Methods and compositions relating to airway dysfunction
Described herein are methods relating to the diagnosis, prognosis, and treatment of airway dysfunction, e.g., bronchiectasis by detecting gene expression in a sample obtained from a subject. Exemplary samples include a bronchial brushing, nasal brushing, sputum, or peripheral blood sample.
1. A method comprising detecting the level of expression of one or more genes selected from at least one of:
at least one gene of Group A, at least one gene of Group B, at least one gene of Group C,
at least one gene of Group D, and at least one gene of Group E;
in a bronchial brushing, nasal brushing, or sputum sample obtained from a subject; and
the level of expression products of no more than 100 other genes is determined;
wherein:
i) the at least one gene of Group A comprises Zinc Finger Protein 493 (ZNF493);
ii) the at least one gene of Group B comprises Fat Atypical Cadherin 2 (FAT2);
iii) the at least one gene of Group C comprises at least one of: Argininosuccinate Lyase (ASL) and Coiled-Coil Domain Containing 160 (CCDC160);
iv) the at least one gene of Group D comprises at least one of: Long Intergenic Non-Protein Coding RNA 888 (LINC00888) and F-Box Protein 16 (FBX016); or
v) the at least one gene of Group E comprises DnaJ Heat Shock Protein Family Member C22 (DNAJC22); and
wherein Group A consists of:
ZNF493; ZNF519; ENSG00000271430; MYH7B; MKRNSP; ENSG00000270574;
VN1R83P; ENSG00000268555; ZNF577; NBPF11; SCUBE2; SGK2; BNIPL;
ENSG00000271533; PCDHGB6; LRP1; PCDHGB7; ENSG00000262877; ABCC5;
PMS2P4; TTC28-AS1; PRR24; CD81; RGL3; PTPRS; ENSG00000271011; ZNF286B;
GNB1L; PCDHGA12; SLC16A10; ZNF66; ENSG00000261584; ZNF311; ZNF718;
ENSG00000223745; RAB40A; ENSG00000268119; PCDHGA4; ENSG00000270589;
ENSG00000256142; DLL1; BRAFP1; PCDHGA11; FTX; FLYWCH1; NOVA1;
KANSL1; ZNF826P; ENSG00000196295; ENSG00000229036; TLE3; KLF8; LONRF2;
PCDHGB8P; ENSG00000259326; AOC2; RAPGEFL1; ARL10; ADAMTS10;
ENSG00000250303; TSHZ2; CRYM-AS1; ENSG00000213971; TVP23CP2;
ENSG00000234978; ZBTB12; PCDHGA9; RPS3AP29; KSR2; ENOSF1;
ENSG00000233175; ENSG00000260729; LINC00664; ZNF257; POU5F1P5; FN3K;
ZNF814; CYP2C19; ENSG00000270096; PDE11A; FAM13A-AS1; KCNMA1;
ENSG00000247270; ENSG00000270019; ENSG00000270154; ENSG00000248445;
ENSG00000234129; ENSG00000267169; ENSG00000261423; C1RL-AS1; NONOP2;
SLC26A5; STX18-AS1; AMT; ENSG00000232626; ENSG00000235834; RN7SL648P;
ENSG00000254634; ENSG00000236144; ACAP2-IT1; ENSG00000268472; TDRD6;
ENSG00000272563; SUDS3P1; PCDHGB4; FOXO3B; ENSG00000272977;
