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Bedeutung von Komorbiditäten bei der idiopathische Lungenfibrose

  • M. Polke
  • M. KreuterEmail author
Leitthema

Zusammenfassung

Komorbiditäten der idiopathischen Lungenfibrose (IPF) sind sehr häufig und zumeist mit einer verschlechterten Lebensqualität und Prognose der Patienten verbunden. Vor allem pulmonale Hypertonie, chronische obstruktive Lungenerkrankung/Lungenemphysem, Lungenkarzinom und die koronare Herzerkrankung sind prognostisch relevant. Während Mikroaspirationen zwar als möglicher Auslöser und Progressionsfaktor einer IPF diskutiert werden, ist die Refluxerkrankung jedoch mit einer besseren Prognose assoziiert. Die Ursachen hierfür sind noch unklar, möglicherweise handelt es sich um einen „lead time bias“ oder einen Therapieeffekt des Refluxes; allerdings spricht die aktuelle Datenlage gegen einen solchen Zusammenhang für antazide Medikamente. Das Risiko ein Lungenkarzinom zu entwickeln, ist bei IPF signifikant höher im Vergleich zur Normalbevölkerung und die zweithäufigste respiratorische Todesursache bei der IPF. Eine Therapie des nicht-kleinzelligen Bronchialkarzinoms (NSCLC) ist jedoch nur im frühen Stadium der IPF mit einem verbesserten Outcome assoziiert, in anderen Fällen allerdings mit einem sehr hohen periinterventionellen Risiko. Bisherige Daten suggerieren, dass ein Screening auf Komorbiditäten und deren konsequente Therapie zu einer verbesserten Lebensqualität und Prognose der chronisch erkrankten IPF-Patienten führen könnten.

Schlüsselwörter

Lungenfibrose  Komorbiditäten Lebensqualität Gastroösophageale Refluxerkrankung Nicht-kleinzelliges Bronchialkarzinom 

Importance of comorbidities in idiopathic pulmonary fibrosis

Abstract

Comorbidities of idiopathic pulmonary fibrosis (IPF) are very frequent and mostly associated with a reduced quality of life and poorer prognosis for the patient. In particular, pulmonary hypertension, chronic obstructive pulmonary disease/lung emphysema, lung cancer and coronary heart disease are prognostically relevant. While microaspiration might be a possible trigger and a progression factor in IPF, gastroesophageal reflux disease (GERD) is associated with a better prognosis. The reasons for this are still unclear but could possibly be explained by a lead time bias or a therapeutic effect of GERD treatment; however, such an association with antacid medication is not supported by the currently available data. The risk of developing lung cancer is significantly higher in IPF than in the general population and is the second most common respiratory cause of death in IPF; however, treatment of non-small cell lung cancer (NSCLC) is only associated with a better outcome in patients with an early stage of IPF, in other cases patients have a higher peri-interventional risk. Current data suggest that screening for comorbidities followed by consistent treatment could lead to an improvement of the quality of life and prognosis in patients with chronic IPF.

Keywords

Pulmonary fibrosis Comorbidities Quality of life Gastroesophageal reflux disease Non-small cell lung cancer 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

