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Relationship Between Abnormalities on High-Resolution Computerized Tomography, Pulmonary Function, and Bronchoalveolar Lavage in Progressive Systemic Sclerosis

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Relationship Between Abnormalities on High-Resolution Computerized Tomography, Pulmonary Function, and Bronchoalveolar Lavage in Progressive Systemic Sclerosis Original article: Clinical research SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES 2016; 33; 349-354 © Mattioli 1885 Relationship between abnormalities on high-resolution computerized tomography, pulmonary function, and bronchoalveolar lavage in progressive systemic sclerosis Gulfidan Cakmak¹, Tuba Selcuk Can², Sule Gungogdu3, Canan Akman4, Hande Ikitimur5, Benan Musellim3, Gul Ongen3 1 Haseki Education and Research Hospital, Department of Pulmonary Diseases, Istanbul; 2 Haseki Education and Research Hospital, De- partment of Radiology, Istanbul, Gelisim University, Medical Vocational High School, Istanbul; 3 Istanbul University Cerrahpasa Medical Faculty, Department of Pulmonary Diseases; 4 Istanbul University Cerrahpasa Medical Faculty, Department of Radiology; 5 Istanbul Private Medicana Bahcelievler Hospital, Department of Pulmonary Diseases Abstract. Introduction and aim: Progressive systemic sclerosis (pSS) is a multisystemic connective tissue disease characterized by fibrosis of the skin and internal organs including lung. The mechanisms that leads to progres- sive lung fibrosis in scleroderma remain obscure. In this study, we aimed to investigate the correlation between HRCT findings and patients’ clinical and functional status and the degree of alveolitis based on the BAL results. Materials and methods: 65 patients with pSS were evaluated. Thoracic HRCT, pulmonary function tests, and dyspnea measurements were applied, and BAL was performed. The parenchymal abnormalities identified on HRCT were coded, and scored according to Warrick et al. Results: Among parameters investigated, a correla- tion was found between the number of segments with subpleural cysts and the duration of disease. Also there was a correlation between the HRCT score and patient age whereas no correlation was detected between the duration of the disease, manifestation of the symptoms, and the x-ray findings. A correlation was found between the percentage of neutrophils detected in BAL and the extent of the honeycombing on HRCT. Conclusion: This study showed a strong correlation between the extent of x-ray abnormalities and FVC, RV, and DLCO, as well as an increase in the percentage of BAL fluid neutrophils in patients with SSc-PI.(Sarcoidosis Vasc Diffuse Lung Dis 2016; 33: 349-354) Key words: scleroderma, high resolution computed tomography, pulmonary function test Introduction macrovascular damage, and is characterized by fi- brosis of the skin and internal organs (1-3). In pSS, Progressive systemic sclerosis (pSS) is a mul- lung involvement may occur in two ways: isolated tisystemic connective tissue disease with unknown pulmonary hypertension and interstitial lung fi- etiology, which leads to diffuse microvascular and brosis (4-7). Lung involvement is common and is probably the leading cause of death in these patients Received: 6 June 2015 (8-11). Plain chest x-rays, the pulmonary function Accepted after revision: 20 July 2016 test, and thoracic high-resolution computed tomog- Correspondence: Tuba Selcuk Can Haseki Education and Research Hospital, raphy (HRCT) are standard noninvasive tests used Department of Radiology, to evaluate suspected lung involvement. It has been Gelisim University, Medical Vocational High School, Istanbul suggested that chest x-ray abnormalities are present Adnan Adivar Street, Fatih, Istanbul Fax +90 212 5299787 in up to two-thirds of patients with pSS. Because E-mail:[email protected] HRCT is more sensitive than the other standard 350 G. Cakmak, T. Selcuk Can, S. Gundogdu, et al. noninvasive tests, lung involvement may be detected performed on patients who had no recent history or on HRCT scans, even though the chest x-ray find- signs of respiratory infection. ings are normal (12). In an HRCT-histopathological The x-rays were evaluated and scored by an in- correlation, significant inflammation in the open- dependent radiologist who had 5 years of experience lung biopsy specimen was almost entirely correlated in interstitial lung disease radiology and was blinded with ground glass opacity on HRCT scans in a large to the patients’ clinical data. The parenchymal abnor- group of patients (13). malities identified on HRCT were coded, and a score The mechanisms that leads to progressive lung was defined according to Warrick et al. (16). A point fibrosis in scleroderma remain obscure. Lung inflam- value was assigned to each abnormality (Table 2). For mation strikes a subset of patients, and its presence, each patient, the disease severity score was obtained as assessed with the neutrophil or eosinophil bron- by adding up the points. The extent of disease score choalveolar lavage (BAL) cell differential, indicates was the total number of bronchopulmonary segments greater risk for progressive lung fibrosis and death involved (Table 3). Finally, the disease severity and (14). extent of disease scores were summed to form the In this study, we aimed to investigate