Allergic bronchopulmonary aspergillosis

2019 ◽  
Vol 40 (6) ◽  
pp. 421-424 ◽  
Author(s):  
Gayatri Patel ◽  
Paul A. Greenberger
Keyword(s):  
Cystic Fibrosis ◽  
Aspergillus Fumigatus ◽  
Mhc Class Ii ◽  
Peripheral Blood ◽  
Immunoglobulin E ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Total Serum ◽  
Drug Induced ◽  
Positive Skin ◽  
Pulmonary Infiltrates

Allergic bronchopulmonary aspergillosis (ABPA) occurs in patients with asthma or cystic fibrosis, and results in pulmonary infiltrates, tenacious mucus plugs that harbor hyphae of Aspergillus fumigatus, elevations of total serum immunoglobulin E concentration and peripheral blood and sputum eosinophilia. Bronchiectasis is an irreversible complication of ABPA. The key to early diagnosis is to consider ABPA in anyone with asthma or cystic fibrosis and with a positive skin test result for Aspergillus, and/or recurrent infiltrates on radiographs. The differential diagnosis for ABPA in patients with asthma includes diseases in which there is an overlap of asthma, peripheral blood eosinophilia, and radiographic infiltrates. Examples include chronic eosinophilic pneumonia, Churg-Strauss syndrome, drug-induced pulmonary infiltrates, infection with a parasite, asthma with atelectasis, and lymphoma. Mucus plugging that causes a “tree in bud” pattern on computerized tomography examination of the lungs may be from ABPA or other conditions, such as nontuberculous (atypical) mycobacteria (Mycobacteria avium‐Mycobacteria intracellulare complex). Prednisone is indicated to clear pulmonary infiltrates, and a usual course is for 3 months. Itraconazole and voriconazole are adjunctive, and drug-drug interactions must be considered because azoles decrease elimination of various medications. Although not familial in most patients, presentation of Aspergillus fumigatus f1 (Asp f1) antigen is restricted to specific major histocompatibility complex (MHC) class II molecules, Human Leukocyte Antigen-DR2 (HLA-DR2), and HLA-DR5. There is an increased number of CD4+ T-helper type 2 lymphocytes in bronchoalveolar lavage, and A. fumigatus can serve as a growth factor of eosinophils potentiating the effects of interleukin (IL) 3, IL-5, and Granulocyte-colony stimulating factor (G-CSF). Eosinophils interact directly with A. fumigatus spores and generate extracellular traps, which can injure the bronchial epithelium.

Allergic Bronchopulmonary Aspergillosis

Asthma ◽  
2014 ◽  
pp. 21-31
Author(s):  
Paul A. Greenberger
Keyword(s):  
Cystic Fibrosis ◽  
Differential Diagnosis ◽  
Immunoglobulin E ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Oral Steroid ◽  
Total Serum ◽  
Meaningful Improvement ◽  
Sputum Eosinophilia ◽  
Pulmonary Infiltrates ◽  
Oral Glucocorticoids

Allergic bronchopulmonary aspergillosis (ABPA), a disease that complicates asthma and cystic fibrosis, is in the differential diagnosis of pulmonary infiltrates, peripheral blood or sputum eosinophilia, elevated total serum immunoglobulin E concentration, and bronchiectasis, any or all of which may occur in patients with established asthma. ABPA is one of the most important comorbid, coexisting subtypes of asthma because it results in irreversible lung destruction and may convert intermittent or persistent mild asthma into persistent severe asthma. The fact that the treatment of choice to clear pulmonary infiltrates and sputum eosinophilia is an oral steroid but not antifungal therapy remains true after 50 years of attempts to improve our understanding and treatment of ABPA. It remains to be established whether monoclonal antibodies will contribute to meaningful improvement in management of patients, or what combination therapy will be optimum instead of relying on oral glucocorticoids. Certainly, innovative, safe, and effective approaches to treatment are needed to decrease the harmful impact that untreated or inadequately treated ABPA can have on patients with asthma.

scholarly journals Concurrent sensitization to Aspergillus Fumigatus in tropical pulmonary eosinophilia

2016 ◽  
Vol 81 (1-2) ◽  
Author(s):  
Sunil K. Chhabra ◽  
Devi Jyoti Dash
Keyword(s):  
Aspergillus Fumigatus ◽  
Severe Asthma ◽  
Lung Tissue ◽  
Peripheral Blood ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Pulmonary Eosinophilia ◽  
Blood Eosinophilia ◽  
Future Risk ◽  
Serum Total Ige ◽  
Peripheral Blood Eosinophilia

