Allergic bronchopulmonary aspergillosis - CHEST Publications ...

Table 2—Genetic Factors Involved in the Pathogenesis
of ABPA*
HLA associations: presence of HLA DR-2 and absence of
HLA-DQ2 sequences 42,44,45
IL-10 promoter polymorphisms 49
Polymorphism at position 1,082 produces higher levels of IL-10
if 1082G allele is present and lower levels of IL-10 if the
1082A allele is present
In patients with CF there is a relationship between the 1082GG
genotype with both Aspergillus colonization and ABPA
Surfactant protein A gene polymorphisms 48,53
A significantly higher frequency of the AGA allele (A1660G) of
SP-A2 found in patients with ABPA vs control subjects.
Coexistence of A1660G polymorphism with SP-A2 G1649C
(Ala91Pro) found with 10-fold higher odds in patients with
ABPA. Patients with ABPA with GCT and AGG alleles
showed significantly higher levels of total IgE and percentage
eosinophilia vs patients with ABPA with CCT and AGA
alleles 48
The T allele at T1492C and G allele at G1649C of SP-A2
observed at higher frequencies in ABPA patients than in
controls. Also there is a higher frequency of the TT genotype
at position1492 of SP-A2 than controls 53
There were no polymorphisms found in SP-A1 gene 53
CFTR gene mutation: 43,46,47 increased frequency of CFTR
mutations in patients with ABPA vs skin-prick test positive or
negative patients with bronchial asthma
IL-15 polymorphisms: 52 higher frequency of IL-15 13689*A
allele and A/A genotype
TNF- polymorphisms: 52 lower frequency of the TNF- 308 * A/A
genotype
Mannose-binding lectins: 53 the intronic single nucleotide
polymorphism G1011A of mannose-binding lection seen with
increased frequency in patients with ABPA
IL-4 receptor polymorphisms: 51 single nucleotide polymorphism of
the extracellular IL-4R ile75val observed in 80% of ABPA
patients
IL-13 polymorphisms: 50 the arg110gln polymorphism found with
increased frequency in ABPA and the combination of IL-4R
ile75val/IL-13 arg110gln polymorphism found with an even
higher frequency
Toll-like receptor gene polymorphisms: 54 susceptibility to ABPA
was associated with allele C on T1237C (TLR9)
*HLA human leukocyte antigen; TNF tumor necrosis factor;
CFTR CF transmembrane conductance regulator.
multinucleated giant cells centered on the airway, are
also seen. 68,69 Rarely, invasive aspergillosis complicating
the course of ABPA has also been described. 70–74
Clinical Features
There is no gender predilection and majority of the
cases present in the third to fourth decade. A family
history of ABPA may be elicited occasionally. 75 Table 3
summarizes the clinical features of ABPA encountered
in three large series from our institute. 19,21,23
Most present with low-grade fever, wheezing, bronchial
hyperreactivity, hemoptysis, or productive
cough. Expectoration of brownish black mucus plugs
is seen in 31 to 69% of patients. 21,23,34 The symptoms
of hemoptysis, expectoration of brownish black mucus
plugs, and history of pulmonary opacities in an
asthmatic patient suggests ABPA. Patients can occasionally
be asymptomatic, and the disorder is
diagnosed on routine screening of asthmatic patients.
22,23,33 Physical examination can be normal or
may reveal polyphonic wheeze. Clubbing is rare,
seen in only 16% of patients. On auscultation, coarse
crackles can be heard in 15% of patients. 23 Physical
examination can also detect complications such as
pulmonary hypertension and/or respiratory failure. 76
During exacerbations of ABPA, localized findings of
consolidation and atelectasis can occur that needs to
be differentiated from other conditions.
Laboratory Findings
Aspergillus Skin Test: The Aspergillus skin test is
performed using an A fumigatus antigen, either
commercial (eg, Aspergillin; Hollister-Stier Laboratories;
Spokane, WA) or locally prepared. The test is
read every 15 min for 1 h, and then after 6 to 8 h.
The reactions are classified as type I if a wheal and
erythema developed within 1 min, reaches a maximum
after 10 to 20 min, and resolves within 1 to 2 h.
A type III reaction is read after 6 h, and any amount
of subcutaneous edema is considered a positive
result. An immediate cutaneous hypersensitivity to A
fumigatus antigens is a characteristic finding of
ABPA and represents the presence A fumigatusspecific
IgE antibodies, whereas a type III skin
reaction probably represents the immune complex
hypersensitivity reaction, although its exact significance
remains unclear. The test can be performed
using either a skin-prick test or intradermal injection
with the latter being more sensitive. 30,77,78 A skinprick
test should be performed for Aspergillus skin
testing, and if the results are negative should be
confirmed by an intradermal test. 30 There is no
difference on the outcome of the test and the type of
antigen (locally prepared or commercial) used for
performance of the test. 30
Total Serum IgE Levels: The total IgE level is the
most useful test for diagnosis and follow-up of ABPA. A
normal serum IgE level excludes ABPA as the cause of
the patient’s current symptoms. The only situation
where IgE levels can be normal in active ABPA is when
the patient is already on glucocorticoid therapy for any
reason and investigation for IgE levels has been conducted.
After treatment with glucocorticoids, the serum
IgE levels decline, and a 35 to 50% decrease is
taken as a criteria for remission. 79 The serum IgE
determination is also used for follow-up, and a doubling
of the patient’s baseline IgE levels indicates relapse of
ABPA. 80,81
808 Global Medicine
Downloaded From: http://jupcvss.chestpubs.org/ on 08/01/2013