{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T10:48:22Z","timestamp":1788518902269,"version":"build-2803163510"},"reference-count":108,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2020,8,27]],"date-time":"2020-08-27T00:00:00Z","timestamp":1598486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fractional exhaled nitric oxide (FeNO) is a well-known and widely accepted biomarker of airways inflammation that can be useful in the therapeutic management, and adherence to inhalation therapy control, in asthmatic patients. However, the multiple-flows assessment of FeNO can provide a reliable measurement of bronchial and alveolar production of NO, supporting its potential value as biomarker also in peripheral lung diseases, such as interstitial lung diseases (ILD). In this review, we first discuss the role of NO in the pathobiology of lung fibrosis and the technique currently approved for the measurement of maximum bronchial flux of NO (J\u2019awNO) and alveolar concentration of NO (CaNO). We systematically report the published evidence regarding extended FeNO analysis in the management of patients with different ILDs, focusing on its potential role in differential diagnosis, prognostic evaluation and severity assessment of disease. The few available data concerning extended FeNO analysis, and the most common comorbidities of ILD, are explored too. In conclusion, multiple-flows FeNO analysis, and CaNO in particular, appears to be a promising tool to be implemented in the diagnostic and prognostic pathways of patients affected with ILDs.<\/jats:p>","DOI":"10.3390\/ijms21176187","type":"journal-article","created":{"date-parts":[[2020,8,27]],"date-time":"2020-08-27T08:05:18Z","timestamp":1598515518000},"page":"6187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Extended Exhaled Nitric Oxide Analysis in Interstitial Lung Diseases: A Systematic Review"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8639-2882","authenticated-orcid":false,"given":"Paolo","family":"Cameli","sequence":"first","affiliation":[{"name":"Respiratory Diseases Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8351-3703","authenticated-orcid":false,"given":"Elena","family":"Bargagli","sequence":"additional","affiliation":[{"name":"Respiratory Diseases Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1118-3223","authenticated-orcid":false,"given":"Laura","family":"Bergantini","sequence":"additional","affiliation":[{"name":"Respiratory Diseases Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2368-5722","authenticated-orcid":false,"given":"Miriana","family":"d\u2019Alessandro","sequence":"additional","affiliation":[{"name":"Respiratory Diseases Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Pieroni","sequence":"additional","affiliation":[{"name":"Respiratory Diseases Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni A.","family":"Fontana","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piersante","family":"Sestini","sequence":"additional","affiliation":[{"name":"Respiratory Diseases Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa Metella","family":"Refini","sequence":"additional","affiliation":[{"name":"Respiratory Diseases Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/0006-291X(91)91268-H","article-title":"Endogenous nitric oxide is present in the exhaled air of rabbits, guinea pigs and humans","volume":"181","author":"Gustafsson","year":"1991","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1007\/s00280-011-1654-4","article-title":"Nitric oxide: Role in tumour biology and iNOS\/NO-based anticancer therapies","volume":"67","author":"Singh","year":"2011","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1172\/JCI119750","article-title":"Nitric oxide synthases: Which, where, how, and why?","volume":"100","author":"Michel","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"American Thoracic Society, and European Respiratory Society (2005). ATS\/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide. Am. J. Respir. Crit. Care Med., 171, 912\u2013930.","DOI":"10.1164\/rccm.200406-710ST"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.amjms.2020.04.038","article-title":"Fraction of exhaled nitric oxide is elevated in patients with stable chronic obstructive pulmonary disease: A meta-analysis","volume":"360","author":"Gong","year":"2020","journal-title":"Am. J. Med. