Compounds > palovarotene
Page last updated: 2024-11-12

palovarotene

Description

Palovarotene: a retinoic acid receptor gamma agonist; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID10295295
CHEMBL ID2105648
CHEBI ID188559
SCHEMBL ID4658931
MeSH IDM0542895

Synonyms (52)

Synonym
D09365
palovarotene (usan/inn)
410528-02-8
CHEBI:188559
palovarotene
4-[(e)-2-[5,5,8,8-tetramethyl-3-(pyrazol-1-ylmethyl)-6,7-dihydronaphthalen-2-yl]ethenyl]benzoic acid
palovarotene [usan:inn]
ipn60120
who 9025
benzoic acid, 4-((1e)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-3-(1h-pyrazol-1-ylmethyl)-2-naphthalenyl)ethenyl)-
r 667
ro3300074
unii-28k6i5m16g
rg-667
4-((1e)-2-(5,5,8,8-tetramethyl-3-(1h-pyrazol-1-ylmethyl)-5,6,7,8-tetrahydronaphthalen-2-yl)ethenyl)benzoic acid
clm-001
28k6i5m16g ,
ro 3300074
r-667
ro-3300074
ipn-60120
CHEMBL2105648
palovarotene [usan]
palovarotene [jan]
4-{(1e)-2-[5,5,8,8-tetramethyl-3-(1h-pyrazol-1-ylmethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]ethenyl}benzoic acid
palovarotene [who-dd]
palovarotene [inn]
sohonos
CS-2031
HY-14799
YTFHCXIPDIHOIA-DHZHZOJOSA-N
4-[(e)-2-(5,5,8,8-tetramethyl-3-pyrazol-1-ylmethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)vinyl]benzoic acid
SCHEMBL4658931
gtpl8276
r667
AKOS030526809
palovarotene(r 667)
(e)-4-(2-(3-((1h-pyrazol-1-yl)methyl)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl)benzoic acid
DB12320
BCP16664
ZB1580
Q15708269
EX-A3101
A914214
MS-27181
DTXSID301025696
r 667;ro 3300074
palovaroteno
4-((1e)-2-(5,5,8,8-tetramethyl-3-((1h-pyrazol-1-yl)methyl)-5,6,7,8-tetrahydronaphthalen-2-yl)ethenyl)benzoic acid
palovarotenum
clementia (proposed trade name)
AC-36331

Research Excerpts

Overview

Palovarotene (Sohonos™) is an orally bioavailable selective retinoic acid receptor (RAR)γ agonist being developed by Ipsen for the reduction of heterotopic ossification (HO) formation in patients with fibrodysplasia ossificans progressiva (FOP) At 20 mg/day is a not a clinical inducer of CYP3A4.

ExcerptReferenceRelevance
"Palovarotene (Sohonos™) is an orally bioavailable selective retinoic acid receptor (RAR)γ agonist being developed by Ipsen for the reduction of heterotopic ossification (HO) formation in patients with fibrodysplasia ossificans progressiva (FOP). "( Palovarotene: First Approval.
Hoy, SM, 2022)		3.61
"Palovarotene at 20 mg/day is a not a clinical inducer of CYP3A4."( The Pharmacokinetic Profile of Palovarotene: An Open-Label Phase I Trial Investigating the Effect of Food and Potential for Drug-Drug Interaction in Healthy Participants.
Dube, L; Le Quan Sang, KH; Marino, R; Ogier, J, 2023)		1.92
"Palovarotene is a therapeutic retinoid that has been developed for the treatment of FOP."( The Pharmacokinetic Profile of Palovarotene: An Open-Label Phase I Trial Investigating the Effect of Food and Potential for Drug-Drug Interaction in Healthy Participants.
Dube, L; Le Quan Sang, KH; Marino, R; Ogier, J, 2023)		1.92
"Palovarotene is a selective retinoic acid receptor gamma agonist."( Study methodology and insights from the palovarotene clinical development program in fibrodysplasia ossificans progressiva.
Al Mukaddam, M; Baujat, G; Brown, MA; De Cunto, C; Grogan, DR; Hsiao, EC; Kaplan, FS; Keen, R; Le Quan Sang, KH; Marino, R; Pignolo, RJ; Strahs, AR, 2023)		1.9
"Palovarotene (PVO) is a retinoic acid receptor γ selective agonist, which is being investigated as a potential drug for fibrodysplasia ossificans progressiva (FOP), another genetic bone disorder with features that overlap with those of MHE."( Palovarotene Inhibits Osteochondroma Formation in a Mouse Model of Multiple Hereditary Exostoses.
Inubushi, T; Irie, F; Lemire, I; Yamaguchi, Y, 2018)		2.64
"Palovarotene is an oral γ-selective retinoid agonist. "( Randomised controlled trial for emphysema with a selective agonist of the γ-type retinoic acid receptor.
Abboud, RT; Barros-Tizon, JC; Burdon, JG; Chapman, KR; Cooper, BG; Decramer, M; Garrett, JE; Lomas, DA; MacNee, WA; Mannes, GP; Piitulainen, E; Rames, A; Russi, EW; Seersholm, N; Stockley, RA; Stoel, BC; Stolk, J; Wouters, EF, 2012)		1.82