LINC00176; MY015A; GHRLOS; TTC28; ENSG00000271840; NBPF20; VANGL2;
JMJD7-PLA2G4B; ENSG00000267940; OGDHL; ENSG00000206195; KLF11;
TAPT1-AS1; TMEM59L; ACKR3; ENSG00000184441; KAT2A; SULT1A3; SIPA1L2;
RPL5P4; CTSF; ZNF208; CYP2E1; L3MBTL1; BENDS; ACACB; ENSG00000261087;
NFATC4; CES4A; ZFP2; BSN; ENSG00000254469; ZNF514; ENSG00000176593;
ENSG00000232116; OTX1; ENSG00000269918; AVIL; ENSG00000271971; MICU3;
GRAMD1A; C1QTNF6; KIF3C; ZACN; RPL7P46; PLA2G4F; SLX1A-SULT1A3;
ZNF135; OR2A9P; TMEM63C; TG; ENSG00000261502; ARLSB-AS1; ZNF705E;
PCDHGC5; GOLGA8A; PLEKHH1; PPAP2B; ENSG00000267481; OR7E7P;
ENSG00000259585; ENSG00000225210; TSSK1B; ENSG00000215022; STRC;
ENSG00000250290; UBAP1L; ENSG00000264112; LINC00959; SPATA41; CRYGS;
ZNF862; ENSG00000225032; PCED1B; SMAD6; ENSG00000264538; FRS3;
ENSG00000256139; NSUN5P1; LTBP4; ENSG00000267053; ENSG00000171282;
PCDHGA7; GREB1; ADAM1A; ENSG00000251323; ENSG00000271917;
ENSG00000253366; ENSG00000225241; IL11RA; PCDHB18; FAM85A; UPK3BP1;
ACADL; ENSG00000236055; ZNF285; and ENSG00000239665;
wherein Group B consists of:
LRP4; ZNF578; FAT2; FGFR3; MCC; SLC26A9; MKL2; AGKP1; KRT15; CSRNP3;
PKP1; FSTL3; NEURL1; JAG2; DACT2; TRO; NDRG1; ADCY2; IGSF3; NLGN4Y;
SALL2; SUSD4; ARSG; BCL11A; RNF165; TP63; UGT1A7; CACNA1A; PAPPA;
SULF2; RGS17; PIK3R1; SNX31; COL4A5; SNAI2; UGT1A5; SYNGR1;
ENSG00000213963; SV2A; FGFR2; KANK1; WNTSA; FZD7; SRRM3; SEMASA;
ZNF471; HYKK; PPM1L; ARHGAP28; UGT1A8; ARHGEF10; MT1X; FOXN1;
NTF3; SMOC2; USP44; FBXL16; EPAS1; EGFR; PTPRG; NEB; GDNF-AS1;
FAM117B; RERG; ZBTB47; ADAMTS9-AS2; PAPLN; NCKAP5; STK32A; FAT4;
LGR6; TPTE2P1; SLITRK6; TNC; EVPLL; POMGNT1; KCTD15; WSCD1; KIF7;
KIF1A; FRAS1; KRT5; ENSG00000174171; CDH11; ZFP28; GPRASP1; PRKY;
COL4A6; LSAMP; SYDE1; ENSG00000271880; RGMA; BOC; SLC2A9; WNT2B;
CDHR1; ENSG00000248705; TGFB2; NCAM1; LTB4R; TLE2; AP3B2; LRRC2;
MEGF6; RNF212; FBLN1; SLCO4C1; WNT3A; ZNF665; ESYT3; FREM2;
ARHGEF4; LURAP1; SETP21; COL7A1; B4GALNT4; FBN1; ZNF90; LRP1B;
ABCC9; ENSG00000256995; S1PR5; EFS; NPTX1; ENSG00000260197; UGT1A2P;
SLC16A2; MAN1C1; MARVELD1; FGF9; CIB2; LGR5; KIRREL; LTB4R2; SPTB;
ITPRIPL1; PHLDB1; SPRY1; DEPTOR; EPHA4; TTTY10; TET1; ZNF667; EPHB6;
ENSG00000250685; ENSG00000271738; IGFBP4; ARHGEF25; TRPV6; KCNB2;
SPRY2; DLK2; and CLUL1;
wherein Group C consists of:
ENSG00000258545; ENSG00000257512; ASL; CCDCl60; SMIM6; PLCB1;
TMEM125; C20orf201; CD38; ENSG00000268129; TSPAN2; DAPP1; IDH2; APOL4;
HRASLS2; C9orf66; BFSP1; DLG1-AS1; C16orf54; LAMP3; LYSMD2; PSMB9;
NR5A2; ENSG00000005189; COCH; CCDC67; XK; OR7E14P; LINC00589; F5;
