Presentation on theme: "Chronic pulmonary aspergillosis"— Presentation transcript:
1Chronic pulmonary aspergillosis David W. DenningWythenshawe HospitalUniversity of Manchester
2Interaction of Aspergillus with the host A unique microbial-host interaction Acute IAABPAAllergic sinusitisSubacute IACNPAFrequency of aspergillosisFrequency of aspergillosisAspergillomaChronic cavitaryChronic fibrosingImmune dysfunctionImmune hyperactivity.
3Sub-acute invasive aspergillosis in AIDS 2 month history of cough and weight loss
5Sub-acute invasive aspergillosis Less immunocompromised patientsSlower progression of disease (> 1 month)Cavitary or nodular pulmonary disease typicalVascular invasion less commonDissemination less commonAntigen testing less usefulAntibody testing may be helpful in diagnosis
24Chronic pulmonary aspergillosis - serology All 18 patients had positive Aspergillus precipitins ( )All 18 patients had elevated inflammatory markers, CRP, PV and / or ESR14 of 18 (78%) had elevated total IgE (>20), 13 >200 and 7 >4009 of 14 (67%) had Aspergillus specific IgE (RAST)Denning DW et al, Clin Infect Dis 2003; 37:S265
25Chronic pulmonary aspergillosis – invasive procedures Lung resection - histological confirmation in 4 patients, hyphae in cavities, not tissueBronchoscopic biopsy - negative for hyphae in 8/9 - chronic inflammatory changes, fibrosis ± granuloma formation (n=1)Percutaneous biopsy – hyphae in 1/7 cases - chronic inflammatory changes and fibrosisDenning DW et al, Clin Infect Dis 2003; 37:S265
26Chronic pulmonary aspergillosis -microbiology Sputum culture was positive - 10 patients sporadicallySputum microscopy was positive - 1 patientBAL culture positive in 4 of 10 (40%)Lung biopsy positive 1 of 5 patients (20%)Pleural aspiration 3 of 3 (100%)Denning DW et al, Clin Infect Dis 2003; 37:S265
27Mannose Binding Lectin (MBL)- a key part of the innate immune system Crosdale et al J Infect Dis 2001;184:653
28Mannose Binding Protein Mutations5 mutations described2 in promoter region (less important)3 in open reading frame (M52, M54, M57)Codon 54 mutation present in 16% of Caucasianshomozygous in 2%Defects associated with bacterial infections in children and hepatitis B carriageEisen & Minchinton Clin Infect Dis 2003;37:1496
29CPA and human gene defects Probably not related to coeliac disease (<1 in 30)UnpublishedInnate immunity8 of 11pts had low MBL genotypes p=<0.05 (compared to normal controls)Crosdale et al J Infect Dis 2001;184:653.
30Treatment failure / progression Treatment of chronic cavitary pulmonary aspergillosisTreatmentNo of coursesStable or improved (%)Treatment failure / progressionToxicityItraconazole primary therapy1712 (71)53Voriconazole9/11 (82)212Amphotericin B IV119 (82)7Gamma IFN with itraconazoleItraconazole maintenance after AmB IV6Denning DW et al, Clin Infect Dis 2003; 37:S265; Jain AAA 2004
31Chronic cavitary pulmonary aspergillosis an example of radiographic failure Patient SSApril 2004Patient SSJuly 2004, despite receiving itraconazole for 3 months