Biomarkers for the diagnosis and treatment of fibrotic lung disease

Abstract

The present disclosure provides a method of treating a fibrotic lung disease in a subject comprising administering to the subject an effective amount of a therapeutic agent, wherein the subject is asymptomatic and wherein the subject is at risk of developing the fibrotic lung disease.

What is claimed is: 
     
         1 . A method of treating a fibrotic lung disease in a subject comprising administering to the subject an effective amount of a therapeutic agent, wherein the subject is asymptomatic and wherein the subject is at risk of developing the fibrotic lung disease. 
     
     
         2 . The method of  claim 1 , wherein the subject presents radiographic Usual Interstitial Pneumonia (UIP). 
     
     
         3 . The method of  claim 1  or  2 , wherein the subject has fibrotic interstitial lung disease (FILD). 
     
     
         4 . The method of  claim 1  or  2 , wherein the subject has an interstitial lung disease (ILD). 
     
     
         5 . The method of  claim 4 , where in the subject has rheumatoid arthritis-associated interstitial lung disease (RA-ILD). 
     
     
         6 . The method of any one of  claims 1 - 3 , wherein the subject has a blood relative with familial interstitial pneumonia (FIP). 
     
     
         7 . The method of  claim 6 , wherein the blood relative is a sibling. 
     
     
         8 . The method of any one of  claims 1 - 7 , wherein the subject has a mutation in a sequence encoding Mucin 5B (MUC5B), Telomerase RNA Component (TERC), Family with sequence similarity 13 member A (FAM13A), Telomerase Reverse Transcriptase (TERT), Desmoplakin (DSP), Zinc-alpha 2-Glycoprotein 1 (AZGP1), Oligonucleotide/oligosaccharide-binding Fold Containing 1 (OBFC1), ATPase Phospholipid Transporting 11A (ATP11A), Isovaleryl-CoA dehydrogenase (IVD)/Dispatched RND Transporter Family Member 2 (DISP2), Dipeptidyl Peptidase 9 (DPP9), Sialic Acid Binding Ig-Like Lectin 14 (SIGLEC14), Adrenomedullin 2 (ADM2), Tetraspanin 5 (TSPAN5), Calcium/Calmodulin-Dependent Protein Kinase Kinase 1 (CAMKK1), zinc figner with KRAB and SCAN domains 1 (ZKSCAN1), isovaleryl-CoA dehydrogenase (IVD), ATPase phospholipid transporting 11A (AK025511) or Matrix Metalloprotease-7 (MMP-7). 
     
     
         9 . The method of  claim 8 , wherein the mutation comprises a polymorphism in a sequence encoding a MUC5B promoter. 
     
     
         10 . The method of  claim 9 , wherein the polymorphism is rs35705950. 
     
     
         11 . The method of  claim 8 , wherein the mutation comprises a polymorphism in a sequence encoding a TERC 3′ untranslated region (UTR). 
     
     
         12 . The method of  claim 11 , wherein the polymorphism is rs2293607. 
     
     
         13 . The method of  claim 8 , wherein the mutation comprises a polymorphism in a sequence encoding intronic FAM13A. 
     
     
         14 . The method of  claim 13 , wherein the polymorphism is rs2609260. 
     
     
         15 . The method of  claim 8 , wherein the mutation comprises a polymorphism in a sequence encoding intronic TERT. 
     
     
         16 . The method of  claim 15 , wherein the polymorphism is rs4449583. 
     
     
         17 . The method of  claim 8 , wherein the mutation comprises a polymorphism in a sequence encoding intronic DSP. 
     
     
         18 . The method of  claim 17 , wherein the polymorphism is rs2076295. 
     
     
         19 . The method of  claim 8 , wherein the mutation comprises a polymorphism in a sequence encoding intronic ZKSCAN1. 
     
     
         20 . The method of  claim 19 , wherein the polymorphism is rs6963345. 
     
     
         21 . The method of  claim 8 , wherein the mutation comprises a polymorphism in a sequence encoding intronic OBFC1. 
     
     
         22 . The method of  claim 21 , wherein the polymorphism is rs2488000. 
     
