Biomarkers for the diagnosis and treatment of fibrotic lung disease

A method of treating a fibrotic lung disease in an asymptomatic subject within an at-risk population comprising:

• a) identifying a subject with pre-clinical pulmonary fibrosis (PrePF) or a subject that has a blood relative with a lung disease selected from the group consisting of familial interstitial pneumonia (FIP), pre-clinical pulmonary disease, pulmonary fibrosis, idiopathic pulmonary fibrosis (IPF), an interstitial lung abnormality (ILA), an asymptomatic ILA, interstitial lung disease (ILD), fibrotic interstitial lung disease (FILD) and rheumatoid arthritis-associated interstitial lung disease (RA-ILD);
• b) determining that the subject has a mutation comprising a polymorphism in a sequence encoding a MUC5B promoter and at least one mutation selected from
• (i) a polymorphism in a sequence encoding intronic FAM13A or a regulatory sequence thereof;
• (ii) a polymorphism in a sequence encoding intronic TERT or a regulatory sequence thereof;
• (iii) a polymorphism in a sequence encoding intronic ZKSCAN1 or a regulatory sequence thereof;
• (iv) a polymorphism in a sequence encoding intronic OBFC1 or a regulatory sequence thereof;
• (v) a polymorphism in a sequence encoding intronic IVD or a regulatory sequence thereof;
• and
• (vi) a polymorphism in a sequence encoding ATP11A or a regulatory sequence thereof;
• and
• c) administering a therapeutic agent in an amount effective for the treatment of fibrotic lung disease to the subject, wherein the therapeutic agent:
• (i) prevents the onset or development of a sign or symptom of the fibrotic lung disease;
• (ii) delays the onset or development of a sign or symptom of the fibrotic lung disease when compared to the expected onset of the sign or symptom in the absence of treatment with the therapeutic agent;
• or
• (iii) agent reduces the severity of a sign or symptom of the fibrotic lung disease when compared to the expected severity of the sign or symptom in the absence of treatment with the therapeutic agent.