Assessment of posaconazole salvage therapy in chronic pulmonary aspergillosis using predefined response criteria.

OBJECTIVES: Chronic pulmonary aspergillosis (CPA) is a progressive infection that destroys lung tissue in non-immunocompromised patients. First-line therapies for CPA (itraconazole and/or voriconazole) are often curtailed due to toxicity or the development of drug resistance. Posaconazole is a potential alternative for these patients. METHODS: Use of posaconazole was funded by the National Health Service Highly Specialised National Commissioners on an individual basis for patients who failed or did not tolerate first-line therapy; those who met predefined criteria for improvement at 4 and 6 months (weight gain and/or improvement in St George's Respiratory Questionnaire) continued posaconazole long-term. We recorded response, failure, discontinuation rates, and adverse events. RESULTS: Seventy-eight patients received posaconazole as salvage therapy. Thirty-four (44%) achieved targets for continuation of therapy. Fourteen (18%) failed therapy; five (36%) patients did not achieve clinical targets at 4 or 6 months of assessment and nine (64%) developed clinical and/or radiological failure. Twenty-eight (36%) discontinued their trial early; 8 (29%) died and 20 (71%) had significant side effects. One patient was non-compliant and another was lost to follow up. CONCLUSIONS: Establishing criteria for therapeutic success offered a clear, safe and sustainable method of identifying patients who benefit from additional therapy, and minimised continuation of ineffective therapy in those who did not.

Predictors of mortality in chronic pulmonary aspergillosis.

Chronic pulmonary aspergillosis (CPA) is a chronic progressive infection that destroys lung tissue in non-immunocompromised patients. Contemporary series suggest 50-85% 5-year mortality, with few prognostic factors identified.A cohort of 387 CPA patients referred to the UK's National Aspergillosis Centre from 1992 to June 2012 was studied until June 2015. The impact of objective and subjective variables including age, sex, previous pulmonary conditions, dyspnoea score, quality of life, serum albumin and C-reactive protein and radiological appearances were assessed using Kaplan-Meier curves, log rank tests and Cox proportional hazards modelling. In samples of patients, retrospective review of time from likely onset of CPA to referral and cause of death were also investigated.Survival was 86%, 62% and 47% at 1, 5 and 10 years, respectively. Increased mortality was associated with nontuberculous mycobacterial infection (hazard ratio 2.07, 95% CI 1.22-3.52; p<0.001) and chronic obstructive pulmonary disease (1.57, 1.05-2.36; p=0.029) as well as higher age (1.053, 1.03-1.07 per year; p<0.001), lower albumin (0.92, 0.87-0.96 per g·L-1), lower activity (1.021, 1.01-1.03 per point increase in St George's Respiratory Questionnaire activity domain; p<0.001) and having one, and especially, bilateral aspergillomas (p<0.001).Several factors impact on mortality of CPA, and can be evaluated as tools to assess CPA prognosis.

Impact of liposomal amphotericin B therapy on chronic pulmonary aspergillosis.

OBJECTIVES: To assess the clinical response and renal toxicity observed in chronic pulmonary aspergillosis (CPA) patients receiving ≥1 short-courses of liposomal amphotericin (LAmB) (AmBisome®) therapy. METHODS: A retrospective audit of clinical response and renal function was undertaken in 71 CPA patients (41 male) treated with LAmB at the National Aspergillosis Centre, including 20 patients receiving repeated treatment courses or long-term therapy (n = 5). RESULTS: Median age was 64 years (range 29-86 years). Treatment indications included respiratory symptoms (n = 33; 46.5%), constitutional symptoms (n = 2; 2.8%) or both (n = 36; 50.7%). 48 patients (73.8%) responded to their first LAmB course. Quality of life (QOL) improvements occurred in 37 (92.5%) of 40 patients with sufficient data available. Response rates for repeated short-courses of LAmB were 76.6%; QOL improvements were observed in 91.7% of treatment courses. All patients on long-term therapy demonstrated a response. 34 (50%) and 17 (25%) patients respectively developed an increased risk of acute kidney injury (AKI) or actual AKI with their first treatment; a significant reduction in geometric mean eGFR was observed and a similar pattern occurred following their second treatment course. CONCLUSIONS: Whilst CPA is responsive to LAmB, caution should be exercised with repeated courses, if other treatments are available.

Should we consider patients with coexistent hepatitis B or C infection for orthotopic heart transplantation?

Heart transplantation (HTX) is the gold standard surgical treatment for patients with advanced heart failure. The prevalence of hepatitis B and hepatitis C infection in HTX recipients is over 10%. Despite its increased prevalence, the long-term outcome in this cohort is still not clear. There is a reluctance to place these patients on transplant waiting list given the increased incidence of viral reactivation and chronic liver disease after transplant. The emergence of new antiviral therapies to treat this cohort seems promising but their long-term outcome is yet to be established. The aim of this paper is to review the literature and explore whether it is justifiable to list advanced heart failure patients with coexistent hepatitis B/C infection for HTX.