Clinical significance of microscopic polyangiitis with interstitial lung disease and bronchiectasis: probability of preexisting comorbidities

Figures & data

Figure 1. Flowchart of the study. MPA: microscopic polyangiitis; ILD: interstitial lung disease; BE: bronchiectasis; DAH: diffuse alveolar haemorrhage.

Table 1. Comparison between the MPA-ILD group and MPA-BE group in terms of demographic and clinical characteristics.

Characteristic	All pulmonary involvement (n = 47)	MPA-ILD (n = 37)	MPA-BE (n = 12)	p Value
Age (years)	70.34 ± 12.61	72.03 ± 11.19	69.83 ± 9.90	.548
	70.00 [62.50–82.00]	73.00 [61.50–82.50]	65.00 [63.00–77.00]	.509
M/F	26/21	23/14	5/7	.362
Smoking	17 (36.17%)	16 (43.24%)	1 (8.33%)	.063
Follow-up time, months	25.00 [10.00–44.00]	25.00 [10.50–45.50]	15.00 [4.50–30.25]	.153
Symptoms
Fever	22 (46.81%)	16 (43.24%)	7 (58.33%)	.788
Cough	29 (61.70%)	21 (56.76%)	10 (83.33%)	.189
Dyspnoea	22 (46.81%)	17 (45.95%)	6 (50.00%)	.940
Haemoptysis	9 (19.15%)	4 (10.81%)	5 (41.67%)	.049
Arthralgia	14 (29.79%)	12 (32.43%)	3 (25.00%)	.901
Rash	11 (23.40%)	9 (24.32%)	2 (16.67%)	.877
Systematic involvement
Renal	28 (59.57%)	21 (56.76%)	8 (66.67%)	.788
Nervous system	20 (42.55%)	16 (43.24%)	6 (50.00%)	.904
Cardiovascular	7 (14.89%)	5 (13.51%)	2 (16.67%)	.839
Diffuse alveolar haemorrhage	2 (4.26%)	1 (2.70%)	0 (0%)	.549
Chronology of ILD/BE diagnosis
Before MPA	28 (59.57%)	21 (56.76%)	9 (75.00%)	.432
Simultaneously	18 (38.30%)	15 (40.54%)	3 (25.00%)	.531
After MPA	1 (2.13%)	1 (2.70%)	0 (0%)	.549
Treatment
Glucocorticoid	31 (65.96%)	25 (67.57%)	8 (66.67%)	.767
Cyclophosphamide	20 (42.55%)	16 (43.24%)	6 (50.00%)	.747
Rituximab	2 (4.26%)	2 (5.41%)	0 (0%)	.986
Nintedanib/pirfenidone	3 (6.38%)	3 (8.11%)	0 (0%)	.745
None	16 (34.04%)	12 (32.43%)	4 (33.33%)	.767
Outcome
Death of all cause	18 (38.30%)	15 (40.54%)	4 (33.33%)	.917

MPA: microscopic polyangiitis; ILD: interstitial lung disease; BE: bronchiectasis; M: male; F: female.

Data are presented as the median [IQR] or mean ± SD or no. (%), and p < .05 was considered significant.

Bold values indicates statistical differences.

Table 2. Comparison between the MPA-ILD group and MPA-BE group in terms of laboratory tests, PFTs and HRCT patterns.