     
         23 . The method of  claim 8 , wherein the mutation comprises a polymorphism in a sequence encoding an AK025511 3′ UTR. 
     
     
         24 . The method of  claim 23 , wherein the polymorphism is rs1278769. 
     
     
         25 . The method of  claim 8 , wherein the mutation comprises a polymorphism in a sequence encoding IVD. 
     
     
         26 . The method of  claim 25 , wherein the polymorphism is rs35700143. 
     
     
         27 . The method of  claim 8 , wherein the mutation comprises a polymorphism in a sequence encoding intronic DPP9. 
     
     
         28 . The method of  claim 27 , wherein the polymorphism is rs12610495. 
     
     
         29 . The method of any one of  claims 1 - 28 , wherein the fibrotic lung disease is pulmonary fibrosis, idiopathic pulmonary fibrosis (IPF), an interstitial lung abnormality (ILA), an asymptomatic ILA, interstitial lung disease (ILD) or rheumatoid arthritis-associated interstitial lung disease (RA-ILD). 
     
     
         30 . The method of any one of  claims 1 - 28 , wherein the fibrotic lung disease is ILD or RA-ILD. 
     
     
         31 . The method of any one of  claims 1 - 28 , wherein the fibrotic lung disease is pulmonary fibrosis or IPF. 
     
     
         32 . The method of any one of  claims 1 - 28 , wherein the fibrotic lung disease is IPF. 
     
     
         33 . The method of any one of  claims 1 - 32 , wherein the therapeutic agent comprises a N-acetylcysteine, pirfenidone, and nintedanib. 
     
     
         34 . The method of any one of  claims 1 - 32 , wherein the therapeutic agent comprises pirfenidone. 
     
     
         35 . The method of  claim 34 , wherein the effective dosage is about 2400 mg/day. 
     
     
         36 . The method of  claim 35 , wherein the effective dosage is administered orally as a capsule or a tablet. 
     
     
         37 . The method of  claim 35  or  36 , wherein the effective dosage is administered three times per day. 
     
     
         38 . The method of any one of  claims 35 - 37 , wherein the effective dosage is administered according to an escalating dosage regimen. 
     
     
         39 . The method of  claim 39 , wherein the escalating dosage regimen comprises
 (a) administering to the subject about 800 mg of pirfenidone per day for a first week;   (b) administering to the subject about 1600 mg of pirfenidone per day for a second week; and   (c) administering to the subject about 2400 mg of pirfenidone per day for the remainder of the treatment.   
     
     
         40 . The method of  claim 38 , wherein the escalating dosage regimen comprises
 (a) administering to the subject a capsule or tablet comprising about 250 mg of pirfenidone three times a day for a first week;   (b) administering to the subject two capsules or tablets comprising about 250 mg of pirfenidone three times a day for a second week; and   (c) administering to the subject three capsules or tablets comprising about 250 mg of pirfenidone three times a day for the remainder of the treatment.   
     
     
         41 . The method of  claim 40 , wherein the capsule or tablet comprises 267 mg of pirfenidone. 
     
     
         42 . The method of any one of  claims 1 - 32 , wherein the therapeutic agent comprises nintedanib. 
     
     
         43 . The method of  claim 42 , wherein the effective dosage is administered orally as a capsule or a tablet. 
     
     
         44 . The method of  claim 43 , wherein the effective dosage is about 300 mg/day. 
     
     
         45 . The method of  claim 42  or  43 , wherein the effective dosage is about 150 mg administered twice per day, wherein the daily doses are administered about 12 hours apart from one another. 
     
     
         46 . The method of  claim 43 , wherein the effective dosage is about 200 mg/day. 
     
     
         47 . The method of  claim 43  or  46 , wherein the effective dosage is about 100 mg administered twice per day, wherein the daily doses are administered about 12 hours apart from one another. 
     
     
         48 . The method of any one of  claims 42 - 47 , wherein the effective dosage is administered according to a modified or interrupted dosage regimen. 
     
     
         49 . The method of  claim 48 , wherein the modified or interrupted dosage regimen comprises
 (a) administering to the subject about 300 mg of nintedanib per day until the subject presents an elevated level of liver enzymes compared to a control level of liver enzymes;   (b) administering to the subject about 200 mg of nintedanib per day until the subject presents the control level of liver enzymes; and   (c) administering to the subject about 300 mg of nintedanib per day for the remainder of the treatment;   wherein the control level of liver enzymes is a level detected in the subject prior to an initiation of the treatment.   
     
