Journal Article

Twelve-month clinical outcomes of 206 patients with chronic pulmonary aspergillosis

Hayes, Gemma, Denning, David W., Harris, Chris, Bongomin, Felix, Kosmidis, Chris

2018

Overview

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 naïve 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Aged / Aged, 80 and over / Analysis / Antifungal agents / Antifungal Agents - administration & dosage / Antifungal Agents - therapeutic use / Antimicrobial agents / Aspergillosis / Aspergillus / Aspergillus - drug effects / Aspergillus - immunology / Aspergillus fumigatus / Biology / Biology and Life Sciences / Body Weight - drug effects / Care and treatment / Chronic Disease - drug therapy / Clinical outcomes / Clinical trials / Disease / Drug dosages / Dyspnea / Embolization / Female / Fungal infections / Fungicides / Health services / Hospitals / Humans / Immunoglobulin G / Infections / Itraconazole / Itraconazole - administration & dosage / Itraconazole - therapeutic use / Lungs / Male / Medical prognosis / Medical research / Medicine / Medicine and Health Sciences / Middle Aged / Patient outcomes / Patients / Physical Sciences / Posaconazole / Pulmonary aspergillosis / Pulmonary Aspergillosis - drug therapy / Quality of Life / Research and Analysis Methods / Retrospective Studies / Therapy / Treatment Outcome / Voriconazole / Voriconazole - administration & dosage / Voriconazole - therapeutic use / Young Adult