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1080\/15412555.2018.1485637","article-title":"Investigating fractional exhaled nitric oxide in chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap (ACO): A scoping review","volume":"15","author":"Naderi","year":"2018","journal-title":"COPD"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Krauss, E., Froehler, M., Degen, M., Mahavadi, P., Dartsch, R.C., Korfei, M., Ruppert, C., Seeger, W., and Guenther, A. (2019). Exhalative breath markers do not offer for diagnosis of interstitial lung diseases: Data from the european IPF registry (eurIPFreg) and Biobank. J. Clin. Med., 8.","DOI":"10.3390\/jcm8050643"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"026008","DOI":"10.1088\/1752-7163\/ab0233","article-title":"Evaluation of multiple-flows exhaled nitric oxide in idiopathic and non-idiopathic interstitial lung disease","volume":"27","author":"Cameli","year":"2019","journal-title":"J. Breath Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1600965","DOI":"10.1183\/13993003.00965-2016","article-title":"A european respiratory society technical standard: Exhaled biomarkers in lung disease","volume":"49","author":"Barnes","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1080\/14728222.2018.1541318","article-title":"Oxidative\/nitrosative stress, autophagy and apoptosis as therapeutic targets of melatonin in idiopathic pulmonary fibrosis","volume":"22","author":"Hosseinzadeh","year":"2018","journal-title":"Exp. Opin. Ther. Targets"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10753-019-01059-1","article-title":"Oxidant\/antioxidant disequilibrium in idiopathic pulmonary fibrosis pathogenesis","volume":"43","author":"Cameli","year":"2020","journal-title":"Inflammation"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e44","DOI":"10.1164\/rccm.201807-1255ST","article-title":"Diagnosis of idiopathic pulmonary fibrosis. An official ATS\/ERS\/JRS\/ALAT clinical practice guideline","volume":"198","author":"Raghu","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_13","first-page":"19","article-title":"Idiopathic pulmonary fibrosis: Pathogenesis and management","volume":"22","author":"Sgalla","year":"2018","journal-title":"Respir. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1089-8603(02)00002-2","article-title":"Nitric oxide and wound repair: Role of cytokines?","volume":"7","author":"Schwentker","year":"2002","journal-title":"Nitric Oxide"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Gutierrez, H.H., Pitt, B.R., Schwarz, M., Watkins, S.C., Lowenstein, C., Caniggia, I., Chumley, P., and Freeman, B.A. (1995). Pulmonary alveolar epithelial inducible No synthase gene expression: Regulation by inflammatory mediators. Am. J. Physiol.","DOI":"10.1152\/ajplung.1995.268.3.L501"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1002\/path.1116","article-title":"iNOS gene upregulation is associated with the early proliferative response of human lung fibroblasts to cytokine stimulation","volume":"197","author":"Romanska","year":"2002","journal-title":"J. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/BF02970129","article-title":"Nitric oxide production by rat bronchoalveolar macrophages or polymorphonuclear leukocytes following intratracheal instillation of lipopolysaccharide or silica","volume":"28","author":"Huffman","year":"2003","journal-title":"J. Biosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.1002\/jcb.25192","article-title":"Nitric oxide mediates bleomycin-induced angiogenesis and pulmonary fibrosis via regulation of VEGF","volume":"116","author":"Iyer","year":"2015","journal-title":"J. Cell Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.7150\/ijbs.41653","article-title":"Downregulation of nitric oxide collaborated with radiotherapy to promote anti-tumor immune response via inducing cd8+ t cell infiltration","volume":"16","author":"Xu","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s00134-003-2129-9","article-title":"Expression of nitric oxide synthase, aquaporin 1 and aquaporin 5 in rat after bleomycin inhalation","volume":"30","author":"Jang","year":"2004","journal-title":"Intensiv. Care Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Pullamsetti, S.S., Savai, R., Dumitrascu, R., Dahal, B.K., Wilhelm, J., Konigshoff, M., Zakrezwicz, D., Ardeschir Ghofrani, H., Weissmann, N., and Eickelberg, O. (2011). The role of dimethylarginine dimethylaminohydrolase in idiopathic pulmonary fibrosis. Sci. Transl. Med.","DOI":"10.1126\/scitranslmed.3001725"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1002\/path.4127","article-title":"The role of dimethylarginine dimethylaminohydrolase (DDAH) in pulmonary fibrosis","volume":"229","author":"Janssen","year":"2013","journal-title":"J. