Comorbid Metabolic Disorders in Chronic Lung Diseases
BACKGROUND. Chronic obstructive pulmonary disease (COPD), asthma and interstitial lung diseases (ILD) are often accompanied by various metabolic disorders, aggravating the course and worsening the prognosis of pulmonary pathology. The study of the mechanisms of interaction of systemic inflammatory reactions associated with chronic lung diseases in patients with concomitant metabolic disorders will improve methods for prevention and treatment of complications of this comorbid pathology.
MATERIALS AND METHODS. In the PubMed and Google Scholar databases, a literature search has been conducted on the relationship between chronic pulmonary disease and metabolic disorders, as well as the metabolomics of chronic pulmonary disease.
RESULTS. Available evidence indicates the role of endocrine system disorders in the pathogenesis of chronic pulmonary pathology. In particular, metabolic concomitant diseases significantly worsen the quality of life of patients and increase mortality. On the other hand, improvement in the metabolic profile in certain categories of patients with chronic lung diseases can positively affect the course of the disease. Preclinical studies indicate the importance of therapeutic recovery of metabolic disorders and the use of circulating metabolites as biomarkers for disease prognosis and treatment response.
CONCLUSIONS. Monitoring of metabolic parameters, in particular glucose, lipids, thyroid hormones, calcium and vitamin D, should be a part of everyday clinical practice in all patients with COPD, asthma and ILD. Prescribing specific treatment based on the patient’s metabolic profile can slow progression and reduce mortality in chronic lung diseases.
Dursunoglu N, Kokturk N, Baha A, et al. Comorbidities and their impact on chronic obstructive pulmonary disease. Tuberk Toraks (2016) 64 (4): 289-98.
Spagnolo P, Tzouvelekis A, Maher TM. Personalized medicine in idiopathic pulmonary fibrosis: facts and promises. Curr Opin Pulm Med (2015) 21 (5): 470-8.
Farag AM. Head and neck manifestations of endocrine disorders. Atlas Oral Maxillofac Surg Clin North Am (2017) 25 (2): 197-207.
Raghu G, Amatto VC, Behr J, Stowasser S. Comorbidities in idiopathic pulmonary fibrosis patients: a systematic literature review. Eur Respir J (2015) 46 (4): 1113-30.
Soriano JB, Visick GT, Muellerova H, et al. Patterns of comorbidities in newly diagnosed COPD and asthma in primary care. Chest (2005) 128 (4): 2099-107.
Naik D, Joshi A, Paul TV, Thomas N. Chronic obstructive pulmonary disease and the metabolic syndrome: consequences of a dual threat. Indian J Endocrinol Metab (2014) 18 (5): 608-16.
Oppedal RJ, Khan DA, Brown ES. Hypothyroidism in patients with asthma and major depressive disorder. Prim Care Companion J Clin Psychiatry (2007) 9 (6): 467-8.
Mannino DM, Thorn D, Swensen A, Holguin F. Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD. Eur Respir J (2008) 32 (4): 962-9.
Schols AM. Nutritional advances in patients with respiratory diseases. Eur Respir Rev (2015) 24 (135): 17-22.
Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell (2013) 153 (6): 1194-217.
Mullerova H, Agusti A, Erqou S, Mapel DW. Cardiovascular comorbidity in COPD: systematic literature review. Chest (2013) 144 (4): 1163-78.
Laghi F, Adiguzel N, Tobin MJ. Endocrinological derangements in COPD. Eur Respir J (2009) 34 (4): 975-96.
Walter RE, Beiser A, Givelber RJ, et al. Association between glycemic state and lung function: the Framingham Heart Study. Am J Respir Crit Care Med (2003) 167 (6): 911-6.
de Lucas-Ramos P, Izquierdo-Alonso JL, Rodriguez-Gonzalez Moro JM, et al. Chronic obstructive pulmonary disease as a cardiovascular risk factor. Results of a case-control study (CONSISTE study). Int J Chron Obstruct Pulmon Dis (2012) 7: 679-86.
Graat-Verboom L, Wouters EF, Smeenk FW, et al. Current status of research on osteoporosis in COPD: a systematic review. Eur Respir J (2009) 34 (1): 209-18.
Terzano C, Romani S, Paone G, et al. COPD and thyroid dysfunctions. Lung (2014) 192 (1): 103-9.
Sarinc Ulasli S, Bozbas SS, Ozen ZE, et al. Effect of thyroid function on COPD exacerbation frequency: a preliminary study. Multidiscip Respir Med (2013) 8 (1): 64.