PDE3A; RTP4; ENSG00000253474; ANTXR2; HCG4P3; FATE1; FBLN5;
ENSG00000259153; NMI; ENSG00000231901; PSMB8; SERF1A; MOCOS; GSTM1;
RAMP1; LINC00643; PRKG1; ENSG00000225335; LMO3; ENSG00000270659;
CNTF; ENSG00000272463; ENSG00000260552; FHL1; KIF18A; RARRES3;
TNFAIP8L3; PSMB10; ENSG00000227053; DPF1; GSTT2; TMEM176B; RPL7AP64;
CDKN2D; ENSG00000196826; MUC12; ENSG00000260806; GLIPR2; USP18;
ENSG00000238837; Cl9orf38; ABCC2; VWASA; SGOL2; PKIB; KLB; TMEM200C;
and SHH;
wherein Group D consists of:
LINC00888; FBX016; SCRN1; ENSG00000259508; LINC00467; MPC2; KIAA0895;
SEPW1; CALML4; ERICH2; SLC51B; FAM69A; ENSG00000259802;
ENSG00000249241; MRPS31; CCDCl76; DUSP14; TMEM17; VIM-AS1; GSTP1;
CCT6B; RUVBL1; ENSG00000267325; AAED1; SLC25A4; Clorf192; DYRK3;
ELK3; ENSG00000272092; LINC00326; B9D2; LINC00240; IFT43; CPNE8; SMIM22;
PHTF1; Cllorf70; APOO; SPAG1; CCDC65; DPCD; CCDCl04; RABL5;
ENSG00000263450; DNPH1; ENSG00000234478; ENSG00000233170; LINC01132;
IQCK; ENSG00000257698; ROPN1L; AHSA1; C21orf59; C15orf65;
ENSG00000271133; IL7; LXN; DNAL4; C6orf99; MAPS; Clorf189; LINC00948;
DHX40; GFM2; LRRC34; SPA17; ENSG00000261465; C21orf119; TUBA1A; GJB7;
TOMM34; NUDT7; LINC00908; ClOorf107; C20orf85; ARL3; DNAL1; CNTN5;
MYCBP; ENSG00000266916; ENSG00000260057; CYSTM1; ENSG00000236028;
UFC1; C9orf135; ENSG00000263011; DSTN; IFT57; C9orf116; MORN2; PPIL6;
LCA5L; DPY30; CEP97; AKAP14; ENSG00000272514; CAPSL; CC2D2A; OSCP1;
DYX1C1; PNLDC1; SPATA4; ZNF165; IGFBP7; CXorf58; C15orf26;
ENSG00000224049; TCTEX1D2; TCEAL3; ENSG00000258940; DYNC2LI1; and
PKIG; and
wherein Group E consists of:
C8orf76; DNAJC22; ENSG00000250508; SEC23B; SLC35B1; KRT23; MRPL47; NIP7;
NDUFV2; KCTD14; GTF3C6; ISOC2; SAP30; HSBP1; PSMA5; ENSG00000262823;
SEC61B; TIMM17A; CLIC5; RPN1; LACC1; MRPL54; PSMB5; UCHL3; C14orf166;
C2orf47; PPP1R2; C5orf15; DNAJA1; HIGD1A; MIF; RAB9A; CASP7; POMP;
SERHL2; BCCIP; GRK5; UBB; PARK7; CHCHD2; FAR2; DNAJC12; NT5C3A;
UFM1; CDK7; CCDCl67; CCT2; MORF4L2; CALM2; C4orf19; PSENEN; HSPA8;
GTF2B; NDUFAB1; DAD1; SMS; KBTBD4; AGR3; GPR160; TCP1; PSMA3; STS;
LAMTOR5; COX17; UGCG; PSMA6; COX6A1; SLC41A2; HSP90B1; PDIA4; NXT2;
LACTB2; RFK; DYNLT1; COX7A2; BOLA3; MTFP1; FOLH1; PSMD10; NDUFB4;
MRPL39; Clorf122; MMADHC; SEC61G; NDUFB3; SSR4; NRIP1; ANG; WBP5;
ABRACL; BIK; MRPS36; MOSPD1; SLIRP; MRPL13; CD24P4; ENSG00000113811;
LINC00493; SOD1; IGFBP6; PRDX4; ACTR6; SDF2L1; C19orf10; IL23A; BZW1P2;
CXCL17; and USMG5.
2. The method of claim 1 , wherein the sample obtained from the subject is a bronchial brushing or nasal brushing sample.
