From January 2012 to August 2021, 75 patients with RP were screened in this study. 2 patients with positive for ANCA against MPO (myeloperoxidase) diagnosed as Systemic vasculitis and 1 patient with positive for ANCA against PR3 (proteinase-3) diagnosed as ANCA associated vasculitis were excluded. The diagnosis based on Damiani and Levine’s criteria was confirmed in 45 patients (62.5%), either Michet or Damiani criteria were fulfilled in 66 patients (91.6%). 16 patients (22.2%) met all the three criteria, 6 (8.3%) patients did not fulfil any set of criteria, but the improvement of auricular inflammation and respiratory symptoms after corticosteroid treatment was typical for RP. We reviewed previous chest CT images and found respiratory wall thickening sparing the posterior membranous wall was identified in 43 patients (59.7%) (shown in Fig. 1a), respiratory wall calcification sparing the posterior membranous wall was identified in 24 patients (33.3%) (shown in Fig. 1b and c), respiratory stenosis was identified in 10 patients (13.8%) (shown in Fig. 1d), 29 (40.3%) patients did not show the above typical CT findings of RP. Thus, there were 43 (59.7%) and 29 (40.3%) patients in the respiratory involvement and non-respiratory involvement subgroups. 64 patients received treatments, with a base of prednisone of 0.5-1mg/Kg/d, 25%(n=18), 19.4%(n=14) of patients were being treated with methotrexate (MTX) and cyclophosphamide (CYC), respectively.
Demographic Characteristics
A total of 42 male and 30 female patients were included in our study, 29 of 72 patients smoked. The average age at the time of first symptoms was 54.03±13.10 years and the average age at diagnosis was 55.20±12.59 years. The delay from the time of the first symptom to the diagnosis was 6(2-24) months, and the duration of follow-up since the establishment of diagnosis was 4 (3-6) years. Finally, 5 patients died during the follow-up. We did not find significant differences in the demographic features of two subgroups (Table 2).
Table 2
Comparison of patients with respiratory involvement and non- respiratory involvement
Variables | All patients (n=72) | Non-airway involvement (n=29) | airway involvement (n=43) | P value |
Male | 42(58.3%) | 19(65.5%) | 24(55.8%) | 0.26 |
Smoke | 29(40.3%) | 11(37.9%) | 18(41.9%) | 0.73 |
Age at the time of first symptoms (years) | 54.03±13.10 | 56.36±16.18 | 52.48±10.71 | 0.39 |
The time of the first symptom to the diagnosis (months) | 6(2-24) | 4.5(2-15) | 7(2-24) | 0.52 |
Age at diagnosis(years) | 55.20±12.59 | 57.29±15.44 | 53.81±10.45 | 0.43 |
Clinical features, n (%) | | | | |
Laryngeal involvement | 8(11.1%) | 2(6.9%) | 6(14%) | 0.35 |
Auricular chondritis | 26(36.1%) | 19(65.5%) | 7(16.2%) | 0.001* |
Inflammatory arthritis | 6(8.3%) | 2(6.8%) | 4(9.3%) | 0.72 |
Nasal chondritis | 11(15.3%) | 4(13.8%) | 7(16.3%) | 0.77 |
Inflammatory eye disease | 18(25%) | 13(44.8%) | 5(11.6%) | 0.001* |
Sensorineural hear loss | 18(25%) | 10(34.5%) | 8(18.6%) | 0.13 |
Cutaneous manifestations | 4(5.6%) | 2(6.9%) | 2(4.7%) | 0.68 |
Costochondritis | 14(19.4%) | 2(6.9%) | 12(27.9%) | 0.03* |
Fever | 26(36.1%) | 11(37.9%) | 15(34.9%) | 0.79 |
Pulmonary infection | 14(19.4%) | 3(10.3%) | 11(25.6%) | 0.06 |
Myocardial infarction | 4(5.6%) | 2(6.9%) | 2(4.7%) | 0.65 |
Laboratory findings | | | | |
IgG (mg/dl) | 1139.82±317.57 | 1062.2±307.62 | 1187.87±321.38 | 0.27 |
IgA (mg/dl) | 272.5(182.5-370.25) | 266(93.45-318) | 277(190.5-405.5) | 0.40 |