     
         50 . The method of  claim 48 , wherein the modified or interrupted regimen comprises
 (a) administering to the subject a capsule or tablet comprising about 150 mg of nintedanib twice per day until the subject presents an elevated level of liver enzymes compared to a control level of liver enzymes;   (b) administering to the subject two capsules or tablets comprising about 100 mg twice per day until the subject presents an elevated level of liver enzymes compared to a control level of liver enzymes; and   (c) administering to the subject a capsule or tablet comprising about 150 mg of nintedanib twice per day for the remainder of the treatment;   wherein the control level of liver enzymes is a level detected in the subject prior to an initiation of the treatment.   
     
     
         51 . The method of any one of  claims 1 - 50 , wherein the therapeutic agent prevents the onset or development of a sign or symptom of the fibrotic lung disease. 
     
     
         52 . The method of any one of  claims 1 - 50 , wherein the therapeutic agent delays the onset or development of a sign or symptom of the fibrotic lung disease when compared to the expected onset of the a sign or symptom in the absence of treatment with the therapeutic agent. 
     
     
         53 . The method of any one of  claims 1 - 50 , wherein the therapeutic agent reduces the severity of a sign or symptom of the fibrotic lung disease when compared to the expected severity of the a sign or symptom in the absence of treatment with the therapeutic agent. 
     
     
         54 . The method of any one of  claims 51 - 53 , wherein at least one sign of the fibrotic lung disease is detectable before the subject presents a symptom of the fibrotic lung disease. 
     
     
         55 . The method of  claim 54 , wherein the at least one sign comprises gradual or unintended weight loss, clubbing of the fingers or toes, rapid and shallow breathing, fibrotic lesions in one or both lungs detectable by radiography, or a cough. 
     
     
         56 . The method of  claim 54 , wherein the symptom comprises shortness of breath during exercise, shortness of breath at rest, a dry and hacking cough, repeated bouts of coughing, and uncontrollable bouts of coughing. 
     
     
         57 . The method of any one of  claims 1 - 56 , wherein the method prevents the onset of a secondary condition associated with a severe form of the fibrotic lung disease. 
     
     
         58 . The method of  claim 57 , wherein secondary condition comprises a collapsed lung, an infected lung, a blood clot in a lung, lung cancer, respiratory failure, pulmonary hypertension, heart failure or death. 
     
     
         59 . A method of identifying a therapeutic agent or target thereof for the treatment of a fibrotic lung disease, comprising administering to a non-human subject a dose of a composition that modifies transcription or translation of a sequence encoding Mucin 5B (MUC5B), Telomerase RNA Component (TERC), Family with sequence similarity 13 member A (FAM13A), Telomerase Reverse Transcriptase (TERT), Desmoplakin (DSP), Zinc-alpha 2-Glycoprotein 1 (AZGP1), Oligonucleotide/oligosaccharide-binding Fold Containing 1 (OBFC1), ATPase Phospholipid Transporting 11A (ATP11A), Isovaleryl-CoA dehydrogenase (IVD)/Dispatched RND Transporter Family Member 2 (DISP2), Dipeptidyl Peptidase 9 (DPP9), Sialic Acid Binding Ig-Like Lectin 14 (SIGLEC14), Adrenomedullin 2 (ADM2), Tetraspanin 5 (TSPAN5), Calcium/Calmodulin-Dependent Protein Kinase Kinase 1 (CAMKK1) or Matrix Metalloprotease-7 (MMP-7), wherein the dose of the composition is tolerable to the non-human subject and wherein the dose of the composition is therapeutically effective. 
     
     
         60 . A method of identifying a therapeutic agent or target thereof for the treatment of a fibrotic lung disease, comprising administering to a non-human subject a composition that modifies an activity of a product of a sequence encoding MUC5B, TERC, FAM13A, TERT, DSP, AZGP1, OBFC1, ATP11A, IVD/DISP2, DPP9, SIGLEC14, ADM2, TSPAN5, CAMKK1 or MMP-7, wherein the dose of the composition is tolerable to the non-human subject and wherein the dose of the composition is therapeutically effective. 
     
