Demographic features of all patients
Comparisons of the gender ratio, age of diagnosis, smoking history, pneumothorax and family history are listed in Table 1. All patients from the different families were of Chinese Han origin. Females were predominant in all groups. Among the patients with BHD, almost half of patients were misdiagnosed with primary spontaneous pneumothorax. The longest misdiagnosis duration for patients with BHD was 38 years. The average misdiagnosis delay for patients with BHD was 7.73 years. Eighteen (54.5%, 18/33) patients had cutaneous lesions. Renal impairment was observed in 11 (33%, 11/33) patients. Compared with the NBNL group, patients with BHD syndrome were more likely to have past medical histories of pneumothoraxes (p=0.003), but there was no difference between BHD and LAM (BHD 17/33 [51.5%] vs LAM 12/33 [36.4%], p=0.215). Significant difference was noted in family history of pneumothoraxes between the BHD group and either the LAM or the NBNL group. Smoking history had no significant difference between the BHD group and either the LAM or the NBNL group. (Table 1)
Table 1. Demographic features of the BHD and non-BHD groups
Characteristic
|
BHD
|
LAM
|
NBNL DCLD§
|
P*
|
P**
|
N=33
|
N=33
|
N=23
|
Female, N (%)
|
31 (93.9)
|
33 (100)
|
18 (78.3)
|
0.473
|
0.182
|
Age of diagnosis, Mean (SD)
|
48±12
|
37±8
|
40±14
|
<0.001
|
0.020
|
Pneumothorax antecedent, N (%)
|
17 (51.5)
|
12 (36.4)
|
3 (13.0)
|
0.215
|
0.003
|
Smoking history, N (%)
|
1 (3.0)
|
0 (0)
|
8 (34.8)
|
0.314
|
0.001
|
Family history, N (%)
|
25 (75.8)
|
0 (0)
|
0 (0)
|
<0.001
|
<0.001
|
*P values are for comparison between the BHD and LAM groups.
**P values are for comparison between the BHD and NBNL DCLD groups.
§The NBNL (no-BHD and no-LAM) DCLD group includes 15 cases of lymphocytic interstitial pneumonia associated with Sjogren’s syndrome (SS), 7 cases of pulmonary Langerhans cell histiocytosis (PLCH), 1 case with Langerhans cell histiocytosis (LCH) and 1 case of Castleman Disease.
The P value was calculated with the use of the unpaired t-test to compare continuous variables.
The P value was calculated with the use of Pearson's chi-squared test for categorical variables.
Abbreviations: BHD: Birt-Hogg-Dubé syndrome, DCLD: diffuse cystic lung disease, NBNL: no-BHD and no-LAM; SD: standard deviation.
Radiological features of pulmonary cysts in BHD and non-BHD
Cysts were bilateral in all patients. Lower lung-predominant cysts were more likely to be found in patients with BHD syndrome (58% of patients) than in patients in the LAM (no patients, p<0.001) or the NBNL group (26% of patients, p=0.020). Significant difference was also found in the axial distribution of pulmonary cysts. All cysts were diffuse in the non-BHD group, and 18 of 33 patients (55%) in the BHD group had cysts predominance near the mediastinum (p<0.001).
The morphology of the pulmonary cysts was variable within individual patients. The appearance of fusiform cysts was observed in 27 patients in the BHD group (82%), while only 5 cases had fusiform cysts in the LAM group (15%, p<0.001) and 5 patients in the NBNL group (22%, p<0.001).
In terms of the number of cysts, 58% of patients in the BHD group had fewer than 50 lung cysts, while all patients in the LAM group (p<0.001) and 78% patients in the NBNL group had more than 50 lung cysts (p=0.008).
The distribution of the largest cysts was different. The largest cyst was located in the lower lobe in 28 patients (85%) in the BHD group, while 11 of 33 patients (33%) in the LAM group and 10 patients (43%) in the NBNL group had the largest cyst in the lower lobe. When comparing the diameters of the largest cysts between patients in two groups, the median diameters were 45 mm in the BHD group and 16.5 mm in the LAM group. Significant differences in the distribution of the diameter of the largest cysts were noted between the BHD and LAM groups (p<0.001) and the NBNL group (p=0.001) (Table 2).
Table 2. Radiological characteristics of pulmonary cysts in BHD and non-BHD
Characteristic
|
BHD
N=33
|
LAM
N=33
|
NBNL DCLD
N=23
|
P*
|
P**
|
P***
|
Cranial-caudal distribution
|
Upper lung, N (%)
|
2 (6)
|
0 (0)
|
6 (26)
|
<0.001
|
0.473
|
0.086
|
Lower lung, N (%)
|
19 (58)
|
0 (0)
|
6 (26)
|
<0.001
|
<0.001
|
0.020
|
Diffuse, N (%)
|
12 (36)
|
33 (100)
|
11 (48)
|
<0.001
|
<0.001
|
0.391
|
Axial distribution
|
Mediastinum, N (%)
|
18 (55)
|
0 (0)
|
0 (0)
|
<0.001
|
<0.001
|
<0.001
|
Peripheral pleural, N (%)
|
3 (9)
|
0 (0)
|
0 (0)
|
0.074
|
0.237
|
0.237
|
Diffuse, N (%)
|
12 (36)
|
33 (100)
|
23 (100)
|
<0.001
|
<0.001
|
<0.001
|
Fusiform Cysts, N (%)
|
27 (82)
|
5 (15)
|
5 (22)
|
<0.001
|
<0.001
|
<0.001
|
No. of Lung Cysts
|
<10, N (%)
|
2 (6)
|
0 (0)
|
0 (0)
|
0.180
|
0.473
|
0.638
|
10-20, N (%)
|
4 (12)
|
0 (0)
|
0 (0)
|
0.030
|
0.122
|
0.228
|
20-50, N (%)
|
13 (39)
|
0 (0)
|
5 (22)
|
<0.001
|
<0.001
|
0.164
|
>50, N (%)
|
14 (42)
|
33 (100)
|
18 (78)
|
<0.001
|
<0.001
|
0.008
|
Maximum Cyst
|
Lower lung, N (%)
|
28 (85)
|
11 (33)
|
10 (43)
|
0.023
|
<0.001
|
0.001
|
Bigger cyst diameter, median (IQR)
|
45(30, 55)
|
16.5(10,20)
|
35(20,50)
|
<0.001
|
<0.001
|
0.121
|
P*values are for comparison within the three groups together by Kruskal-Wallis test.
P**values are for comparison between the BHD and LAM groups.
P*** values are for comparison between the BHD and NBNL DCLD groups.
The P value was calculated with the use of Pearson's chi-squared test for categorical variables.
The P value was calculated with the use of the Wilcoxon rank-sum test to compare continuous variables.