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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2019, Vol. 13 Issue (2) : 259-266
Clinical characteristics in lymphangioleiomyomatosis-related pulmonary hypertension: an observation on 50 patients
Xiuxiu Wu1, Wenshuai Xu1, Jun Wang1, Xinlun Tian1, Zhuang Tian2, Kaifeng Xu1()
1. Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
2. Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
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Lymphangioleiomyomatosis (LAM) is a rare diffuse cystic lung disease. Knowledge on LAM-related pulmonary hypertension (PH) is limited. This study aimed to analyze the clinical characteristics of LAM with elevated pulmonary artery pressure (PAP) and evaluate the potential efficacy of sirolimus. The study involved 50 LAM patients who underwent echocardiography. According to the tricuspid regurgitation velocity (TRV), these patients were divided into the TRV≤2.8 m/s group and TRV>2.8 m/s group. Both groups comprised 25 females with an average age of 38.6±8.1 and 41.5±8.9 years. In the TRV>2.8 m/s group, the estimated systolic PAP (SPAP) was significantly elevated (52.08±12.45 mmHg vs. 30.24±5.25 mmHg, P<0.01). Linear analysis showed that SPAP was correlated with forced expiratory volume in 1 s (FEV1), diffusing capacity of the lungs for carbon monoxide, alveolar arterial oxygen gradient (PA-aO2), and 6 min walking distance (r = −0.392, −0.351, 0.450, and −0.591, respectively; P<0.05), in which PA-aO2 was a risk factor for SPAP elevation (β = 0.064, OR= 1.066, P<0.05). Moreover, in 10 patients who received sirolimus therapy, SPAP decreased from 57.0±12.6 mmHg to 35.2±11.1 mmHg. The study showed that LAM patients with PH exhibit poor pulmonary function and hypoxemia and may benefit from sirolimus treatment.

Keywords lymphangioleiomyomatosis      pulmonary hypertension      pulmonary function      hypoxemia      sirolimus     
Corresponding Author(s): Kaifeng Xu   
Just Accepted Date: 09 March 2018   Online First Date: 18 April 2018    Issue Date: 28 March 2019
 Cite this article:   
Xiuxiu Wu,Wenshuai Xu,Jun Wang, et al. Clinical characteristics in lymphangioleiomyomatosis-related pulmonary hypertension: an observation on 50 patients[J]. Front. Med., 2019, 13(2): 259-266.
Fig.1  Patient screening chart. TRV, tricuspid regurgitation velocity; SPAP, pulmonary artery systolic pressure; PFT, pulmonary function test; ABG, arterial blood gas; 6MWD, 6 min walking distance; SGRQ, St George’s respiratory questionnaire.
Variables TRV≤2.8m/s
n = 25
TRV>2.8 m/s
n = 25
P value
Age (mean years) 38.64±8.10 41.48±8.93 0.245
Cigarette smoking 0 0 1
Weight (kg) 53.66±5.65 51.68±7.15 0.283
Body mass index (kg/m2) 20.97±2.21 20.51±2.71 0.512
LAM diagnosis
Definite (%)
Probable (%)
Tuberous sclerosis complex (%) 8% 8% 1
Renal angiomyolipoma (%) 20% 12% 0.702
History of pneumothorax (%) 32% 28% 0.758
History of chylothorax (%) 28% 40% 0.370
WHO functional class
I–II (%) 92% 76% 0.247
III–IV (%) 8% 24%
SPAP (mmHg) 30.24±5.25 52.08±12.45 0.000
Supplemental oxygen 20% 72% 0.000
Tab.1  Demographics and clinical characteristics of TRV≤2.8 m/s group and TRV>2.8 m/s group
Fig.2  Correlation between systolic pulmonary artery pressure (SPAP) and pulmonary function, oxygenation, and 6 min walking distance (6MWD). SPAP was negatively correlated with forced vital capacity (FVC) % predicted, forced expiratory volume in 1 s (FEV1) % predicted, diffusing capacity of the lungs for carbon monoxide (DLCO) % predicted, arterial oxygen pressure (PaO2), arterial oxygen saturation (SaO2), and 6MWD (A–F) and positively correlated with alveolar arterial PO2 difference (PA-aO2) (G).