Characteristic	All pulmonary involvement (n = 47)	MPA-ILD (n = 37)	MPA-BE (n = 12)	p Value
Laboratory findings
WBC (×10^9/L)	8.13 ± 2.28	8.19 ± 2.37	8.10 ± 1.87	.900
HB (g/L)	115.43 ± 24.70	116.73 ± 26.67	120.42 ± 19.15	.627
PLT (×10^9/L)	261.07 ± 119.72	244.04 ± 121.68	308.00 ± 93.23	.103
CRP (g/L)	44.89 ± 41.08	39.63 ± 34.44	55.93 ± 56.12	.233
ESR (mm/h)	66.38 ± 41.01	63.32 ± 42.37	75.08 ± 36.98	.394
LDH (U/L)	212.60 ± 63.76	222.86 ± 68.19	171.58 ± 31.43	.016
Cr (μmol/L)	132.42 ± 162.69	140.47 ± 181.80	94.80 ± 34.34	.395
IgG (g/L)	17.29 ± 5.70	17.16 ± 5.79	17.68 ± 7.18	.802
RF positivity	25 (53.19%)	20 (54.05%)	6 (50.00%)	.807
ANA positivity	22 (46.81%)	19 (51.35%)	4 (33.33%)	.754
P-ANCA positivity	42 (89.36%)	32 (86.49%)	11 (91.67%)	.634
MPO-ANCA positivity	42 (89.36%)	32 (86.49%)	12 (100.00%)	.179
C-ANCA positivity	1 (2.13%)	1 (2.70%)	0 (0.00%)	.565
PR3-ANCA positivity	1 (2.13%)	1 (2.70%)	0 (0.00%)	.565
Blood gas analysis^a
pH	7.42 ± 0.059	7.42 ± 0.061	7.43 ± 0.052	.639
PaO2 (mmHg)	82.95 ± 22.68	80.63 ± 23.78	97.07 ± 24.91	.086
PaCO2 (mmHg)	39.22 ± 7.55	38.44 ± 6.52	41.19 ± 9.94	.347
OI (mmHg)	346.75 ± 93.08	331.53 ± 93.10	403.37 ± 74.06	.044
P(A-a) O2 (mmHg)	42.20 ± 36.79	48.51 ± 38.71	23.40 ± 18.71	.071
Pulmonary function tests^b
FEV1% predicted	77.16 ± 24.29	81.56 ± 19.54	65.45 ± 33.27	.342
FVC% predicted	71.32 ± 20.10	71.82 ± 17.80	70.00 ± 27.55	.856
FEV1/FVC ratio	82.89 ± 12.49	86.91 ± 6.25	72.87 ± 18.58	.016
DLCO% predicted	56.98 ± 21.37	54.64 ± 18.70	63.20 ± 28.37	.416
HRCT patterns
UIP	–	20 (54.05%)	–
NSIP	–	11 (29.73%)	–
Unclassifiable	–	6 (16.22%)	–
CPFE	–	11 (29.73%)	–
SPAP^c (mmHg)	33.60 ± 17.51	31.67 ± 13.65	36.27 ± 25.60	.448

ANCA: anti-neutrophil cytoplasmic antibody; IIP: idiopathic interstitial pneumonia; MPA: microscopic polyangiitis; ILD: interstitial lung disease; WBC: white blood cell; HB: haemoglobin; PLT: platelet; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; ALT: alanine aminotransferase; AST: aspartate aminotransferase; Alb: albumin; Glo: globulin; CK: creatine kinase; LDH: lactate dehydrogenase; Cr: creatinine; β2-MG: beta2-microglobulin; RF: rheumatoid factor; ANA: antinuclear antibody; MPO: myeloperoxidase; PR3: proteinase 3 antibody; PaO₂: arterial oxygen tension; PaCO₂: arterial carbon dioxide tension; OI: oxygenation index; P_(A-a)O₂: alveolar-arterial oxygen gradient; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; DLCO: diffusing capacity of lung for carbon monoxide; UIP: usual interstitial pneumonia; NSIP: nonspecific interstitial pneumonia; CPFE: combined pulmonary fibrosis and emphysema; SPAP: systolic pulmonary artery pressure.

Data are presented as the median [IQR] or mean ± SD or no. (%), and p < .05 was considered significant.

Bold values indicates statistical differences.

^a Arterial blood gas analysis (including pH, PaO₂, PaCO₂, OI, P_(A-a)O₂ and lactate) was not performed in 10 patients in the MPA-ILD group and three patients in the MPA-BE group.

^b PFTs (including FEV1, FVC and DLCO) were not performed in 21 patients in the MPA-ILD group and six patients in the MPA-BE group.

^c Although echocardiography was performed for every patient, systolic pulmonary artery pressure was not estimated in two patients in the MPA-ILD group and one patient in the MPA-BE group.

Figure 2. The Kaplan–Meier survival curves of the MPA with pulmonary involvement patients with different variables. MPA: microscopic polyangiitis; Cr: creatinine; GCs: glucocorticoids; CYC: cyclophosphamide.

Table 3. Univariate and multivariate analyses of the risk of all-cause mortality in MPA patients with pulmonary involvement.

Variables	Univariate		Multivariate
	HR (95% CI)	p Value	HR (95% CI)	p Value
Age >70 years	1.12 (0.44–2.83)	.799
Sex (male)	1.17 (0.46–2.94)	.719
Smoking	2.15 (0.80–5.81)	.302
A diagnosis of MPA-ILD	0.80 (0.21–3.06)	.720
Systematic manifestations
Renal involvement	1.55 (0.61–3.92)	.302
Nervous system involvement	0.94 (0.37–2.42)	.897
Cardiovascular involvement	1.53 (0.43–5.44)	.439
Laboratory findings
Anaemia	1.66 (0.62–4.46)	.263
CRP > 40 mg/L	0.90 (0.35–2.28)	.813
ESR > 60 mm/h	1.19 (0.45–3.14)	.713
Alb < 30 g/L	2.17 (0.77–6.16)	.084	–	NS
Cr elevated	2.64 (1.04–6.70)	.031	4.08 (1.38–12.05)	.011
LDH elevated	1.66 (0.66–4.17)	.267
RF positivity	0.68 (0.28–1.69)	.376
IgG elevated	3.25 (1.29–8.19)	.021	–	NS
MPO-ANCA positivity	0.57 (0.13–2.62)	.358
PaCO2 > 45 mmHg^a	7.31 (0.21–257.50)	.001
OI < 300 mmHg^a	1.72 (0.61–4.83)	.211
P(A-a)O2 >50 mmHg^a	0.92 (0.33–2.57)	.858
SPAP ≥ 35 mmHg^a	1.82 (0.71–4.67)	.176
Treatment
GCs	0.42 (0.15–1.22)	.048	–	NS
GCs + CYC	0.19 (0.076–0.48)	.002	0.095 (0.019–0.47)	.004