Effects

ExcerptReferenceRelevance
"Palovarotene has been shown to reduce bone formation in traumatic and genetic models of HO."( Palovarotene inhibits connective tissue progenitor cell proliferation in a rat model of combat-related heterotopic ossification.
Boehm, CA; Bova, W; Cilwa, KE; Davis, TA; Dey, D; Forsberg, JA; Iwamoto, M; Muschler, GF; Potter, BK; Qureshi, AT; Sanders, EM; Seavey, JG; Tomasino, AM; Wheatley, BM, 2018)		2.64

Treatment

Palovarotene treated animals exhibited significantly decreased expression of osteo- and chondrogenic genes by POD-7, including BMP4 (p = 0.02) pretreatment did not reduce FAPs' skeletogenic potential, indicating that efficacy requires chronic administration.

ExcerptReferenceRelevance
"All palovarotene-treated patients reported ≥1 adverse event (AE); 97.0% reported ≥1 retinoid-associated AE; 29.3% reported ≥1 serious AE, including premature physeal closure (PPC)/epiphyseal disorder in 21/57 (36.8%) patients aged <14 years."( Reduction of New Heterotopic Ossification (HO) in the Open-Label, Phase 3 MOVE Trial of Palovarotene for Fibrodysplasia Ossificans Progressiva (FOP).
Al Mukaddam, M; Baujat, G; Berglund, SK; Brown, MA; Cheung, AM; De Cunto, C; Delai, P; Haga, N; Hsiao, EC; Kannu, P; Kaplan, FS; Keen, R; Le Quan Sang, KH; Mancilla, EE; Marino, R; Pignolo, RJ; Strahs, A, 2023)		1.61
"Palovarotene treated animals exhibited significantly decreased expression of osteo- and chondrogenic genes by POD-7, including BMP4 (p = 0.02)."( Palovarotene inhibits connective tissue progenitor cell proliferation in a rat model of combat-related heterotopic ossification.
Boehm, CA; Bova, W; Cilwa, KE; Davis, TA; Dey, D; Forsberg, JA; Iwamoto, M; Muschler, GF; Potter, BK; Qureshi, AT; Sanders, EM; Seavey, JG; Tomasino, AM; Wheatley, BM, 2018)		2.64
"Palovarotene pretreatment did not reduce FAPs' skeletogenic potential, indicating that efficacy requires chronic administration."( Palovarotene reduces heterotopic ossification in juvenile FOP mice but exhibits pronounced skeletal toxicity.
Devarakonda, PM; Goldhamer, DJ; Lees-Shepard, JB; Nicholas, SE; Schneider, MJ; Stoessel, SJ; Yamamoto, M, 2018)		2.64
"Treatment with Palovarotene was found to dampen the systemic inflammatory response including the cytokines IL-6 (p = 0.01), TNF-α (p = 0.001), and IFN-γ (p = 0.03) as well as the local inflammatory response via a 76% reduction in the cellular infiltration at post-operative day (POD)-7 (p = 0.03)."( Palovarotene inhibits connective tissue progenitor cell proliferation in a rat model of combat-related heterotopic ossification.
Boehm, CA; Bova, W; Cilwa, KE; Davis, TA; Dey, D; Forsberg, JA; Iwamoto, M; Muschler, GF; Potter, BK; Qureshi, AT; Sanders, EM; Seavey, JG; Tomasino, AM; Wheatley, BM, 2018)		2.26

Toxicity

ExcerptReferenceRelevance
" Overall, 89 treatment-emergent ocular adverse events (TEOAEs) were reported by 22 participants (61."( A Randomised Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of Palovarotene Ophthalmic Solution.
Foster, WJ; Roach, JM; Small, KW; Strahs, AL, 2023)		1.13

Pharmacokinetics

Japanese and non-Japanese groups had similar pharmacokinetic profiles. Palovarotene dose adjustments are not necessary for Japanese patients with FOP.