     
         61 . The method of  claim 59 , wherein the composition that modifies transcription or translation decreases or inhibits transcription or translation. 
     
     
         62 . The method of  claim 61 , wherein the composition decreases or inhibits transcription or translation of a sequence encoding a gene selected from the group consisting of Leukotriene A4 Hydrolase (LTA4H), Surfactant Protein B (SFTPB), Breast Cancer Anti-Estrogen Resistance 3 (BCAR3), C-X-C motif Chemokine Ligand 13 (CXCL13), EPH Receptor A2 (EPHA2), Serum Amyloid A1 (SAA1), Phospholipase A2 Group IIA (PLA2G2A), Insulin-Like Growth Factor Binding Protein 3 (IGFBP3), C-C Motif Chemokine Ligand 28 (CCL28), S100 Calcium Binding Protein A12 (S100A12), Thromboxane A Synthase 1 (TBXAS1), Leukocyte Cell Derived Chemotaxin 1 (LECT1), Complement C3 (C3), Gastrin Releasing Peptide (GRP), C-Reactive Protein (CRP), Vitrin (VIT), Insulin-Like Growth Factor Binding Protein 1 (IGFBP1), Family with Sequence Similarity 173 Member A (FAM173A), Natriuretic Peptide A (NPPA), Secreted Frizzled Related Protein 1 (SFRP1), Ezrin (EZR), Inter-Alpha-Trypsin Inhibitor Heavy Chain Family Member 5 (ITIH5), Pleckstrin and Sec7 Domain Containing 2 (PSD2), Galectin 3 Binding Protein (LGALS3BP), Catenin Beta 1 (CTNNB1), Chromodomain Y Like 2 (CDYL2), Matrix Metallopeptidase 7 (MMPI), Apolipoprotein B (APOB), Proline and Arginine Rich End Leucine Rich Repeat Protein (PRELP), Eukaryotic Translation Initiation Factor 1A, X-linked (EIF1AX), Mesencephalic Astrocyte Derived Neurotrophic Factor (MANF), TNF Receptor Superfamily Member 13C (TNFRSF13C), Deformed Epidermal Autoregulatory Factor 1 transcription factor (DEAF1), Tumor Protein Translationally-Controlled 1 (TPT1), Unc-5 Netrin Receptor B (UNCSB), Phosphatidylethanolamine Binding Protein 1 (PEBP1), Syntaxin 8 (STX8), Polymeric Immunoglobulin Receptor (PIGR), Adenine Phosphoribosyltransferase (APRT), Matrix Metallopeptidase 3 (MMP3), Galectin 7 (LGALS7), Bruton Tyrosine Kinase (BTK), NSFL1 Cofactor (NSFL1C), FER Tyrosine Kinase (FER), Regenerating Family Member 1 Beta (REG1B), SMAD Family Member 2 (SMAD2), Interleukin 1 Receptor Like 1 (IL1RL1), C-C Motif Chemokine Ligand 18 (CCL18), Acid Phosphatase 2 Lysosomal (ACP2), Eukaryotic Translation Initiation Factor 4E Family Member 2 (EIF4E2), Neurexin 3 (NRXN3), IGF Like Family Member 1 (IGFL1), NME/NM23 Nucleoside Diphosphate Kinase 1 (NME1), Potassium Voltage-Gated Channel Isk-Related Family Member 1-Like (KCNE1L) or Neurexophilin 2 (NXPH2). 
     
     
         63 . The method of  claim 59 , wherein the composition that modifies transcription or translation increases or activates transcription or translation. 
     
     
         64 . The method of  claim 63 , wherein the composition increases or activates transcription or translation of a sequence encoding a gene selected from the group consisting of Surfactant Protein D (SFTPD), Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH), Histone Cluster 1 H1 Family Member C (HIST1H1C), YTH Domain Containing 1 (YTHDC1), Plexin A1 (PLXNA1), Serine Peptidase Inhibitor Kazal Type 6 (SPINK6), LDL Receptor Related Protein Associated Protein 1 (LRPAP1), Secretoglobin Family 3A Member 1 (SCGB3A1), H2A Histone Family Member Z (H2AFZ) or Chromosome 1 Open Reading Frame 162 (C1 orf162). 
     
