Respiratory system disorder

disease

On this page

Also known as disease of respiratory systemdisease or disorder of respiratory systemdisorder of respiratory systemrespiratory diseaserespiratory disorderrespiratory system diseaserespiratory system disease or disorder

Summary

Respiratory system disorder (MONDO:0005087) is a disease (an umbrella term covering 59 Mondo subtypes) with 316 GWAS associations across 86 studies and 289 clinical trials. Top therapeutic interventions include caffeine citrate, dupilumab, and fludeoxyglucose. A subtype of disease by body system or component — broader associated-gene and molecular evidence is on the parent page (see Disease family below).

At a glance

Umbrella term: 59 Mondo subtypes
GWAS associations: 316
Clinical trials: 289

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	respiratory system disorder
Mondo ID	MONDO:0005087
EFO	EFO:0000684
MeSH	D012140
DOID	DOID:1579
ICD-10-CM	J00-J99
NCIT	C26871
SNOMED CT	50043002
UMLS	C0035204
MedGen	48421
Anatomy (UBERON)	UBERON:0001004
Is cancer (heuristic)	no

Also known as: disease of respiratory system · disease or disorder of respiratory system · disorder of respiratory system · respiratory disease · respiratory disorder · respiratory system disease · respiratory system disease or disorder · respiratory system disorder

Data availability: 316 GWAS associations (86 studies).

Disease family

An umbrella term covering 59 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › respiratory system disorder

Subtypes (59): lower respiratory tract disorder, respiratory system cancer, respiratory system benign neoplasm, allergic respiratory disease, paranasal sinus disorder, upper respiratory tract disorder, pertussis, severe acute respiratory syndrome, sleep apnea syndrome, diaphragm disorder, pulmonary tuberculosis, altitude sickness, perinatal asphyxia, pulmonary nodular lymphoid hyperplasia, tracheobronchopathia osteochondroplastica, Williams-Campbell syndrome, cystic fibrosis, growth delay-hydrocephaly-lung hypoplasia syndrome, laryngo-onycho-cutaneous syndrome, congenital pulmonary lymphangiectasia, familial primary pulmonary hypoplasia, Mounier-Kuhn syndrome, Young syndrome, lung agenesis-heart defect-thumb anomalies syndrome, sudden infant death-dysgenesis of the testes syndrome, alpha 1-antitrypsin deficiency, hereditary sclerosing poikiloderma with tendon and pulmonary involvement, autoimmune interstitial lung disease-arthritis syndrome, mucopolysaccharidosis-plus syndrome, congenital bronchobiliary fistula, bronchogenic cyst, primary ciliary dyskinesia, congenital pulmonary airway malformation, transient hyperammonemia of the newborn, congenital pulmonary sequestration, Siegler-Brewer-Carey syndrome, tracheal agenesis, 16q24.1 microdeletion syndrome, staphylococcal necrotizing pneumonia, pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis, plastic bronchitis, recurrent respiratory papillomatosis, IgG4-related mediastinitis, bronchopulmonary dysplasia, infantile apnea, diffuse alveolar hemorrhage, respiratory or thoracic malformation, pulmonary agenesis, eosinophilic granuloma, disorder of pharynx, respiratory tract neoplasm, pulmonary alveolar proteinosis with hypogammaglobulinemia, respiratory tract infectious disorder, Middle East respiratory syndrome, reactive airway disease, acinar dysplasia, pulmonary hypoplasia, isolated left bronchial isomerism, bronchiectasis and nasal polyposis