IgM (mg/dl) | 78..35(61.45-130.25) | 73.1(61.75-114.55) | 82.8(60.2-132) | 0.68 |
C3 (mg/dl) | 109.72±21.34 | 102.86±18.31 | 113.97±22.38 | 0.14 |
C4 (mg/dl) | 28.8(22.45-34.18) | 25.61 (22-30.65) | 29.31(22.3-35.75) | 0.26 |
Albumin (g/L) | 36.31±5.80 | 37.04±7.36 | 35.85±4.73 | 0.57 |
Total cholesterol (mmol/l) | 4.23(3.85-5.09) | 4.67(3.72-5.09) | 4.12(3.83-5.11) | 0.62 |
HDL-C (mmol/l) | 1.1(0.8-1.59) | 1.1(0.87-1.65) | 1.02(0.77-1.54) | 0.51 |
LDL-C (mmol/l) | 2.75(2.48-3.32) | 2.8(2.2-3.1) | 2.72(2.53-3.77) | 0.68 |
Triglyceride (mmol/l) | 1.04(0.8-1.23) | 1.09(0.85-1.34) | 0.98(0.74-1.11) | 0.08* |
LDH (u/l) | 190.5(158.75-216.25) | 191(170-214.5) | 190(140.5-229) | 0.83 |
Creatinine (umol/l) | 61.1(49.13-70.13) | 69.8(50.5-79.35) | 55.8(44.35-66.25) | 0.02* |
Uric acid (umol/l) | 266.85±89.99 | 320.15±88.02 | 233.88±75.66 | 0.01* |
HbA1c (%) | 5.95(5.52-7.34) | 5.9(5.51-7.45) | 6(5.55-7.57) | 0.62 |
White blood cells (10^9) | 8.06(6.54-10.05) | 7.18 (5.64-10.66) | 8.16 (7.04-9.57) | 0.4 |
Neutrophils (10^9) | 5.77(4.23-7.58) | 5.61(3.05-7.07) | 6.21(4.51-8) | 0.23 |
Lymphocyte (10^9) | 1.48(0.87-2.19) | 1.85 (0.99-2.86) | 1.32 (0.87-2.01) | 0.29 |
Monocyte (10^9) | 0.47 (0.41-0.66) | 0.43 (0.38-0.72) | 0.47 (0.44-0.68) | 0.4 |
Hemoglobin (g/l) | 124.4±21.8 | 122.38±28.68 | 123.95±14.87 | 0.84 |
Platelet (10^9) | 289.5(190.75-355.02) | 245(175-311) | 298(267.5-376.5) | 0.15 |
CRP (mg/l) | 2.31(0.61-8.19) | 0.96(0.43-4.50) | 3.96(1.74-9.78) | 0.03* |
ESR (mm/h) | 25.5(13.75-44) | 20 (13-28) | 30(14-60.5) | 0.04* |
CAR | 0.07(0.19-0.26) | 0.23(0.14-0.11) | 0.11(0.04-0.29) | 0.04* |
NLR | 4.26(1.78-7.06) | 1.80(1.47-6.08) | 4.46(3.02-9.05) | 0.03* |
PLR | 197.59(124.29-286.34) | 132.43(76.10)-202.32 | 223.08(185.8-7-334.14) | 0.01* |
Outcomes | | | | |
Mortality | 5(6.9%) | 2(6.9%) | 3(7%) | 0.72 |
Note: Data are presented as median (interquartile range), mean (standard deviation) or n (%) |
Abbreviations: HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; LDH, lactate dehydrogenase; CRP, c-active protein; ESR, erythrocyte sedimentation rate; CAR C reactive protein to albumin ratio; NLR neutrophil to lymphocyte ratio |
PLR platelet to lymphocyte ratio |
*p<0.05 |
Subgroup Analyses Of Clinical Characteristic And Correlation Analysis
Respiratory involvement (n=43) and auricular chondritis (n=26) were the most frequent manifestations, followed by ocular involvement consisting of scleritis and uveitis (n=18), sensorineural hear loss (n=18), costochondritis (n=14), nasal chondritis (n=11). Patients in respiratory involvement subgroup had a significantly higher occurrence of costochondritis (p=0.03) and a less occurrence of auricular chondritis (p=0.001), inflammatory eye disease (p=0.001) than non-respiratory involvement subgroup. Laryngeal involvement in 8 patients, Inflammatory arthritis in 6 patients, cutaneous manifestations in 4 patients were other common seen manifestations, there was no significant difference in above clinical manifestations between the two groups. Although not statistically significant, there was a clear trend toward a higher frequency of pulmonary infection in respiratory involvement subgroups (p=0.06). Cardiac involvement in the form of myocardial infarction or ventricular tachycardia was seen in 4 patients. One patient developed cytopenia after treatment with glucocorticoids and immunosuppressants, bone marrow biopsy showed bone marrow suppression.
