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Short Communication

Nanoparticles in induced sputum – a window to airway inflammation among active smokers

    Ophir Freund

    *Author for correspondence:

    E-mail Address: ophir068@gmail.com

    The Institute of Pulmonary Medicine, Tel-Aviv Sourasky Medical Center & Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 6423906, Israel

    ,
    Michal Rotem-Green

    The Institute of Pulmonary Medicine, Tel-Aviv Sourasky Medical Center & Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 6423906, Israel

    ,
    Maya Rahat

    The Institute of Pulmonary Medicine, Tel-Aviv Sourasky Medical Center & Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 6423906, Israel

    ,
    Evgeni Gershman

    The Institute of Pulmonary Medicine, Tel-Aviv Sourasky Medical Center & Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 6423906, Israel

    ,
    Noa Ophir

    The Institute of Pulmonary Medicine, Tel-Aviv Sourasky Medical Center & Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 6423906, Israel

    ,
    Elizabeth Fireman

    The Institute of Pulmonary Medicine, Tel-Aviv Sourasky Medical Center & Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 6423906, Israel

    ,
    Shani Shenhar-Tsarfaty

    Internal Medicine C, Tel Aviv Sourasky Medical Center & Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 6423906, Israel

    &
    Amir Bar-Shai

    The Institute of Pulmonary Medicine, Tel-Aviv Sourasky Medical Center & Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 6423906, Israel

    Published Online:https://doi.org/10.2217/nnm-2022-0269

    Aims: To evaluate the role of nanoparticles (NP) in sputum samples of active smokers as markers of inflammation and disease. Materials & methods: 29 active smokers were included (14 with chronic obstructive pulmonary disease [COPD]) and underwent clinical assessment, pulmonary function tests, sputum induction (with NP analysis) and blood sampling. Results: Higher particle and NP concentrations and smaller mean size directly correlated with clinical parameters such as the COPD Assessment Test score and impulse oscillometry results. Similar correlations were found between NPs and increased sputum IL-1β, IL-6 and TNF-α. Among COPD patients, higher IL-8 and lower IL-10 serum levels also correlated with NP concentrations. Conclusion: This proof-of-concept study shows the potential of sputum NPs as markers of airway inflammation and disease.

    Plain language summary

    What is this article about? Identifying markers of lung inflammation and diseases could offer early diagnosis and treatment. In this study, we questioned whether nanoparticles in the sputum of active smokers correlate with lung inflammation and disease. What were the results? We found that higher nanoparticle concentration in the sputum and lower mean nanoparticle size correlated with different clinical parameters and inflammatory markers. What do the results mean? This proof-of-concept study suggests that nanoparticle analysis in the sputum of active smokers has potential as a marker that correlates with lung inflammation and disease. Our results should encourage additional research in this field to better understand the role of nanoparticles in the diagnosis, prognosis and treatment of active smokers.

    Tweetable abstract

    Analysis of nanoparticle characteristics from the sputum of active smokers. Nanoparticle concentration and mean size were found to correlate with sputum inflammatory markers and clinical variables.