Genetics & variants

GWAS landscape

316 GWAS associations across 86 studies. Top hits map to 32 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs35705950	1e-323	MUC5AC - MUC5B	G	0.99
rs72823641	4e-101	IL18R1, IL1RL1	?
rs7936312	2e-91	EMSY - LINC02757	?
rs3939286	3e-86	GTF3AP1 - IL33	?
rs34290285	5e-77	D2HGDH	?
rs6594499	3e-65	WDR36 - RPS3AP21	?
rs59185885	1e-59	IL1RL1, IL18R1	?
rs5743618	4e-58	TLR1	?
rs72743461	1e-57	SMAD3	?
rs9303279	3e-57	GSDMB	?
rs12935657	2e-52	CLEC16A	?
rs2197415	4e-49	LINC02676 - LINC00709	?
rs4795401	4e-45	GSDMB	?
rs12123821	3e-42	CCDST	?
rs1837253	2e-39	BCLAF1P1 - TSLP	?
rs11742240	1e-38	IL7R - CAPSL	?
rs148639908	3e-37	BACH2	?
rs1059513	2e-36	STAT6	?
rs17454584	5e-36	ADAD1 - IL2	?
rs115008099	1e-34	TH2LCRR	?
rs117710327	1e-34	SLC7A10 - CEBPA	?
rs891058	7e-33	LINC00299	?
rs1689510	1e-32	SUOX	?
rs2076295	2e-30	DSP	T	0.24
rs11071559	2e-28	RORA	?
rs36045143	9e-28	CLEC16A	?
rs61816761	2e-27	FLG, CCDST	?
rs3122929	3e-27	STAT6	?
rs72925996	3e-26	BACH2	?
rs1723016	3e-26	CD247	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90044359	Jiang L	2021	309,586	145,863	A generalized linear mixed model association tool for biobank-scale data.
GCST90476039	Verma A	2024	173,161	201,912	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90478181	Verma A	2024	49,035	50,175	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90473740	UK Biobank Whole-Genome Sequencing Consortium	2025	28,848	429,592	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90103959	Tangden T	2022	23,560	313,924	A genome-wide association study in a large community-based cohort identifies multiple loci associated with susceptibility to bacterial and viral infections.
GCST90473745	UK Biobank Whole-Genome Sequencing Consortium	2025	22,373	436,067	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90478179	Verma A	2024	20,097	28,437	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90080161	Backman JD	2021	14,771	367,671	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084147	Backman JD	2021	14,771	367,671	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90436256	Zhou W	2018	9,436	399,525	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	4
Tier 2: splice/UTR	2
Tier 3: regulatory	3
Tier 4: intronic/intergenic	41

MAF distribution

Bucket	Variants
common (>=0.05)	48
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	2