     
         65 . The method of  claim 60 , wherein the composition that modifies an activity decreases or inhibits the activity. 
     
     
         66 . The method of  claim 65 , wherein the composition decreases or inhibits the activity of a sequence encoding a gene selected from Leukotriene A4 Hydrolase (LTA4H), Surfactant Protein B (SFTPB), Breast Cancer Anti-Estrogen Resistance 3 (BCAR3), C-X-C motif Chemokine Ligand 13 (CXCL13), EPH Receptor A2 (EPHA2), Serum Amyloid A1 (SAA1), Phospholipase A2 Group IIA (PLA2G2A), Insulin-Like Growth Factor Binding Protein 3 (IGFBP3), C-C Motif Chemokine Ligand 28 (CCL28), 5100 Calcium Binding Protein A12 (S100A12), Thromboxane A Synthase 1 (TBXAS1), Leukocyte Cell Derived Chemotaxin 1 (LECT1), Complement C3 (C3), Gastrin Releasing Peptide (GRP), C-Reactive Protein (CRP), Vitrin (VIT), Insulin-Like Growth Factor Binding Protein 1 (IGFBP1), Family with Sequence Similarity 173 Member A (FAM173A), Natriuretic Peptide A (NPPA), Secreted Frizzled Related Protein 1 (SFRP1), Ezrin (EZR), Inter-Alpha-Trypsin Inhibitor Heavy Chain Family Member 5 (ITIH5), Pleckstrin and Sec7 Domain Containing 2 (PSD2), Galectin 3 Binding Protein (LGALS3BP), Catenin Beta 1 (CTNNB1), Chromodomain Y Like 2 (CDYL2), Matrix Metallopeptidase 7 (MMPI), Apolipoprotein B (APOB), Proline and Arginine Rich End Leucine Rich Repeat Protein (PRELP), Eukaryotic Translation Initiation Factor 1A, X-linked (EIF1AX), Mesencephalic Astrocyte Derived Neurotrophic Factor (MANF), TNF Receptor Superfamily Member 13C (TNFRSF13C), Deformed Epidermal Autoregulatory Factor 1 transcription factor (DEAF1), Tumor Protein Translationally-Controlled 1 (TPT1), Unc-5 Netrin Receptor B (UNCSB), Phosphatidylethanolamine Binding Protein 1 (PEBP1), Syntaxin 8 (STX8), Polymeric Immunoglobulin Receptor (PIGR), Adenine Phosphoribosyltransferase (APRT), Matrix Metallopeptidase 3 (MMP3), Galectin 7 (LGALS7), Bruton Tyrosine Kinase (BTK), NSFL1 Cofactor (NSFL1C), FER Tyrosine Kinase (FER), Regenerating Family Member 1 Beta (REG1B), SMAD Family Member 2 (SMAD2), Interleukin 1 Receptor Like 1 (IL1RL1), C-C Motif Chemokine Ligand 18 (CCL18), Acid Phosphatase 2 Lysosomal (ACP2), Eukaryotic Translation Initiation Factor 4E Family Member 2 (EIF4E2), Neurexin 3 (NRXN3), IGF Like Family Member 1 (IGFL1), NME/NM23 Nucleoside Diphosphate Kinase 1 (NME1), Potassium Voltage-Gated Channel Isk-Related Family Member 1-Like (KCNE1L) or Neurexophilin 2 (NXPH2). 
     
     
         67 . The method of  claim 60 , wherein the composition that modifies an activity increases or activates the activity. 
     
     
         68 . The method of  claim 67 , wherein the composition increases or activates the activity of a sequence encoding Surfactant Protein D (SFTPD), Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH), Histone Cluster 1 H1 Family Member C (HIST1H1C), YTH Domain Containing 1 (YTHDC1), Plexin A1 (PLXNA1), Serine Peptidase Inhibitor Kazal Type 6 (SPINK6), LDL Receptor Related Protein Associated Protein 1 (LRPAP1), Secretoglobin Family 3A Member 1 (SCGB3A1), H2A Histone Family Member Z (H2AFZ) or Chromosome 1 Open Reading Frame 162 (Clorf162). 
     