3. A method of treating airway dysfunction, the method comprising administering:
a) a chest CT, smoking cessation, and/or avoiding aspiration risk and inhalational injury to a subject determined to have a decreased level of expression of at least one of:
at least one gene of Group A, and at least one gene of Group B; and/or
an increased level of expression of at least one of:
at least one gene of Group C, at least one gene of Group D, and at least one gene of Group E;
b) an immunosuppressant and/or a more aggressive immunosuppressant regimen to a subject who had previously received and lung transplant and was determined to have a decreased level of expression of at least one of:
at least one gene of Group A, and at least one gene of Group B; and/or
an increased level of expression of at least one of:
at least one gene of Group C, at least one gene of Group D, and at least one gene of Group E; or
c) an immunosuppressant and/or a more aggressive immunosuppressant regimen to a subject who had previously received a bone marrow or blood stem cell transplant and was determined to have a decreased level of expression of at least one of:
at least one gene of Group A, and at least one gene of Group B; and/or
an increased level of expression of at least one of:
at least one gene of Group C, at least one gene of Group D, and at least one gene of Group E;
d) an inhibitor of dipeptidyl peptidase 1 (DPP1) to a subject who had previously received a bone marrow or blood stem cell transplant and was determined to have a decreased level of expression of at least one of:
at least one gene of Group A, and at least one gene of Group B; and/or
an increased level of expression of at least one of:
at least one gene of Group C, at least one gene of Group D, and at least one gene of Group E; and/or
e) an inhibitor of DPP1 to a subject who has chronic obstructive pulmonary disease (COPD), asthma, or rheumatoid arthritis and was determined to have a decreased level of expression of at least one of:
at least one gene of Group A, and at least one gene of Group B; and/or
an increased level of expression of at least one of:
at least one gene of Group C, at least one gene of Group D, and at least one gene of Group E; and
wherein a decreased level of expression is decreased relative to the level of the at least one gene in a population of subject who do not have or are not diagnosed as having, and/or do not exhibit signs or symptoms of airway dysfunction, and an increased level of expression is increased relative to the level of the at least one gene in a population of subject who do not have or are not diagnosed as having, and/or do not exhibit signs or symptoms of airway dysfunction;
wherein Group A consists of:
ZNF493; ZNF519; ENSG00000271430; MYH7B; MKRN5P; ENSG00000270574;
VN1R83P; ENSG00000268555; ZNF577; NBPF11; SCUBE2; SGK2; BNIPL;
ENSG00000271533; PCDHGB6; LRP1; PCDHGB7; ENSG00000262877; ABCC5;
PMS2134; TTC28-AS1; PRR24; CD81; RGL3; PTPRS; ENSG00000271011; ZNF286B;