M. Polke und M. Kreuter geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

Literatur

  1. 1.
    Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK et al (2011) An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 183(6):788–824PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Ley B, Collard HR, King TE Jr. (2011) Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 183(4):431–440PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Kreuter M, Swigris J, Pittrow D, Geier S, Klotsche J, Prasse A et al (2017) Health related quality of life in patients with idiopathic pulmonary fibrosis in clinical practice: insights-IPF registry. Respir Res 18(1):139PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Kreuter M, Ehlers-Tenenbaum S, Palmowski K, Bruhwyler J, Oltmanns U, Muley T et al (2016) Impact of comorbidities on mortality in patients with idiopathic pulmonary fibrosis. PLoS ONE 11(3):e151425PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Kreuter M, Swigris J, Pittrow D, Geier S, Klotsche J, Prasse A et al (2019) The clinical course of idiopathic pulmonary fibrosis and its association to quality of life over time: longitudinal data from the INSIGHTS-IPF registry. Respir Res 20(1):59PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Raghu G, Amatto VC, Behr J, Stowasser S (2015) Comorbidities in idiopathic pulmonary fibrosis patients: a systematic literature review. Eur Respir J 46(4):1113–1130PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Schwarzkopf L, Witt S, Waelscher J, Polke M, Kreuter M (2018) Associations between comorbidities, their treatment and survival in patients with interstitial lung diseases—a claims data analysis. Respir Res 19(1):73PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Lee JS, Song JW, Wolters PJ, Elicker BM, King TE Jr., Kim DS et al (2012) Bronchoalveolar lavage pepsin in acute exacerbation of idiopathic pulmonary fibrosis. Eur Respir J 39(2):352–358PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Kreuter M, Kirsten D, Bahmer T, Penzel R, Claussen M, Ehlers-Tenenbaum S et al (2016) Screening for helicobacter pylori in idiopathic pulmonary fibrosis lung biopsies. Respiration 91(1):3–8PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Lee JS, Ryu JH, Elicker BM, Lydell CP, Jones KD, Wolters PJ et al (2011) Gastroesophageal reflux therapy is associated with longer survival in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 184(12):1390–1394PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Lee JS, Collard HR, Anstrom KJ, Martinez FJ, Noth I, Roberts RS et al (2013) Anti-acid treatment and disease progression in idiopathic pulmonary fibrosis: an analysis of data from three randomised controlled trials. Lancet Respir Med 1(5):369–376PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Raghu G, Rochwerg B, Zhang Y, Garcia CA, Azuma A, Behr J et al (2015) An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis. An update of the 2011 clinical practice guideline. Am J Respir Crit Care Med 192(2):e3–19PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Kreuter M, Wuyts W, Renzoni E, Koschel D, Maher TM, Kolb M et al (2016) Antacid therapy and disease outcomes in idiopathic pulmonary fibrosis: a pooled analysis. Lancet Respir Med 4(5):381–389PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Kreuter M, Spagnolo P, Wuyts W, Renzoni E, Koschel D, Bonella F et al (2017) Antacid therapy and disease progression in patients with idiopathic pulmonary fibrosis who received pirfenidone. Respiration 93(6):415–423PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Costabel U, Behr J, Crestani B, Stansen W, Schlenker-Herceg R, Stowasser S et al (2018) Anti-acid therapy in idiopathic pulmonary fibrosis: insights from the INPULSIS(R) trials. Respir Res 19(1):167PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Behr J, Gunther A, Bonella F, Geissler K, Koschel D, Kreuter M et al (2017) German guideline for idiopathic pulmonary fibrosis—update on pharmacological therapies 2017. Pneumologie 71(7):460–474PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Raghu G, Pellegrini CA, Yow E, Flaherty KR, Meyer K, Noth I et al (2018) Laparoscopic anti-reflux surgery for the treatment of idiopathic pulmonary fibrosis (WRAP-IPF): a multicentre, randomised, controlled phase 2 trial. Lancet Respir Med 6(9):707–714PubMedCrossRefGoogle Scholar
  18. 18.
    Le Jeune I, Gribbin J, West J, Smith C, Cullinan P, Hubbard R (2007) The incidence of cancer in patients with idiopathic pulmonary fibrosis and sarcoidosis in the UK. Respir Med 101(12):2534–2540PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Ozawa Y, Suda T, Naito T, Enomoto N, Hashimoto D, Fujisawa T et al (2009) Cumulative incidence of and predictive factors for lung cancer in IPF. Respirology 14(5):723–728PubMedCrossRefGoogle Scholar
  20. 20.
    Natsuizaka M, Chiba H, Kuronuma K, Otsuka M, Kudo K, Mori M et al (2014) Epidemiologic survey of Japanese patients with idiopathic pulmonary fibrosis and investigation of ethnic differences. Am J Respir Crit Care Med 190(7):773–779PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Baumgartner KB, Samet JM, Stidley CA, Colby TV, Waldron JA (1997) Cigarette smoking: a risk factor for idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 155(1):242–248PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Vancheri C (2012) Idiopathic pulmonary fibrosis: an altered fibroblast proliferation linked to cancer biology. Proc Am Thorac Soc 9(3:153–157CrossRefGoogle Scholar
  23. 23.
