Emerging diagnostic techniques for connective tissue disease associated interstitial lung disease: exploration and translation

Abstract

Connective tissue disease associated interstitial lung disease (CTD-ILD) is a major cause of morbidity and mortality. Accurate diagnosis can be challenging due to marked variability in disease behaviour and no consensus for its assessment or classification. The studies comprising this thesis centre on the evolving classification and novel diagnostic techniques for CTD-ILD.

We describe the first Australian interstitial pneumonia with autoimmune features (IPAF) cohort, encompassing ILD patients with incomplete features for a definable CTD. IPAF identified a heterogeneous phenotype overlapping with CTD-ILD that was not predictive of survival outcomes.

The myositis autoantibody line immunoblot assay (MA-LIA) is increasingly used for idiopathic inflammatory myositis (IIM)-ILD diagnosis, but not validated in ILD. The MA-LIA supported IIM-ILD diagnosis with high specificity, and clinical interpretation was optimised by the level of MA-positivity and clinicoradiologic features.

Nailfold capillaroscopy (NFC), validated in systemic sclerosis (SSc), has been proposed to identify CTD-ILD. Studies in well-defined ILD populations are lacking, and traditional NFC techniques are not widely accessible. In prospective study, NFC by handheld smartphone-dermatoscope improved CTD-ILD identification beyond routine ILD assessment.

Finally, 28 serum biomarkers for SSc-ILD diagnosis were explored in 640 patients with SSc (with and without ILD), IPF (fibrotic controls), and healthy controls. A simple, three-biomarker index was predictive of the presence SSc-ILD relative to non-fibrotic controls, with internal replication and adjustment for clinical variables.

Conclusion: We describe the evolving role of non-invasive, diagnostic modalities with routine assessment for CTD-ILD diagnosis in defined, real-world ILD cohorts. Clinical translation and interrogation of the prognostic utility in prospective, multicentre studies is required. The management and prognosis of IPAF remains a critical unmet need.