Details of Disease

General Information of Disease (ID: DISGGAGJ)

• Disease Name: Respiratory disease
• Synonyms: disorder of respiratory system; respiratory disorder; respiratory system disorder; respiratory system disease or disorder; disease or disorder of respiratory system; respiratory system disease; disease of respiratory system; respiratory disease
• Disease Class: CB40-CB7Z: Respiratory system disease
• Definition: A non-neoplastic or neoplastic disorder that affects the respiratory system. Representative examples include pneumonia, chronic obstructive pulmonary disease, pulmonary failure, lung adenoma, lung carcinoma, and tracheal carcinoma.
• Disease Hierarchy:
  DISH7H5I: Human disease
  DISGGAGJ: Respiratory disease
• ICD Code: ICD-11: ICD-11: CB40
• Disease Identifiers:
  MONDO ID: MONDO_0005087
  MESH ID: D012120
  UMLS CUI: C0035204
  MedGen ID: 48421
  SNOMED CT ID: 50043002

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 3 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Doxapram	DMCYANK	Approved	Small molecular drug	[1]
IG-RD-001	DMPKTLI	Approved	NA	[2]
Mequitazine	DMAFBCY	Approved	Small molecular drug	[3]

This Disease is Treated as An Indication in 6 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
E-4716	DMC5PB2	Phase 2	NA	[4]
RBx-10017609	DMTYMSH	Phase 2	NA	[5]
AM-461	DM7Z8NP	Phase 1	NA	[6]
MK-7246	DMLQOF1	Phase 1	Small molecular drug	[7]
PF-4764793	DMFKD1K	Phase 1	NA	[8]
PUR-118	DMPQM5R	Phase 1	NA	[9]

This Disease is Treated as An Indication in 1 Discontinued Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Ibuproxam	DMSO2T9	Withdrawn from market	Small molecular drug	[10]

This Disease is Treated as An Indication in 6 Investigative Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
AG-PPC709	DMZGUEY	Investigative	NA	[11]
BIA-13	DMJGVCY	Investigative	NA	[11]
MD-990	DM2OO0H	Investigative	NA	[11]
ORP-100	DMH1URD	Investigative	NA	[11]
SIG-003	DM3PJ03	Investigative	NA	[11]
VA-118020	DM65GQD	Investigative	NA	[12]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 18 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
MUC5AC	TTEL90S	Limited	Altered Expression	[13]
CLCA1	TT3AF4R	Disputed	Biomarker	[14]
ADRB2	TTG8ZWP	Strong	Biomarker	[15]
BPI	TTXCSDR	Strong	Biomarker	[16]
CHIA	TTJB1O0	Strong	Biomarker	[17]
CYSLTR1	TTGKOY9	Strong	Genetic Variation	[18]
CYSLTR2	TT0PZR5	Strong	Genetic Variation	[18]
DGKA	TTGL8F0	Strong	Biomarker	[19]
FUT3	TTUPAD7	Strong	Altered Expression	[20]
HRH4	TTXJ178	Strong	Biomarker	[21]
LTC4S	TTW7OTG	Strong	Genetic Variation	[18]
PBRM1	TTH8ZRL	Strong	Genetic Variation	[22]
PDE4A	TTZ97H5	Strong	Altered Expression	[23]
PDE4B	TTVIAT9	Strong	Biomarker	[24]
SFTPD	TTGLMU7	Strong	Biomarker	[25]
SLC29A1	TTLXAKE	Strong	Genetic Variation	[26]
TMPRSS11D	TTWHYC8	Strong	Biomarker	[27]
SCGB1A1	TTONPVW	Definitive	Biomarker	[28]

This Disease Is Related to 2 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
ABCA3	DT2T6VQ	Limited	Genetic Variation	[29]
ATP12A	DT5NLZA	Strong	Biomarker	[30]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
CYP2A13	DEXZA9U	Strong	Biomarker	[31]