<p>Tropical pulmonary eosinophilia (TPE) is characterized by lung tissue and peripheral blood eosinophilia. Serum total IgE is also markedly increased in TPE. However, an association with asthma or other hypersensitivity conditions has not been described. During the diagnostic workup of three patients eventually confirmed to have TPE, hypersensitivity to the fungus, <em>Aspergillus Fumigatus </em>was found. However, there was no evidence of diseases of aspergillus hypersensitivity such as severe asthma with fungal sensitization (SAFS) and allergic bronchopulmonary aspergillosis (ABPA). This association however raises the possibility of a future risk of these potentially serious allergic respiratory manifestations.</p><p><strong>Riassunto</strong></p><p>L’eosinofilia polmonare tropicale (TPE) è caratterizzata da tessuto polmonare e eosinofilia nel sangue periferico. Anche il siero IgE totale è notevolmente aumentato in TPE. Tuttavia, un’associazione con asma o altre condizioni di ipersensibilità non è stata descritta. Durante l'iter diagnostico di tre pazienti, che alla fine si sono rivelati presentare TPE, ipersensibilità al fungo, è stato trovato l’<em>Aspergillus fumigatus</em>. Tuttavia, non vi era alcuna evidenza di malattie di <em>Aspergillus</em> ipersensibilità come l'asma grave con sensibilizzazione fungina (SAF) e aspergillosi broncopolmonare allergica (ABPA). Questa associazione pone tuttavia la possibilità di un rischio futuro di queste potenzialmente gravi manifestazioni allergiche respiratorie.</p>

scholarly journals High Prevalence of Azole-Resistant Aspergillus fumigatus in Adults with Cystic Fibrosis Exposed to Itraconazole

2011 ◽  
Vol 56 (2) ◽  
pp. 869-874 ◽  
Author(s):  
Pierre-Régis Burgel ◽  
Marie-Thérèse Baixench ◽  
Michaël Amsellem ◽  
Etienne Audureau ◽  
Jeanne Chapron ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Aspergillus Fumigatus ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Previous Treatment ◽  
University Hospital ◽  
Clinical Implications ◽  
Content Type ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
High Prevalence

ABSTRACTAspergillus fumigatusis the most frequent fungus found in the sputum of cystic fibrosis (CF) subjects. Itraconazole is prescribed for allergic bronchopulmonary aspergillosis (ABPA) orAspergillusbronchitis in CF subjects. We hypothesized thatA. fumigatusisolates in the sputum of CF subjects with previous exposure to itraconazole was associated with higher prevalence of azole resistance. From June 2010 to April 2011, sputum samples from adult CF subjects at Cochin University Hospital (France) were examined systematically for the detection ofA. fumigatus. MICs ofA. fumigatusisolates against azoles were screened using Etest, and reduced susceptibility to azoles was confirmed using the CLSI broth microdilution method.A. fumigatuswas isolated from the sputum of 131/249 (52.6%) adult CF subjects, and 47/131 (35.9%) subjects had received previous treatment with itraconazole. ReducedA. fumigatussusceptibility to itraconazole (MIC, ≥2 mg/liter) was confirmed in 6/131 (4.6%) subjects. All 6 isolates also had reduced susceptibility to posaconazole (MIC, ≥0.5 mg/liter), and 3/6 isolates had reduced susceptibility to voriconazole (MIC, ≥2 mg/liter). Mutations in thecyp51Agene were detected at positions previously implicated to cause resistance in 5 isolates. Azole-resistantA. fumigatusisolates were found in 5/25 (20%) subjects exposed to itraconazole within the previous 3 years. High rates of azole-resistantA. fumigatusisolates were present in adult CF subjects and were associated with recent itraconazole exposure. Although the clinical implications of these findings will require further studies, the cautious use of itraconazole in adult CF subjects can be recommended.

scholarly journals Use of a Synthetic Peptide Epitope of Asp f 1, a Major Allergen or Antigen of Aspergillus fumigatus, for Improved Immunodiagnosis of Allergic Bronchopulmonary Aspergillosis

2004 ◽  
Vol 11 (3) ◽  
pp. 552-558 ◽  
Author(s):  
Taruna Madan ◽  
Priyanka Priyadarsiny ◽  
Mudit Vaid ◽  
Neel Kamal ◽  
Ashok Shah ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Synthetic Peptide ◽  
Immunoglobulin E ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Major Allergen ◽  
Specific Ige ◽  
Diagnostic Efficiency ◽  
Intradermal Testing ◽  
Peptide Epitope ◽  
Asp F 1

