PMC:7306567 / 19219-26142 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7306567","sourcedb":"PMC","sourceid":"7306567","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7306567","text":"Consensus case definition for IAPA\nThe expert panel discussed which case definition of IAPA would be appropriate to use in clinical studies, initially considering various aspects regarding four main areas of focus: entry criteria of the consensus definition, host, clinical features and mycological evidence similar to the currently used EORTC/MSGERC classification.\n\nEntry criterion\nIn addition to having a positive diagnostic test for influenza, patients would require to have a clinical syndrome compatible with influenza disease as part of the definition. This criterion should be termed the ‘entry criterion’ and not ‘host factor’ for clarity. To avoid the risk of missing patients who initially tested negative with a rapid influenza antigen test but subsequently tested positive (by PCR) for influenza when admitted to hospital, a recommendation on a timescale, such as between 1 week before ICU admission and 72–96 h post-admission, was included. The consensus on the entry criterion was: a patient requiring ICU admission for respiratory distress with a positive influenza PCR or antigen test temporally related to ICU admission.\n\nHost factors\nHost factors are considered in the EORTC/MSGERC definition and AspICU algorithm [10, 11], but the system of taking host factors into account was a necessity because the risk of a false-positive Aspergillus test increases substantially when the test is done in patients at low risk of the disease. Clinicians had to take into account the type of host in order to increase the pretest probability of an invasive fungal disease being present. However, for IAPA the key question is whether the disease is present or not, and not whether the patient group has a higher risk than other patient groups for developing the disease. More importantly, the incidence of IAPA in patients admitted to the ICU with influenza may be higher in some centers [9, 21]. No further host factors are needed to increase the pretest probability in this patient population. Although most IAPA cases have at least one underlying condition or steroid use, host factors were not be included in the case definition for IAPA.\n\nCriteria to define proven and probable cases of IAPA\nThe distinction between proven and probable IAPA is important for clinical trials, while in clinical practice, people should not distinguish between proven and probable disease.\nThe criteria for proven disease include a patient fulfilling the entry criterion plus histological evidence of invasive fungal elements and mycological evidence for the presence of Aspergillus (obtained by Aspergillus PCR or culture from tissue). Tracheobronchitis (tracheal and/or bronchial ulcerations or nodules, pseudomembranes or plaques visualized at bronchoscopy), as also described in the EORTC/MSGERC definitions [10], is a separate entity. Although a tissue biopsy would normally be required to prove a case of IAPA, in tracheobronchitis cases hyphal elements suggestive of Aspergillus seen on sloughed-off pseudomembrane, and Aspergillus identified on culture or PCR, can also be considered proven disease (Table 1).\nTable 1 Proposed case definition for IAPA in ICU patients\nEntry criteria: influenza-like illness + positive influenza PCR or antigen + temporally relationship\nAspergillus tracheobronchitis IAPA in patients without documented Aspergillus tracheobronchitis\nProven Biopsy or brush specimen of airway plaque, pseudomembrane or ulcer showing hyphal elements and Aspergillus growth on culture or positive Aspergillus PCR in tissue Lung biopsy showing invasive fungal elements and Aspergillus growth on culture or positive Aspergillus PCR in tissue\nProbable Airway plaque, pseudomembrane or ulcer\nand at least one of the following:\nSerum GM index \u003e 0.5\nor\nBAL GM index ≥ 1.0\nor\nPositive BAL culture\nor\nPositive tracheal aspirate culture\nor\nPositive sputum culture\nor\nHyphae consistent with Aspergillus A: Pulmonary infiltrate\nand at least one of the following:\nSerum GM index \u003e 0.5\nor\nBAL GM index ≥ 1.0\nor\nPositive BAL culture\nOR\nB: Cavitating infiltrate (not attributed to another cause)\nand at least one of the following:\nPositive sputum culture\nor\nPositive tracheal aspirate culture\nA patient fulfilling the case definition of probable IAPA is required to fulfill the entry criterion. A positive serum GM (GM index \u003e 0.5) is important evidence for the diagnosis of IAPA, in patients with pulmonary infiltrates on chest X-ray or other imaging modality or bronchoscopic evidence of tracheobronchitis (Table 1). In patients with tracheobronchitis, an infiltrate is not required.\nIn patients with endobronchial plaques or pulmonary infiltrates, a positive BAL GM or culture of a tracheal aspirate is considered mycological evidence that supports a probable IAPA diagnosis. In patients with bacterial pneumonia where Aspergillus is cultured only from a sputum sample, there may be a risk of overdiagnosis and thus over-treatment. For clinical practice, clinicians should take into account that a positive culture of an upper airway sample may indicate IAPA, but that confirmation with serum or BAL GM or BAL culture should be pursued. However, one problem is that the background incidence varies in different regions, making it difficult to develop generalized guidelines that apply uniformly. The significance of a positive sputum culture thus depends on the background incidence in a specific unit. Although any Aspergillus-positive respiratory sample is in itself insufficient to classify patients as probable IAPA, a new pulmonary cavitating infiltrate is indicative of IAPA in patients who meet the entry criterion. Therefore, any Aspergillus-positive respiratory sample is sufficient evidence to classify patients as probable IAPA provided that a pulmonary cavitating infiltrate is present (Table 1; Fig. 1).\nFig. 1 Flowchart of probable IAPA classification. (*)If hyphae consistent with Aspergillus are documented in a biopsy of an airway lesion AND Aspergillus is grown from sputum or a tracheal aspirate, the case fulfills the definition of proven IAPA\nA BAL GM index cutoff of ≥ 1.0 is recommended as this cutoff value ensures high specificity, without decreasing sensitivity significantly, which is also in line with other definitions and recommendations [10, 57]. Aspergillus PCR is not recommended as a primary diagnostic tool because of concerns about its reliability and positive predictive value for the diagnosis of IPA. However, Aspergillus PCR is recommended in the proven category because it enables Aspergillus identification in tissue samples.\nIn some patients, discordant results are obtained, for instance a positive sputum culture but negative BAL GM. For most situations, IAPA classification relies on a positive GM test, as a positive sputum culture with a negative GM result would be interpreted as a lower probability of IAPA (unless a pulmonary cavity or tracheobronchitis is 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