Decrements of body mass index are associated with poor outcomes of idiopathic pulmonary fibrosis patients


Autoři: Tejaswini Kulkarni aff001;  Kaiyu Yuan aff001;  Thi K. Tran-Nguyen aff001;  Young-il Kim aff001;  Joao A. de Andrade aff001;  Tracy Luckhardt aff001;  Vincent G. Valentine aff001;  Daniel J. Kass aff004;  Steven R. Duncan aff001
Působiště autorů: Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America aff001;  Department of Medicine, Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America aff002;  Birmingham VA Medical Center, Birmingham, Alabama, United States of America aff003;  Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America aff004
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0221905

Souhrn

Background

The processes that result in progression of idiopathic pulmonary fibrosis (IPF) remain enigmatic. Moreover, the course of this disease can be highly variable and difficult to accurately predict. We hypothesized analyses of body mass index (BMI), a simple, routine clinical measure, may also have prognostic value in these patients, and might provide mechanistic insights. We investigated the associations of BMI changes with outcome, plasma adipokines, and adaptive immune activation among IPF patients.

Methods

Data were analyzed in an IPF discovery cohort (n = 131) from the University of Pittsburgh, and findings confirmed in patients from the University of Alabama at Birmingham (n = 148). Plasma adipokines were measured by ELISA and T-cell phenotypes determined by flow cytometry.

Results

Transplant-free one-year survivals in subjects with the greatest rates of BMI decrements, as percentages of initial BMI (>0.68%/month), were worse than among those with more stable BMI in both discovery (HR = 1.8, 95%CI = 1.1–3.2, p = 0.038) and replication cohorts (HR = 2.5, 95%CI = 1.2–5.2, p = 0.02), when adjusted for age, baseline BMI, and pulmonary function. BMI decrements >0.68%/month were also associated with greater mortality after later lung transplantations (HR = 4.6, 95%CI = 1.7–12.5, p = 0.003). Circulating leptin and adiponectin levels correlated with BMI, but neither adipokine was prognostic per se. BMI decrements were significantly associated with increased proportions of circulating end-differentiated (CD28null) CD4 T-cells (CD28%), a validated marker of repetitive T-cell activation and IPF prognoses.

Conclusions

IPF patients with greatest BMI decrements had worse outcomes, and this effect persisted after lung transplantation. Weight loss in these patients is a harbinger of poor prognoses, and may reflect an underlying systemic process, such as adaptive immune activation.

Klíčová slova:

Body mass index – Leptin – Pulmonary fibrosis – T cells – Weight loss – Lung transplantation – Adiponectin – Adipokines


Zdroje

1. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. American journal of respiratory and critical care medicine. 2011;183(6):788–824. doi: 10.1164/rccm.2009-040GL 21471066.

2. Puxeddu E RP. Prognostic scoring systems for clinical course and survival in idiopathic pulmonary fibrosis. World J Respirol. 2016;6(1):14–23. doi: 10.5320/wjr.v6.i1.14

3. Robbie H, Daccord C, Chua F, Devaraj A. Evaluating disease severity in idiopathic pulmonary fibrosis. Eur Respir Rev. 2017;26(145). doi: 10.1183/16000617.0051–2017 28877976.

4. du Bois RM, Weycker D, Albera C, Bradford WZ, Costabel U, Kartashov A, et al. Ascertainment of individual risk of mortality for patients with idiopathic pulmonary fibrosis. American journal of respiratory and critical care medicine. 2011;184(4):459–66. doi: 10.1164/rccm.201011-1790OC 21616999.

5. Collard HR, King TE Jr., Bartelson BB, Vourlekis JS, Schwarz MI, Brown KK. Changes in clinical and physiologic variables predict survival in idiopathic pulmonary fibrosis. American journal of respiratory and critical care medicine. 2003;168(5):538–42. doi: 10.1164/rccm.200211-1311OC 12773325.

