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Volume 24, Number 8—August 2018
Online Report

Case Definition of Chronic Pulmonary Aspergillosis in Resource-Constrained Settings

David W. DenningComments to Author , Iain D. Page, Jeremiah Chakaya, Kauser Jabeen, Cecilia M. Jude, Muriel Cornet, Ana Alastruey-Izquierdo, Felix Bongomin, Paul Bowyer, Arunaloke Chakrabarti, Sara Gago, John Guto, Bruno Hochhegger, Martin Hoenigl, Muhammad Irfan, Nicholas Irurhe, Koichi Izumikawa, Bruce Kirenga, Veronica Manduku, Samihah Moazam, Rita O. Oladele, Malcolm D. Richardson, Juan Luis Rodriguez Tudela, Anna Rozaliyani, Helmut J.F. Salzer, Richard Sawyer, Nasilele F. Simukulwa, Alena Skrahina, Charlotte Sriruttan, Findra Setianingrum, Bayu A.P. Wilopo, Donald C. Cole, and Haileyesus Getahun
Author affiliations: University of Manchester, Manchester, UK (D.W. Denning, I.D. Page, F. Bongomin, P. Bowyer, S. Gago, R.O. Oladele, C. Sriruttan, F. Setianingrum, B.A.P. Wilopo); Wythenshawe Hospital Manchester University NHS Foundation Trust, Manchester (D.W. Denning, I.D. Page, S. Moazam, M.D. Richardson, R. Sawyer); The Global Action Fund for Fungal Infections, Geneva, Switzerland (D.W. Denning, J. Guto, J.L. Rodriguez Tudela); Kenya Medical Research Institute, Nairobi, Kenya (J. Chakaya, V. Manduku); Aga Khan University, Karachi, Pakistan (K. Jabeen, M. Irfan); Olive View–UCLA Medical Center, Sylmar, California, USA (C.M. Jude); Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France (M. Cornet); Instituto de Salud Carlos III, Madrid, Spain (A. Alastruey-Izquierdo); Postgraduate Institute of Medical Education and Research, Chandigarh, India (A. Chakrabarti); Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil (B. Hochhegger); University of California San Diego, San Diego, California, USA (M. Hoenigl); Medical University of Graz, Graz, Austria (M. Hoenigl); Center for Biomarker Research in Medicine, Graz (M. Hoenigl); Lagos University Teaching Hospital, Lagos, Nigeria (N. Irurhe); Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan (K. Izumikawa); Mulago Hospital and Makerere University, Kampala, Uganda (B. Kirenga); University of Lagos, Lagos (R.O. Oladele); Universitas Indonesia, Jakarta, Indonesia (A. Rozaliyani, F. Setianingrum); Research Center Borstel, Borstel, Germany (H.J.F. Salzer); Royal Liverpool University Hospital, Liverpool, UK (N.F. Simukulwa); The Republican Scientific and Practical Centre for Pulmonology and TB, Minsk, Belarus (A. Skrahina, C. Sriruttan); National Institute for Communicable Diseases, Johannesburg, South Africa (C. Sriruttan); University of the Witwatersrand, Johannesburg (C. Sriruttan); Universitas Padjadjaran, Bandung, Indonesia (B.A.P. Wilopo); University of Toronto, Toronto, Ontario, Canada (D.C. Cole); World Health Organization, Geneva (H. Getahun)

Main Article

Table 1

Published diagnostic features and criteria for chronic pulmonary aspergillosis*

>1 of the following for 3 mo: WL, productive cough, hemoptysis plus absence of overt immunosuppression
>1 of the following (no duration specified): fever, WL, sputum production, cough, hemoptysis, fatigue, shortness of breath
Performance status 1–2
All of the following required for 1–6 mo: fever, cough, sputum production, weight loss
>1 of the following for 3 mo: weight loss, productive cough, hemoptysis plus absence of overt immunosuppression
“Significant pulmonary and/or systemic symptoms for 3 months or more”; no specific symptoms listed
>1 of the following: cavitary lesion with paracavitary fibrosis, new or expanding cavity on serial imaging
>1 of the following: new infiltrates, cavity formation, expansion of preexisting cavities; with or without the following: pericavitary infiltrates, adjacent pleural thickening
Compatible chest CT scan or photo-graphically confirmed endoscopic lesion
Cavitary pulmonary lesion with evidence of pericavitary infiltrates and adjacent pleural thickening with/without fungal ball
>1 of the following: cavitary lesion with paracavitary fibrosis, new or expanding cavity on serial imaging
Both required: >1 pulmonary cavities with either thick or thin wall, possibly containing aspergilloma or irregular intraluminal material; overt radiologic progression over >3 mo required (new cavities, increasing pericavitary infiltrates, or increasing fibrosis)
Aspergillus antibody/ culture
Either positive precipitins, or, culture from pulmonary or pleural cavity
>1 of the following: platelia serum galactomannan index >1.0, positive precipitins, positive (1,3)-β-D-glucan, evidence of Aspergillus spp. by molecular diagnosis, culture or pathological findings
Positive serologic test required by both of the following: precipitins by CIE with >2 lines, second serologic test positive by any method; and microbiological evidence by 1 of the following sources from BAL or sputum samples: >2 or more positive cultures, 1 positive culture and positive microscopy
Culture from sputum or BAL mandatory, antibodies not required
Either raised Aspergillus-specific IgG or culture from pulmonary or
pleural cavity
If fungal ball present: Aspergillus-IgG/precipitins or other evidence of Aspergillus. If no fungal ball but >1 cavities, then any of the following: Aspergillus-specific IgG, Aspergillus precipitins, strongly positive Aspergillus antigen or DNA in respiratory fluids, percutaneous or excision biopsy showing fungal hyphae on microscopy, growing Aspergillus from a cavity. These tests on respiratory samples not sufficient in isolation: culture, PCR, microscopy
Inflammatory markers
Raised levels of either: CRP, ESR, plasma viscosity
>1 of the following raised: leukocyte count, CRP, ESR
Not required
Not required
Raised levels of either: CRP, ESR
Not required
Exclusion of other pathogens Required with the following examples: mycobacteria, endemic mycoses Lack of improvement with >3 d of broad-spectrum antimicrobial drugs required; patients with infectious diseases 
other than aspergillosis excluded Not required Required with the following examples: TB, other mycoses, granulomatosis with polyangiitis, ABPA, invasive aspergillosis, simple aspergilloma† Not specifically required Required with the following examples: TB, atypical mycobacteria, necrotizing lung cancer, pulmonary infarction, vasculitides, rheumatoid nodule, histoplasmosis/ coccidioidomycosis/ paracoccidioido-mycosis in those with relevant travel history

*ABPA, allergic bronchopulmonary aspergillosis; BAL, bronchoalveolar lavage; CIE, counterimmunoelectrophoresis; CNPA, chronic necrotizing pulmonary aspergillosis; CRP, C-reactive protein: CT, computed tomography; ESR, erythrocyte sedimentation rate; TB, tuberculosis; WL, weight loss.
†This definition includes CNPA cases with 1–3 mo symptoms. Note: precipitins sensitivity even lower than culture. Pleural thickening seems to be a mandatory criterion.

Main Article

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