Functional consequences

Consequence	Count
intron_variant	32
intergenic_variant	7
missense_variant	3
regulatory_region_variant	2
splice_region_variant	1
3_prime_UTR_variant	1
TF_binding_site_variant	1
stop_gained	1
unknown	1
non_coding_transcript_exon_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs35705950	11	1219991	G>A,T	0.089	splice_region_variant	MUC5AC - MUC5B	1e-323	Tier 2: splice/UTR
rs72823641	2	102319699	T>A,C	0.05	intron_variant	IL18R1, IL1RL1	4e-101	Tier 4: intronic/intergenic
rs7936312	11	76582682	G>C,T	0.05	intergenic_variant	EMSY - LINC02757	2e-91	Tier 4: intronic/intergenic
rs3939286	9	6210099	T>A,C	0.05	intergenic_variant	GTF3AP1 - IL33	3e-86	Tier 4: intronic/intergenic
rs34290285	2	241759225	G>A	0.05	intron_variant	D2HGDH	5e-77	Tier 4: intronic/intergenic
rs6594499	5	111134439	C>A	0.05	regulatory_region_variant	WDR36 - RPS3AP21	3e-65	Tier 3: regulatory
rs59185885	2	102327786	T>A,C,G	0.05	intron_variant	IL1RL1, IL18R1	1e-59	Tier 4: intronic/intergenic
rs5743618	4	38797027	C>A,G	0.05	missense_variant	TLR1	4e-58	Tier 1: coding
rs72743461	15	67149412	C>A,T	0.05	intron_variant	SMAD3	1e-57	Tier 4: intronic/intergenic
rs9303279	17	39917715	G>A,C	0.05	intron_variant	GSDMB	3e-57	Tier 4: intronic/intergenic
rs12935657	16	11125184	G>A,T	0.05	intron_variant	CLEC16A	2e-52	Tier 4: intronic/intergenic
rs2197415	10	9020893	T>C,G	0.05	intergenic_variant	LINC02676 - LINC00709	4e-49	Tier 4: intronic/intergenic
rs4795401	17	39911280	A>C,G	0.05	intron_variant	GSDMB	4e-45	Tier 4: intronic/intergenic
rs12123821	1	152206676	C>T	0.05	intron_variant	CCDST	3e-42	Tier 4: intronic/intergenic
rs1837253	5	111066174	T>C	0.05	intron_variant	BCLAF1P1 - TSLP	2e-39	Tier 4: intronic/intergenic
rs11742240	5	35881274	G>A,T	0.05	intergenic_variant	IL7R - CAPSL	1e-38	Tier 4: intronic/intergenic
rs148639908	6	90253896	AT>A,ATT,ATTT	0.05	intron_variant	BACH2	3e-37	Tier 4: intronic/intergenic
rs1059513	12	57095926	T>A,C,G	0.05	3_prime_UTR_variant	STAT6	2e-36	Tier 2: splice/UTR
rs17454584	4	122432277	A>G	0.05	intergenic_variant	ADAD1 - IL2	5e-36	Tier 4: intronic/intergenic
rs115008099	5	132656189	C>T	0.05	intron_variant	TH2LCRR	1e-34	Tier 4: intronic/intergenic
rs117710327	19	33235672	C>A	0.05	TF_binding_site_variant	SLC7A10 - CEBPA	1e-34	Tier 3: regulatory
rs891058	2	8302417	G>A	0.05	regulatory_region_variant	LINC00299	7e-33	Tier 3: regulatory
rs1689510	12	56002984	G>A,C	0.05	intron_variant	SUOX	1e-32	Tier 4: intronic/intergenic
rs2076295	6	7562999	T>A,C,G	0.458	intron_variant	DSP	2e-30	Tier 4: intronic/intergenic
rs11071559	15	60777789	C>T	0.05	intron_variant	RORA	2e-28	Tier 4: intronic/intergenic
rs36045143	16	11131109	A>G	0.05	intron_variant	CLEC16A	9e-28	Tier 4: intronic/intergenic
rs61816761	1	152313385	G>A,C,T	0.05	stop_gained	FLG, CCDST	2e-27	Tier 1: coding
rs3122929	12	57115319	C>T	0.05	intergenic_variant	STAT6	3e-27	Tier 4: intronic/intergenic
rs72925996	6	90220794	T>A,C	0.05	intron_variant	BACH2	3e-26	Tier 4: intronic/intergenic
rs1723016	1	167463819	T>A,C	0.05	intron_variant	CD247	3e-26	Tier 4: intronic/intergenic

Genes & proteins

No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).

Function

No pathway enrichment — requires an associated-gene cohort.

Therapeutics

Drugs indicated for this disease

7 approved, 12 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Almitrine	Approved (phase 4)
Colfosceril Palmitate	Approved (phase 4)
Doxapram	Approved (phase 4)
Ivacaftor	Approved (phase 4)
Nitric Oxide	Approved (phase 4)
Palivizumab	Approved (phase 4)
Pirfenidone	Approved (phase 4)
Acetylcysteine	Phase 3 (in late-stage trials)
Ambroxol	Phase 3 (in late-stage trials)
Bcg Vaccine	Phase 3 (in late-stage trials)
Budesonide	Phase 3 (in late-stage trials)
Ciclesonide	Phase 3 (in late-stage trials)
Linagliptin	Phase 3 (in late-stage trials)
Methylprednisolone	Phase 3 (in late-stage trials)
Naphazoline	Phase 3 (in late-stage trials)
Nitazoxanide	Phase 3 (in late-stage trials)
Panthenol	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Zinc Ion	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Alectinib, Aspirin, Dupilumab, Glycine, Varicella Zoster Virus Envelope Glycoprotein E.