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/pmic.201500171","article-title":"A proteomics approach to identifying key protein targets involved in VEGF inhibitor mediated attenuation of bleomycin-induced pulmonary fibrosis","volume":"16","author":"Kulkarni","year":"2016","journal-title":"Proteomics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1186\/s12931-017-0654-2","article-title":"Anti-fibrotic efficacy of nintedanib in pulmonary fibrosis via the inhibition of fibrocyte activity","volume":"18","author":"Sato","year":"2017","journal-title":"Respir. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1093\/rheumatology\/41.8.843","article-title":"Beauty and the beast. The nitric oxide paradox in systemic sclerosis","volume":"41","author":"Kahaleh","year":"2002","journal-title":"Rheumatology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"036007","DOI":"10.1088\/1752-7155\/9\/3\/036007","article-title":"Increased exhaled nitric oxide precedes lung fibrosis in two murine models of systemic sclerosis","volume":"9","author":"Bei","year":"2015","journal-title":"J. Breath Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s12931-014-0092-3","article-title":"Nitric oxide exerts protective effects against bleomycin-induced pulmonary fibrosis in mice","volume":"15","author":"Noguchi","year":"2014","journal-title":"Respir. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1152\/japplphysiol.00950.2003","article-title":"Modeling pulmonary nitric oxide exchange","volume":"96","author":"George","year":"2003","journal-title":"J. Appl. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1152\/japplphysiol.00533.2006","article-title":"A simple technique to characterize proximal and peripheral nitric oxide exchange using constant flow exhalations and an axial diffusion model","volume":"102","author":"Condorelli","year":"2007","journal-title":"J. Appl. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"016002","DOI":"10.1088\/1752-7155\/8\/1\/016002","article-title":"A practical approach to the theoretical models to calculate NO parameters of the respiratory system","volume":"8","author":"Thornadtsson","year":"2014","journal-title":"J. Breath Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1152\/jappl.1998.85.2.653","article-title":"A two-compartment model of pulmonary nitric oxide exchange dynamics","volume":"85","author":"Tsoukias","year":"1998","journal-title":"J. Appl. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1164\/rccm.2104003","article-title":"Partitioning of alveolar and conducting airway nitric oxide in scleroderma lung disease","volume":"165","author":"Girgis","year":"2002","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_33","first-page":"S5","article-title":"Increased alveolar nitric oxide in early systemic sclerosis","volume":"28","author":"Wuttge","year":"2010","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"71","DOI":"10.23736\/S0026-4806.17.05285-5","article-title":"Serum surfactant protein D and exhaled nitric oxide as biomarkers of early lung damage in systemic sclerosis","volume":"109","author":"Benfante","year":"2018","journal-title":"Minerva Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.3899\/jrheum.090915","article-title":"Increased alveolar concentration of nitric oxide is related to serum-induced lung fibroblast proliferation in patients with systemic sclerosis","volume":"37","author":"Tiev","year":"2010","journal-title":"J. Rheumatol."},{"key":"ref_36","first-page":"32","article-title":"Diagnostic value of exhaled nitric oxide to detect interstitial lung disease in systemic sclerosis","volume":"26","author":"Tiev","year":"2009","journal-title":"Sarcoidosis Vasc. Diffuse Lung Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1183\/09031936.00129806","article-title":"Severity of scleroderma lung disease is related to alveolar concentration of nitric oxide","volume":"30","author":"Tiev","year":"2007","journal-title":"Eur. Respir. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1136\/thoraxjnl-2011-200499","article-title":"Alveolar concentration of nitric oxide predicts pulmonary function deterioration in scleroderma","volume":"67","author":"Tiev","year":"2012","journal-title":"Thorax"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.niox.2014.04.011","article-title":"Exhaled NO predicts cyclophosphamide response in scleroderma-related lung disease","volume":"40","author":"Tiev","year":"2014","journal-title":"Nitric Oxide"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1055\/s-0030-1255958","article-title":"Nitric oxide in exhaled breath of patients with interstitial lung diseases","volume":"65","author":"Schildge","year":"2011","journal-title":"Pneumologie"},{"key":"ref_41","first-page":"3015","article-title":"Characteristics of pulmonary inflammation in combined pulmonary fibrosis and emphysema","volume":"125","author":"Zhao","year":"2012","journal-title":"Chin. Med. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.resp.2014.03.011","article-title":"Exhaled nitric oxide in interstitial lung diseases","volume":"197","author":"Cameli","year":"2014","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_43","first-page":"39","article-title":"Exhaled nitric oxide is not increased in pulmonary sarcoidosis","volume":"33","author":"Cameli","year":"2016","journal-title":"Sarcoidosis Vasc. Diffuse Lung Dis."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Kotecha, J., Shulgina, L., Sexton, D.W., Atkins, C.P., and Wilson, A.M. (2016). Plasma vascular endothelial growth factor concentration and alveolar nitric oxide as potential predictors of disease progression and mortality in idiopathic pulmonary fibrosis. J. Clin. Med., 5.","DOI":"10.3390\/jcm5090080"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.niox.2019.05.001","article-title":"Alveolar concentration of nitric oxide as a prognostic biomarker in idiopathic pulmonary fibrosis","volume":"89","author":"Cameli","year":"2019","journal-title":"Nitric Oxide"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Cameli, P., Bergantini, L., D\u2019alessandro, M., Vietri, L., Refini, R.M., Pieroni, M., Sestini, P., and Bargagli, E. (2019). Alveolar nitric oxide is related to periostin levels in idiopathic pulmonary fibrosis. Minerva Med.","DOI":"10.23736\/S0026-4806.19.06321-3"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1034\/j.1399-3003.1999.14d17.x","article-title":"Nitric oxide levels in exhaled air and inducible nitric oxide synthase immunolocalization in pulmonary sarcoidosis","volume":"14","author":"Moodley","year":"1999","journal-title":"Eur. Respir. J."},{"key":"ref_48","first-page":"98","article-title":"Multiple flow rates measurement of exhaled nitric oxide in patients with sarcoidosis: A pilot feasibility study","volume":"26","author":"Choi","year":"2009","journal-title":"Sarcoidosis Vasc. Diffuse Lung Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"036015","DOI":"10.1088\/1752-7163\/ab1284","article-title":"The role of measuring exhaled breath biomarkers in sarcoidosis: A systematic review","volume":"24","author":"Terrington","year":"2019","journal-title":"J. Breath Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1111\/j.1440-1843.2010.01726.x","article-title":"Elevated alveolar nitric oxide concentration after environmental challenge in hypersensitivity pneumonitis","volume":"15","author":"Shirai","year":"2010","journal-title":"Respirology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/j.rmed.2013.07.007","article-title":"Can exhaled nitric oxide differentiate causes of pulmonary fibrosis?","volume":"107","author":"Guilleminault","year":"2013","journal-title":"Respir. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1136\/thx.2006.067868","article-title":"Increased alveolar nitric oxide concentration and high levels of leukotriene B(4) and 8-isoprostane in exhaled breath condensate in patients with asbestosis","volume":"62","author":"Lehtonen","year":"2007","journal-title":"Thorax"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/j.1440-1843.2006.00852.x","article-title":"Fractional exhaled nitric oxide concentration is increased in asbestosis and pleural plaques","volume":"11","author":"Sandrini","year":"2006","journal-title":"Respirology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/1465-9921-12-81","article-title":"Increase of nitrosative stress in patients with eosinophilic pneumonia","volume":"12","author":"Furukawa","year":"2011","journal-title":"Respir. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"036001","DOI":"10.1088\/1752-7163\/aa6c4b","article-title":"Exhaled nitric oxide measurements in patients with acute-onset interstitial lung disease","volume":"11","author":"Oishi","year":"2017","journal-title":"J. Breath Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1136\/ard.2006.066068","article-title":"Changes in causes of death in systemic sclerosis, 1972\u20132002","volume":"66","author":"Steen","year":"2007","journal-title":"Ann. Rheum. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1136\/annrheumdis-2017-211448","article-title":"Mapping and predicting mortality from systemic sclerosis","volume":"76","author":"Elhai","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1056\/NEJMoa1903076","article-title":"Nintedanib for systemic sclerosis-associated interstitial lung disease","volume":"380","author":"Distler","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_59","first-page":"547","article-title":"Increased nitric oxide in exhaled air in patients with systemic sclerosis","volume":"16","author":"Fajac","year":"1998","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1378\/chest.119.5.1449","article-title":"Exhaled nitric oxide is elevated in patients with progressive systemic sclerosis without interstitial lung disease","volume":"119","author":"Moodley","year":"2001","journal-title":"Chest"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1136\/thx.52.12.1051","article-title":"Decreased nitric oxide in the exhaled air of patients with systemic sclerosis with pulmonary hypertension","volume":"52","author":"Kharitonov","year":"1997","journal-title":"Thorax"},{"key":"ref_62","first-page":"1693","article-title":"Exhaled nitric oxide in systemic sclerosis: Relationships with lung involvement and pulmonary hypertension","volume":"27","author":"Rolla","year":"2000","journal-title":"J. Rheumatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1164\/rccm.201308-1483ST","article-title":"an official american thoracic society\/european respiratory society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias","volume":"188","author":"Travis","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_64","first-page":"646","article-title":"Krebs von den Lungen-6 as biomarker for disease severity assessment in interstitial lung disease: A comprehensive review","volume":"158","author":"Bergantini","year":"2020","journal-title":"Biomark. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1586\/17476348.2015.1062367","article-title":"Facts and promises on lung biomarkers in interstitial lung diseases","volume":"9","author":"Campo","year":"2015","journal-title":"Exp. Rev. Respir. Med."},{"key":"ref_66","first-page":"1119","article-title":"Periostin, A Matrix Protein, Is A Novel Biomarker For Idiopathic Interstitial Pneumonias With Active Fibrosis","volume":"37","author":"Hoshino","year":"2011","journal-title":"B67. Fibroblast Biol. Nov. Biomark. Microenviron."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1164\/rccm.200509-1518OC","article-title":"A vicious circle of alveolar macrophages and fibroblasts perpetuates pulmonary fibrosis via CCL18","volume":"173","author":"Prasse","year":"2006","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_68","first-page":"1","article-title":"Serum CD59: A novel biomarker of idiopathic pulmonary fibrosis?","volume":"11","author":"Cameli","year":"2020","journal-title":"Panminerva Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1183\/09031936.00141013","article-title":"Serum lysyl oxidase-like 2 levels and idiopathic pulmonary fibrosis disease progression","volume":"43","author":"Chien","year":"2014","journal-title":"Eur. Respir. J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1164\/ajrccm.155.5.9154889","article-title":"Increased production of the potent oxidant peroxynitrite in the lungs of patients with idiopathic pulmonary fibrosis","volume":"155","author":"Saleh","year":"1997","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_71","first-page":"54","article-title":"Bronchoalveolar glutathione and nitrite\/nitrate in idiopathic pulmonary fibrosis and sarcoidosis","volume":"19","author":"Montaldo","year":"2002","journal-title":"Sarcoidosis Vasc. Diffuse Lung Dis."},{"key":"ref_72","first-page":"21","article-title":"Nitric oxide derivative in bronchoalveolar lavage fluid from patients with idiopathic pulmonary fibrosis","volume":"44","author":"Behera","year":"2002","journal-title":"Indian J. Chest Dis. Allied Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0002-9440(10)65261-3","article-title":"Expression of inducible nitric oxide synthase in human granulomas and histiocytic reactions","volume":"154","author":"Facchetti","year":"1999","journal-title":"Am. J. Pathol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"290","DOI":"10.5603\/ARM.28237","article-title":"Concentration of nitric oxide in exhaled air in patients with sarcoidosis--pilot study","volume":"70","author":"Ziora","year":"2002","journal-title":"Pneumonol. Alergol. Pol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1136\/thx.2004.033852","article-title":"Exhaled nitric oxide in sarcoidosis","volume":"60","author":"Wilsher","year":"2005","journal-title":"Thorax"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1183\/09031936.04.00110803","article-title":"An increase in exhaled nitric oxide is not associated with activity in pulmonary sarcoidosis","volume":"24","author":"Ziora","year":"2004","journal-title":"Eur. Respir. J."