Fouda MA, Alhamad EH, Al-Hajjaj MS, et al. A study of chronic obstructive pulmonary disease-specific causes of osteoporosis with emphasis on the emphysema phenotype. Ann Thorac Med (2017) 12 (2): 101-6.
Chen SJ, Liao WC, Huang KH, et al. Chronic obstructive pulmonary disease and allied conditions is a strong independent risk factor for osteoporosis and pathologic fractures: a population-based cohort study. QJM (2015) 108 (8): 633-40.
Inoue D, Watanabe R, Okazaki R. COPD and osteoporosis: links, risks, and treatment challenges. Int J Chron Obstruct Pulmon Dis (2016) 11: 637-48.
Cavailles A, Brinchault-Rabin G, Dixmier A, et al. Comorbidities of COPD. Eur Respir Rev (2013) 22 (130): 454-75.
Tzouvelekis A, Siafakas N, Bouros D. Comorbidities and chronic obstructive pulmonary disease: is there a place for lung fibrosis? Am J Respir Crit Care Med (2013) 188 (11): 1367.
Chen W, Thomas J, Sadatsafavi M, FitzGerald JM. Risk of cardiovascular comorbidity in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis. Lancet Respir Med (2015) 3 (8): 631-9.
Watz H, Waschki B, Boehme C, et al. Extrapulmonary effects of chronic obstructive pulmonary disease on physical activity: a cross-sectional study. Am J Respir Crit Care Med (2008) 177 (7): 743-51.
Rana JS, Mittleman MA, Sheikh J, et al. Chronic obstructive pulmonary disease, asthma, and risk of type 2 diabetes in women. Diabetes Care (2004) 27 (10): 2478-84.
Lange P, Groth S, Kastrup J, et al. Diabetes mellitus, plasma glucose and lung function in a cross-sectional population study. Eur Respir J (1989) 2 (1): 14-9.
Davis WA, Knuiman M, Kendall P, et al. Glycemic exposure is associated with reduced pulmonary function in type 2 diabetes: the Fremantle Diabetes Study. Diabetes Care (2004) 27 (3): 752-7.
Lee CT, Mao IC, Lin CH, et al. Chronic obstructive pulmonary disease: a risk factor for type 2 diabetes: a nationwide population-based study. Eur J Clin Invest (2013) 43 (11): 1113-9.
Mirrakhimov AE. Chronic obstructive pulmonary disease and glucose metabolism: a bitter sweet symphony. Cardiovasc Diabetol (2012) 11: 132.
Caughey GE, Preiss AK, Vitry AI, et al. Comorbid diabetes and COPD: impact of corticosteroid use on diabetes complications. Diabetes Care (2013) 36 (10):3009-14.
Lahousse L, Loth DW, Joos GF, et al. Statins, systemic inflammation and risk of death in COPD: the Rotterdam study. Pulm Pharmacol Ther (2013) 26 (2): 212-7.
Wang MT, Lo YW, Tsai CL, et al. Statin use and risk of COPD exacerbation requiring hospitalization. Am J Med (2013) 126 (7): 598-606.
Saaresranta T, Polo O. Hormones and breathing. Chest (2002) 122 (6): 2165-82.
Klein I, Ojamaa K. Thyroid (neuro)myopathy. Lancet (2000) 356 (9230): 614.
Chopra IJ. Clinical review 86: euthyroid sick syndrome: is it a misnomer? J Clin Endocrinol Metab (1997) 82 (2): 329-34.
Siafakas NM, Salesiotou V, Filaditaki V, et al. Respiratory muscle strength in hypothyroidism. Chest (1992) 102 (1): 189-94.
Martinez FJ, Bermudez-Gomez M, Celli BR. Hypothyroidism. A reversible cause of diaphragmatic dysfunction. Chest (1989) 96 (5): 1059-63. DOI:10.1378/chest.96.5.1059
Ali NS, Nanji K. A review on the role of vitamin D in asthma. Cureus (2017) 9 (5): e1288.
Heck S, Al-Shobash S, Rapp D, et al. High probability of comorbidities in bronchial asthma in Germany. NPJ Prim Care Respir Med (2017) 27 (1): 28.
Karampitsakos T, Gourgoulianis KI. Asthma-COPD overlap syndrome (ACOS): single disease entity or not? Could exhaled nitric oxide be a useful biomarker for the differentiation of ACOS, asthma and COPD? Med Hypotheses (2016) 91:20-3.