     
         69 . The method of any one of  claims 60 - 68 , wherein the non-human subject is a mammal. 
     
     
         70 . The method of any one of  claims 60 - 69 , wherein the mammal is genetically-modified. 
     
     
         71 . The method of  claim 70 , wherein the genetically-modified mammal is a model organism for the fibrotic lung disease. 
     
     
         72 . The method of any one of  claims 60 - 71 , wherein the fibrotic lung disease is pulmonary fibrosis, idiopathic pulmonary fibrosis (IPF), an interstitial lung abnormality (ILA), or an asymptomatic ILA. 
     
     
         73 . The method of any one of  claims 60 - 71 , wherein the fibrotic lung disease is pulmonary fibrosis or IPF. 
     
     
         74 . The method of any one of  claims 60 - 71 , wherein the fibrotic lung disease is IPF. 
     
     
         75 . The method of any one of  claims 60 - 74 , wherein the non-human subject carries a mutation in a sequence encoding MUC5B. 
     
     
         76 . The method of  claim 75 , wherein the mutation comprises a polymorphism in a sequence encoding a MUC5B promoter. 
     
     
         77 . The method of  claim 76 , wherein the polymorphism is rs35705950. 
     
     
         78 . The method of any one of  claims 60 - 77 , wherein the non-human subject carries a mutation in a sequence encoding TERC, FAM13A, TERT, DSP, AZGP1, OBFC1, ATP11A, IVD/DISP2, DPP9, SIGLEC14, ADM2, TSPAN5, CAMKK1 or MMP-7. 
     
     
         79 . The method of any one of  claims 60 - 78 , wherein the composition prevents the onset or development of a sign or symptom of the fibrotic lung disease. 
     
     
         80 . The method of any one of  claims 60 - 78 , wherein the composition delays the onset or development of a sign or symptom of the fibrotic lung disease when compared to the expected onset of the a sign or symptom in the absence of treatment with the composition. 
     
     
         81 . The method of  claim 80 , wherein the composition 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 when treated using a standard therapeutic intervention. 
     
     
         82 . The method of any one of  claims 60 - 78 , wherein the composition 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 composition. 
     
     
         83 . The method of  claim 24 , wherein the composition reduces the severity of a sign or symptom of the fibrotic lung disease when compared to the expected severity of the sign or symptom when treated using a standard therapeutic intervention. 
     
     
         84 . The method of  claim 81  or  83 , wherein the standard therapeutic intervention comprises a N-acetylcysteine, pirfenidone, and nintedanib. 
     
     
         85 . The method of  claim 81  or  83 , wherein the standard therapeutic intervention comprises pirfenidone. 
     
     
         86 . The method of  claim 85 , wherein an effective dosage of pirfenidone is about 2400 mg/day. 
     
     
         87 . The method of  claim 86 , wherein the effective dosage is administered orally as a capsule or a tablet. 
     
     
         88 . The method of  claim 86  or  87 , wherein the effective dosage is administered three times per day. 
     
     
         89 . The method of any one of  claims 85 - 88 , wherein the effective dosage is administered according to an escalating dosage regimen. 
     
     
         90 . The method of  claim 85 ,  86  or  89 , wherein the escalating dosage regimen comprises
 (a) administering to the non-human subject about 800 mg of pirfenidone per day for a first week; 
 (b) administering to the non-human subject about 1600 mg of pirfenidone per day for a second week; and 
 (c) administering to the non-human subject about 2400 mg of pirfenidone per day for the remainder of the treatment. 
 
     
     
         91 . The method of  claim 85 ,  86  or  89 , wherein the escalating dosage regimen comprises
 (a) administering to the non-human subject a capsule or tablet comprising about 250 mg of pirfenidone three times a day for a first week; 
 (b) administering to the non-human subject two capsules or tablets comprising about 250 mg of pirfenidone three times a day for a second week; and 
 (c) administering to the non-human subject three capsules or tablets comprising about 250 mg of pirfenidone three times a day for the remainder of the treatment. 
 
