CT findings in fibrotic lung disease: reassessment of the reliability and utility of the status quo in diagnosis and outcome

Abstract

Hypersensitivity pneumonitis is a pulmonary disease thought to result from an inappropriate immune response to inhaled organic antigens. Whilst historically classified by the duration of symptoms, a categorisation based on the presence of pulmonary fibrosis is now favoured, as this is related to disease course and response to treatment. Furthermore, the presence of fibrosis invokes a different radiological differential diagnosis. In addition to this paradigm shift, several short comings of the literature in fibrotic lung disease require scrutiny. CT guidelines use the presence of ‘mosaic attenuation’ to distinguish fibrotic hypersensitivity pneumonitis (FHP) from its closest radiological differential, idiopathic pulmonary fibrosis (IPF), but these are unvalidated and indeed untested. The presence of increased proportion of lymphocytes on bronchoalveolar lavage (BAL) is used to support a diagnosis of FHP, but this technique has never been validated with regards to diagnostic utility or prognosis. Finally, the majority of publications examining CT signs of fibrotic lung disease are subject to incorporation bias, whereby the CT data under study is also used to define cases. A re-examination of the CT signs in three separate cohorts of patients with fibrotic lung diseases is presented. Firstly, undertaking a detailed examination of the various forms of mosaic attenuation, against high confidence diagnoses FHP and IPF agnostic to CT data, in a test and validation cohort. A large prospective cohort of patients undergoing BAL who have a ‘reasonable differential’ for FHP, defined without CT data, is also examined. An overlooked CT sign of mosaic attenuation, the ‘headcheese’ sign, is found to be highly specific for a diagnosis of FHP, as opposed to IPF, and is validated in an external cohort. BAL lymphocyte proportion is shown to relate to disease extent, and BAL lymphocytosis is found to be prognostic in fibrotic lung disease.