GNB1L; PCDHGA12; SLC16A10; ZNF66; ENSG00000261584; ZNF311; ZNF718;
ENSG00000223745; RAB40A; ENSG00000268119; PCDHGA4; ENSG00000270589;
ENSG00000256142; DLL1; BRAFP1; PCDHGA11; FTX; FLYWCH1; NOVA1;
KANSL1; ZNF826P; ENSG00000196295; ENSG00000229036; TLE3; KLF8; LONRF2;
PCDHGB8P; ENSG00000259326; A0C2; RAPGEFL1; ARL10; ADAMTS10;
ENSG00000250303; TSHZ2; CRYM-AS1; ENSG00000213971; TVP23CP2;
ENSG00000234978; ZBTB12; PCDHGA9; RPS3AP29; KSR2; ENOSF1;
ENSG00000233175; ENSG00000260729; LINC00664; ZNF257; POU5F1P5; FN3K;
ZNF814; CYP2C19; ENSG00000270096; PDE11A; FAM13A-AS1; KCNMA1;
ENSG00000247270; ENSG00000270019; ENSG00000270154; ENSG00000248445;
ENSG00000234129; ENSG00000267169; ENSG00000261423; C1RL-AS1; NONOP2;
SLC26A5; STX18-AS1; AMT; ENSG00000232626; ENSG00000235834; RN7SL648P;
ENSG00000254634; ENSG00000236144; ACAP2-IT1; ENSG00000268472; TDRD6;
ENSG00000272563; SUDS3P1; PCDHGB4; FOX03B; ENSG00000272977;
LINC00176; MY015A; GHRLOS; TTC28; ENSG00000271840; NBPF20; VANGL2;
JMID7-PLA2G4B; ENSG00000267940; OGDHL; ENSG00000206195; KLF11;
TAPT1-AS1; TMEM59L; ACKR3; ENSG00000184441; KAT2A; SULT1A3; SIPA1L2;
RPL5134; CTSF; ZNF208; CYP2E1; L3MBTL1; BENDS; ACACB; ENSG00000261087;
NFATC4; CES4A; ZFP2; BSN; ENSG00000254469; ZNF514; ENSG00000176593;
ENSG00000232116; OTX1; ENSG00000269918; AVIL; ENSG00000271971; MICU3;
GRAMD1A; C1QTNF6; KIF3C; ZACN; RPL7P46; PLA2G4F; SLX1A-SULT1A3;
ZNF135; OR2A9P; TMEM63C; TG; ENSG00000261502; ARL5B-AS1; ZNF705E;
PCDHGC5; GOLGA8A; PLEKH111; PPAP2B; ENSG00000267481; OR7E71P;
ENSG00000259585; ENSG00000225210; TSSK1B; ENSG00000215022; STRC;
ENSG00000250290; UBAP1L; ENSG00000264112; LINC00959; SPATA41; CRYGS;
ZNF862; ENSG00000225032; PCED1B; SMAD6; ENSG00000264538; FRS3;
ENSG00000256139; NSUN5P1; LTB134; ENSG00000267053; ENSG00000171282;
PCDHGA7; GREB1; ADAM1A; ENSG00000251323; ENSG00000271917;
ENSG00000253366; ENSG00000225241; IL11RA; PCDHB18; FAM85A; UPK3BP1;
ACADL; ENSG00000236055; ZNF285; and ENSG00000239665;
wherein Group B consists of:
LRP4; ZNF578; FAT2; FGFR3; MCC; SLC26A9; MKL2; AGKP1; KRT15; CSRNP3;
PKP1; FSTL3; NEURL1; JAG2; DACT2; TRO; NDRG1; ADCY2; IGSF3; NLGN4Y;
SALL2; SUSD4; ARSG; BCL11A; RNF165; TP63; UGT1A7; CACNA1A; PAPPA;
SULF2; RGS17; PIK3R1; SNX31; COL4A5; SNAI2; UGT1A5; SYNGR1;
ENSG00000213963; SV2A; FGFR2; KANK1; WNT5A; FZD7; SRRM3; SEMA5A;
ZNF471; HYKK; PPM1L; ARHGAP28; UGT1A8; ARHGEF10; MT1X; FOXN1;
NTF3; SMOC2; USP44; FBXL16; EPAS1; EGFR; PTPRG; NEB; GDNF-AS1;
FAM117B; RERG; ZBTB47; ADAMTS9-AS2; PAPLN; NCKAP5 STK32A; FAT4;
LGR6; TPTE2P1; SLITRK6; EVPLL; POMGNT1; KCTD15; WSCD1; KIF7; KIF1A;
FRAS1; KRT5 ENSG00000174171; CDH11; ZFP28; GPRASP1; PRKY; COL4A6;
LSAMP; SYDE1; ENSG00000271880; RGMA; BOC; SLC2A9; WNT2B; CDHR1;
ENSG00000248705; TGFB2; NCAM1; LTB4R; TLE2; AP3B2; LRRC2; MEGF6;
RNF212; FBLN1; SLCO4C1; WNT3A; ZNF665; ESYT3; FREM2; ARHGEF4;
LURAP1; SETP21; COL7A1; B4GALNT4; FBN1; ZNF90; LRP1B; ABCC9;
ENSG00000256995; S1PR5; EFS; NPTX1; ENSG00000260197; UGT1A2P; SLC16A2;
MAN1C1; MARVELD1; FGF9; CIB2; LGR5; KIRREL; LTB4R2; SPTB; ITPRIPL1;