ExcerptReferenceRelevance
" Blood samples for pharmacokinetic assessments were collected before and after dose administration."( A Randomised Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of Palovarotene Ophthalmic Solution.
Foster, WJ; Roach, JM; Small, KW; Strahs, AL, 2023)		1.13
" Similar pharmacokinetic profiles were observed for the once-daily and twice-daily regimens following multiple ascending doses of PVO-OS."( A Randomised Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of Palovarotene Ophthalmic Solution.
Foster, WJ; Roach, JM; Small, KW; Strahs, AL, 2023)		1.13
" This phase I trial (NCT04829786) compared the pharmacokinetic profile of palovarotene in healthy Japanese and non-Japanese participants and evaluated the safety of single doses."( A Pharmacokinetic, Safety, and Tolerability Trial of Palovarotene in Healthy Japanese and Non-Japanese Participants.
Dube, L; Grogan, D; Haga, N; Le Quan Sang, KH; Ogier, J, 2023)		1.39
" The pharmacokinetic parameters of palovarotene were similar between groups at both dose levels."( A Pharmacokinetic, Safety, and Tolerability Trial of Palovarotene in Healthy Japanese and Non-Japanese Participants.
Dube, L; Grogan, D; Haga, N; Le Quan Sang, KH; Ogier, J, 2023)		1.44
"Japanese and non-Japanese groups had similar pharmacokinetic profiles, indicating that palovarotene dose adjustments are not necessary for Japanese patients with FOP."( A Pharmacokinetic, Safety, and Tolerability Trial of Palovarotene in Healthy Japanese and Non-Japanese Participants.
Dube, L; Grogan, D; Haga, N; Le Quan Sang, KH; Ogier, J, 2023)		1.38

Compound-Compound Interactions

ExcerptReferenceRelevance
" The trial also examined how palovarotene might interact with other treatments that are broken down by the body in the same way as palovarotene."( The Pharmacokinetic Profile of Palovarotene: An Open-Label Phase I Trial Investigating the Effect of Food and Potential for Drug-Drug Interaction in Healthy Participants.
Dube, L; Le Quan Sang, KH; Marino, R; Ogier, J, 2023)		1.49

Bioavailability

ExcerptReferenceRelevance
"Palovarotene (Sohonos™) is an orally bioavailable selective retinoic acid receptor (RAR)γ agonist being developed by Ipsen for the reduction of heterotopic ossification (HO) formation in patients with fibrodysplasia ossificans progressiva (FOP)."( Palovarotene: First Approval.
Hoy, SM, 2022)		3.61

Dosage Studied

Palovarotene inhibited chondrogenic differentiation in vitro and reduced HO in juvenile FOP mice. Daily dosing resulted in aggressive synovial joint overgrowth and long bone growth plate ablation.

ExcerptRelevanceReference
" Importantly, Palovarotene seemed to exert moderate inhibitory effects on wound healing, raising potential safety concerns related to dosing and timing."( Targeted stimulation of retinoic acid receptor-γ mitigates the formation of heterotopic ossification in an established blast-related traumatic injury model.
Agarwal, S; Bishop, DK; Davis, TA; Forsberg, JA; Honnold, CL; Iwamoto, M; Levi, B; Loder, S; Pacifici, M; Pavey, GJ; Potter, BK; Qureshi, AT; Tomasino, AM, 2016)		0.79
" Although palovarotene inhibited chondrogenic differentiation in vitro and reduced HO in juvenile FOP mice, daily dosing resulted in aggressive synovial joint overgrowth and long bone growth plate ablation."( Palovarotene reduces heterotopic ossification in juvenile FOP mice but exhibits pronounced skeletal toxicity.
Devarakonda, PM; Goldhamer, DJ; Lees-Shepard, JB; Nicholas, SE; Schneider, MJ; Stoessel, SJ; Yamamoto, M, 2018)		2.33
" Twelve-month interim analyses met futility criteria; dosing was paused."( Reduction of New Heterotopic Ossification (HO) in the Open-Label, Phase 3 MOVE Trial of Palovarotene for Fibrodysplasia Ossificans Progressiva (FOP).
Al Mukaddam, M; Baujat, G; Berglund, SK; Brown, MA; Cheung, AM; De Cunto, C; Delai, P; Haga, N; Hsiao, EC; Kannu, P; Kaplan, FS; Keen, R; Le Quan Sang, KH; Mancilla, EE; Marino, R; Pignolo, RJ; Strahs, A, 2023)		1.13
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
stilbenoidAny olefinic compound characterised by a 1,2-diphenylethylene backbone.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Research

Studies (26)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's1 (3.85)29.6817
2010's15 (57.69)24.3611
2020's10 (38.46)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 44.52