HR: hazard ratio; 95% CI: 95% confidence interval; NS: nonsignificant; MPA: microscopic polyangiitis; ILD: interstitial lung disease; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; Alb: albumin; Cr: creatinine; LDH: lactate dehydrogenase; RF: rheumatoid factor; ANCA: antineutrophil cytoplasmic antibody; MPO: myeloperoxidase; PaCO₂: arterial carbon dioxide tension; OI: oxygenation index; P_(A-a)O₂: alveolar-arterial oxygen gradient; SPAP: systolic pulmonary artery pressure; GCs: glucocorticoids; CYC: cyclophosphamide.

p < .05 was considered significant.

Bold values indicates statistical differences.

^a Due to the lack of some data, PaCO₂, OI, P_(A-a)O₂ and SPAP were not included in the multivariate Cox regression model.

Table 4. Univariate and multivariate analyses of the risk of all-cause mortality in MPA-ILD patients.

	Univariate		Multivariate
Variables	HR (95% CI)	p Value	HR (95% CI)	p Value
Age > 70 years	1.34 (0.48–3.68)	.560
Sex (male)	1.52 (0.55–4.17)	.374
Smoking	2.27 (0.78–6.62)	.187
Systematic manifestations
Renal involvement	1.24 (0.45–3.42)	.671
Nervous system involvement	0.82 (0.29–2.33)	.696
Cardiovascular involvement	1.50 (0.35–6.37)	.517
Acute exacerbations of ILD	2.84 (0.98–8.21)	.020	4.55 (1.16–17.86)	.029
Laboratory findings
Anaemia	1.92 (0.64–5.70)	.189
CRP > 40 mg/L	0.75 (0.27–2.07)	.543
ESR > 60 mm/h	1.13 (0.39–3.33)	.801
Alb < 30 g/L	2.42 (0.77–7.62)	.054	–	NS
Cr elevated	2.30 (0.82–6.47)	.079	4.95 (1.39–17.54)	.014
LDH elevated	2.58 (0.94–7.09)	.078	–	NS
RF positivity	0.69 (0.26–1.88)	.436
IgG elevated	3.67 (1.33–10.11)	.023	–	NS
MPO-ANCA positivity	0.55 (0.12–2.58)	.324
PaCO2 > 45 mmHg^a	20.84 (0.06–7099)	<.001
OI < 300 mmHg^a	2.22 (0.71–6.88)	.016
P(A-a)O2 > 50 mmHg^a	1.04 (0.34–3.23)	.937
HRCT patterns
UIP pattern	2.54 (0.92–7.04)	.055	–	NS
NSIP pattern	0.58 (0.20–1.63)	.294
CPFE	1.83 (0.53–6.29)	.237
SPAP ≥ 35 mmHg^a	1.99 (0.70–5.71)	.154
Treatment
GCs	0.31 (0.090–1.06)	.012	0.057 (0.012–0.28)	<.001
GCs + CYC	0.23 (0.083–0.63)	.008	–	NS

HR: hazard ratio; 95% CI: 95% confidence interval; NS: nonsignificant; MPA: microscopic polyangiitis; ILD: interstitial lung disease; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; Alb: albumin; Cr: creatinine; LDH: lactate dehydrogenase; RF: rheumatoid factor; ANCA: antineutrophil cytoplasmic antibody; MPO: myeloperoxidase; PaCO₂: arterial carbon dioxide tension; OI: oxygenation index; P_(A-a)O₂: alveolar-arterial oxygen gradient; UIP: usual interstitial pneumonia; NSIP: nonspecific interstitial pneumonia; CPFE: combined pulmonary fibrosis and emphysema; SPAP: systolic pulmonary artery pressure; GCs: glucocorticoids; CYC: cyclophosphamide.

p < .05 was considered significant.

Bold values indicates statistical differences.

^a Due to the lack of some data, PaCO₂, OI, P_(A-a)O₂ and SPAP were not included in the multivariate Cox regression model.

Data availability statement

The data supporting our findings are available from the corresponding author on reasonable request.