Diagnosing allergic bronchopulmonary aspergillosis/mycosis: Return to lost horizons

Despite being recognized as a distinct clinical entity nearly 70 years ago, allergic bronchopulmonary aspergillosis/mycosis (ABPA), which is what we would today—with our vastly greater understanding of pathobiology—term an asthma endotype,1Lötvall J. Akdis C.A. Bacharier L.B. Bjermer L. Casale T.B. Custovic A. et al.Asthma endotypes: new approach to classification disease entities within the syndrome.J Allergy Clin Immunol. 2011; 127: 355-360Abstract Full Text PDF PubMed Scopus (812) Google Scholar remains difficult and often long-delayed diagnosis. It notable that in 1952 landmark study by Hinson al,2Hinson K.F. Moon A.J. Plummer N.S. Broncho-pulmonary aspergillosis: review report eight cases.Thorax. 1952; 7: 317-333Crossref essential components diagnosis were “recurrent pyrexial attacks, radiological evidence recurrent collapse consolidation different areas, purulent sputum containing ‘plugs’ fungus [emphasis added], blood eosinophilia 1,000 per c.mm. or more,” with description text focused on findings mycelia eosinophilic inflammation (including growth Aspergillis fumigatus Charcot-Leyden crystals) mucus plugs from bronchial exudates examined at necroscopy after surgical lobar excision. Thus, histopathology mycology central initial features recognizing ABPA. In 1970s, identification IgE antibody isotype underlying disease, serology came occupy role diagnosing A codification diagnostic criteria pioneering work Rosenberg al Northwestern University Chicago emphasized presence antibodies (at time, detected primarily immediate allergen skin testing crude fungal extracts [a method has now been largely supplanted standardized vitro serum-specific immunoassays]), elevation total serum concentration, precipitating (now supplemented, if not entirely displaced, IgG immunoassays), peripheral eosinophilia.3Rosenberg M. Patterson R. Mintzer Cooper B.J. Roberts Harris K.E. Clinical immunologic for aspergillosis.Ann Intern Med. 1977; 86: 405-414Crossref (589) 2012 review, Knutsen posited minimal required ABPA (1) cystic fibrosis (CF) deterioration lung function, (2) Aspergillus species test reactivity, (3) level 1000 ng/mL (416 IU/mL) greater, (4) increased concentrations species–specific antibodies, (5) chest radiographic infiltrates.4Knutsen A.P. Bush R.K. Demain J.G. Denning D.W. Dixit Fairs al.Fungi lower respiratory diseases.J 2012; 129: 280-291Abstract (328) But this raises thorny issue serologic cutoff values, continue be debated today. Statistical methods such receiver operating characteristics latent class analysis have yielded varying cutoffs global perspective, seem dependent part subject population demographics geography, climate, ethnicity, age, well assay methdology.5Agarwal Maskey D. Aggarwal A.N. Saikia B. Garg Gupta al.Diagnostic performance various tests employed analysis.PLoS One. 2013; 8e61105Crossref (111) Scholar,6Saxena P. Choudhary H. Muthu V. Sehgal I.S. Dhooria S. Prasad K.T. al.Which are optimal aspergillosis? analysis.J Immunol Pract. 2021; 9: 328-335Abstract (17) addition, when fungi other than fumigatus—which account least 5% mycoses—underlie process, appropriate immunoassays unavailable unstandardized.7Deepak Singh Rajput Sharma Chowdhary Allergic mycosis due Aspergillus.Eur Ann 2019; 51: 75-79Crossref (8) Improvements imaging technology frequently resulted replacement plain radiography bronchography high-resolution computed tomography magnetic resonance imaging.8Agarwal Chakrabarti Shah Meis J.F. Guleria al.Allergic literature proposal criteria.Clin Exp Allergy. 