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index44.52 (24.57)
Research Supply Index3.47 (2.92)
Research Growth Index5.30 (4.65)
Search Engine Demand Index63.74 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (44.52)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials5 (19.23%)5.53%
Reviews5 (19.23%)6.00%
Case Studies1 (3.85%)4.05%
Observational0 (0.00%)0.25%
Other15 (57.69%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
midazolam
Midazolam: A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH.. midazolam : An imidazobenzodiazepine that is 4H-imidazo[1,5-a][1,4]benzodiazepine which is substituted by a methyl, 2-fluorophenyl and chloro groups at positions 1, 6 and 8, respectively.		3.9911imidazobenzodiazepine;
monofluorobenzenes;
organochlorine compound		anticonvulsant;
antineoplastic agent;
anxiolytic drug;
apoptosis inducer;
central nervous system depressant;
GABAA receptor agonist;
general anaesthetic;
muscle relaxant;
sedative
activins
Activins: Activins are produced in the pituitary, gonads, and other tissues. By acting locally, they stimulate pituitary FSH secretion and have diverse effects on cell differentiation and embryonic development. Activins are glycoproteins that are hetero- or homodimers of INHIBIN-BETA SUBUNITS.		2.1710
prednisone
Prednisone: A synthetic anti-inflammatory glucocorticoid derived from CORTISONE. It is biologically inert and converted to PREDNISOLONE in the liver.. prednisone : A synthetic glucocorticoid drug that is particularly effective as an immunosuppressant, and affects virtually all of the immune system. Prednisone is a prodrug that is converted by the liver into prednisolone (a beta-hydroxy group instead of the oxo group at position 11), which is the active drug and also a steroid.		2.131011-oxo steroid;
17alpha-hydroxy steroid;
20-oxo steroid;
21-hydroxy steroid;
3-oxo-Delta(1),Delta(4)-steroid;
C21-steroid;
glucocorticoid;
primary alpha-hydroxy ketone;
tertiary alpha-hydroxy ketone		adrenergic agent;
anti-inflammatory drug;
antineoplastic agent;
immunosuppressive agent;
prodrug
nicotine
(S)-nicotine : A 3-(1-methylpyrrolidin-2-yl)pyridine in which the chiral centre has S-configuration. The naturally occurring and most active enantiomer of nicotine, isolated from Nicotiana tabacum.		2.05103-(1-methylpyrrolidin-2-yl)pyridineanxiolytic drug;
biomarker;
immunomodulator;
mitogen;
neurotoxin;
nicotinic acetylcholine receptor agonist;
peripheral nervous system drug;
phytogenic insecticide;
plant metabolite;
psychotropic drug;
teratogenic agent;
xenobiotic
stilbenes
Stilbenes: Organic compounds that contain 1,2-diphenylethylene as a functional group.. trans-stilbene : The trans-isomer of stilbene.		10.21223stilbene
isotretinoin
Isotretinoin: A topical dermatologic agent that is used in the treatment of ACNE VULGARIS and several other skin diseases. The drug has teratogenic and other adverse effects.. isotretinoin : A retinoic acid that is all-trans-retinoic acid in which the double bond which is alpha,beta- to the carboxy group is isomerised to Z configuration. A synthetic retinoid, it is used for the treatment of severe cases of acne and other skin diseases.		2.0510retinoic acidantineoplastic agent;
keratolytic drug;
teratogenic agent
sirolimus
Sirolimus: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.. sirolimus : A macrolide lactam isolated from Streptomyces hygroscopicus consisting of a 29-membered ring containing 4 trans double bonds, three of which are conjugated. It is an antibiotic, immunosupressive and antineoplastic agent.		4.2220antibiotic antifungal drug;
cyclic acetal;
cyclic ketone;
ether;
macrolide lactam;
organic heterotricyclic compound;
secondary alcohol		antibacterial drug;
anticoronaviral agent;
antineoplastic agent;
bacterial metabolite;
geroprotector;
immunosuppressive agent;
mTOR inhibitor
th9507
tesamorelin: a peptide; a stabilized analogue of the growth hormone releasing factor; aimed at reducing excess abdominal fat or VAT in lipodystrophy and HIV patients. tesamorelin : A polypeptide that is a synthetic analogue of human GRF (Growth Releasing Factor) comprised of the 44 amino-acid sequence of human GRF with a hex-3-enoyl moiety attached to the tyrosine residue at the N-terminal part of the molecule. It is used to stimulate human GRF receptors.		2.0610
ConditionIndicatedRelationship StrengthStudiesTrials
Fibrodysplasia Ossificans Progressiva
[description not available]		05.65100
Ectopic Ossification
[description not available]		05.94140
Myositis Ossificans