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s00408-015-9824-5","article-title":"Utility of exhaled nitric oxide fraction for the diagnosis of hypersensitivity pneumonitis","volume":"194","author":"Ojanguren","year":"2016","journal-title":"Lung"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1172\/JCI3169","article-title":"Asbestos inhalation induces reactive nitrogen species and nitrotyrosine formation in the lungs and pleura of the rat","volume":"102","author":"Tanaka","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s00204-004-0608-6","article-title":"Production of nitric oxide elevates nitrosothiol formation resulting in decreased glutathione in macrophages exposed to asbestos or asbestos substitutes","volume":"79","author":"Nishiike","year":"2005","journal-title":"Arch. Toxicol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.tiv.2014.12.010","article-title":"Cytotoxicity, oxidative stress and genotoxicity induced by glass fibers on human alveolar epithelial cell line A549","volume":"29","author":"Rapisarda","year":"2015","journal-title":"Toxicol. In Vitro"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"685870","DOI":"10.1155\/2011\/685870","article-title":"Inducible nitric oxide synthase genetic polymorphism and risk of asbestosis","volume":"2011","author":"Franko","year":"2011","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"405743","DOI":"10.1155\/2013\/405743","article-title":"The influence of gene-gene and gene-environment interactions on the risk of asbestosis","volume":"2013","author":"Franko","year":"2013","journal-title":"Biomed. Res. Int."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.ccm.2016.04.015","article-title":"Eosinophilic lung diseases","volume":"37","author":"Cottin","year":"2016","journal-title":"Clin. Chest Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"41","DOI":"10.3389\/fped.2019.00041","article-title":"The role of FeNO in predicting asthma","volume":"7","author":"Pijnenburg","year":"2019","journal-title":"Front. Pediatr."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.chest.2017.06.008","article-title":"Pulmonary hypertension in parenchymal lung diseases: Any future for new therapies?","volume":"153","author":"Harari","year":"2018","journal-title":"Chest"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1378\/chest.129.3.746","article-title":"Prevalence and outcomes of pulmonary arterial hypertension in advanced idiopathic pulmonary fibrosis","volume":"129","author":"Lettieri","year":"2006","journal-title":"Chest"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1016\/j.rmed.2012.07.013","article-title":"Impact of pulmonary hemodynamics on 6-min walk test in idiopathic pulmonary fibrosis","volume":"106","author":"Minai","year":"2012","journal-title":"Respir. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1177\/1076029617702243","article-title":"Fractional exhaled nitric oxide measurement in pulmonary hypertension: A follow-up study","volume":"24","author":"Akbay","year":"2018","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Malekmohammad, M., Folkerts, G., Kashani, B.S., Naghan, P.A., Dastenae, Z.H., Khoundabi, B., Garssen, J., Mortaz, E., and Adcock, I.M. (2019). Exhaled nitric oxide is not a biomarker for idiopathic pulmonary arterial hypertension or for treatment efficacy. BMC Pulm. Med., 19.","DOI":"10.1186\/s12890-019-0954-z"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1378\/chest.06-2929","article-title":"Exhaled nitric oxide levels in systemic sclerosis with and without pulmonary involvement","volume":"132","author":"Malerba","year":"2007","journal-title":"Chest"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"7292045","DOI":"10.1155\/2018\/7292045","article-title":"Exhaled nitric oxide and exhaled breath temperature as potential biomarkers in patients with pulmonary hypertension","volume":"2018","author":"Carpagnano","year":"2018","journal-title":"Biomed. Res. Int."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1086\/688768","article-title":"Exhaled nitric oxide in pulmonary arterial hypertension associated with systemic sclerosis","volume":"6","author":"Cao","year":"2016","journal-title":"Pulm. Circ."