Usefulness of Lung Ultrasound as a Method for Early Diagnosis of Interstitial Lung Disease in Patients with Rheumatoid Arthritis

Figures & data

Table 1 Demographic and Clinical Characteristics of the Study Population

Characteristics	Total Population n=192
Age (years), Mean ± SD	68.9 ± 8.9
Sex (woman), n (%)	151 (78.6)
Medical history^a
Smoking, n (%)	85 (44.3)
Arterial hypertension, n (%)	73 (38.0)
Diabetes mellitus, n (%)	15 (7.8)
Cardiovascular disease, n (%)	14 (7.3)
Cancer, n (%)	13 (6.8)
Others^b, n (%)	9 (4.7)
RA diagnosis information
Time of evolution of the disease, mean ± SD	16.8 ± 11.1
DAS28, mean ± SD	2.5 ± 1.1
Functional disability (HAQ), mean ± SD	0.39 ± 0.7
Current treatment of RA
Methotrexate, n (%)	124 (64.6)
csDMARDs, n (%)	110 (57.3)
TNFi, n (%)	23 (12.0)
Biological non-TNFi, n (%)	22 (11.5)
Analgesics, n (%)	123 (64.1)
Glucocorticoids, n (%)	94 (49.0)
Recent respiratory symptoms^a
Dyspnea, n (%)	47 (24.5)
Chronic cough, n (%)	57 (29.7)
Fatigue, n (%)	55 (28.6)
Clinical condition and laboratories
Body mass index, mean ± SD	24.5 ± (4.1)
O2 saturation, mean ± SD	92.5 ± (3.2)
Positive Rheumatoid Factor, n (%)	152 (80.0)
Positive anticitrullinated antibodies, n (%)	142 (74.0)

Notes: ^a, nonexclusive category; ^b, hypothyroidism, osteoporosis, depression and fibromyalgia, insulin resistance.

Abbreviations: csDMARDs, conventional disease-modifying antirheumatic drugs; DAS28, disease activity score-28; HAQ, Health Assessment Questionnaire; RA, Rheumatoid arthritis; SD, Standard deviation; TNFi, tumor necrosis factor inhibitors.

Table 2 Diagnostic Usefulness of LUS and CXR Compared to HRCT in the Diagnosis of ILD

Test	HRCT
	Positive	Negative	Total
LUS
Positive	115	64	179	S 98.3%	PPV 64.2%	LR+ 1.15
Negative	2	11	13	Sp 14.7%	NPV 84.6%	LR- 1.15
CXR
Positive	35	4	39	S 29.9%	PPV 89.7%	LR+ 5.61
Negative	82	71	153	Sp 94.7%	NPV 46.4%	LR- 0.74

Abbreviations: CXR, chest X-ray; HRCT, high resolution computed tomography; ILD, interstitial lung disease; LR, likelihood ratio; LUS, lung ultrasound; NPV, negative predictive value; PPV, positive predictive value; S, Sensitivity; Sp, Specificity.