Schatz M, Hsu JW, Zeiger RS, et al. Phenotypes determined by cluster analysis in severe or difficult-to-treat asthma. J Allergy Clin Immunol (2014) 133(6):1549-56.
Aranceta-Bartrina J, Perez-Rodrigo C, Alberdi-Aresti G, et al. Prevalence of general obesity and abdominal obesity in the Spanish adult population (aged 25-64 years) 2014-2015: the ENPE study. Rev Esp Cardiol (Engl Ed) (2016) 69 (6): 579-87.
Chinellato I, Piazza M, Sandri M, et al. Vitamin D serum levels and markers of asthma control in Italian children. J Pediatr (2011) 158(3):437-41.
Devereux G, Wilson A, Avenell A, et al. A case-control study of vitamin D status and asthma in adults. Allergy (2010) 65 (5): 666-7.
Forrest KY, Stuhldreher WL. Prevalence and correlates of vitamin D deficiency in US adults. Nutr Res (2011) 31 (1): 48-54.
Baffi CW, Wood L, Winnica D, et al. Metabolic syndrome and the Lung. Chest (2016) 149 (6): 1525-34.
Leone N, Courbon D, Thomas F, et al. Lung function impairment and metabolic syndrome: the critical role of abdominal obesity. Am J Respir Crit Care Med (2009) 179 (6): 509-16.
Brumpton BM, Camargo CA, Jr, Romundstad PR, et al. Metabolic syndrome and incidence of asthma in adults: the HUNT study. Eur Respir J (2013) 42 (6): 1495-502.
Cottrell L, Neal WA, Ice C, et al. Metabolic abnormalities in children with asthma. Am J Respir Crit Care Med (2011) 183 (4): 441-8.
Sodoyez-Goffaux FR, Sodoyez JC, De Vos CJ. Insulin receptors in the fetal rat lung. A transient characteristic of fetal cells? Pediatr Res (1981) 15 (9): 1303-7.
Unger RH. Minireview: weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome. Endocrinology (2003) 144 (12): 5159-65.
Ronmark E, Andersson C, Nystrom L, et al. Obesity increases the risk of incident asthma among adults. Eur Respir J (2005) 25 (2): 282-8.
Sideleva O, Suratt BT, Black KE, et al. Obesity and asthma: an inflammatory disease of adipose tissue not the airway. Am J Respir Crit Care Med (2012) 186 (7): 598-605.
Guerre-Millo M. Adipose tissue hormones. J Endocrinol Invest (2002) 25 (10): 855-61.
Sutter SA, Stein EM. The skeletal effects of inhaled glucocorticoids. Curr Osteoporos Rep (2016) 14 (3): 106-13.
Barnig C, Veaudor M, Gautier C, et al. [How to consider triggers and comorbid conditions in severe asthma in adults]. Presse Med (2016) 45 (11): 1030-42.
Dam TT, Harrison S, Fink HA, et al. Osteoporotic Fractures in Men Research Group Bone mineral density and fractures in older men with chronic obstructive pulmonary disease or asthma. Osteoporos Int (2010) 21 (8): 1341-9.
Richy F, Bousquet J, Ehrlich GE, et al. Inhaled corticosteroids effects on bone in asthmatic and COPD patients: a quantitative systematic review. Osteoporos Int (2003) 14 (3): 179-90.
Israel E, Banerjee TR, Fitzmaurice GM, et al. Effects of inhaled glucocorticoids on bone density in premenopausal women. N Engl J Med (2001) 345 (13): 941-7.
Wong CA, Walsh LJ, Smith CJ, et al. Inhaled corticosteroid use and bone-mineral density in patients with asthma. Lancet (2000) 355 (9213): 1399-403.
Sosa M, Saavedra P, Valero C, et al. Inhaled steroids do not decrease bone mineral density but increase risk of fractures: data from the GIUMO Study Group. J Clin Densitom (2006) 9 (2): 154-8.
Kuan YC, How SH, Azian AA, et al. Bone mineral density in asthmatic patients on inhaled corticosteroids in a developing country. Ann Thorac Med (2012) 7 (2): 69-73.
de Vries F, Pouwels S, Lammers JW, et al. Use of inhaled and oral glucocorticoids, severity of inflammatory disease and risk of hip/femur fracture: a population-based case-control study. J Intern Med (2007) 261 (2): 170-7.
Iordanidou M, Paraskakis E, Giannakopoulou E, et al. Vitamin D receptor ApaI a allele is associated with better childhood asthma control and improvement in ability for daily activities. OMICS (2014) 18 (11): 673-81.