Then, we performed correlation analysis between different organ involvement and found a negative correlation between respiratory involvement and auricular chondritis (r=-0.58, p < 0.01), and also between respiratory involvement and inflammatory eye disease (r=-0.45, P < 0.01). Auricular chondritis was positively correlated with inflammatory eye disease (r=0.49, P < 0.01) A weak positive correlation was also revealed between auricular chondritis and pulmonary infection (r=-0.39, P < 0.05). (shown in Fig. 2)
Comparisons Of Laboratory Findings And Subgroup Analysis
The respiratory involvement subgroup had higher CRP and ESR concentrations than non-respiratory involvement subgroup (p=0.03, p=0.04). Creatinine and Uric acid in the non-respiratory involvement subgroup were significantly higher than in respiratory involvement subgroup (p=0.02, p=0.01). Novel inflammatory markers associated with RP disease activity index NLR, PLR were higher in respiratory involvement subgroup (p=0.03, p=0.01), but CAR was lower (p=0.04, p=0.01). We further conducted subgroup analysis on whether patients with respiratory involvement had pulmonary infection, and found no statistical difference in inflammatory indicators between the two groups of patients. (Table.3)
Table 3. Subgroup analysis of respiratory involvement patients with pulmonary infection or without pulmonary infection
|
Without pulmonary infection
(n=32)
|
With pulmonary infection
(n=11)
|
p
|
CRP (mg/l)
|
4.35(2-8.4)
|
3.49(0.7-10.7)
|
0.81
|
ESR (mm/h)
|
37.5(25-58.3)
|
24(13-62)
|
0.46
|
CRP/Albumin
|
0.11(0.05-0.31)
|
0.09(0.02-0.29)
|
0.38
|
Neutrophil/lymphocyte
|
4.11(2.51-10.04)
|
5.06(3.91-8.23)
|
0.55
|
Platelet/Lymphocyte
|
243.8(185.45-453.12)
|
209.85(181.31-288.53)
|
0.91
|
Note: Values are median (IQR).
Abbreviations: CRP, c-active protein; ESR, erythrocyte sedimentation rate CAR C reactive protein to albumin ratio; NLR neutrophil to lymphocyte ratio; PLR platelet to lymphocyte ratio
*p<0.05
PFTs were performed in 22 patients with respiratory involvement, and showed respiratory obstruction in all patients, obviously reducing in forced expiratory volume in 1 second (FEV1) 1.21±0.54L, forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) 42.11±14.84%, Residual volume (RV), total lung capacity (TLC), Residual volume /total lung capacity (RV/TLC) were usually normal.
Positive antinuclear antibodies were found in 8 patients in a titre of 1: 320, rheumatoid factor was positive in 4 patients, antineutrophil cytoplasmic antibodies were positive in 4 patients, but no particular specificities were found.
Survivals
After a follow-up period of 6 (3-8) years since the first symptoms, 6.9% of the patients (n = 5) had died (Table.2), K-M curve and Log-rank test also showed the probability of survival was not statistically different between patients with and without respiratory involvement (shown in Fig. 3).