Table 3 Imaging Results and Lung Function in the Rheumatoid Arthritis Patients

Imaging Results	n = 192
Positive LUS for ILD, n (%)	179 (93.2)
Mild involvement (6–15 B lines), n (%)	13 (6.8)
Moderate involvement (16–30 B lines), n (%)	66 (34.4)
Severe involvement (> 30 B lines), n (%)	100 (52)
Irregularity of pleural lines, n (%)	179 (93.2)
Positive radiograph for ILD, n (%)	39 (20.3)
HRCT positive for ILD, n (%)	117 (60.9)
Ground glass opacities, n (%)	59 (50.4)
Irregular pleural margins, n (%)	19 (16.2)
Septal/subpleural lines, n (%)	98 (83.8)
Honeycomb, n (%)	51 (43.6)
Subpleural cysts, n (%)	36 (30.8)
Disease extension index (Warrick index), n (%)
1–3 lung segments	17 (14.5)
4–9 lung segments	75 (64.1)
> 9 lung segments	25 (21.4)
HCRT pattern, n (%)
Usual interstitial pneumonia	51 (43.6)
Nonspecific interstitial pneumonia	47 (40.2)
Bronchiolitis	10 (8.5)
Bronchiectasis	4 (3.4)
Organized pneumonia	5 (4.3)
Pulmonary function tests
Normal FVC^a, n (%)	137 (71.4)
FVC value, mean (SD)	2.7 (2.5)
FVC%, mean (SD)	94.0 (22.7)
FEV1 normal^b, n (%)	147 (76.6)
FEV1, mean (SD)	2.0 (0.6)
FEV1%, mean (SD)	95.1 (23.3)
FEV1/FVC Ratio, n (%)
Restrictive	27 (79.4)
Obstructive	7 (20.6)
DLCO corrected value, mean (SD)*	8.6 (9.6)
DLCO% corrected predicted value, mean (SD)*	109.4 (28.9)
CO transfer pattern, n (%)
Normal (≥ LLN y ≤ ULN, entre 80 y 120%), n (%)	86 (61.9)
Lower limit of normal n (%)	18 (16.9)
Upper limit of normal n (%)	35 (25.2)

Notes: ^a, abnormal FVC: <80% of expected; ^b, FEV1 normal:> 70% or > ULN. *Adjusted by barometric pressure in Bogota (Colombia), along with factors such as height, sex, hemoglobin value, and alveolar volume.

Abbreviations: CO, Carbon Monoxide; DLCO, diffusing capacity of the lungs for carbon monoxide; FEV1, forced expiratory volume at the first second; FVC, forced vital capacity; FEV1/FVC ratio, forced expiratory volume at the first second / forced vital capacity ratio; ILD, interstitial lung disease; HRCT, high resolution computed tomography; LUS, lung ultrasound; LLN, Lower limit of normal; ULN, Upper limit of normal.

Table 4 Characterization of Subjects with False Positives for Interstitial Lung Disease at Lung Ultrasound

Characteristics	True Positives n =115	False Positives n =64	True Negatives n =11	False Negatives n =2	p value
Age, mean (SD)	69.7 (9.1)	67.9 (8.1)	68.8 (10.1)	54.5 (3.5)	0.068
BMI, mean (SD)	24.5 (4.0)	24.1 (4.2)	26.6 (2.9)	26.9 (6.2)	0.108
Smoking, n (%)	45 (39.1)	25 (39.1)	3 (27.3)	0 (0.0)	0.603
Dyspnea, n (%)	25 (21.7)	13 (20.3)	9 (81.8)	0 (0.0)	0.000
Chronic cough, n (%)	39 (33.9)	13 (20.3)	4 (36.4)	1 (50.0)	0.230
Fatigue, n (%)	35 (30.4)	15 (23.4)	5 (45.5)	0 (0.0)	0.340
Normal CXR	64 (83.1)	51 (83.6)	10 (100)	0 (0.0)	0.041
Total B Lines, mean (SD)	36.9 (19.3)	31.5 (21.0)	18.6 (18.0)	27.5 (13.4)	0.004
Lines B, n (%)					0.000
Normal (<5)	0 (0.0)	0 (0.0)	11 (100)	2 (100)
Mild involvement (6–15)	5 (4.3)	8 (12.5)	0 (0.0)	0 (0.0)
Moderate involvement (16– 30)	39 (33.9)	27 (42.2)	0 (0.0)	0 (0.0)
Severe involvement (> 30)	71 (61.7)	29 (45.3)	0 (0.0)	0 (0.0)
Irregularity of pleural lines	112 (97.4)	56 (87.5)	9 (81.8)	2 (100)	0.031

Abbreviations: BMI, Body mass index; CXR, Chest X-ray; SD, standard deviation.

Figure 1 ROC curves for the prediction of ILD with total B lines and DLCO in subjects with Rheumatoid arthritis.

Abbreviation: DLCO, diffusing capacity of the lungs for carbon monoxide.