    Poletti V, Ravaglia C, Buccioli M, Tantalocco P, Piciucchi S, Dubini A et al (2013) Idiopathic pulmonary fibrosis: diagnosis and prognostic evaluation. Respiration 86(1):5–12PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Yano M, Sasaki H, Moriyama S, Hikosaka Y, Yokota K, Kobayashi S et al (2012) Post-operative acute exacerbation of pulmonary fibrosis in lung cancer patients undergoing lung resection. Interact Cardiovasc Thorac Surg 14(2):146–150PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Han S, Lee YJ, Park JS, Cho YJ, Yoon HI, Lee JH et al (2019) Prognosis of non-small-cell lung cancer in patients with idiopathic pulmonary fibrosis. Sci Rep 9(1):12561PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Kreuter M, Ehlers-Tenenbaum S, Schaaf M, Oltmanns U, Palmowski K, Hoffmann H et al (2015) Treatment and outcome of lung cancer in idiopathic interstitial pneumonias. Sarcoidosis, vasculitis, and diffuse lung diseases. Off J WASOG 31(4):266–274Google Scholar
  27. 27.
    Enomoto T, Usuki J, Azuma A, Nakagawa T, Kudoh S (2003) Diabetes mellitus may increase risk for idiopathic pulmonary fibrosis. Chest 123(6):2007–2011PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Kim YJ, Park JW, Kyung SY, Lee SP, Chung MP, Kim YH et al (2012) Clinical characteristics of idiopathic pulmonary fibrosis patients with diabetes mellitus: the national survey in Korea from 2003 to 2007. J Korean Med Sci 27(7):756–760PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Hunt WR, Zughaier SM, Guentert DE, Shenep MA, Koval M, McCarty NA et al (2014) Hyperglycemia impedes lung bacterial clearance in a murine model of cystic fibrosis-related diabetes. Am J Physiol Lung Cell Mol Physiol 306(1):L43–9PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Kyung SY, Byun KH, Yoon JY, Kim YJ, Lee SP, Park JW et al (2014) Advanced glycation end-products and receptor for advanced glycation end-products expression in patients with idiopathic pulmonary fibrosis and NSIP. Int J Clin Exp Pathol 7(1):221–228PubMedPubMedCentralGoogle Scholar
  31. 31.
    Kheirollahi V, Wasnick RM, Biasin V, Vazquez-Armendariz AI, Chu X, Moiseenko A et al (2019) Metformin induces lipogenic differentiation in myofibroblasts to reverse lung fibrosis. Nat Commun 10(1):2987PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Spagnolo P, Kreuter M, Maher TM, Wuyts W, Bonella F, Corte TJ et al (2018) Metformin Does Not Affect Clinically Relevant Outcomes in Patients with Idiopathic Pulmonary Fibrosis. Respiration 96(4):314–322PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Mermigkis C, Bouloukaki I, Schiza SE (2017) Sleep as a new target for improving outcomes in idiopathic pulmonary fibrosis. Chest 152(6):1327–1338PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Mermigkis C, Bouloukaki I, Antoniou K, Papadogiannis G, Giannarakis I, Varouchakis G et al (2015) Obstructive sleep apnea should be treated in patients with idiopathic pulmonary fibrosis. Sleep Breath 19(1):385–391PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Collard HR, Ward AJ, Lanes S, Hayflinger CD, Rosenberg DM, Hunsche E (2012) Burden of illness in idiopathic pulmonary fibrosis. J Med Econ 15(5):829–835PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Nathan SD, Basavaraj A, Reichner C, Shlobin OA, Ahmad S, Kiernan J et al (2010) Prevalence and impact of coronary artery disease in idiopathic pulmonary fibrosis. Respir Med 104(7):1035–1041PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Bansilal S, Castellano JM, Fuster V (2015) Global burden of CVD: focus on secondary prevention of cardiovascular disease. Int J Cardiol 201(Suppl 1):S1–7PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Cholesterol Treatment Trialists C, Baigent C, Blackwell L, Emberson J, Holland LE, Reith C et al (2010) Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 376(9753):1670–1681CrossRefGoogle Scholar
  39. 39.
    Xu JF, Washko GR, Nakahira K, Hatabu H, Patel AS, Fernandez IE et al (2012) Statins and pulmonary fibrosis: the potential role of NLRP3 inflammasome activation. Am J Respir Crit Care Med 185(5:547–556CrossRefGoogle Scholar
  40. 40.
    Kreuter M, Bonella F, Maher TM, Costabel U, Spagnolo P, Weycker D et al (2017) Effect of statins on disease-related outcomes in patients with idiopathic pulmonary fibrosis. Thorax 72(2):148–153PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Kreuter M, Lederer DJ, Molina-Molina M, Noth I, Valenzuela C, Frankenstein L et al (2019) Association of angiotensin modulators with the course of idiopathic pulmonary fibrosis. Chest 156(4):706–714PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Kotani I, Sato A, Hayakawa H, Urano T, Takada Y, Takada A (1995) Increased procoagulant and antifibrinolytic activities in the lungs with idiopathic pulmonary fibrosis. Thromb Res 77(6):493–504PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Kubo H, Nakayama K, Yanai M, Suzuki T, Yamaya M, Watanabe M et al (2005) Anticoagulant therapy for idiopathic pulmonary fibrosis. Chest 128(3):1475–1482PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Noth I, Anstrom KJ, Calvert SB, de Andrade J, Flaherty KR, Glazer C et al (2012) A placebo-controlled randomized trial of warfarin in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 186(1):88–95PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Kreuter M, Wijsenbeek MS, Vasakova M, Spagnolo P, Kolb M, Costabel U et al (2016) Unfavourable effects of medically indicated oral anticoagulants on survival in idiopathic pulmonary fibrosis: methodological concerns. Eur Respir J 48(5):1524–1526PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2019

Authors and Affiliations

  1. 1.Pneumologie und Beatmungsmedizin, Zentrum für interstitielle und seltene Lungenerkrankungen, ThoraxklinikUniversitätsklinikum HeidelbergHeidelbergDeutschland

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