6. Ley B, Ryerson CJ, Vittinghoff E, Ryu JH, Tomassetti S, Lee JS, et al. A multidimensional index and staging system for idiopathic pulmonary fibrosis. Ann Intern Med. 2012;156(10):684–91. doi: 10.7326/0003-4819-156-10-201205150-00004 22586007.

7. Kondoh S, Chiba H, Nishikiori H, Umeda Y, Kuronuma K, Otsuka M, et al. Validation of the Japanese disease severity classification and the GAP model in Japanese patients with idiopathic pulmonary fibrosis. Respir Investig. 2016;54(5):327–33. doi: 10.1016/j.resinv.2016.02.009 27566380.

8. Lee SH, Park JS, Kim SY, Kim DS, Kim YW, Chung MP, et al. Comparison of CPI and GAP models in patients with idiopathic pulmonary fibrosis: a nationwide cohort study. Sci Rep. 2018;8(1):4784. doi: 10.1038/s41598-018-23073-3 29555917; PubMed Central PMCID: PMC5859191.

9. Sharp C, Adamali HI, Millar AB. A comparison of published multidimensional indices to predict outcome in idiopathic pulmonary fibrosis. ERJ Open Res. 2017;3(1). doi: 10.1183/23120541.00096–2016 28326312; PubMed Central PMCID: PMC5349096.

10. Silhan LL JC, Shah PD, Danoff SK. Comparison of the GAP Model and the Lung Allocation Score in Patients with Idiopathic Pulmonary Fibrosis/Interstitial Lung Disease Undergoing Lung Transplantation. J Pulm Med Respir Res. 2016;2:007.

11. Celli BR, Cote CG, Marin JM, Casanova C, Montes de Oca M, Mendez RA, et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med. 2004;350(10):1005–12. doi: 10.1056/NEJMoa021322 14999112.

12. Prescott E, Almdal T, Mikkelsen KL, Tofteng CL, Vestbo J, Lange P. Prognostic value of weight change in chronic obstructive pulmonary disease: results from the Copenhagen City Heart Study. Eur Respir J. 2002;20(3):539–44. doi: 10.1183/09031936.02.00532002 12358326.

13. Baker JF, Billig E, Michaud K, Ibrahim S, Caplan L, Cannon GW, et al. Weight Loss, the Obesity Paradox, and the Risk of Death in Rheumatoid Arthritis. Arthritis Rheumatol. 2015;67(7):1711–7. doi: 10.1002/art.39136 25940140; PubMed Central PMCID: PMC4826750.

14. Fonarow GC, Srikanthan P, Costanzo MR, Cintron GB, Lopatin M, Committee ASA, et al. An obesity paradox in acute heart failure: analysis of body mass index and inhospital mortality for 108,927 patients in the Acute Decompensated Heart Failure National Registry. Am Heart J. 2007;153(1):74–81. doi: 10.1016/j.ahj.2006.09.007 17174642.

15. Alakhras M, Decker PA, Nadrous HF, Collazo-Clavell M, Ryu JH. Body mass index and mortality in patients with idiopathic pulmonary fibrosis. Chest. 2007;131(5):1448–53. doi: 10.1378/chest.06-2784 17400656.

16. Kishaba T, Nagano H, Nei Y, Yamashiro S. Body mass index-percent forced vital capacity-respiratory hospitalization: new staging for idiopathic pulmonary fibrosis patients. J Thorac Dis. 2016;8(12):3596–604. doi: 10.21037/jtd.2016.12.49 28149554; PubMed Central PMCID: PMC5227212.

17. Nakatsuka Y, Handa T, Kokosi M, Tanizawa K, Puglisi S, Jacob J, et al. The Clinical Significance of Body Weight Loss in Idiopathic Pulmonary Fibrosis Patients. Respiration. 2018;96(4):338–47. doi: 10.1159/000490355 30130749.

18. Pugashetti J, Graham J, Boctor N, Mendez C, Foster E, Juarez M, et al. Weight loss as a predictor of mortality in patients with interstitial lung disease. Eur Respir J. 2018;52(3). doi: 10.1183/13993003.01289–2018 30072505.

