Consensus Treatment Outcome Definitions for Chronic Pulmonary Aspergillosis

Establishing consensus definitions for chronic pulmonary aspergillosis (CPA) treatment outcomes has been a top research priority of the chronic pulmonary aspergillosis network (CAPnet). Toward that end, a consensus statement with definitions of treatment outcomes for CPA was recently published in the European Respiratory Journal.

Although current guidelines on the diagnosis and management of CPA provide diagnostic criteria for CPA, they do not provide any clear definitions of treatment outcomes. Because of this lack of standardization of endpoints, there has been a limited number of randomized controlled trials (RCTs) on antifungal treatment for CPA. Other than several larger retrospective, nonrandomized, prospective studies, a scarcity of high-quality data on CPA treatment exist. Thus, the establishment of a consensus on definitions of treatment outcomes for CPA was considered to be 1 of the top 4 research priorities of the CAPnet, an international research collaboration established in 2017 and funded by the European Respiratory Society (ERS) in 2020.

The recently published consensus statement, developed by a panel 29 international researchers and experts, includes detailed definitions of the following outcomes: 1) cure (defined as completion of CPA therapy and meeting 3 specified criteria over a 2-year period that involve: improvement in Respiratory Symptom Score [RSS]; microbiological cure defined by negative culture from respiratory specimen; and sustained radiological treatment response); 2) treatment completed; 3) radiological treatment response; 4) radiological treatment deterioration; 5) clinical treatment response; 6) clinical treatment deterioration; 7) serological improvement; 8) serological deterioration; 9) overall treatment response; 10) overall stability under treatment; 11) treatment failure; 12) relapse after treatment; 13) death; 14) death due to CPA; 15) lost to follow up.

The experts and researchers who developed the consensus definitions evaluated treatment response on 3 levels: (1) clinical response evaluated by the Respiratory Symptom Score, which takes into account 6 cardinal symptoms: cough, dyspnea, sputum, hemoptysis, chest pain, and nocturnal awakening; (2) microbiologic response defined by negative fungal cultures; and (3) radiologic response through evaluation of cavity wall thickness and pleural thickness.

Consensus statement authors noted that the definition of clinical cure in CPA is “complicated by any remaining symptoms relating to underlying non-CPA lung disease,” and is therefore based on a Respiratory Symptom Score improvement of at least 25%.

They further noted that “The definition of cure in CPA is further hampered by the fact that there is no standard of care concerning treatment duration in CPA, except for the minimum duration of 6 months recommended in the current European and American guidelines for CCPA.”

Microbiologic cure in CPA may be difficult to demonstrate because culture of Aspergillus species lacks both sensitivity and specificity. Another notable limitation is the fact that radiologic changes require careful assessment, and computed tomography (CT) image quality parameters can vary. Additional studies are warranted, to define the most relevant CT imaging variables for evaluating treatment response.

Developers of the treatment outcome definitions described them as an important first step in moving toward more qualitative, prospective data on CPA, with the highest priority given to the development of state-of-the-art RCTs to study the treatment of CPA.

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference 

Van Braeckel E, Page I, Davidsen JR, et al; CPAnet. Treatment outcome definitions in chronic pulmonary aspergillosis: a CPAnet consensus statement. Eur Respir J. Published online March 2, 2022. doi:10.1183/13993003.02950-2021