Interferon-gamma as Adjunctive Therapy in Chronic Pulmonary Aspergillosis: a Randomised Feasibility Study

This study explores the role of treatment with interferon‐gamma to improve outcomes inchronic pulmonary aspergillosis (CPA). CPA is a progressive infection caused by thefungus Aspergillus affecting patients with chronic lung disease like Chronic ObstructiveLung Disease (COPD) or previously treated tuberculosis (TB). It causes gradualdestruction of lung tissue by slowly enlarging cavities, frequent secondary infectionsand poor quality of life. Because of its indolent nature and nonspecific x‐ray findings,it often remains unrecognised for years. Around 3600 people live with CPA in the UnitedKingdom. Mortality from CPA may be up to 40% in five years.Treatment for CPA relies on antifungals for prolonged periods, but only around 60% ofpatients improve. It is often long‐term or lifelong as the response is slow and somepatients experience relapses. In addition, only one class of oral antifungal drugs islicensed for CPA, and they are associated with side effects and high cost. Bettertreatments are needed for CPA. We do not know why many patients do not respond totreatment. Maybe CPA patients have a weakened immune system and are more susceptible toAspergillus. Our data suggest that CPA patients produce lower amounts of ΙFNγ, asubstance that facilitates the immune system's response against Aspergillus. We have alsoshown that, when given to patients with CPA who have failed to improve on antifungaltreatment, interferon‐gamma leads to improvement in important patient‐centred outcomeslike flares of lung disease or hospital admissions. Interferon‐gamma is already in use inthe National Health Service of the United Kingdom for other indications. Therefore, itsuse in CPA should be explored. However, CPA is a rare condition and the tolerability ofinterferon‐gamma is not fully established in these patients. To understand whether alarge‐scale study is feasible in CPA, we first need preliminary data in smaller numbersof patients.We are conducting a randomised trial of interferon‐gamma in addition to antifungals inCPA. Patients with CPA starting antifungal treatment are eligible. Participants (25 pergroup) are randomly assigned to interferon‐gamma for 12 weeks (in addition toantifungals) or antifungals only. To test whether the treatment works, we will usemeasurements of the cavities on chest CT scan and scores on a quality‐of‐lifequestionnaire. We will assess for tolerability of treatment at intervals similar toclinical practice. Criteria for progression to the large‐scale study will be set based onthe proportion of patients willing to participate, and on the proportion who complete thetreatment. Data collected on those parameters will allow us to determine the numberneeded for a definite study.If the large‐scale study confirms our observations that interferon‐gamma improvesoutcomes in CPA, then treatment duration can be shortened and relapses avoided. Inaddition, interferon‐gamma can then be explored in other chronic lung disease.