A disease characterized by bony deposits or the ossification of muscle tissue.		17.65100
Innate Inflammatory Response
[description not available]		05.1631
Inflammation
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.		05.1631
Orphan Diseases
Rare diseases that have not been well studied.		03.6420
Encephalopathy, Traumatic
[description not available]		03.1210
Anoxemia
[description not available]		03.1210
Blast Injuries
Injuries resulting when a person is struck by particles impelled with violent force from an explosion. Blast causes pulmonary concussion and hemorrhage, laceration of other thoracic and abdominal viscera, ruptured ear drums, and minor effects in the central nervous system. (From Dorland, 27th ed)		03.7730
Complication, Postoperative
[description not available]		03.1210
Injuries, Spinal Cord
[description not available]		03.1210
Injuries
Used with anatomic headings, animals, and sports for wounds and injuries. Excludes cell damage, for which pathology is used.		03.4820
Brain Injuries, Traumatic
A form of acquired brain injury which occurs when a sudden trauma causes damage to the brain.		03.1210
Hypoxia
Sub-optimal OXYGEN levels in the ambient air of living organisms.		03.1210
Burns
Injuries to tissues caused by contact with heat, steam, chemicals (BURNS, CHEMICAL), electricity (BURNS, ELECTRIC), or the like.		03.1210
Postoperative Complications
Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery.		03.1210
Spinal Cord Injuries
Penetrating and non-penetrating injuries to the spinal cord resulting from traumatic external forces (e.g., WOUNDS, GUNSHOT; WHIPLASH INJURIES; etc.).		03.1210
Wounds and Injuries
Damage inflicted on the body as the direct or indirect result of an external force, with or without disruption of structural continuity.		03.4820
Bone Cancer
[description not available]		02.2510
Bone Neoplasms
Tumors or cancer located in bone tissue or specific BONES.		02.2510
Chondrosarcoma
A slowly growing malignant neoplasm derived from cartilage cells, occurring most frequently in pelvic bones or near the ends of long bones, in middle-aged and old people. Most chondrosarcomas arise de novo, but some may develop in a preexisting benign cartilaginous lesion or in patients with ENCHONDROMATOSIS. (Stedman, 25th ed)		02.2510
Intertrochanteric Fractures
[description not available]		02.2510
Hip Fractures
Fractures of the FEMUR HEAD; the FEMUR NECK; (FEMORAL NECK FRACTURES); the trochanters; or the inter- or subtrochanteric region. Excludes fractures of the acetabulum and fractures of the femoral shaft below the subtrochanteric region (FEMORAL FRACTURES).		07.2510
Inflammatory Response Syndrome, Systemic
[description not available]		02.1710
War-Related Injuries
WOUNDS and INJURIES and PSYCHOLOGICAL TRAUMA sustained during WAR.		02.1710
Systemic Inflammatory Response Syndrome
A systemic inflammatory response to a variety of clinical insults, characterized by two or more of the following conditions: (1) fever		02.1710
Bessel-Hagen Disease
[description not available]		03.0910
Experimental Neoplasms
[description not available]		03.0910
Chondrosteoma
[description not available]		02.1710
Orthopedic Disorders
[description not available]		03.1210
Musculoskeletal Diseases
Diseases of the muscles and their associated ligaments and other connective tissue and of the bones and cartilage viewed collectively.		03.1210
Pregnancy
The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.		03.1210
Body Weight
The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.		02.1310
Disease Models, Animal
Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.		02.8230
Disease Exacerbation
[description not available]		02.1310
Emphysema
A pathological accumulation of air in tissues or organs.		010.6132
Centriacinar Emphysema
[description not available]		03.8521
alpha 1-Antitrypsin Deficiency
Deficiency of the protease inhibitor ALPHA 1-ANTITRYPSIN that manifests primarily as PULMONARY EMPHYSEMA and LIVER CIRRHOSIS.		03.4411
Airflow Obstruction, Chronic
[description not available]		02.4620
Smoking Cessation
Discontinuing the habit of SMOKING.		02.0510
Pulmonary Disease, Chronic Obstructive
A disease of chronic diffuse irreversible airflow obstruction. Subcategories of COPD include CHRONIC BRONCHITIS and PULMONARY EMPHYSEMA.		02.4620
Weight Reduction
[description not available]		02.0610
Cachexia
General ill health, malnutrition, and weight loss, usually associated with chronic disease.		02.0610
Weight Loss
Decrease in existing BODY WEIGHT.		02.0610
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