Aspergillus species. The clinical spectrum of pulmonary aspergillosis

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1 Pentalfa 3 maart 2016 The clinical spectrum of pulmonary aspergillosis Pascal Van Bleyenbergh, Pneumologie UZ Leuven Aspergillus species First described in 1729 * >250 species * ubiquitous Inhalation of conidia common * only minority lung disease Most common cause of mortality due to invasive mycosis Variety of clinical syndromes Latge JP. Clin Microbiol Rev 1999; 12:

2 Broad Spectrum of Pulmonary Aspergillosis SAFS Kosmidis C, Denning DW. Thorax 2015; 70(3): Broad Spectrum of Pulmonary Aspergillosis Hope WW et al. Med Mycol 2005; 43(Suppl 1):

3 Chronic pulmonary aspergillosis (CPA) Chronic pulmonary aspergillosis (CPA) : parasitic vegetable structures (Bennett J) : mega-mycetoma intra-bronchiectasique (Deve F) : amphotericine B for treating chronic aspergillosis complicating TB (Kelmenson VA) : semi-invasive pulmonary aspergillosis (Gefter WB et al.) : chronic necrotizing pulmonary aspergillosis (Binder RE et al.) Gefter WB et al. Radiology 1981; 140: Binder RE et al. Medicine 1982; 61:

4 Chronic Pulmonary Aspergillosis (CPA) 4

5 Simple (single) aspergilloma Fungal ball (= hyphae and extracellular matrix) Pre-existing cavity: lung, pleura, ectatic bronchus Characteristic imaging features (RX / CT) Serological or microbiological evidence implicating Aspergillus No progression over 3 months No or very few pulmonary/systemic symptoms Non-immunocompromised patient Simple (single) aspergilloma 5

6 Aspergillus nodule One or more nodules <3cm,only rarely >3cm (with necrotic centre) Usually no cavitation No tissue invasion Unusual presentation of CPA Broad differential diagnosis (lung carcinoma, metastases, other fungal infection,...) Aspergillus nodule 6

7 Chronic cavitary pulmonary aspergillosis (CCPA) Multiple cavities +/- fungal ball Radiological progression over 3 months (new cavities, increasing infiltrates, increasing fibrosis) Significant pulmonary/systemic symptoms Serological or microbiological evidence implicating Aspergillus CFPA (chronic fibrosing pulmonary aspergillosis) is end result of CCPA with extensive fibrotic destruction of at least two lobes! = most frequent presentation of CPA! Denning DW et al. Clin Infect Dis 2003; 37(Suppl3): Chronic cavitary pulmonary aspergillosis (CCPA) Denning DW et al. Clin Infect Dis 2003; 37(Suppl3):

8 Chronic cavitary pulmonary aspergillosis (CCPA) Denning DW et al. Clin Infect Dis 2003; 37(Suppl3): Subacute invasive pulmonary aspergillosis (SAIA) chronic necrotizing or semi-invasive pulmonary aspergillosis Clinically and radiologically similar to CCPA but more rapid in progression (<<3 months) Mildly immunocompromised patient / structural lung disease (diabetes, malnutrition, alcoholism, advanced age, prolonged corticosteroid therapy, COPD, connective tissue disorder, radiation therapy, NTM disease, HIV, ) Serological or microbiological evidence implicating Aspergillus Signs of invasive disease possible (hyphae in lung tissue) 8

9 Subacute invasive pulmonary aspergillosis (SAIA) Subacute invasive pulmonary aspergillosis (SAIA) 9

10 Chronic pulmonary aspergillosis diagnostic criteria Chronic pulmonary aspergillosis diagnostic criteria 1.1 Characteristic CT appearance of a fungus ball in a pulmonary or pleural cavity, or dilated bronchus 10

11 Chronic pulmonary aspergillosis diagnostic criteria 1.1 Characteristic CT appearance of a fungus ball in a pulmonary or pleural cavity, or dilated bronchus OR 1.2 Radiological features consistent with chronic pulmonary aspergillosis (cavities, pleural thickening, extensive fibrosis, nodules, ) Chronic pulmonary aspergillosis diagnostic criteria 1.1 Characteristic CT appearance of a fungus ball in a pulmonary or pleural cavity, or dilated bronchus OR 1.2 Radiological features consistent with chronic pulmonary aspergillosis (cavities, pleural thickening, extensive fibrosis, nodules, ) AND 2. Clinical or radiological evidence of at least 3 months disease (shorter duration possible for SAIA) 11