Baeke F, Takiishi T, Korf H, et al. Vitamin D: modulator of the immune system. Curr Opin Pharmacol (2010) 10 (4): 482-96.
Korn S, Hubner M, Jung M, et al. Severe and uncontrolled adult asthma is associated with vitamin D insufficiency and deficiency. Respir Res (2013) 14: 25.
Gupta A, Dimeloe S, Richards DF, et al. Defective IL‑10 expression and in vitro steroid-induced IL‑17A in paediatric severe therapy-resistant asthma. Thorax (2014) 69 (6): 508-15.
Urashima M, Segawa T, Okazaki M, et al. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr (2010) 91 (5): 1255-60.
Majak P, Olszowiec-Chlebna M, Smejda K, Stelmach I. Vitamin D supplementation in children may prevent asthma exacerbation triggered by acute respiratory infection. J Allergy Clin Immunol (2011) 127 (5): 1294-6.
Yadav M, Mittal K. Effect of vitamin D supplementation on moderate to severe bronchial asthma. Indian J Pediatr (2014) 81 (7): 650-4.
Martineau AR, Cates CJ, Urashima M, et al. Vitamin D for the management of asthma. Cochrane Database Syst Rev (2016) 9: CD011511.
Antoniou KM, Margaritopoulos GA, Tomassetti S, et al. Interstitial lung disease. Eur Respir Rev (2014) 23 (131): 40-54.
Wells AU, Denton CP. Interstitial lung disease in connective tissue disease – mechanisms and management. Nat Rev Rheumatol (2014) 10 (12): 728-39.
Fischer A, du Bois R. Interstitial lung disease in connective tissue disorders. Lancet (2012) 380 (9842): 689-98.
Karampitsakos T, Woolard T, Bouros D, Tzouvelekis A. Toll-like receptors in the pathogenesis of pulmonary fibrosis. Eur J Pharmacol (2017) 808: 35-43.
Tzouvelekis A, Tzilas V, Papiris S, et al. Diagnostic and prognostic challenges in idiopathic pulmonary fibrosis: a patient’s “Q and A” approach. Pulm Pharmacol Ther (2017) 42: 21-4.
Kim D, Cho SK, Choi CB, et al. Impact of interstitial lung disease on mortality of patients with rheumatoid arthritis. Rheumatol Int (2017) 37: 1735-45.
Mikolasch TA, Garthwaite HS, Porter JC. Update in diagnosis and management of interstitial lung disease. Clin Med (Lond) (2016) 16 (Suppl 6): s71-8.
Oldham JM, Collard HR. Comorbid conditions in idiopathic pulmonary fibrosis: recognition and management. Front Med (2017) 4: 123.
Tzouvelekis A, Wang R, Herazo-Maya J, et al. Thyroid hormone as a novel therapeutic agent in lung fibrosis through restoration of AECs mitochondrial homeostasis. Am J Respir Crit Care Med (2016) 193: A4537–A.
Gribbin J, Hubbard R, Smith C. Role of diabetes mellitus and gastro-oesophageal reflux in the aetiology of idiopathic pulmonary fibrosis. Respir Med (2009) 103 (6): 927-31.
Enomoto T, Usuki J, Azuma A, et al. Diabetes mellitus may increase risk for idiopathic pulmonary fibrosis. Chest (2003) 123 (6): 2007-11.
Lamas DJ, Kawut SM, Bagiella E, et al. Delayed access and survival in idiopathic pulmonary fibrosis: a cohort study. Am J Respir Crit Care Med (2011) 184 (7): 842-7.
Kaddah S, Ahmed S. Lifestyle associated diseases and risk of pulmonary hypertension in patients with idiopathic pulmonary fibrosis. Egypt J Chest Dis Tuberc (2016) 65 (1): 127-33.
Sherbini N, Feteih MN, Wali SO, et al. Idiopathic pulmonary fibrosis in Saudi Arabia: demographic, clinical, and survival data from two tertiary care hospitals. Ann Thorac Med (2014) 9 (3): 168-72.
Oldham JM, Kumar D, Lee C, et al. Thyroid disease is prevalent and predicts survival in patients with idiopathic pulmonary fibrosis. Chest (2015) 148 (3): 692-700.
Nowinski A, Puscinska E, Goljan A, et al. The influence of comorbidities on mortality in sarcoidosis: a observational prospective cohort study. Clin Respir J (2017) 11 (5): 648-56.
