PMID- 29634721 OWN - NLM STAT- MEDLINE DCOM- 20180710 LR - 20240314 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 13 IP - 4 DP - 2018 TI - Twelve-month clinical outcomes of 206 patients with chronic pulmonary aspergillosis. PG - e0193732 LID - 10.1371/journal.pone.0193732 [doi] LID - e0193732 AB - There is a paucity of evidence surrounding the optimal antifungal therapy for use in chronic pulmonary aspergillosis (CPA) and the duration of therapy remains unclear. We retrospectively evaluated treatment outcomes, including change in quality of life scores (St George's Respiratory Questionnaire (QoL)), weight and Aspergillus IgG at 6 and 12 months following initiation of therapy in a cohort of 206 CPA patients referred to the UK National Aspergillosis Centre (NAC), Manchester between April 2013 and March 2015. One hundred and forty-two patients (69%) were azole naive at presentation and 105 (74%) (Group A) were commenced on itraconazole, 27 (19%) on voriconazole, and 10 (7%) were not treated medically. The remainder (64 patients, 31%) had previously trialled, or remained on, azole therapy at inclusion (Group B) of whom 46 (72%) received itraconazole, 16 (25%) voriconazole, and 2 (3%) posaconazole. Initial therapy was continued for 12 months in 78 patients (48%) of those treated; the azole was changed in 62 (32%) patients and discontinued in 56 (29%) patients for adverse reactions (32, 57%), azole resistance (11, 20%), clinical failure (8, 14%) or clinical stability (5, 9%). Azole discontinuation rates were higher in Group B than in Group A (42% vs. 22%, p = 0.003). For all patients who survived, weight increased (median of 62.2Kg at baseline, to 64.8 at 12 months), mean Aspergillus IgG declined from 260 (baseline) to 154 (12 months) and QoL improved from 62.2/100 (baseline) to 57.2/100 (12 months). At 12 months, there was no difference in median survival between Groups A and B (95% vs. 91%, p = 0.173). The rate of emergence of resistance during therapy was 13% for itraconazole compared to 5% for voriconazole. Bronchial artery embolization was done in 9 (4.4%) patients and lobectomy in 7 (3.2%). The optimal duration of azole therapy in CPA is undetermined due to the absence of evidenced based endpoints allowing clinical trials to be undertaken. However we have demonstrated itraconazole and voriconazole are modestly effective for CPA, especially if given for 12 months, but fewer than 50% of patients manage this duration. This suggests extended therapy may be required for demonstrable clinical improvement. FAU - Bongomin, Felix AU - Bongomin F AD - The National Aspergillosis Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom. AD - Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom. FAU - Harris, Chris AU - Harris C AD - The National Aspergillosis Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom. FAU - Hayes, Gemma AU - Hayes G AD - The National Aspergillosis Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom. AD - Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom. FAU - Kosmidis, Chris AU - Kosmidis C AD - The National Aspergillosis Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom. AD - Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom. AD - The Manchester Academic Health Service Centre, Manchester, United Kingdom. FAU - Denning, David W AU - Denning DW AUID- ORCID: 0000-0001-5626-2251 AD - The National Aspergillosis Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom. AD - Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom. AD - The Manchester Academic Health Service Centre, Manchester, United Kingdom. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180410 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Antifungal Agents) RN - 0 (Immunoglobulin G) RN - 304NUG5GF4 (Itraconazole) RN - JFU09I87TR (Voriconazole) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antifungal Agents/administration & dosage/*therapeutic use MH - Aspergillus/drug effects/immunology MH - Body Weight/drug effects MH - Chronic Disease/drug therapy MH - Female MH - Humans MH - Immunoglobulin G MH - Itraconazole/administration & dosage/*therapeutic use MH - Male MH - Middle Aged MH - Pulmonary Aspergillosis/*drug therapy MH - *Quality of Life MH - Retrospective Studies MH - Treatment Outcome MH - Voriconazole/administration & dosage/*therapeutic use MH - Young Adult PMC - PMC5892866 COIS- Competing Interests: Dr. David W. Denning and family hold Founder shares in F2G Ltd, a University of Manchester spin-out antifungal discovery company. He acts or has recently acted as a consultant to Astellas, Sigma Tau, Basilea, Scynexis, Cidara, Biosergen, Quintilles, Zambon, Pulmatirx, and Pulmocide. In the last 3 years, he has been paid for talks on behalf of Astellas, Dynamiker, Gilead, Merck, Mylan, and Pfizer. He is a longstanding member of the Infectious Disease Society of America Aspergillosis Guidelines group, the European Society for Clinical Microbiology and Infectious Diseases Aspergillosis Guidelines group and the British Society for Medical Mycology Standards of Care committee. This study was also supported by an educational grant from Cidara Therapeutics. There are no patents, products in development, or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials. EDAT- 2018/04/11 06:00 MHDA- 2018/07/11 06:00 PMCR- 2018/04/10 CRDT- 2018/04/11 06:00 PHST- 2017/09/14 00:00 [received] PHST- 2018/02/16 00:00 [accepted] PHST- 2018/04/11 06:00 [entrez] PHST- 2018/04/11 06:00 [pubmed] PHST- 2018/07/11 06:00 [medline] PHST- 2018/04/10 00:00 [pmc-release] AID - PONE-D-17-31921 [pii] AID - 10.1371/journal.pone.0193732 [doi] PST - epublish SO - PLoS One. 2018 Apr 10;13(4):e0193732. doi: 10.1371/journal.pone.0193732. eCollection 2018.