TABLE 2.

IPA in special populations^15,60,62

Disease	Classification	Host factors/Entry criterion	Clinical factors	Radiographic findings	Mycological evidence
COPD	Proven	History of COPD		Any pulmonary lesion present for <3 months	Histopathological or cytopathological examination, from needle aspiration or biopsy specimen obtained from pulmonary lesion showing hyphae consistent with Aspergillus and evidence of associated tissue damage if accompanied by one of the following: Positive culture of Aspergillus spp. from any LRT sample Positive serum antibody/antigen testing for A fumigatus (including precipitins). Confirmation that hyphae observed are those of Aspergillus by a direct molecular, immunological method and/or culture.
	Probable	As for proven IPA but without confirmation that Aspergillus is responsible.
		Patients with a pulmonary functional level of stage III or IV according to the GOLD guidelines. Recent exacerbation of dyspnoea Patients treated with steroids, with no strict requirement regarding the usage, dosage or duration.	Exacerbation of dyspnoea or bronchospasm resistant to appropriate treatment including antibiotics.	Pulmonary lesions on chest imaging (radiograph or CT scan) findings <3 months, unresponsive to appropriate treatment including antibiotics	One of the following: Positive culture and/or microscopy findings for Aspergillus from the LRTs. Positive serum antibody/antigen test for A fumigatus (including precipitin). Two consecutive positive serum galactomannan tests. Confirmation that the hyphae observed are those of Aspergillus by a direct molecular, immunological method and/or culture.
	Possible	a1.Patients with a pulmonary functional level of stage III or IV according to the GOLD guidelines. e2.Recent exacerbation of dyspnoea a3.Patients treated with steroids, with no strict requirement regarding the usage, dosage or duration.	Exacerbation of dyspnoea or bronchospasm resistant to appropriate treatment including antibiotics.	Pulmonary lesions on chest imaging (radiograph or CT scan) findings <3 months, unresponsive to appropriate treatment including antibiotics	Without positive Aspergillus culture or serology.
	Colonisation	History of COPD	No exacerbation of dyspnoea, bronchospasm	No new pulmonary infiltrate	Positive Aspergillus culture from LRT.
Influenza	Tracheobronchitis, Proven	Admission to ICU with positive influenza test (PCR or rapid Ag) within 1 week prior to or 72–96 h post-admission to ICU.	ICU admission for respiratory distress with positive influenza test temporally related to ICU admission.	No requirements	Biopsy or brush specimen of airway plaque, pseudomembrane or ulcer showing one of the following: Hyphal elements and Aspergillus growth on culture. Positive Aspergillus PCR in tissue.
	Tracheobronchitis, Probable	Admission to ICU with positive influenza test (PCR or rapid Ag) within 1 week prior to or 72–96 h post-admission to ICU.	ICU admission for respiratory distress with positive influenza test temporally related to ICU admission.	No requirements	Biopsy or brush specimen of airway plaque, pseudomembrane or ulcer showing one of the following: Serum GM index >0.5 BAL GM index ≥1.0 Positive BAL culture Positive tracheal aspirate culture Positive sputum culture Hyphae consistent with Aspergillus
	Influenza-Associated Pulmonary Aspergillosis (IAPA), Proven	Admission to ICU with positive influenza test (PCR or rapid Ag) within 1 week prior to or 72–96 h post-admission to ICU.	ICU admission for respiratory distress with positive influenza test temporally related to ICU admission.	Pulmonary infiltrate	Lung biopsy showing invasive fungal elements and Aspergillus growth on culture or positive Aspergillus PCR in tissue.
	Influenza-Associated Pulmonary Aspergillosis (IAPA), Probable	Admission to ICU with positive influenza test (PCR or rapid Ag) within 1 week prior to or 72–96 h post-admission to ICU.	ICU admission for respiratory distress with positive influenza test temporally related to ICU admission.	Pulmonary infiltrate	At least one of the following: Serum GM index >0.5 BAL GM index ≥1.0 Positive BAL culture