    Graphical abstract

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1. Reitsma MB, Kendrick PJ, Ababneh E et al. Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and attributable disease burden in 204 countries and territories, 1990-2019: a systematic analysis from the Global Burden of Disease Study 2019. Lancet 397(10292), 2337–2360 (2021).
    • 2. Jha P, Ranson MK, Nguyen SN, Yach D. Estimates of global and regional smoking prevalence in 1995, by age and sex. Am. J. Public Health 92(6), 1002–1006 (2002).
    • 3. Anderson JO, Thundiyil JG, Stolbach A. Clearing the air: a review of the effects of particulate matter air pollution on human health. J. Med. Toxicol. Off. J. Am. Coll. Med. Toxicol. 8(2), 166–175 (2012).
    • 4. Stämpfli MR, Anderson GP. How cigarette smoke skews immune responses to promote infection, lung disease and cancer. Nat. Rev. Immunol. 9(5), 377–384 (2009).
    • 5. Strzelak A, Ratajczak A, Adamiec A, Feleszko W. Tobacco smoke induces and alters immune responses in the lung triggering inflammation, allergy, asthma and other lung diseases: a mechanistic review. Int. J. Environ. Res. Public Health 15(5), 1033 (2018).
    • 6. Singh D, Agusti A, Anzueto A et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease: the GOLD science committee report 2019. Eur. Respir. J. 53(5), (2019).
    • 7. Woodruff PG, Barr RG, Bleecker E et al. Clinical significance of symptoms in smokers with preserved pulmonary function. N. Engl. J. Med. 374(19), 1811–1821 (2016).
    • 8. Bazzan E, Semenzato U, Turato G et al. Symptomatic smokers without COPD have physiological changes heralding the development of COPD. ERJ Open Res. 8(2), (2022).
    • 9. Han MK, Agusti A, Celli BR et al. From GOLD 0 to pre-COPD. Am. J. Respir. Crit. Care Med. 203(4), 414–423 (2021).
    • 10. da Silva AL, Cruz FF, Rocco PRM, Morales MM. New perspectives in nanotherapeutics for chronic respiratory diseases. Biophys. Rev. 9(5), 793–803 (2017).
    • 11. Huang F, Dempsey C, Chona D, Suh J. Quantitative nanoparticle tracking: applications to nanomedicine. Nanomedicine (Lond.) 6(4), 693–700 (2011).
    • 12. Cheng W, Liu Y, Tang J et al. Carbon content in airway macrophages and genomic instability in Chinese carbon black packers. Arch. Toxicol. 94(3), 761–771 (2020).
    • 13. Bai Y, Bové H, Nawrot TS, Nemery B. Carbon load in airway macrophages as a biomarker of exposure to particulate air pollution; a longitudinal study of an international panel. Part Fibre Toxicol. 15(1), 14 (2018).
    • 14. Comfort N, Cai K, Bloomquist TR et al. Nanoparticle tracking analysis for the quantification and size determination of extracellular vesicles. J. Vis. Exp. (169), (2021).
    • 15. Buxton DB, Lee SC, Wickline SA, Ferrari M. Recommendations of the national heart, lung, and blood institute nanotechnology working group. Circulation 108(22), 2737–2742 (2003).
    • 16. Ophir N, Bar Shai A, Korenstein R et al. Functional, inflammatory and interstitial impairment due to artificial stone dust ultrafine particles exposure. Occup. Environ. Med. 76(12), 875–879 (2019).
    • 17. Fireman E, Edelheit R, Stark M, Shai AB. Differential pattern of deposition of nanoparticles in the airways of exposed workers. J. Nanoparticle Res. 19(2), 30 (2017).
    • 18. Virmani T, Kumar G, Virmani R et al. Nanocarrier-based approaches to combat chronic obstructive pulmonary disease. Nanomedicine (Lond.) 17(24), 1833–1854 (2022).
    • 19. Bar-Shai A, Alcalay Y, Sagiv A et al. Fingerprint of lung fluid ultrafine particles, a novel marker of acute lung inflammation. Respiration 90(1), 74–84 (2015). •• Assess the role of ultra-fine particles in lung fluid of mice as markers of inflammation.
    • 20. Lee S-D, Huang M-S, Kang J et al. The COPD assessment test (CAT) assists prediction of COPD exacerbations in high-risk patients. Respir. Med. 108(4), 600–608 (2014).
    • 21. Crapo RO, Casaburi R, Coates AL et al. ATS statement: guidelines for the six-minute walk test. Am. J. Respir. Crit. Care Med. 166(1), 111–117 (2002).
    • 22. Graham BL, Steenbruggen I, Miller MR et al. Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement. Am. J. Respir. Crit. Care Med. 200(8), e70–e88 (2019).
    • 23. King GG, Bates J, Berger KI et al. Technical standards for respiratory oscillometry. Eur. Respir. J. 55(2), (2020).
    • 24. Weiszhar Z, Horvath I. Induced sputum analysis: step by step. Breathe 9(4), 300–306 (2013).