PHLDB1; SPRY1; DEPTOR; EPHA4; TTTY10; TET1; ZNF667; EPHB6;
ENSG00000250685; ENSG00000271738; IGFBP4; ARHGEF25; TRPV6; KCNB2;
SPRY2; DLK2; and CLUL1;
wherein Group C consists of:
ENSG00000258545; ENSG00000257512; ASL; CCDCl60; SMIM6; PLCB1;
TMEM125; C20orf201; CD38; ENSG00000268129; TSPAN2; DAPP1; IDH2; APOL4;
HRASLS2; C9orf66; BFSP1; DLG1-AS1; C16orf54; LAMP3; LYSMD2; PSMB9;
NR5A2; ENSG00000005189; COCH; CCDC67; XK; OR7E14P; LINC00589; F5;
PDE3A; RTP4; ENSG00000253474; ANTXR2; HCG4P3; FATE1; FBLN5
ENSG00000259153; NMI; ENSG00000231901; PSMB8 SERF1A; MOCOS; GSTM1;
RAMP1; LINC00643; PRKG1; ENSG00000225335; ENSG00000270659; CNTF;
ENSG00000272463; ENSG00000260552; FHL1; KIF18A; RARRES3; TNFAIP8L3;
PSMB10; ENSG00000227053; DPF1; GSTT2; TMEM176B; RPL7AP64; CDKN2D;
ENSG00000196826; MUC12; ENSG00000260806; GLIPR2; USP18;
ENSG00000238837; C19orf38; ABCC2; VWA5A; SGOL2; PKIB; KLB; TMEM200C;
and SHH;
wherein Group D consists of:
LINC00888; FBX016; SCRN1; ENSG00000259508; LINC00467; MPC2; KIAA0895;
SEPW1; CALML4; ERICH2; SLC51B; FAM69A; ENSG00000259802;
ENSG00000249241; MRPS31; CCDCl76; DUSP14; TMEM17; VIM-AS1; GSTP1;
CCT6B; RUVBL1; ENSG00000267325; AAED1; SLC25A4; Clorf192; DYRK3;
ELK3; ENSG00000272092; LINC00326; B9D2; LINC00240; IFT43; CPNE8; SMIM22;
PHTF1; C11orf70; APOO; SPAG1; CCDC65; DPCD; CCDCl04; RABL5;
ENSG00000263450; DNPH1; ENSG00000234478; ENSG00000233170; LINC01132;
IQCK; ENSG00000257698; ROPN1L; AHSA1; C21orf59; Cl5orf65;
ENSG00000271133; IL7; LXN; DNAL4; C6orf99; MAPS; C1orf189; LINC00948;
DHX40; GFM2; LRRC34; SPA17; ENSG00000261465; C21orf119; TUBA1A; GJB7;
TOMM34; NUDT7; LINC00908; C10orf107; C20orf85; ARL3; DNAL1; CNTN5
MYCBP; ENSG00000266916; ENSG00000260057; CYSTM1; ENSG00000236028;
UFC1; C9orf135; ENSG00000263011; DSTN; IFT57; C9orf116; MORN2; PPIL6;
LCA5L; DPY30; CEP97; AKAP14; ENSG00000272514; CAPSL; CC2D2A; OSCP1;
DYX1C1; PNLDC1; SPATA4; ZNF165; IGFBP7; CXorf58; C15orf26;
ENSG00000224049; TCTEX1D2; TCEAL3; ENSG00000258940; DYNC2111; and
PKIG; and
wherein Group E consists of:
C8orf76; DNAJC22; ENSG00000250508; SEC23B; SLC35B1; KRT23; MRPL47; NIP7;
NDUFV2; KCTD14; GTF3C6; ISOC2; SAP30; HSBP1; PSMA5; ENSG00000262823;
SEC61B; TIMM17A; CLIC5; RPN1; LACC1; MRPL54; PSMB5; UCHL3; C14orf166;
C2orf47; PPP1R2; C5orf15; DNAJA1; HIGD1A; MIF; RAB9A; CASP7; POMP;
SERHL2; BCCIP; GRK5; UBB; PARK7; CHCHD2; FAR2; DNAJC12; NT5C3A;
UFM1; CDK7; CCDCl67; CCT2; MORF4L2; CALM2; C4orf19; PSENEN; HSPA8;
GTF2B; NDUFAB1; DAD1; SMS; KBTBD4; AGR3; GPR160; TCP1; PSMA3; STS;
LAMTOR5 COX17; UGCG; PSMA6; COX6A1; SLC41A2; HSP90B1; PDIA4; NXT2;
LACTB2; RFK; DYNLT1; COX7A2; BOLA3; MTFP1; FOLH1; PSMD10; NDUFB4;
MRPL39; C1orf122; MMADHC; SEC61G; NDUFB3; SSR4; NRIP1; ANG; WBP5
ABRACL; BIK; MRPS36; MOSPD1; SLIRP; MRPL13; CD24P4; ENSG00000113811;
LINC00493; SOD1; IGFBP6; PRDX4; ACTR6; SDF2L1; C19orf10; IL23A; BZW1P2;
CXCL17; and USMG5; and
wherein the airway dysfunction is COPD, asthma, bronchiolitis, bronchiectasis, lung transplant rejection, rheumatoid arthritis, graft versus host disease (GvHD), or autoimmune pneumonitis.