12 Chronic pulmonary aspergillosis diagnostic criteria 1.1 Characteristic CT appearance of a fungus ball in a pulmonary or pleural cavity, or dilated bronchus OR 1.2 Radiological features consistent with chronic pulmonary aspergillosis (cavities, pleural thickening, extensive fibrosis, nodules, ) AND 2. Clinical or radiological evidence of at least 3 months disease (shorter duration possible for SAIA) AND 3. Histological or microbiological or immunological evidence of Aspergillus infection (hyphae in biopsy or Asp. culture in cavity aspiration, strongly positive BAL GM, positive IgG/precipitins). Respiratory tract cultures or PCR positive for Aspergillus is supportive. Histological or microbiological or immunological evidence of Aspergillus infection Biopsy or resection of lesions: definitive distinction between SAIA and CCPA Presence of Aspergillus in respiratory secretions (stain, cultures, PCR) - supportive but not diagnostic - suboptimal sensitivity (56%-81%) - culture: media specific for fungi - PCR more sensitive than culture - persistance during antifungal therapy resistance! Galactomannan - BAL >> serum - much higher sensitivity and specificity (85,7% & 77%) Aspergillus antibodies (IgG, precipitins no role of IgA & IgM) - key diagnostic feature in CPA - antibody titers no correlation with extent of severity of disease ( ) 12

13 Chronic pulmonary aspergillosis diagnostic criteria 1.1 Characteristic CT appearance of a fungus ball in a pulmonary or pleural cavity, or dilated bronchus 1.2 Radiological features consistent with chronic pulmonary aspergillosis 2. Clinical or radiological evidence of at least 3 months disease 3. Histological or microbiological or immunological evidence of Aspergillus infection AND Exclusion of - active bacterial infection, including mycobacterial infection - actinomycosis - histoplasmosis and (para)coccidioidomycosis in endemic areas - malignancies, vasculitides, rheumatoid nodules, Diagnosis of SAIA = diagnosis of IPA in the immunocompromised host (EORTC) De Pauw B et al. Clin Infect Dis 2008; 46:

14 Diagnosis of SAIA = diagnosis of IPA in the immunocompromised host (EORTC) 4) Positive BAL galactomannan test Bulpa P et al. Eur Resp J 2007; 30: Underlying conditions in pts with CPA Smith NL et al. Eur Respir J 2011; 37: Godet C et al. Resp 2014; 88:

15 CPA in patients with COPD COPD admissions 16,3 Asp.+/1000 admissions 53 probable PA 3,6/1000 admissions 22,1% if Asp.+ Guinea J et al. Clin Microbiol Infect 2010; 16: CPA in patients with NTM disease 11% of NTM patients (3,9% - 16,7%) CCPA >> CNPA (89% vs 11%) Cavitary NTM disease Prior use of corticosteroids Poorer prognosis Interactions with azoles! CPA >> NTM treatment Kunst H et al. Eur Resp J 2006; 28: Kazuaki T et al. Med Myc 2016; 54:

16 Therapy for CPA Cohort studies and case reports; only 2 larger prospective studies Aspergilloma: surgery is first choice! Oral azole therapy for CCPA is standard of care! itraconazole, voriconazole, posaconazole Agarwal R et al. Mycoses 2013; 56: Therapy for CPA Cohort studies and case reports; only 2 larger prospective studies Aspergilloma: surgery is first choice! Oral azole therapy for CCPA is standard of care! itraconazole, voriconazole, posaconazole SAIA: treat as invasive pulmonary aspergillosis! (IDSA/ATS guidelines) Response to antifungal treatment is slow Duration: 4-6 months 9 months 12 months Quid indefinite long-term suppressive therapy? Agarwal R et al. Mycoses 2013; 56:

17 CPA: treatment needs to be long term CPA: treatment needs to be long term Cadranel J et al. Eur J Clin Microbiol Infect Dis 2012; 31: Al-shair K et al. Clin Infect Dis 2013; 57: Agarwal R et al. Mycosis 2013; 56:

18 CPA: global treatment strategy Attention for co-morbidities smoking, alcohol intake malnutrition corticosteroids Pulmonary rehabilitation Godet C et al. Resp 2014; 88: Ohara S et al. Resp Invest 2016; 54: