PMID- 35428607
OWN - NLM
STAT- MEDLINE
DCOM- 20220712
LR  - 20220712
IS  - 2212-5353 (Electronic)
IS  - 2212-5345 (Linking)
VI  - 60
IP  - 4
DP  - 2022 Jul
TI  - Hierarchical cluster analysis based on disease-associated manifestations of 
      patients with lymphangioleiomyomatosis: An analysis of the national database of 
      designated intractable diseases of Japan.
PG  - 570-577
LID - S2212-5345(22)00028-4 [pii]
LID - 10.1016/j.resinv.2022.03.003 [doi]
AB  - BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare multisystem disease with 
      variable manifestations and differing rates of progression among individuals. 
      Classification of its phenotypes is an issue for consideration. We hypothesized 
      that clinical manifestations associated with LAM cluster together and identifying 
      these associations would be useful for identifying phenotypes. METHODS: Using 
      cross-sectional data from the National Database of Designated Intractable 
      Diseases of Japan, we performed a hierarchical cluster analysis based on 
      disease-associated manifestations. RESULTS: Four clusters were identified from 
      404 patients (50.4% of 801 LAM patients registered in 2016). Patients in cluster 
      1 had only dyspnea on exertion, relatively low lung function, the earliest onset 
      age, and the lowest prevalence of tuberous sclerosis complex (TSC). Those in 
      cluster 2 had various manifestations with the highest prevalence of TSC. Patients 
      in cluster 3 had major respiratory symptoms (cough, sputum, or dyspnea on 
      exertion) or fatigue and the lowest lung function. Those in cluster 4 were 
      asymptomatic and had the latest onset age, shortest disease duration, and 
      relatively high prevalence of TSC. Patients in cluster 1 had the highest rate of 
      receiving mechanistic target of rapamycin (mTOR) inhibitor treatment, suggesting 
      that cluster 1 included those with declining lung function for which mTOR 
      inhibitor treatment was required. CONCLUSIONS: Hierarchical cluster analysis 
      based on manifestations data identified four clusters. The characteristics of 
      cluster 1 are noteworthy in relation to the indication for mTOR inhibitor 
      treatment. A cluster analysis of accumulated and longitudinal data that allows 
      valid clustering and outcome comparisons is required in the future.
CI  - Copyright (c) 2022 The Japanese Respiratory Society. Published by Elsevier B.V. All 
      rights reserved.
FAU - Hayashida, Mie
AU  - Hayashida M
AD  - First Department of Internal Medicine, Shinshu University School of Medicine, 
      Matsumoto, Japan. Electronic address: mie@shinshu-u.ac.jp.
FAU - Kinjo, Takumi
AU  - Kinjo T
AD  - First Department of Internal Medicine, Shinshu University School of Medicine, 
      Matsumoto, Japan.
FAU - Wada, Yosuke
AU  - Wada Y
AD  - First Department of Internal Medicine, Shinshu University School of Medicine, 
      Matsumoto, Japan.
FAU - Kitaguchi, Yoshiaki
AU  - Kitaguchi Y
AD  - First Department of Internal Medicine, Shinshu University School of Medicine, 
      Matsumoto, Japan.
FAU - Hanaoka, Masayuki
AU  - Hanaoka M
AD  - First Department of Internal Medicine, Shinshu University School of Medicine, 
      Matsumoto, Japan.
LA  - eng
PT  - Journal Article
DEP - 20220412
PL  - Netherlands
TA  - Respir Investig
JT  - Respiratory investigation
JID - 101581124
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Cluster Analysis
MH  - Cross-Sectional Studies
MH  - Dyspnea/epidemiology/etiology
MH  - Humans
MH  - Japan/epidemiology
MH  - *Lymphangioleiomyomatosis/diagnosis/epidemiology
MH  - Rare Diseases/complications
MH  - TOR Serine-Threonine Kinases
MH  - *Tuberous Sclerosis/complications/diagnosis/epidemiology
OTO - NOTNLM
OT  - Cluster analysis
OT  - Database
OT  - Lymphangioleiomyomatosis
OT  - Manifestation
OT  - Treatment
COIS- Conflict of Interest None of the authors have any conflicts of interest.
EDAT- 2022/04/17 06:00
MHDA- 2022/07/14 06:00
CRDT- 2022/04/16 05:20
PHST- 2022/01/15 00:00 [received]
PHST- 2022/03/09 00:00 [revised]
PHST- 2022/03/10 00:00 [accepted]
PHST- 2022/04/17 06:00 [pubmed]
PHST- 2022/07/14 06:00 [medline]
PHST- 2022/04/16 05:20 [entrez]
AID - S2212-5345(22)00028-4 [pii]
AID - 10.1016/j.resinv.2022.03.003 [doi]
PST - ppublish
SO  - Respir Investig. 2022 Jul;60(4):570-577. doi: 10.1016/j.resinv.2022.03.003. Epub 
      2022 Apr 12.