     
     
         92 . The method of  claim 91 , wherein the capsule or tablet comprises 267 mg of pirfenidone. 
     
     
         93 . The method of  claim 81  or  83 , wherein the standard therapeutic intervention comprises nintedanib. 
     
     
         94 . The method of  claim 93 , wherein an effective dosage of nintedanib is administered orally as a capsule or a tablet. 
     
     
         95 . The method of  claim 94 , wherein the effective dosage is about 300 mg/day. 
     
     
         96 . The method of  claim 94  or  95 , wherein the effective dosage is about 150 mg administered twice per day, wherein the daily doses are administered about 12 hours apart from one another. 
     
     
         97 . The method of  claim 94 , wherein the effective dosage is about 200 mg/day. 
     
     
         98 . The method of  claim 94  or  95 , wherein the effective dosage is about 100 mg administered twice per day, wherein the daily doses are administered about 12 hours apart from one another. 
     
     
         99 . The method of any one of  claims 79 - 98 , wherein the non-human subject presents at least one sign of the fibrotic lung disease. 
     
     
         100 . The method of  claim 99 , wherein the at least one sign comprises gradual or unintended weight loss, clubbing of the fingers or toes, rapid and shallow breathing, fibrotic lesions in one or both lungs detectable by radiography, or a cough. 
     
     
         101 . The method of any one of  claims 60 - 100 , wherein the compound prevents the onset of a secondary condition associated with a severe form of the fibrotic lung disease. 
     
     
         102 . The method of  claim 100 , wherein the compound prevents the onset for at 1 year, 2 years, 3 years, 4 years, 5 years or any whole or fractional number of years in between. 
     
     
         103 . The method of  claim 101  or  102 , wherein secondary condition comprises a collapsed lung, an infected lung, a blood clot in a lung, lung cancer, respiratory failure, pulmonary hypertension, heart failure or death. 
     
     
         104 . A composition for the treatment of a fibrotic lung disease identified by the method of any one of  claims 60 - 103 . 
     
     
         105 . A method of treating a fibrotic lung disease in a human subject comprising administering to the subject the composition of  claim 104 , wherein the subject is asymptomatic and wherein the subject is at risk of developing the fibrotic lung disease. 
     
     
         106 . The method of  claim 105 , wherein the human subject presents radiographic Usual Interstitial Pneumonia (UIP). 
     
     
         107 . The method of  claim 105  or  106 , wherein the human subject has fibrotic interstitial lung disease (FILD). 
     
     
         108 . The method of any one of  claims 105 - 107 , wherein the human subject has a blood relative with familial interstitial pneumonia (FIP). 
     
     
         109 . The method of  claim 108 , wherein the blood relative is a sibling. 
     
     
         110 . The method of any one of  claims 105 - 109 , wherein the human subject has a mutation in a sequence encoding MUC5B, TERC, FAM13A, TERT, DSP, AZGP1, OBFC1, ATP11A, IVD/DISP2, DPP9, SIGLEC14, ADM2, TSPAN5, CAMKK1 or MMP-7. 
     
     
         111 . The method of  claim 110 , wherein the mutation comprises a polymorphism in a sequence encoding a MUC5B promoter. 
     
     
         112 . The method of  claim 111 , wherein the polymorphism is rs35705950. 
     
     
         113 . The method of any one of  claims 105 - 112 , wherein the fibrotic lung disease is pulmonary fibrosis, idiopathic pulmonary fibrosis (IPF), an interstitial lung abnormality (ILA), or an asymptomatic ILA. 
     
     
         114 . The method of any one of  claims 105 - 112 , wherein the fibrotic lung disease is pulmonary fibrosis or IPF. 
     
     
         115 . The method of any one of  claims 105 - 112 , wherein the fibrotic lung disease is IPF. 
     
     
         116 . The method of any one of  claims 105 - 112 , wherein the method prevents the onset of a secondary condition associated with a severe form of the fibrotic lung disease. 
     
     
         117 . The method of  claim 116 , wherein secondary condition comprises a collapsed lung, an infected lung, a blood clot in a lung, lung cancer, respiratory failure, pulmonary hypertension, heart failure or death.