Variables TRV≤2.8 m/s
n = 25
TRV>2.8 m/s
n = 25
P value
Pulmonary function
FVC% pred 87.82±16.3 69.82±20.21 0.001
FEV1% pred 67.63±24.30 43.71±19.97 0.000
FVC/FEV1% 66.66±22.00 52.62±14.82 0.012
TLC% pred 109.66±19.29 112.42±19.73 0.646
RV% pred 157.08±66.20 191.53±75.65 0.115
RV/TLC% 44.61±1 2.06 53.54±14.46 0.031
DLCO% pred 45.92±18.75 30.42±16.78 0.005
Arterial blood gas
PaO2 (mmHg) 78.10±13.39 60.60±14.31 0.000
PA-aO2 (mmHg) 30.61±15.60 56.24±26.14 0.000
PaCO2 (mmHg) 34.96±4.31 35.40±8.97 0.827
SaO2 (%) 94.53±2.72 90.45±5.07 0.001
6MWD (m) 476.15±88.62 344.11±104.19 0.000
Borg dyspnea index 1.94±2.40 2.77±2.22 0.217
Symptom (score) 40.04±24.82 47.68±20.48 0.241
Activity ability (score) 45.88±26.43 67.80±16.92 0.001
Disease impact (score) 33.84±22.15 54.80±21.94 0.001
Total score (score) 38.80±21.89 57.52±17.13 0.002
Tab.2  Evaluations of the TRV≤2.8 m/s and TRV>2.8 m/s groups
Variables β OR (95%CI) P value
FEV1% pred −0.029 0.971 (0.922–1.023) 0.276
DLCO% pred 0.028 1.028 (0.963–1.097) 0.404
PA-aO2 0.064 1.066 (1.006–1.129) 0.031
6MWD −0.0.007 0.993 (0.984–1.002) 0.105
Tab.3  Multivariate logistic analyses for predicting the probability of PH in LAM
Variables Baseline After sirolimus Paired t test
d t P value
SPAP (mmHg) 57.00±12.59 35.17±11.07 −21.83±10.21 −6.755 0.000
FVC% pred 55.62±14.23 82.85±25.07 27.23±19.36 4.446 0.002
FEV1% pred 30.52±12.00 45.11±23.47 14.59±15.68 2.941 0.016
DLCO% pred 22.75±6.69 29.69±19.13 6.94±14.32 1.52 0.16
PaO2 (mmHg) 55.03±6.59 71.53±10.75 16.50±15.18 3.436 0.007
SaO2 (%) 87.01±4.38 94.02±2.23 7.01±5.22 4.244 0.002
PA-aO2 (mmHg) 54.40±9.11 38.13±13.37 −16.27±15.86 −3.243 0.01
6MWD (m) 294.75±83.45 394.40±71.69 99.65±68.29 4.614 0.001
Tab.4  Improvement in clinical features after sirolimus treatment
Fig.3  Improvement in clinical features after sirolimus treatment. (A) Pulmonary artery systolic pressure (SPAP) was significantly decreased after treatment with sirolimus. (B, C) Pulmonary function, including forced vital capacity (FVC) % pred and forced expiratory volume in 1 s (FEV1) % pred, were significantly increased. (D, E, F) Oxygenation indicators, such as arterial oxygen pressure (PaO2) and arterial oxygen saturation (SaO2), were significantly increased, and alveolar arterial oxygen gradient (PA-aO2) was significantly decreased. (G) Six minute walking distance (6MWD) was significantly improved after sirolimus treatment compared with the baseline.
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