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"6736239","DOI":"10.1155\/2017\/6736239","article-title":"Exhaled nitric oxide in systemic sclerosis lung disease","volume":"2017","author":"Kozij","year":"2017","journal-title":"Can. Respir. J."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.rmed.2010.12.004","article-title":"Airway and alveolar nitric oxide measurements in obstructive sleep apnea syndrome","volume":"105","author":"Fortuna","year":"2011","journal-title":"Respir. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1007\/s11325-018-1760-1","article-title":"Measurement of fractional exhaled nitric oxide and nasal nitric oxide in male patients with obstructive sleep apnea","volume":"23","author":"Zhang","year":"2019","journal-title":"Sleep Breath"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.trsl.2007.09.004","article-title":"Exhaled pH, exhaled nitric oxide, and induced sputum cellularity in obese patients with obstructive sleep apnea syndrome","volume":"151","author":"Carpagnano","year":"2008","journal-title":"Transl. Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"529","DOI":"10.5664\/jcsm.2740","article-title":"Long-term continuous positive airway pressure therapy normalizes high exhaled nitric oxide levels in obstructive sleep apnea","volume":"9","author":"Chua","year":"2013","journal-title":"J. Clin. Sleep Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s11325-015-1198-7","article-title":"Exhaled nitric oxide from the central airway and alveoli in OSAHS patients: The potential correlations and clinical implications","volume":"20","author":"Liu","year":"2016","journal-title":"Sleep Breath"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s11325-017-1579-1","article-title":"Sleep disorders and health-related quality of life in patients with interstitial lung disease","volume":"22","author":"Mavroudi","year":"2018","journal-title":"Sleep Breath"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1378\/chest.08-2776","article-title":"Obstructive sleep apnea is common in idiopathic pulmonary fibrosis","volume":"136","author":"Lancaster","year":"2009","journal-title":"Chest"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1007\/s00408-017-0031-4","article-title":"OSA and prolonged oxygen desaturation during sleep are strong predictors of poor outcome in ipf","volume":"195","author":"Bosi","year":"2017","journal-title":"Lung"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1183\/09031936.05.00021005","article-title":"Combined pulmonary fibrosis and emphysema: A distinct underrecognised entity","volume":"26","author":"Cottin","year":"2005","journal-title":"Eur. Respir. J."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1183\/09031936.00038709","article-title":"Pulmonary hypertension in patients with combined pulmonary fibrosis and emphysema syndrome","volume":"35","author":"Cottin","year":"2010","journal-title":"Eur. Respir. J."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"4144","DOI":"10.21037\/jtd.2019.10.01","article-title":"Real world data of combined lung cancer and interstitial lung disease","volume":"11","author":"Kawahara","year":"2019","journal-title":"J. Thorac. Dis."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"374","DOI":"10.4143\/crt.2017.119","article-title":"Interstitial lung disease and lung cancer development: A 5-year nationwide population-based study","volume":"50","author":"Choi","year":"2018","journal-title":"Cancer Res. Treat."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1016\/j.chest.2019.06.041","article-title":"Interstitial lung abnormalities and lung cancer risk in the national lung screening trial","volume":"156","author":"Padilla","year":"2019","journal-title":"Chest"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1038\/sj.bjc.6602061","article-title":"The epidemiology of interstitial lung disease and its association with lung cancer","volume":"91","author":"Raghu","year":"2004","journal-title":"Br. J. Cancer"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/crj.12471","article-title":"The clinical value of exhaled nitric oxide in patients with lung cancer","volume":"12","author":"Liu","year":"2018","journal-title":"Clin. Respir. J."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/17\/6187\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:07:29Z","timestamp":1760177249000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/17\/6187"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,27]]},"references-count":108,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["ijms21176187"],"URL":"https:\/\/doi.org\/10.3390\/ijms21176187","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,27]]}}}