ABSTRACT Allergic bronchopulmonary aspergillosis (ABPA) is an immunologically complex allergic disorder caused by the fungal pathogen Aspergillus fumigatus. Elevated levels of total immunoglobulin E (IgE), specific IgE, and IgG antibodies in sera are important immunodiagnostic criteria for ABPA. International reference standards or standardized immunodiagnostic assays are not available due to a lack of well-defined diagnostic antigens. The present study was carried out to identify and evaluate the immunodiagnostic relevance of synthetic epitopic peptides of Asp f 1, a major allergen, antigen, or cytotoxin of A. fumigatus. Five overlapping peptides were synthesized from the N terminus of Asp f 1, one of the potential immunodominant regions predicted by algorithmic programs. The 11-amino-acid synthetic peptide (P1) significantly inhibited both IgG binding (89.10% ± 4.45%) and IgE binding (77.32% ± 3.38%) of the standardized diagnostic antigen (SDA) (a well-defined pool of diagnostically relevant allergens and antigens of A. fumigatus). With a panel of sera of ABPA patients, allergic patients with skin test negativity to A. fumigatus, and healthy individuals, P1 showed a higher diagnostic efficiency than SDA (specific IgG, 100%; specific IgE, 98.3%). The diagnostic efficiency of P1 could be attributed to the presence of homologous epitopes in various immunodominant allergens or antigens of A. fumigatus. The ability of P1 to induce histamine release from sensitized mast cells and a Th2 type of cytokine profile in peripheral blood mononuclear cells of ABPA patients suggests its potential for use in intradermal testing. P1 could be further explored for development of a standardized, specific, and sensitive immunodiagnostic test for aspergillosis.

scholarly journals Conformational and Linear B-Cell Epitopes of Asp f 2, a Major Allergen of Aspergillus fumigatus, Bind Differently to Immunoglobulin E Antibody in the Sera of Allergic Bronchopulmonary Aspergillosis Patients

1999 ◽  
Vol 67 (5) ◽  
pp. 2284-2291 ◽  
Author(s):  
Banani Banerjee ◽  
Paul A. Greenberger ◽  
Jordan N. Fink ◽  
Viswanath P. Kurup
Keyword(s):  
Amino Acid ◽  
Aspergillus Fumigatus ◽  
B Cell ◽  
Immunoglobulin E ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Amino Acid Sequences ◽  
Epitope Region ◽  
B Cell Epitopes ◽  
Ige Binding ◽  
Binding Regions

ABSTRACT Asp f 2 is a major Aspergillus fumigatus allergen involved in allergic bronchopulmonary aspergillosis. Knowledge of the B-cell epitopes may contribute to the understanding of immunoregulation and immunodiagnosis. To elucidate the immunoglobulin E (IgE) binding epitopes in the linear sequence of Asp f 2, we synthesized decamer peptides spanning the whole molecule of Asp f 2 on derivatized cellulose membranes and evaluated IgE binding in ABPA patient and control sera. Peptides three to five amino acids long were synthesized based on amino acid sequences within the IgE binding regions and evaluated for the specificity of epitope antibody interactions. Nine IgE binding regions were recognized in this protein of 268 amino acid residues. Of the nine epitopes, seven (ATQRRQI, RKYFG, HWR, YTTRR, DHFAD, ALEAYA, and THEGGQ) are present in the hydrophilic regions of Asp f 2. Immunologic evaluation of the three recombinant fragments, Asp f 2A encompassing the N-terminal epitope region, Asp f 2B without N- and C-terminal regions of the protein, and Asp f 2C representing C-terminal epitopes, revealed that either the N- or C-terminal region of the protein is essential for the correct folding and conformation for IgE antibody binding.

scholarly journals Role of C-Terminal Cysteine Residues of Aspergillus fumigatus Allergen Asp f 4 in Immunoglobulin E Binding

2004 ◽  
Vol 11 (2) ◽  
pp. 261-265 ◽  
Author(s):  
Harikrishnan Ramachandran ◽  
Banani Banerjee ◽  
Paul A. Greenberger ◽  
Kevin J. Kelly ◽  
Jordan N. Fink ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Conformational Changes ◽  
Immunoglobulin E ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Allergic Diseases ◽  
Cysteine Residues ◽  
Conformational Structure ◽  
C Terminus ◽  
Function Relationship

ABSTRACT Among the several allergens cloned and expressed from Aspergillus fumigatus, Asp f 4 is a major one associated with allergic bronchopulmonary aspergillosis (ABPA). The structure-function relationship of allergens is important in understanding the immunopathogenesis, diagnosis, and treatment of allergic diseases. These include the epitopes, conformational or linear, deletion of the N or C terminus or both N and C termini, and glycosylation or nonglycosylation, all of which affect immune responses. Similarly, the role of cysteine residues present in allergens may yield useful information regarding the conformational structure of allergens and the immunoglobulin E (IgE) epitope interaction. Such information may help in developing new strategies towards immunotherapy. In order to define the role of cysteine in the interaction of the antibody with Asp f 4, we have constructed mutants by selectively deleting cysteine residues from the C-terminal region of the Asp f 4. Immunological evaluation of these engineered recombinant constructs was conducted by using sera from patients with ABPA, Aspergillus skin test-positive asthmatics, and healthy controls. The results demonstrate strong IgE binding with Asp f 4 and two truncated mutants, Asp f 41-234 (amino acids [aa] 1 to 234) and Asp f 41-241 (aa 1 to 241), while another mutant, Asp f 41-196 (aa 1 to 196), showed reactivity with fewer patients. The result suggests that deletion of cysteines and the alteration of IgE epitopes at the C-terminal end resulted in conformational changes, which may have a potential role in the immunomodulation of the disease.

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