Induced Sputum in Systemic Sclerosis Interstitial Lung Disease: Comparison to Healthy Controls and Bronchoalveolar Lavage

Abstract

Background: Induced sputum (IS) is a noninvasive tool, which can be used to collect cellular and soluble materials from lung airways. Objective: To evaluate if IS may be a useful and safe tool for the detection of airway inflammation in patients with interstitial lung disease (ILD) in systemic sclerosis (SSc). Methods: Sixty-eight patients with SSc and ILD as well as 18 healthy individuals (controls) were selected and submitted to IS examination. In 34 of 68 patients with SSc, bronchoalveolar lavage (BAL) was also performed. Safety of IS was assessed by comparison of forced expiratory volume in the first second (FEV₁), FEV₁/forced vital capacity ratio and peak expiratory flow before and after the IS procedure. Cell composition in samples collected by BAL and IS was correlated, and IS total and differential cell count in SSc patients and controls were compared. Results: The total number of cells was significantly higher in IS samples of SSc patients compared to those of healthy controls. Mean percentage of neutrophils was also higher in SSc patients (41.79 ± 23.89 vs. 27.37 ± 17.90), as well as lymphocytes (17.42 ± 19.70 vs. 3.13 ± 2.28) and eosinophils (2.35 ± 4.43 vs. 0.41 ± 0.46). On the other hand, mean percentage of macrophages was higher in healthy individuals (69.10 ± 19.15 vs. 36.96 ± 20.68). In fluid recovered by BAL, the most frequent cells were macrophages (67.89% ± 17.26), while neutrophils (14.77 ± 17.18%) and lymphocytes (15.62 ± 13.46%) were less frequent and eosinophils (1.66 ± 2.08%) were rare. A similar pattern of cell composition was found in IS samples (41.15 ± 21.67% of macrophages, 39.72 ± 23.15% of neutrophils, 15.28 ± 19.46% of lymphocytes and 2.56 ± 5.03% of eosinophils). Strength of correlation between BAL and IS was significant for macrophages and neutrophils. After IS procedure was performed, improvement of FEV₁ (mean value before IS was 85.09 ± 14.44 and 88.93 ± 16.40 after IS) and FEV₁/forced vital capacity (mean value before IS was 98.53 ± 12.11 and 105.22 ± 10.78 after IS) was observed. Conclusion: The IS method may allow a noninvasive assessment of cell composition in airway fluid and may contribute to the better understanding of upper/medium airway inflammation in SSc. Future studies are needed to verify whether IS can replace invasive procedures for the detection and monitoring of lung inflammation in SSc.

Bronchial inflammation in hypersensitivity pneumonitis after antigen‐specific inhalation challenge

“…Similar features have been observed in patients with idiopathic pulmonary fibrosis, sarcoidosis and scleroderma . This may be because BAL provides information on the distal airway and alveolar spaces, which are rich in macrophages, whereas induced sputum gives evidence of the state of the upper and middle airway, which presents abundant neutrophils . Furthermore, in FHP patients, the significant increase in IL‐8, IL12‐p70 and IL‐1β as compared with BHP could explain the greater increase in neutrophils observed following exposure to fungi.…”

“…[6][7][8][9][10] This may be because BAL provides information on the distal airway and alveolar spaces, which are rich in macrophages, whereas induced sputum gives evidence of the state of the upper and middle airway, which presents abundant neutrophils. 27,28 Furthermore, in FHP patients, the significant increase in IL-8, IL12-p70 and IL-1β as compared with BHP could explain the greater increase in neutrophils observed following exposure to fungi. Lastly, another possibility would be related to the innate immune response.…”

The IL1-like cytokine IL33 and its receptor ST2 are abnormally expressed in the affected skin and visceral organs of patients with systemic sclerosis

“…Bronchoalveolar lavage (BAL) was performed in the pulmonary lobes that showed interstitial lung disease at high-resolution CT in 10 non-smoking patients with SSc (2 lcSSc, 8 dcSSc) and in 10 non-smoking healthy subjects, as described previously 28. Briefly, BAL fluid was recovered by gentle aspiration and collected into specimen traps, filtered through sterile gauze and centrifuged at 400 g for 15 min at 4°C.…”

Novel Method to Process Cystic Fibrosis Sputum for Determination of Oxidative State

“…In the past years, induced sputum samples are increasingly used, as they are a useful and minimal invasive tool to monitor pulmonary diseases [15,16,17,18,19,20,21,22]. Because of the high viscosity induced sputum samples of CF patients need to be dispersed before analysis.…”