43: 850-873Crossref (478) Use recombinant allergens added dimension options, but their clarifying simplifying uncertain.9Muthu utility antigens aspergillosis.J 2020; 8: 579-587Abstract (13) Now Asano al, pursuing early emphasis plug supported advances T2-high pathogenesis, back these elements identifying ABPA, along contemporary methods, proposed criteria.10Asano K. Hebisawa Ishiguro T. Takayanagi N. Nakamura Y. Suzuki al.New its validation.J 147: 1261-1268Abstract (30) use both pathologic examination physician-based data sets enhances confidence criteria. Additionally, flexible enough allow without direct evaluation plugs. Importantly, filamentous and/or culture places into clear process linking infection (yeasts included, probably owing lack adequate pathogenicity context). At Japanese setting, substantially improved accuracy 1977 Rosenberg-Patterson those put forth 2013 working group International Society Animal Human Mycology (ISHAM).8Agarwal The ISHAM criteria, operationally quite similar also themselves scrutinized incorporation refinements they do address mycology.6Saxena comparison evolution over time (Table I) shows movement toward reliance standardized, quantitative specificity about causation. For example, criteria,3Rosenberg note there no levels standardization testing, definition methodology abnormalities, histopathology, need any secondary evaluating (ie, [ABPM]). criteria,8Agarwal allowance cases CF, allergen, ABPM, methodology, identification/culture. 2020 update, except reduced 500 IU/mL, precipitin removed, rather radiograph used bronchiectasis.6Saxena However, still way clearly evaluate ABPM non–A provision directly indirectly analyze Finally, novel biomarkers might simplify (eg, specific cytokine levels, cell-based assays basophil activation test, allergens, quantification exhaled nitric oxide levels) explored, particularly patients CF.Table IShifting ABPA/ABPMA.Rosenberg-Patterson (1977)3Rosenberg ScholarPrimary∗ABPA “likely” primary 1 6 present “certain” all present.1.Episodic obstruction (asthma)2.Peripheral eosinophilia3.Immediate reactivity antigen4.Precipitating against antigen5.Elevated concentrations6.History pulmonary infiltrates (transient fixed)7.Central bronchiectasisSecondary∗ABPA present.•A (detected repeated microscopic examination)•History expectoration brown flecks•Arthus (late reactivity) antigenB.ISHAM (2013)8Agarwal ScholarPredisposing conditions: asthma, CFObligatoryPositive type result elevated levelsTotal > IU/mL†IgE <1000 IU/mL acceptable present.And ≥2 following:Precipitating fumigatusRadiographic opacities consistent ABPA‡Chest may transient consolidation, nodules, tram-track opacities, toothpaste/finger-in-glove opacities) permanent parallel line ring shadows, bronchiectasis, pleuropulmonary fibrosis).Eosinophil count cells/μL steroid-naive (may historical)C.Modified (2020)6Saxena ScholarPresence following:1.Asthma2.A fumigatus-specific 0.35 KUA/L3.Serum following:(a)A fumigatus–specific 27 mg A/L(b)Bronchiectasis CT scan(c)Eosinophil >500 cells/μL(d)Mucus impaction scanD.Asano (2020) CF10Asano ≥6 following:1.Current previous history asthmatic symptoms2.Peripheral ≥500 cells/mm33.Total ≥ 417 IU/mL4.Positive fungi§Filamentous 4 should identical.5.Presence precipitins fungi6.Positive lavage result7.Fungal hyphae plugs8.Central bronchiectasis scan9.Mucus CT, bronchoscopy, expectoration10.High-attenuation scanCT, Computed tomography.∗ present.† present.‡ Chest fibrosis).§ Filamentous identical. Open table tab tomography. reported hinge confirmation endobronchial colonization conventional manifestations histopathology. This allows firmer certainty, especially causative agent, seems particular problem East Asia. needs considered context some actual potential disadvantages. Although national scope (as acknowledged authors), presented al10Asano somewhat peculiar Japan validation elsewhere world universally adopted. Mucus specimens readily obtainable, proper mycologic expectorated bronchoscopically obtained microscopy trivial it requires access expertise Application CF 2 most common processes leading commonly diagnosed modified reflect predisposing evaluated. Uncertainty regarding impact cross-reactive epitopes immunoassays, remain concerns. Nevertheless, represent return lost horizons looking process—the mucoobstructive, inflammatory provoked susceptible hosts noninvasive growth—directly where occurs, namely, airways. New validationJournal ImmunologyVol. 147Issue 4PreviewThere several aspergillosis (ABPA). validated detail, (ABPM) currently available. Full-Text Access