19. Balasubramanian VP, Varkey B. Chronic obstructive pulmonary disease: effects beyond the lungs. Curr Opin Pulm Med. 2006;12(2):106–12. doi: 10.1097/01.mcp.0000208449.73101.ac 16456379.

20. Konishi M, Ebner N, von Haehling S, Anker SD, Springer J. Developing models for cachexia and their implications in drug discovery. Expert Opin Drug Discov. 2015;10(7):743–52. doi: 10.1517/17460441.2015.1041914 25927848.

21. Sanders KJ, Kneppers AE, van de Bool C, Langen RC, Schols AM. Cachexia in chronic obstructive pulmonary disease: new insights and therapeutic perspective. J Cachexia Sarcopenia Muscle. 2016;7(1):5–22. doi: 10.1002/jcsm.12062 27066314; PubMed Central PMCID: PMC4799856.

22. Brusasco V, Crapo R, Viegi G, American Thoracic S, European Respiratory S. Coming together: the ATS/ERS consensus on clinical pulmonary function testing. Eur Respir J. 2005;26(1):1–2. doi: 10.1183/09031936.05.00034205 15994380.

23. Gilani SR, Vuga LJ, Lindell KO, Gibson KF, Xue J, Kaminski N, et al. CD28 down-regulation on circulating CD4 T-cells is associated with poor prognoses of patients with idiopathic pulmonary fibrosis. PLoS One. 2010;5(1):e8959. doi: 10.1371/journal.pone.0008959 20126467; PubMed Central PMCID: PMC2813297.

24. Studer SM, George MP, Zhu X, Song Y, Valentine VG, Stoner MW, et al. CD28 down-regulation on CD4 T cells is a marker for graft dysfunction in lung transplant recipients. American journal of respiratory and critical care medicine. 2008;178(7):765–73. doi: 10.1164/rccm.200701-013OC 18617642; PubMed Central PMCID: PMC2556458.

25. Paterniti MO, Bi Y, Rekic D, Wang Y, Karimi-Shah BA, Chowdhury BA. Acute Exacerbation and Decline in Forced Vital Capacity Are Associated with Increased Mortality in Idiopathic Pulmonary Fibrosis. Ann Am Thorac Soc. 2017;14(9):1395–402. doi: 10.1513/AnnalsATS.201606-458OC 28388260.

26. Liu Y, Pleasants RA, Croft JB, Lugogo N, Ohar J, Heidari K, et al. Body mass index, respiratory conditions, asthma, and chronic obstructive pulmonary disease. Respir Med. 2015;109(7):851–9. doi: 10.1016/j.rmed.2015.05.006 26006753; PubMed Central PMCID: PMC4487766.

27. Onen ZP, Gulbay BE, Sen E, Yildiz OA, Saryal S, Acican T, et al. Analysis of the factors related to mortality in patients with bronchiectasis. Respir Med. 2007;101(7):1390–7. doi: 10.1016/j.rmed.2007.02.002 17374480.

28. Dumitriu IE. The life (and death) of CD4+ CD28(null) T cells in inflammatory diseases. Immunology. 2015;146(2):185–93. doi: 10.1111/imm.12506 26190355; PubMed Central PMCID: PMC4582960.

29. Bonham C HC, Manns S, Adegunsoye A, Blaine K, Jaffery R, Vij MM, Churpek ME, Strek I, Sperling AI. Stratification of idiopathic pulmoary fibrosis by ICOS and CD28 surface expression on T cells. American Thoracic Society2017.

30. Feghali-Bostwick CA, Tsai CG, Valentine VG, Kantrow S, Stoner MW, Pilewski JM, et al. Cellular and humoral autoreactivity in idiopathic pulmonary fibrosis. J Immunol. 2007;179(4):2592–9. doi: 10.4049/jimmunol.179.4.2592 17675522.