This Disease Is Related to 32 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
MUC5B	OTPW6K5C	Limited	Altered Expression	[32]
SFTPA2	OT6SFOMU	Limited	Genetic Variation	[33]
ARIH1	OTO3XDR2	Disputed	Biomarker	[34]
BTBD8	OT3A3RD7	Strong	Genetic Variation	[35]
CCL13	OTNX0JD0	Strong	Biomarker	[36]
CCL26	OT2B7HR9	Strong	Altered Expression	[37]
CTBP2	OTGZGT87	Strong	Biomarker	[38]
CWC15	OTFFEP9A	Strong	Genetic Variation	[39]
DCTN5	OTESGJ1N	Strong	Genetic Variation	[40]
DDT	OTF5HTYL	Strong	Biomarker	[41]
DNAH11	OT6IYFVV	Strong	Biomarker	[42]
EXOSC3	OTNCF906	Strong	Biomarker	[43]
FAM20C	OTW5YZ7X	Strong	Altered Expression	[44]
FEV	OTYEC4IR	Strong	Biomarker	[45]
GSDMB	OTWA7P10	Strong	Genetic Variation	[46]
LCA5	OTQTCUWS	Strong	Genetic Variation	[47]
MEF2D	OT7CEIG0	Strong	Biomarker	[48]
MS4A2	OTMCAS2D	Strong	Genetic Variation	[49]
NDUFS4	OTJKUYEE	Strong	Genetic Variation	[50]
NKX2-1	OTCMEJTA	Strong	Genetic Variation	[51]
PCBP2	OTXCN9CG	Strong	Altered Expression	[52]
PHOX2B	OT3SFR2O	Strong	Biomarker	[53]
SARS1	OTFKXQ1O	Strong	Biomarker	[54]
SARS2	OTU4T99W	Strong	Biomarker	[54]
SFTPA1	OT87XL1U	Strong	Biomarker	[55]
SFTPB	OTOHS07E	Strong	Biomarker	[56]
SFTPC	OTIZJD09	Strong	Genetic Variation	[57]
TMEM196	OTPFLB1R	Strong	Genetic Variation	[58]
TRIM26	OTS0DJIP	Strong	Genetic Variation	[59]
BATF2	OT4XBZC9	Definitive	Genetic Variation	[60]
GNAS	OTMH8BKJ	Definitive	Biomarker	[61]
PDYN	OTEJ6430	Definitive	Biomarker	[62]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7169).
• [2] Clinical pipeline report, company report or official report of Sorrento Therapeutics.
• [3] ClinicalTrials.gov (NCT01951222) Bronchodilator Properties and Safety in Asthma. U.S. National Institutes of Health.
• [4] Population pharmacokinetics of epinastine, a histamine H1 receptor antagonist, in adults and children. Br J Clin Pharmacol. 2005 Jan;59(1):43-53.
• [5] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029478)
• [6] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031337)
• [7] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031315)
• [8] ClinicalTrials.gov (NCT01272375) This Study Is To Estimate The Time Course Of Pf-04764793 In The Blood Following Dosing By Oral Inhalation From Dry Powder Inhalers. U.S. National Institutes of Health.
• [9] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033342)
• [10] Anti-inflammatory agents: determination of ibuproxam and its metabolite humans. Correlation between bioavailability, tolerance and chemico-physical characteristics. Arzneimittelforschung. 1980;30(9):1607-9.
• [11] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [12] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2865).
• [13] Polyhexamethylene guanidine phosphate-induced upregulation of MUC5AC via activation of the TLR-p38 MAPK and JNK axis.Chem Biol Interact. 2019 May 25;305:119-126. doi: 10.1016/j.cbi.2019.03.030. Epub 2019 Mar 29.
• [14] Soluble mucus component CLCA1 modulates expression of leukotactic cytokines and BPIFA1 in murine alveolar macrophages but not in bone marrow-derived macrophages.Histochem Cell Biol. 2018 Jun;149(6):619-633. doi: 10.1007/s00418-018-1664-y. Epub 2018 Apr 2.