Saidenberg-Kermanac’h N, Valeyre D, Boissier MC. Vitamin D supplementation in patients treated for sarcoidosis: controversy or consensus? Joint Bone Spine (2017) 84 (5): 521-3.
Press DM, Siperstein AE, Berber E, et al. The prevalence of undiagnosed and unrecognized primary hyperparathyroidism: a population-based analysis from the electronic medical record. Surgery (2013) 154 (6): 1232-7; discussion 7-8.
Tomos IP, Tzouvelekis A, Aidinis V, et al. Extracellular matrix remodeling in idiopathic pulmonary fibrosis. It is the “bed” that counts and not “the sleepers”. Expert Rev Respir Med (2017) 11 (4): 299-309.
Karampitsakos T, Tzilas V, Tringidou R, et al. Lung cancer in patients with idiopathic pulmonary fibrosis. Pulm Pharmacol Ther (2017) 45: 1-10.
Tzouvelekis A, Bonella F, Spagnolo P. Update on therapeutic management of idiopathic pulmonary fibrosis. Ther Clin Risk Manag (2015) 11: 359-70.
Oldham J, Demchuk C, Ma S-F, et al. Hypothyroidism in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med (2014) 189: A1497–A.
Idiopathic Pulmonary Fibrosis Clinical Research Network. Raghu G, Anstrom KJ, King TE, Jr, et al. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N Engl J Med (2012) 366 (21): 1968-77.
Hyldgaard C, Hilberg O, Bendstrup E. How does comorbidity influence survival in idiopathic pulmonary fibrosis? Respir Med (2014) 108 (4): 647-53.
Garcia-Sancho Figueroa MC, Carrillo G, Perez-Padilla R, et al. Risk factors for idiopathic pulmonary fibrosis in a Mexican population. A case-control study. Respir Med (2010) 104 (2): 305-9.
Garber JR, Cobin RH, Gharib H, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract (2012) 18 (6): 988-1028.
Vanderpump MP, Tunbridge WM, French JM, et al. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf) (1995) 43 (1): 55-68.
Tzouvelekis A, Yu G, Herazo-Maya J, et al. Thyroid hormone inhibits pulmonary fibrosis through enhancement of mitochondrial function in alveolar epithelial cells. Eur Respir J (2016) 48 (Suppl): 60.
Yu G, Tzouvelekis A, Wang R, et al. Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function. Nat Med (2017).
Furukawa S, Fujita T, Shimabukuro M, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest (2004) 114 (12): 1752-61.
Rice JB, White A, Lopez A, et al. Economic burden of sarcoidosis in a commercially-insured population in the United States. J Med Econ (2017) 20: 1048-55.
Baughman RP, Teirstein AS, Judson MA, et al. Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med (2001) 164 (10 Pt 1): 1885-9.
Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med (1999) 160 (2): 736-55.
Baughman RP, Culver DA, Judson MA. A concise review of pulmonary sarcoidosis. Am J Respir Crit Care Med (2011) 183 (5): 573-81.
Martusewicz-Boros MM, Boros PW, Wiatr E, Roszkowski-Sliz K. What comorbidities accompany sarcoidosis? A large cohort (n=1779) patients analysis. Sarcoidosis Vasc Diffuse Lung Dis (2015) 32 (2): 115-20.
Antonelli A, Fazzi P, Fallahi P, et al. Prevalence of hypothyroidism and Graves disease in sarcoidosis. Chest (2006) 130 (2): 526-32.
Antonelli A, Ferrari SM, Corrado A, et al. Autoimmune thyroid disorders. Autoimmun Rev (2015) 14 (2): 174-80.
Baughman RP, Janovcik J, Ray M, et al. Calcium and vitamin D metabolism in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis (2013) 30 (2): 113-20.
Baughman RP, Papanikolaou I. Current concepts regarding calcium metabolism and bone health in sarcoidosis. Curr Opin Pulm Med (2017) 23 (5): 476-81.
Adams JS, Singer FR, Gacad MA, et al. Isolation and structural identification of 1,25-dihydroxyvitamin D3 produced by cultured alveolar macrophages in sarcoidosis. J Clin Endocrinol Metab (1985) 60 (5): 960-6.
Bell NH, Stern PH, Pantzer E, et al. Evidence that increased circulating 1 alpha, 25-dihydroxyvitamin D is the probable cause for abnormal calcium metabolism in sarcoidosis. J Clin Invest (1979) 64 (1): 218-25.