Clinical trials & evidence

Clinical trials

Clinical trials: 289.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	249
PHASE1	14
PHASE2	9
PHASE4	7
PHASE3	4
PHASE2/PHASE3	2
PHASE1/PHASE2	2
EARLY_PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06926712	PHASE4	NOT_YET_RECRUITING	The Effect of Vitamin E Supplementation on Hospital Stay Duration in Non-cyanotic Heart Disease Children With Lower Respiratory Tract Infections
NCT01443845	PHASE4	COMPLETED	Roflumilast in Chronic Obstructive Pulmonary Disease (COPD) Patients Treated With Fixed Dose Combinations of Long-acting β2-agonist (LABA) and Inhaled Corticosteroid (ICS)
NCT02079701	PHASE4	COMPLETED	Effectiveness of the Pneumococcal Polysaccharide Vaccine in Military Recruits
NCT03334916	PHASE4	COMPLETED	A Clinical Trial to Evaluate the Efficacy and Safety of YMC026 in Respiratory Disease Patients
NCT03937583	PHASE4	UNKNOWN	Screening for Cancer in Patients With Unprovoked VTE
NCT04619680	PHASE4	COMPLETED	The Study of the Use of Nintedanib in Slowing Lung Disease in Patients With Fibrotic or Non-Fibrotic Interstitial Lung Disease Related to COVID-19
NCT04915352	PHASE4	TERMINATED	Interest of Nasal Provocation Tests for Diagnosis of House Mites Allergic Rhinitis
NCT06026163	PHASE2/PHASE3	RECRUITING	Caffeine as an Adjuvant Therapy for Late Preterm Infants With Respiratory Distress
NCT00823056	PHASE3	COMPLETED	The Effect of Probiotics on Infections in Toddlers
NCT01113255	PHASE2/PHASE3	COMPLETED	Validation of a Simulated Clinical Evaluation of Ventilators
NCT04655508	PHASE3	TERMINATED	Efficacy of Fluticasone Propionate Associated With Salmeterol Using Inhalation Chamber Versus Placebo to Improve the Respiratory Function in Children Over Six Years of Age Who Underwent Allogeneic Hematopoietic Stem Cell Transplantation With a Decline of FEV1 ≥10% From Pre Transplantation
NCT04678856	PHASE3	COMPLETED	Dupilumab in CRSsNP
NCT05299385	PHASE3	UNKNOWN	The Study for Evaluating the Clinical Effectiveness and Safety of Respiratory Rehabilitation Software ‘Redpill Breath’(COPD, Asthma, Lung Cancer, Etc.)
NCT02272049	PHASE1/PHASE2	RECRUITING	Use of Hyperpolarized Xenon Gas for Lung Imaging in Children and Adults
NCT02316379	PHASE1/PHASE2	RECRUITING	Use of Hyperpolarized 129Xe MR Lung Imaging in Adults for Calibration
NCT00455767	PHASE2	COMPLETED	Safety and Efficacy Study of Depelestat in Acute Respiratory Distress Syndrome (ARDS) Patients
NCT01255592	PHASE2	COMPLETED	Evaluation of the Effect of AZD5069 in Patients With Bronchiectasis
NCT02075541	PHASE2	COMPLETED	A Study to Evaluate the Safety, Reactogenicity and Immunogenicity of GlaxoSmithkline (GSK) Biologicals’ Investigational Vaccine GSK2838504A When Administered to Chronic Obstructive Pulmonary Disease (COPD) Patients With Persistent Airflow Obstruction.
NCT03281876	PHASE2	COMPLETED	A Study to Test if the Vaccine is Working Well in Chronic Obstructive Pulmonary Disease (COPD) Patients Aged 40 to 80 Years Old to Reduce Episodes of Worsening Symptoms and to Gather Further Information on Safety and Immune Response.
NCT03443427	PHASE2	COMPLETED	A Study to Test if a Third Dose of the Vaccine is Safe in Current and Former Smokers Aged 40 to 80 Years Old and to Gather Information on the Immune Response Following the Third Dose of the Vaccine