• [15] In vitro anti-inflammatory effects of AZD8999, a novel bifunctional muscarinic acetylcholine receptor antagonist /2-adrenoceptor agonist (MABA) compound in neutrophils from COPD patients.PLoS One. 2019 Jan 4;14(1):e0210188. doi: 10.1371/journal.pone.0210188. eCollection 2019.
• [16] Bactericidal/Permeability-increasing protein fold-containing family member A1 in airway host protection and respiratory disease.Am J Respir Cell Mol Biol. 2015 May;52(5):525-34. doi: 10.1165/rcmb.2014-0297RT.
• [17] Acidic mammalian chitinase tuning after enteric helminths eradication in inflammatory respiratory disease patients. Parasite Immunol. 2018 Nov;40(11):e12583.
• [18] Genetics and pharmacogenetics of the leukotriene pathway.J Allergy Clin Immunol. 2009 Sep;124(3):422-7. doi: 10.1016/j.jaci.2009.06.035. Epub 2009 Aug 8.
• [19] DGK in Neutrophil Biology and Its Implications for Respiratory Diseases.Int J Mol Sci. 2019 Nov 13;20(22):5673. doi: 10.3390/ijms20225673.
• [20] Neutrophil interactions with sialyl Lewis X on human nonsmall cell lung carcinoma cells regulate invasive behavior.Cancer. 2011 Oct 1;117(19):4493-505. doi: 10.1002/cncr.26059. Epub 2011 Mar 22.
• [21] The histamine H?receptor: targeting inflammatory disorders.Eur J Pharmacol. 2011 Oct 1;668(1-2):1-5. doi: 10.1016/j.ejphar.2011.06.029. Epub 2011 Jul 3.
• [22] H4N8 subtype avian influenza virus isolated from shorebirds contains a unique PB1 gene and causes severe respiratory disease in mice.Virology. 2012 Feb 5;423(1):77-88. doi: 10.1016/j.virol.2011.11.019. Epub 2011 Dec 20.
• [23] Synthesis and biological evaluation of pyridazinone derivatives as potential anti-inflammatory agents.Eur J Med Chem. 2018 Feb 25;146:139-146. doi: 10.1016/j.ejmech.2018.01.035. Epub 2018 Jan 17.
• [24] The differential impact of PDE4 subtypes in human lung fibroblasts on cytokine-induced proliferation and myofibroblast conversion.J Cell Physiol. 2011 Aug;226(8):1970-80. doi: 10.1002/jcp.22529.
• [25] Surfactant Protein D in Respiratory and Non-Respiratory Diseases.Front Med (Lausanne). 2018 Feb 8;5:18. doi: 10.3389/fmed.2018.00018. eCollection 2018.
• [26] A semi-quantitative translational pharmacology analysis to understand the relationship between in vitro ENT1 inhibition and the clinical incidence of dyspnoea and bronchospasm. Toxicol Appl Pharmacol. 2017 Feb 15;317:41-50. doi: 10.1016/j.taap.2016.12.021. Epub 2016 Dec 29.
• [27] Human airway trypsin-like protease, a serine protease involved in respiratory diseases.Am J Physiol Lung Cell Mol Physiol. 2017 May 1;312(5):L657-L668. doi: 10.1152/ajplung.00509.2016. Epub 2017 Feb 24.
• [28] Nonmalignant respiratory effects of chronic arsenic exposure from drinking water among never-smokers in Bangladesh.Environ Health Perspect. 2008 Feb;116(2):190-5. doi: 10.1289/ehp.9507.
• [29] An intronic ABCA3 mutation that is responsible for respiratory disease.Pediatr Res. 2012 Jun;71(6):633-7. doi: 10.1038/pr.2012.21. Epub 2012 Feb 15.
