patients with unclassi able ILD, including IPAF, were randomized to pirfenidone or placebo in a recent trial. The analysis of secondary endpoints suggested that pirfenidone may reduce lung function decline in unclassi able progressivebrotic ILD [147]. Similarly, pirfenidone was associated with a reduced decline of FVC in patients with progressive pulmonary brosis in the RELIEF trial which included some patients with CTD-ILD [148]. More data are needed to clarify the bene t of anti brotic drugs and to investigate the optimal combination with immunosuppressive therapy.

Lung Transplantation

It remains controversial whether patients with CTD-ILD are eligible for lung transplantation [79]. It is generally believed that due to extrapulmonary disease and a higher risk for allograft rejection, these patients have increased mortality after transplantation [80, 81]. However, recently, several studies have shed light on the role of lung transplantation in scleroderma and non-scleroderma-associated ILD [149]. Selected patients should be considered eligible for transplantation when there is progressive pulmonary disease despite the appropriate immunosuppressive therapy when the systemic component of the disease is well controlled [150, 151]. A recent study suggested that adjusted survival was not signi cantly different among subgroups of myositis-associated ILD patients compared with IPF patients after lung transplantation [149]. There is emergent evidence to support emergency lung transplantation in patients with rapidly progressive ILD associated with anti-MDA5 antibody [152].

Conclusion

Myositis, SLE, SS, and MCTD can affect almost the entire respiratory tract. However, several differences exist mainly regarding the reversibility of lung disease and the prognosis. Pleural effusion in SLE, ILD in myositis, and airway disease in SS represent frequent lung-associated manifestations. ILD and pulmonary hypertension in all these diseases are mainly associated with morbidity and mortality. Diagnosis relies on pulmonary function tests, HRCT, and serological testing. Immunosuppressive agents and steroids are the main treatments to date although randomized trials are lacking. Data regarding long-term follow-up are lacking but it is of great importance to identify patients having a high risk for disease progression and initiate early treatment. Several factors and biomarkers have been proposed to be related to the severity and prognosis of ILD in CTDs, but further research should validate these data in order to evaluate possible pathogenetic associations [153, 154].

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