    • 25. Hacievliyagil SS, Gunen H, Mutlu LC et al. Association between cytokines in induced sputum and severity of chronic obstructive pulmonary disease. Respir. Med. 100(5), 846–854 (2006).
    • 26. Huang A-X, Lu L-W, Liu W-J, Huang M. Plasma inflammatory cytokine IL-4, IL-8, IL-10, and TNF-α levels correlate with pulmonary function in patients with asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome. Med. Sci. Monit. Int. Med. J. Exp. Clin. Res. 22, 2800–2808 (2016).
    • 27. Hollander C, Sitkauskiene B, Sakalauskas R et al. Serum and bronchial lavage fluid concentrations of IL-8, SLPI, sCD14 and sICAM-1 in patients with COPD and asthma. Respir. Med. 101(9), 1947–1953 (2007).
    • 28. Gorska K, Nejman-Gryz P, Paplinska-Goryca M et al. Comparative study of IL-33 and IL-6 levels in different respiratory samples in mild-to-moderate asthma and COPD. COPD J. Chronic Obstr. Pulm. Dis. 15(1), 36–45 (2018).
    • 29. Deveci SE, Deveci F, Açik Y, Ozan AT. The measurement of exhaled carbon monoxide in healthy smokers and non-smokers. Respir. Med. 98(6), 551–556 (2004).
    • 30. Liu H, Li J, Ma Q et al. Chronic exposure to diesel exhaust may cause small airway wall thickening without lumen narrowing: a quantitative computerized tomography study in Chinese diesel engine testers. Part Fibre Toxicol. 18(1), 14 (2021).
    • 31. Fireman Klein E, Adir Y, Krencel A et al. Ultrafine particles in airways: a novel marker of COPD exacerbation risk and inflammatory status. Int. J. Chron. Obstruct. Pulmon. Dis. 14, 557–564 (2019). •• Addresses ultrafine particle characteristics among chronic obstructive pulmonary disease patients.
    • 32. Regan EA, Lynch DA, Curran-Everett D et al. Clinical and radiologic disease in smokers with normal spirometry. JAMA Intern. Med. 175(9), 1539–1549 (2015).
    • 33. Dutta A, Roychoudhury S, Chowdhury S, Ray MR. Changes in sputum cytology, airway inflammation and oxidative stress due to chronic inhalation of biomass smoke during cooking in premenopausal rural Indian women. Int. J. Hyg. Environ. Health 216(3), 301–308 (2013). • Describes the effect of smoke inhalation on sputum characteristics.
    • 34. Chisholm JF, Shenoy SK, Shade JK et al. Nanoparticle diffusion in spontaneously expectorated sputum as a biophysical tool to probe disease severity in COPD. Eur. Respir. J. 54(2), (2019). • Describes the role of nanoparticle diffusion as a tool for chronic obstructive pulmonary disease severity.
    • 35. Fireman E, Lerman Y, Stark M et al. A novel alternative to environmental monitoring to detect workers at risk for beryllium exposure-related health effects. J. Occup. Environ. Hyg. 11(12), 809–818 (2014).
    • 36. Hiraiwa K, van Eeden SF. Contribution of lung macrophages to the inflammatory responses induced by exposure to air pollutants. Mediators Inflamm. 2013, 619523 (2013).
    • 37. Comandini A, Rogliani P, Nunziata A et al. Biomarkers of lung damage associated with tobacco smoke in induced sputum. Respir. Med. 103(11), 1592–1613 (2009).
    • 38. Wei J, Xiong X-F, Lin Y-H et al. Association between serum interleukin-6 concentrations and chronic obstructive pulmonary disease: a systematic review and meta-analysis. Peer J. 3, e1199 (2015).
    • 39. Silva BSA, Lira FS, Ramos D et al. Severity of COPD and its relationship with IL-10. Cytokine 106, 95–100 (2018).
    • 40. MacNee W, Donaldson K. Mechanism of lung injury caused by PM10 and ultrafine particles with special reference to COPD. Eur. Respir. J. 21(Suppl. 40), S47–S51 (2003). • Assesses the mechanism for lung injury by inhaled particles.
    • 41. Guiedem E, Pefura-Yone EW, Ikomey GM et al. Cytokine profile in the sputum of subjects with post-tuberculosis airflow obstruction and in those with tobacco related chronic obstructive pulmonary disease. BMC Immunol. 21(1), 52 (2020).
    • 42. Fabbri LM. Smoking, not COPD, as the disease. N. Engl. J. Med. 374(19), 1885–1886 (2016).
    • 43. Brown JS, Zeman KL, Bennett WD. Ultrafine particle deposition and clearance in the healthy and obstructed lung. Am. J. Respir. Crit. Care Med. 166(9), 1240–1247 (2002). • Describes in detail the airway particle composition among patients with obstructive lung disease.
    • 44. Khatri M, Bello D, Martin J et al. Chronic upper airway inflammation and systemic oxidative stress from nanoparticles in photocopier operators: mechanistic insights. NanoImpact 5, 133–145 (2017).
    • 45. Khatri M, Bello D, Pal AK et al. Toxicological effects of PM 0.25–2.0 particles collected from a photocopy center in three human cell lines. Inhal. Toxicol. 25(11), 621–632 (2013).