• [30] Increased expression of ATP12A proton pump in cystic fibrosis airways.JCI Insight. 2018 Oct 18;3(20):e123616. doi: 10.1172/jci.insight.123616.
• [31] Nicotine Component of Cigarette Smoke Extract (CSE) Decreases the Cytotoxicity of CSE in BEAS-2B Cells Stably Expressing Human Cytochrome P450 2A13.Int J Environ Res Public Health. 2017 Oct 13;14(10):1221. doi: 10.3390/ijerph14101221.
• [32] Role of Spdef in the Regulation of Muc5b Expression in the Airways of Naive and Mucoobstructed Mice.Am J Respir Cell Mol Biol. 2018 Sep;59(3):383-396. doi: 10.1165/rcmb.2017-0127OC.
• [33] Allelic mRNA expression imbalance in C-type lectins reveals a frequent regulatory SNP in the human surfactant protein A (SP-A) gene.Genes Immun. 2013 Mar;14(2):99-106. doi: 10.1038/gene.2012.61. Epub 2013 Jan 17.
• [34] Virome and bacteriome characterization of children with pneumonia and asthma in Mexico City during winter seasons 2014 and 2015.PLoS One. 2018 Feb 15;13(2):e0192878. doi: 10.1371/journal.pone.0192878. eCollection 2018.
• [35] Low interferon-gamma release in response to phytohemagglutinin predicts the high severity of diseases.Medicine (Baltimore). 2019 May;98(22):e15843. doi: 10.1097/MD.0000000000015843.
• [36] Production of the novel C-C chemokine MCP-4 by airway cells and comparison of its biological activity to other C-C chemokines.J Clin Invest. 1997 Mar 1;99(5):926-36. doi: 10.1172/JCI119257.
• [37] Eotaxin-3 as a Plasma Biomarker for Mucosal Eosinophil Infiltration in Chronic Rhinosinusitis.Front Immunol. 2019 Feb 4;10:74. doi: 10.3389/fimmu.2019.00074. eCollection 2019.
• [38] Genome-wide association studies identify susceptibility loci affecting respiratory disease in Chinese Erhualian pigs under natural conditions.Anim Genet. 2017 Feb;48(1):30-37. doi: 10.1111/age.12504. Epub 2016 Sep 12.
• [39] Porcine reproductive and respiratory disease virus: Evolution and recombination yields distinct ORF5 RFLP 1-7-4 viruses with individual pathogenicity.Virology. 2018 Jan 1;513:168-179. doi: 10.1016/j.virol.2017.10.002. Epub 2017 Nov 5.
• [40] DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis.Clin Respir J. 2016 Nov;10(6):777-783. doi: 10.1111/crj.12288. Epub 2015 Apr 15.
• [41] Role of MIF and D-DT in immune-inflammatory, autoimmune, and chronic respiratory diseases: from pathogenic factors to therapeutic targets.Drug Discov Today. 2019 Feb;24(2):428-439. doi: 10.1016/j.drudis.2018.11.003. Epub 2018 Nov 13.
• [42] Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure.Thorax. 2012 May;67(5):433-41. doi: 10.1136/thoraxjnl-2011-200301. Epub 2011 Dec 18.
• [43] The E3 Ubiquitin Ligase Siah-1 Suppresses Avian Reovirus Infection by Targeting p10 for Degradation.J Virol. 2018 Feb 26;92(6):e02101-17. doi: 10.1128/JVI.02101-17. Print 2018 Mar 15.
• [44] The role of reactive oxygen and nitrogen species in airway epithelial gene expression.Environ Health Perspect. 1998 Oct;106 Suppl 5(Suppl 5):1197-203. doi: 10.1289/ehp.98106s51197.
• [45] Lower FEV1 in non-COPD, nonasthmatic subjects: association with smoking, annual decline in FEV1, total IgE levels, and TSLP genotypes.Int J Chron Obstruct Pulmon Dis. 2011;6:181-9. doi: 10.2147/COPD.S16383. Epub 2011 Mar 2.