4. The method of claim 3 , wherein the subject is determined to have a decreased level of expression of one or more genes selected from Group B and/or an increased level of expression of one or more genes selected from Group C;
wherein a decreased level of expression is decreased relative to the level of the at least one gene in a population of subject who do not have or are not diagnosed as having, and/or do not exhibit signs or symptoms of airway dysfunction, and an increased level of expression is increased relative to the level of the at least one gene in a population of subject who do not have or are not diagnosed as having, and/or do not exhibit signs or symptoms of airway dysfunction.
5. The method of claim 3 , wherein the DPP1 inhibitor is AZD7986.
6. The method of claim 3 , wherein the airway dysfunction is bronchial enlargement or dilation.
7. The method of claim 3 , wherein the level of expression is the level in a sample obtained from the subject.
8. The method of claim 7 , wherein the sample is a bronchial brushing, nasal brushing, sputum, or peripheral blood sample.
9. The method of claim 1 , wherein the method comprises determining the level of expression of, at least one gene of Group A, at least one gene of Group B, at least one gene of Group C, at least one gene of Group D, and at least one gene of Group E.
10. The method of claim 1 , wherein the method comprises determining the level of expression of, at least one gene of Group A, at least one gene of Group C, at least one gene of Group D, and at least one gene of Group E.
11. The method of claim 1 , wherein the method comprises determining the level of expression of, at least one gene of Group A, at least one gene of Group C, and at least one gene of Group E.
12. The method of claim 1 , wherein the method comprises determining the level of expression of, at least one gene of Group B and at least one gene of Group C.
13. The method of claim 1 , wherein the at least one gene of Group A comprises at least one of: Zinc Finger Protein 493 (ZNF493) and Zinc Finger Protein 519 (ZNF519).
14. The method of claim 1 , wherein the at least one gene of Group A is comprises ZNF493 and ZNF519.
15. The method of claim 1 , wherein the at least one gene of Group A is comprises ZNF493.
16. The method of claim 1 , wherein the at least one gene of Group B comprises is at least one of: Low Density Lipoprotein Receptor Related Protein 4 (LRP4) and Fat Atypical Cadherin 2 (FAT2).
17. The method of claim 1 , wherein the at least one gene of Group B comprises LRP4 and FAT2.
18. The method of claim 1 , wherein the at least one gene of Group C comprises at least one of: Argininosuccinate Lyase (ASL) and Coiled-Coil Domain Containing 160 (CCDC160).
19. The method of claim 1 , wherein the at least one gene of Group C comprises ASL and CCDC160.
20. The method of claim 1 , wherein the at least one gene of Group C comprises ASL.
21. The method of claim 1 , wherein the at least one gene of Group D comprises at least one of: Long Intergenic Non-Protein Coding RNA 888 (LINC00888) and F-Box Protein 16 (FBXO16).
22. The method of claim 1 , wherein the at least one gene of Group D comprises LINC00888 and FBXO16.
23. The method of claim 1 , wherein the at least one gene of Group D comprises LINC00888.
24. The method of claim 1 , wherein the at least one gene of Group E comprises at least one of: Chromosome 8 Open Reading Frame 76 (C8orf76) and DnaJ Heat Shock Protein Family Member C22 (DNAJC22).
25. The method of claim 1 , wherein the at least one gene of Group E comprises C8orf76 and DNAJC22.
26. The method of claim 1 , wherein the at least one gene of Group E comprises C8orf76.
27. The method of claim 1 , wherein the level of expression is the level of mRNA.
28. The method of claim 3 , wherein the sample obtained from the subject is a bronchial brushing or nasal brushing sample.