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

Abstract

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.

CPAnet Registry—An International Chronic Pulmonary Aspergillosis Registry

“…This first interim analysis of the multicentric multinational CPAnet registry revealed a very similar study population to earlier European studies [ 14 , 16 , 17 ]. It contained mainly older males with a smoking history.…”

Diagnostic Aspects of Chronic Pulmonary Aspergillosis: Present and New Directions

“…There are many different options of serological tests available, including ELISA, with differing performance characteristics [37]. The ELISA capability to measure IgG titre quantitatively is important to monitor CPA progress and treatment [78,79]. The lateral flow assay is an option as a simple diagnostic test for CPA, particularly in a resource-constrained setting.…”

Intravenous therapy for chronic pulmonary aspergillosis: A systematic review and meta‐analysis

“…32 In one study, about 10% of the patients required IV antifungals after failing or developing pan-azole-resistant isolates of Aspergillus spp. 8 One option involves the use of injectable antifungals such as echinocandins and polyenes or potentially synergistic combination of polyene, azole-and echinocandin-based therapies to improve efficacy and minimise adverse events. 32,33 The utility of these antifungals, however, has not been well evaluated and remains controversial because the drugs are expensive and require patients to be admitted to the hospital for their use, at least initially.…”

“…12,13 Antifungal treatment is discontinued in up to 30% of CPA patients due to adverse events, and about 5 to 15% of patients develop resistant Aspergillus isolates during the course of their treatment. 8,14 Current strategies for managing CPA patients with pan-azole resistance or pan-azole cross-intolerance include surgical resection, 15,16 short or long courses of an echinocandin 17 or amphotericin B, 18 and/or supplemental gamma interferon injections. 19 However, the outcomes from these strategies are not well documented in the literature.…”