		Admission to ICU with positive influenza test (PCR or rapid Ag) within 1 week prior to or 72–96 h post-admission to ICU.	ICU admission for respiratory distress with positive influenza test temporally related to ICU admission.	Cavitating infiltrate not attributed to another cause	At least one of the following: Positive sputum culture Positive tracheal aspirate culture
COVID-19	Tracheobronchitis or other pulmonary form, Proven	Respiratory insufficiency requiring intensive care. Positive SARS-CoV-2 RT-PCR anytime during 2 weeks between hospital admission or positive RT-PCR within 72–96 h after ICU admission	Respiratory insufficiency requiring intensive care with clinical symptoms compatible with COVID-19.		At least one of the following: Histopathological or direct microscopic detection of fungal hyphae, showing invasive growth with associated tissue damage. Aspergillus recovered by culture or microscopy or histology PCR obtained by a sterile aspiration or biopsy from a pulmonary site, showing an infectious disease process
	Tracheobronchitis, Probable	Respiratory insufficiency requiring intensive care. Positive SARS-CoV-2 RT-PCR anytime during 2 weeks between hospital admission or positive RT-PCR within 72–96 h after ICU admission	Respiratory insufficiency requiring intensive care with clinical symptoms compatible with COVID-19. Tracheobronchitis, indicated by tracheobronchial ulceration, nodule, pseudomembrane, plaque, or eschar seen on bronchoscopic analysis.		At least one of the following: Microscopic detection of fungal elements in BAL, indicating a mould Positive BAL culture or PCR Serum GM index >0.5 Serum LFA index >0.5 BAL GM index ≥1.0 BAL LFA index ≥1.0
	Pulmonary forms, Probable	Respiratory insufficiency requiring intensive care. Positive SARS-CoV-2 RT-PCR anytime during 2 weeks between hospital admission or positive RT-PCR within 72–96 h after ICU admission	Respiratory insufficiency requiring intensive care with clinical symptoms compatible with COVID-19.	Pulmonary infiltrate, preferable documented by chest CT, or cavitating infiltrate (not attributed to another cause).	At least one of the following: Microscopic detection of fungal elements in BAL, indicating a mould Positive BAL culture Serum GM index >0.5 Serum LFA index >0.5 BAL GM index ≥1.0 BAL LFA index ≥1.0 Two or more positive aspergillus PCR tests in plasma, serum, or whole blooda Single positive Aspergillus PCR in BALF (<36 cycles)a Single positive Aspergillus PCR in plasma, serum, or whole blood AND Single positive Aspergillus PCR in BALF (any cycle threshold)a
	Pulmonary forms, Possible	Respiratory insufficiency requiring intensive care. Positive SARS-CoV-2 RT-PCR anytime during 2 weeks between hospital admission or positive RT-PCR within 72–96 h after ICU admission	Respiratory insufficiency requiring intensive care with clinical symptoms compatible with COVID-19.	Pulmonary infiltrate, preferable documented by chest CT, or cavitating infiltrate (not attributed to another cause).	At least one of the following: Microscopic detection of fungal elements in non-BAL, indicating a mould Positive non-BAL culture Single non-BAL GM index >4.5 Non-BAL GM index >1.2 twice or more Non-BAL GM index >1.2 plus another non-BAL mycology test positive (non-BAL PCR or LFA)

Note: Non-BAL is considered a blind application of 10–20 ml saline recovered by aspiration via the closed suction system in an intubated patient. BAL and non-BAL are not currently considered equal for diagnosing CAPA.

Abbreviations: Ag, antigen; BAL, bronchoalveolar lavage; BALF, bronchoalveolar lavage fluid; COPD, chronic obstructive pulmonary disorder; COVID-19, coronavirus disease 2019;CT, computed tomography; GM, galactomannan; GOLD, Global Initiative for Obstructive Lung Disease; IAPA, influenza-associated pulmonary aspergillosis; ICU, intensive care unit; IPA, invasive pulmonary aspergillosis; LFA, lateral flow assay; LRT, lower respiratory tract; PCR, polymerase chain reaction; RT-PCR, reverse transcription polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; spp, species.

^aIn case of patients with COPD or chronic respiratory disease, the PCR or culture should be confirmed by galactomannan testing to rule out colonisation or chronic aspergillosis.