NCT03894969	PHASE2	COMPLETED	Study to Assess the Immunogenicity and Safety of GSK’s Investigational Vaccine (GSK3277511A) When Given to Healthy Smokers and Ex-smokers After Administration of Shingrix Vaccine
NCT04456088	PHASE2	WITHDRAWN	Inhaled NO for the Treatment of COVID-19 Caused by SARS-CoV-2 (CANADA Trial)
NCT04701502	PHASE2	COMPLETED	Efficacy and Safety of Viusid and Asbrip in Hospitalized Patients With Mild and Moderate COVID-19
NCT06149494	PHASE2	COMPLETED	RCT of Vapendavir in Patients With COPD and Human Rhinovirus/Enterovirus Upper Respiratory Infection
NCT01476046	PHASE1	COMPLETED	Safety Study of GSK1995057 Given as Single and Repeat Intravenous Doses in Healthy Subjects.
NCT01587807	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Doses of Inhaled GSK1995057
NCT01657526	PHASE1	COMPLETED	Safety, Reactogenicity and Immunogenicity of GlaxoSmithKline (GSK) Biologicals’ Non-typeable Haemophilus Influenzae (NTHI) Vaccine
NCT01678677	PHASE1	COMPLETED	A Study to Evaluate the Safety, Reactogenicity and Immunogenicity of GSK Biologicals’ Non-typeable Haemophilus Influenzae (NTHi) Investigational Vaccine (GSK2838497A) in Current and Former Smokers
NCT01818024	PHASE1	COMPLETED	A Study to Investigate the Safety Tolerability Pharmacokinetics, and Pharmacodynamics of Inhaled and Intravenous GSK2862277 in Healthy Volunteers
NCT02322671	PHASE1	COMPLETED	Relative Bioavailability Study of Two Montelukast Sodium (GW483100) 5 Milligrams (mg) Chewable Tablets and One Reference Montelukast Sodium 5 mg Chewable Tablet in Healthy Adult Subjects
NCT02547974	PHASE1	COMPLETED	A Study to Evaluate the Safety, Reactogenicity and Immunogenicity of the Investigational GSK Biologicals’ GSK3277511A Vaccine in Adults.
NCT02658422	PHASE1	COMPLETED	Bioequivalence of GW483100 10 Milligram (mg) Tablets in Healthy Subjects Under Fasting Conditions
NCT02780752	PHASE1	COMPLETED	A Study of Oral Hymecromone and Hyaluronan Synthesis
NCT03201211	PHASE1	COMPLETED	A Long Term Follow-up Study up to 4 Years After Study Vaccination to Assess Immunogenicity and Safety of the Investigational Vaccine in Adults
NCT04097951	PHASE1	UNKNOWN	HDDO-1801 Intervention Trial
NCT04386408	PHASE1	COMPLETED	Evaluation of the Effect of a Combination of Plant Extracts (BSL_EP027) on the Incidence of Respiratory Infections
NCT05962645	PHASE1	COMPLETED	Phase 1 Study Into Pharmacokinetics and Food Effect of Vapendavir in Healthy Participants and Participants With COPD
NCT06170827	PHASE1	COMPLETED	Study to Evaluate the AIO-001 in Healthy Participants
NCT06267859	EARLY_PHASE1	RECRUITING	Development of Methods for Effective Treatment and Improvement of Common Somatic Diseases in Children
NCT03153800	EARLY_PHASE1	UNKNOWN	Autologous Bronchial Basal Cells Transplantation for Treatment of CRD Including COPD, BE and PF

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CAFFEINE CITRATE	4	1
DUPILUMAB	4	1
FLUDEOXYGLUCOSE	4	1
NINTEDANIB	4	1
REMIMAZOLAM BESYLATE	4	1
ROFLUMILAST	4	1
VITAMIN E	4	1
REMIMAZOLAM TOSYLATE	3	1
VAPENDAVIR	2	2
HYMECROMONE	2	1
ALPHA-TOCOPHEROL	0	1
LPS	0	1

Drugs: Caffeine, Dupilumab, Fludeoxyglucose, Nintedanib, Remimazolam, Roflumilast, Vitamin E