• [46] Genetic variants of the gasdermin B gene associated with the development of aspirin-exacerbated respiratory diseases.Allergy Asthma Proc. 2017 Jan 1;38(1):4-12. doi: 10.2500/aap.2017.38.4014.
• [47] Identification of a novel splice-site mutation in the Lebercilin (LCA5) gene causing Leber congenital amaurosis.Mol Vis. 2008 Mar 10;14:481-6.
• [48] Myocyte enhancer factor 2D provides a cross-talk between chronic inflammation and lung cancer.J Transl Med. 2017 Mar 24;15(1):65. doi: 10.1186/s12967-017-1168-x.
• [49] Update on recent advances in the management of aspirin exacerbated respiratory disease.Yonsei Med J. 2009 Dec 31;50(6):744-50. doi: 10.3349/ymj.2009.50.6.744. Epub 2009 Dec 18.
• [50] Identification of a deletion in the NDUFS4 gene using array-comparative genomic hybridization in a patient with suspected mitochondrial respiratory disease.Gene. 2014 Feb 10;535(2):376-9. doi: 10.1016/j.gene.2013.10.074. Epub 2013 Dec 1.
• [51] Heterogeneous pulmonary phenotypes associated with mutations in the thyroid transcription factor gene NKX2-1.Chest. 2013 Sep;144(3):794-804. doi: 10.1378/chest.12-2502.
• [52] Expression Profile of Six RNA-Binding Proteins in Pulmonary Sarcoidosis.PLoS One. 2016 Aug 30;11(8):e0161669. doi: 10.1371/journal.pone.0161669. eCollection 2016.
• [53] Phox2b, congenital central hypoventilation syndrome and the control of respiration.Semin Cell Dev Biol. 2010 Oct;21(8):814-22. doi: 10.1016/j.semcdb.2010.07.006. Epub 2010 Aug 4.
• [54] Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis.mBio. 2018 Oct 9;9(5):e01753-18. doi: 10.1128/mBio.01753-18.
• [55] Germline SFTPA1 mutation in familial idiopathic interstitial pneumonia and lung cancer.Hum Mol Genet. 2016 Apr 15;25(8):1457-67. doi: 10.1093/hmg/ddw014. Epub 2016 Jan 19.
• [56] Genetic disorders of surfactant protein dysfunction: when to consider and how to investigate.Arch Dis Child. 2017 Jan;102(1):84-90. doi: 10.1136/archdischild-2012-303143. Epub 2016 Jul 14.
• [57] Surfactant protein C gene variation in the Finnish population - association with perinatal respiratory disease.Eur J Hum Genet. 2004 Apr;12(4):312-20. doi: 10.1038/sj.ejhg.5201137.
• [58] Associations between TMEM196 polymorphisms and NSAID-exacerbated respiratory disease in asthma.Pharmacogenet Genomics. 2019 Jun;29(4):69-75. doi: 10.1097/FPC.0000000000000367.
• [59] Association study between TRIM26 polymorphisms and risk of aspirin-exacerbated respiratory disease.Int J Mol Med. 2012 May;29(5):927-33. doi: 10.3892/ijmm.2012.898. Epub 2012 Jan 26.
• [60] Evaluation of case definitions to detect respiratory syncytial virus infection in hospitalized children below 5 years in Rural Western Kenya, 2009-2013.BMC Infect Dis. 2016 May 21;16:218. doi: 10.1186/s12879-016-1532-0.
• [61] Depressed heart rate variability and arterial baroreflex in conscious transgenic mice with overexpression of cardiac Gsalpha.Circ Res. 1998 Mar 9;82(4):416-23. doi: 10.1161/01.res.82.4.416.
• [62] Differential cardiovascular effects of mu, delta and kappa opiate agonists at discrete hypothalamic sites in the anesthetized rat.Life Sci. 1982 Nov 15-22;31(20-21):2197-200. doi: 10.1016/0024-3205(82)90117-5.