Kuchay MS, Mishra SK, Bansal B, et al. Glucocorticoid sparing effect of zoledronic acid in sarcoid hypercalcemia. Arch Osteoporos (2017) 12 (1): 68.
Valeyre D, Prasse A, Nunes H, et al. Sarcoidosis. Lancet (2014) 383 (9923): 1155-67.
Gibbs CJ, Peacock M. Hypercalcaemia due to sarcoidosis corrects with bisphosphonate treatment. Postgrad Med J (1986) 62 (732): 937-8.
Xu EY, Schaefer WH, Xu Q. Metabolomics in pharmaceutical research and development: metabolites, mechanisms and pathways. Curr Opin Drug Discov Devel (2009) 12 (1): 40-52.
Nobakht MGBF, Aliannejad R, Rezaei-Tavirani M, Taheri S, Oskouie AA. The metabolomics of airway diseases, including COPD, asthma and cystic fibrosis. Biomarkers (2015) 20 (1): 5-16.
Saude EJ, Skappak CD, Regush S, et al. Metabolomic profiling of asthma: diagnostic utility of urine nuclear magnetic resonance spectroscopy. J Allergy Clin Immunol (2011) 127 (3): e1-6.
Adamko DJ, Nair P, Mayers I, et al. Metabolomic profiling of asthma and chronic obstructive pulmonary disease: a pilot study differentiating diseases. J Allergy Clin Immunol (2015) 136 (3): 571-80. e3.
Cap P, Chladek J, Pehal F, et al. Gas chromatography/mass spectrometry analysis of exhaled leukotrienes in asthmatic patients. Thorax (2004) 59 (6): 465-70.
Ubhi BK, Riley JH, Shaw PA, et al. Metabolic profiling detects biomarkers of protein degradation in COPD patients. Eur Respir J (2012) 40 (2): 345-55.
McClay JL, Adkins DE, Isern NG, et al. (1) H nuclear magnetic resonance metabolomics analysis identifies novel urinary biomarkers for lung function. J Proteome Res (2010) 9 (6): 3083-90.
Paige M, Burdick MD, Kim S, et al. Pilot analysis of the plasma metabolite profiles associated with emphysematous chronic obstructive pulmonary disease phenotype. Biochem Biophys Res Commun (2011) 413 (4): 588-93.
Cloonan SM, Glass K, Laucho-Contreras ME, et al. Mitochondrial iron chelation ameliorates cigarette smoke-induced bronchitis and emphysema in mice. Nat Med (2016) 22 (2): 163-74.
Zhao YD, Yin L, Archer S, et al. Metabolic heterogeneity of idiopathic pulmonary fibrosis: a metabolomic study. BMJ Open Respir Res (2017) 4 (1): e000183.
Kang YP, Lee SB, Lee JM, et al. Metabolic profiling regarding pathogenesis of idiopathic pulmonary fibrosis. J Proteome Res (2016) 15 (5): 1717-24.
Kottmann RM, Kulkarni AA, Smolnycki KA, et al. Lactic acid is elevated in idiopathic pulmonary fibrosis and induces myofibroblast differentiation via pH-dependent activation of transforming growth factor-beta. Am J Respir Crit Care Med (2012) 186 (8): 740-51.
Xie N, Tan Z, Banerjee S, et al. Glycolytic reprogramming in myofibroblast differentiation and lung fibrosis. Am J Respir Crit Care Med (2015) 192 (12): 1462-74.
Bueno M, Lai YC, Romero Y, et al. PINK1 deficiency impairs mitochondrial homeostasis and promotes lung fibrosis. J Clin Invest (2015) 125 (2): 521-38.
Kobayashi K, Araya J, Minagawa S, et al. Involvement of PARK2-mediated mitophagy in idiopathic pulmonary fibrosis pathogenesis. J Immunol (2016) 197 (2): 504-16.
Larson-Case y JL, Deshane JS, Ryan AJ, et al. Macrophage Akt1 kinase-mediated mitophagy modulates apoptosis resistance and pulmonary fibrosis. Immunity (2016) 44 (3): 582-96.
Xie N, Cui H, Ge J, et al. Metabolic characterization and RNA profiling reveal glycolytic dependence of pro-fibrotic phenotype of alveolar macrophages in lung fibrosis. Am J Physiol Lung Cell Mol Physiol (2017) 313 (5): L834-44.
Ryu C, Sun H, Gulati M, et al. Extracellular mitochondrial DNA is generated by fibroblasts and predicts death in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med (2017) 196: 1571-81.
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