the cor- total HRCT score with a possible range of 0 to 30. relation between HRCT findings and patients’ clini- For example, a patient with ground glass appearance cal and functional status and the degree of alveolitis (disease severity score 1) in the five segments of the based on the BAL results. right lower lobe (extent of disease score 2) and hon- eycombing (disease severity score 4) in two segments (extent of disease score 1) would have a total HRCT Materials and methods score of 6. Apart from this scoring, the total number of affected segments in general and the number of In this study, 65 patients with pSS with pul- segments with each abnormality were also evaluated. monary involvement referred to Istanbul University, Spirometry and single-breath carbon monoxide Cerrahpasa Medical Faculty, Department of Pulmo- lung diffusion capacity (DLCO) measurements were nary Diseases between July 1995 and February 2014 performed (Sensor Medics Vmax series 22). Lung were evaluated. The diagnosis had been established volumes were measured with ZAN 500 (nSpire according to the American Rheumatology Associa- Health GmbH, Oberthulba, Germany) plethysmog- tion criteria (15). Patients with other collagen diseas- raphy. es in addition to pSS were excluded. Demographic BAL was performed without premedication characteristics are displayed in Table 1. Patients with under local anesthesia with intravenous (iv) 2% li- systemic sclerosis in whom pulmonary involvement docaine to the middle lobe or lingular segment us- was suspected and who were referred or attended ing five 20 ml aliquots of normal saline solution. The our clinic were evaluated and followed according to a standard protocol. At the time of the first refer- ral, thoracic HRCT, pulmonary function tests, and Table 2. Point values of the abnormalities on thoracic HRCT dyspnea measurements were applied, and BAL was HRCT abnormality Point value Ground glass appearance 1 Irregular pleural margins 2 Table 1. Patients’ demographic characteristics of the patients Septal/subpleural lines 3 Honeycombing 4 Patients (n) 65 Subpleural cysts 5 Age (year) 50.3 ± 13.4 (27-80) Female/male gender (n) 63/2 Duration of disease (year) 11.6 ± 8.0 Duration of respiratory symptoms (year) 2.9 ± 3.4 (median=2) Smoking status (current smoker-n) 5 (median 15 packs/year) Table 3. Extent of disease scores (ex-smoker-n) 11 (median 6 packs/year) Number of bronchopulmonary segments involved Point value (nonsmoker-n) 49 1-3 1 Note. Data are presented as mean ± SD or number of patients unless 4-9 2 otherwise indicated. >9 3 1 pack: 20 cigarettes HRCT findings correlating BAL and pulmonary function tests in progressive systemic sclerosis 351 fluid returned was more than 50% of the saline given. Table 5. Patients’ BAL results, HRCT scores, and dyspnea scores In the differential cell count, the percentage of neu- when pulmonary involvement confirmed trophils, lymphocytes, and eosinophils and the total Mean ± SD cell count were determined. Dyspnea score 1.6 ± 1.1 The Medical Research Council (MRC) dyspnea BAL findings scale was used to measure dyspnea (17). The pulmo- Neutrophils (%) 10.8 ± 7.1 nary function test results, BAL findings, dyspnea Lymphocytes (%) 8.4 ± 4.6 Eosinophils (%) 0.7 ± 1.3 measurements, and HRCT scores were evaluated Alveolitis (n, % all cases) 32 (84.2%) using the Spearman or Pearson correlation test. The Neutrophilic alveolitis 25 (65.8%) results were defined as the mean value ± standard de- Lymphocytic alveolitis 1 (2.6%) viation. Mixed alveolitis 6 (15.8%) X-ray findings HRCT score 14.7 ± 7.4 Total segments involved 8.8 ± 4.0 Results Segments with ground-glass appearance 7.4 ± 3.8 Segments with honeycombing 3.4 ± 3.5 Segments with subpleural cysts 0.9 ± 1.7 When pulmonary involvement was discovered, Segments with septal/subpleural lines 3.8 ± 2.7 65 patients had spirometric evaluation, 63 patients Segments with irregular pleural margins 2.5 ± 2.3 had diffusion capacity measurements, 18 patients had lung volume measurements, and 38 patients had bronchoalveolar lavage results. All patients already had a dyspnea measurement result. Table 4 illustrates lations between the total number of affected segments the results of the pulmonary function tests, when in both lungs and FVC % (p=0.006, r=-0.34), DLCO pulmonary involvement was definitely diagnosed. In % (p=0.001, r=-0.41), total lung capacity (TLC) % 27 (41.5%) patients and in 56 (86.2%) patients, the (p=0.02, r=-0.54), and residual volume (RV) % forced vital capacity (FVC) and DLCO values, re- (p=0.007, r=-0.61) were detected as well as the corre- spectively, were below 75%. BAL findings, dyspnea lation between the total number of affected segments scoring, and thoracic HRCT scores are summarized and the polymorphonuclear leukocytes (PNL) per- in Table 5. In 84.2% of patients, alveolitis was detect- centage in BAL (p=0.008, r=0.43). The correlation ed with BAL, and dyspnea was present with varying between the number of total segments with ground severity in 95.4% of patients. glass opacity and FVC % (p=0.024, r=-0.28), DLCO There was a linear correlation between the total % (p=0.007, r=-0.34), and RV % (p=0.045, r=-0.48) HRCT score and age (p=0.04, r=0.26), CT index and FVC % (p=0.026, r=-0.28) and between the HRCT score and DLCO % (p=0.027, r=-0.28).
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