31. Herazo-Maya JD, Noth I, Duncan SR, Kim S, Ma SF, Tseng GC, et al. Peripheral blood mononuclear cell gene expression profiles predict poor outcome in idiopathic pulmonary fibrosis. Sci Transl Med. 2013;5(205):205ra136. doi: 10.1126/scitranslmed.3005964 24089408; PubMed Central PMCID: PMC4175518.

32. Kahloon RA, Xue J, Bhargava A, Csizmadia E, Otterbein L, Kass DJ, et al. Patients with idiopathic pulmonary fibrosis with antibodies to heat shock protein 70 have poor prognoses. American journal of respiratory and critical care medicine. 2013;187(7):768–75. doi: 10.1164/rccm.201203-0506OC 23262513; PubMed Central PMCID: PMC3678112.

33. Kotsianidis I, Nakou E, Bouchliou I, Tzouvelekis A, Spanoudakis E, Steiropoulos P, et al. Global impairment of CD4+CD25+FOXP3+ regulatory T cells in idiopathic pulmonary fibrosis. American journal of respiratory and critical care medicine. 2009;179(12):1121–30. doi: 10.1164/rccm.200812-1936OC 19342412.

34. Vuga LJ, Tedrow JR, Pandit KV, Tan J, Kass DJ, Xue J, et al. C-X-C motif chemokine 13 (CXCL13) is a prognostic biomarker of idiopathic pulmonary fibrosis. American journal of respiratory and critical care medicine. 2014;189(8):966–74. doi: 10.1164/rccm.201309-1592OC 24628285; PubMed Central PMCID: PMC4098096.

35. Xue J, Kass DJ, Bon J, Vuga L, Tan J, Csizmadia E, et al. Plasma B lymphocyte stimulator and B cell differentiation in idiopathic pulmonary fibrosis patients. J Immunol. 2013;191(5):2089–95. doi: 10.4049/jimmunol.1203476 23872052; PubMed Central PMCID: PMC3804013.

36. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature. 1998;395(6704):763–70. doi: 10.1038/27376 9796811.

37. Neumann E, Lepper N, Vasile M, Riccieri V, Peters M, Meier F, et al. Adipokine expression in systemic sclerosis lung and gastrointestinal organ involvement. Cytokine. 2019;117:41–9. doi: 10.1016/j.cyto.2018.11.013 30784899.

38. Oh YM, Jeong BH, Woo SY, Kim SY, Kim H, Lee JH, et al. Association of plasma adipokines with chronic obstructive pulmonary disease severity and progression. Ann Am Thorac Soc. 2015;12(7):1005–12. doi: 10.1513/AnnalsATS.201501-005OC 26010877.

39. Vernooy JH, Drummen NE, van Suylen RJ, Cloots RH, Moller GM, Bracke KR, et al. Enhanced pulmonary leptin expression in patients with severe COPD and asymptomatic smokers. Thorax. 2009;64(1):26–32. doi: 10.1136/thx.2007.085423 18835960.

40. La Cava A, Matarese G. The weight of leptin in immunity. Nat Rev Immunol. 2004;4(5):371–9. doi: 10.1038/nri1350 15122202.

41. Iikuni N, Lam QL, Lu L, Matarese G, La Cava A. Leptin and Inflammation. Curr Immunol Rev. 2008;4(2):70–9. doi: 10.2174/157339508784325046 20198122; PubMed Central PMCID: PMC2829991.

42. Fantuzzi G, Faggioni R. Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukoc Biol. 2000;68(4):437–46. 11037963.

43. Stofkova A. Leptin and adiponectin: from energy and metabolic dysbalance to inflammation and autoimmunity. Endocr Regul. 2009;43(4):157–68. 19908934.

44. Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol. 2005;115(5):911–9; quiz 20. doi: 10.1016/j.jaci.2005.02.023 15867843.

45. Galli JA, Pandya A, Vega-Olivo M, Dass C, Zhao H, Criner GJ. Pirfenidone and nintedanib for pulmonary fibrosis in clinical practice: Tolerability and adverse drug reactions. Respirology. 2017;22(6):1171–8. doi: 10.1111/resp.13024 28317233.


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