34There are bilateral perihilar areas of shadowing with
bronchial wall thickening and dilatation, indicating central
bronchiectasis. In addition there is a large thick walled cavity in
the periphery of the left mid zone, which also contains an
irregular soft tissue density. This appearance is typical of a
mycetoma in a cavity
.
Fig. Chest CT with central bronchiectasis
Radiologic Investigations
CHEST 2009; 135:805826
( pathognomonic finding with ABPA )
Bronchiectasis : cylindrical when bronchus taper and is 1.5 to
>3 times caliberof diameter of adjacent artery
J Allergy Clin Immunol 2002;110:685-92.
J Allergy Clin Immunol 2002;110:685-92.
38
Primary criteria: Asthma Peripheral blood eosinophilia Positive
skin test for aspergillus Precipitating antibodies(IgG) in serum
Serums Af spesific IgG and IgE IgE elevation (>1000mL) Pulmonary
infiltrations Central bronchiectasis
Secondary criteria: Positive sputum culture for aspergillus
History of brown mucus plug expectoration Positive type III(Arthus)
reaction for aspergillosisABPA Diagnostic CriteriaSoubani AO.Chest
2002;121:1988-1999Lazarus AA. Dis Mon 2008;54:547-564Agarwal R.
Chest 2009;135:805-826
39
ABPA-Central Bronchiectasis (ABPA-SB) Asthma Central
bronchiectasis Immediate cutaneous hyperreactivity to Af antigens
Elevated IgE ( >417 U/L or 1000ng/ml) Raised A fumigatus
specific IgE and IgG
ABPA-Serological (ABPA-S) Asthma Immediate cutaneous
hyperreactivity to Af antigens Elevated IgE ( >417 U/L or
1000ng/ml) Raised Af specific IgE and IgG Transient pulmonary
infiltrates on chest radiograph Rosenberg M.Annals of Intern Med
1977;86:405-414Greenberger PA. JACI 2002;110:685-692Agarwal R.
Chest 2009;135:805-826Rosenberg-Patterson criteria
40
Diagnosis and Diagnostic Criteria(Minimal diagnostic criteria
for ABPA)Minimal ABPA-CBAsthmaImmediate cutaneous hyperreactivity
to Aspergillus antigensElevated IgERaised A fumigatus-specific IgG
and IgECentral bronchiectasis
Minimal ABPA-SAsthmaImmediate cutaneous hyperreactivity to
Aspergillus antigensElevated IgERaised A fumigatus-specific IgG and
IgETransient pulmonary infiltrates on chest radiograph
CHEST 2009; 135:805826
Clinical staging of ABPA
CHEST 2009; 135:805826
All patients with bronchial asthma
PositiveChest radiograph, HRCTIgG/IgE spesific to AfEosinophil
countPrecipitins to AfSpirometry Aspergillus skin testIgE
levelsFollow-up with repeat skin test Yes>1000
IU/mLNegative500-1000 IU/mLMore than two-fold compared AHIgE / yl
ile izlem IgG/IgE spesific to Af NoFollow-up with IgE levels every
6 wkIf increasing or >1000 IU/mLTreatment for ABPA
