Impact of CTD-ILDs

Interstitial lung disease (ILD) is a key driver of early mortality in connective tissue diseases (CTDs)1–6

Julie

FIBROTIC CTD-ILDs ARE CHARACTERIZED BY PULMONARY FIBROSIS THAT CARRIES THE THREAT OF EARLY MORTALITY1–5

5-year mortality rates of CTD-ILDs7–13

Mortality rate estimates for different CTD-ILDs vary between different studies. 5-year mortality rates shown below are based on a range of different estimates from different studies7–13

5-year mortality rate of CTD-ILDs with RA-ILD having the highest rate

 

5-year mortality rates sourced as midpoint values from ranges for CTD-ILD 5-year mortality rate as follows: RA-ILD 5-year mortality rate 35%-39%;7,8 SSc-ILD 5-year mortality rate 10%-18%;9 primary Sjögren’s syndrome-ILD
5-year mortality rate 12%-16%;10–12 PM/DM/CADM (polymyositis/dermatomyositis/clinically amyopathic dermatomyositis) 35% 5-year mortality rate.13

SSC-ILD Mortality

ILD is the leading cause of death in SSc14

Learn more about the impact on mortality in SSc-ILD

RA-ILD Mort

ILD is an important cause of mortality in RA15,16

Learn more about the impact on mortality in RA-ILD

pSS-ILD Mortality

ILD increases the risk of mortality in primary Sjögren’s syndrome10–12,17

Learn more about the impact on mortality in primary Sjögren’s syndrome-ILD

REMEMBER THE RISK FACTORS ASSOCIATED WITH EARLY MORTALITY WHEN ASSESSING YOUR PATIENTS WITH CTD-ILDs

Risk factors for early mortality in CTD-ILDs

HRCT

  • UIP pattern18
  • Traction bronchiectasis19

  • Honeycombing19,20

Lung function

  • Lower baseline DLCO18
  • Reduction in DLCO19

  • Lower baseline 6MWD18

Demographics

  • Male sex18
  • Older age18

Current approaches to lung function monitoring in CTD-ILDs have been influenced by IPF studies, in which serial FVC and DLCO decline has been predictive of earlier mortality21

In SSc, DLCO <40%, FVC <60%, and a restrictive FEV1/FVC ratio are predictive of a marked increase in mortality21

EXTENT OF HONEYCOMBING ON HRCT AS WELL AS DLCO ARE STRONGLY ASSOCIATED WITH MORTALITY IN FIBROTIC CTD-ILDs19,22

Honeycombing present on HRCT is associated with an increased long-term mortality rate in patients with CTD-ILDs vs. no honeycombing present (p<0.001)20
Increased long-term mortality rate in patients with CTD-ILDs with honeycombing on HRCT compared with no honeycombing

10-year survival in patients with CTD-ILDs with honeycombing present or absent.
Adapted from: Adegunso ye A. et al. Ann Am Thorac Soc. 2019;16:580-588.

Find out how to investigate the radiographic characteristics of CTD-ILDs with HRCT

Lower baseline DLCO and reduction in DLCO are associated with increased mortality in fibrotic CTD-ILDs18,19
Lower baseline DLco and reduction in DLco are associated with increased mortality in fibrotic CTD-ILDs

ALTHOUGH RARE, ACUTE EXACERBATION OF ILD IS A DEADLY THREAT IN CTD-ILDs THAT COULD STRIKE AT ANY TIME23-27

Based on patients with IPF, acute exacerbation of ILD is most likely triggered by an acute event, such as infection28
Acute exacerbation

Acute exacerbation of ILD is characterized by rapid respiratory deterioration with severe hypoxemia22,26,27,29,30

 

Learn about acute exacerbation of ILD in SSc-ILD

 
ASDDSD

Acute exacerbation of ILD can occur in patients with CTD-ILDs at any point during the course of disease22,26,27,29,30

 

Learn about acute exacerbation of ILD in RA-ILD

 
Post exacerbation

Post-exacerbation hospital mortality in patients with CTD-ILDs is reported to range from 50%–100%23

 

Learn about acute exacerbation of ILD in primary Sjögren’s syndrome-ILD

 

COUGH AND ACTIVITY-LIMITING DYSPNEA HAVE AN IMPACT ON THE EVERYDAY LIVES OF PATIENTS WITH CTD-ILDs31–33

Symptoms of CTD-ILDs are generally non-specific, such as exertional dyspnea, cough, or fatigue3,4
Cough

Cough

Dyspnea

Dyspnea

Fatigue

Fatigue

Cough and dyspnea have been found to be associated with frustration, shame, anger and isolation among patients, leading to a loss in participation in pleasurable activities, such as walking, dancing or playing with children31

* ILD-related cough adversely impacts physical function, social participation, activities of daily living, and sleep quality31

* Dyspnea impacts the patients’ ability to perform functional activities and life priorities31

CTD-ILD has been associated with both short-term daily disability and long-term difficulties with life planning31

* Patients with CTD-ILDs live with uncertainty and anxiety, and can struggle over self-identity31

* Patients with progressive CTD-ILDs suffer from emotional distress that may include feelings of depression, anxiety and loss of independence34,35

 
How can you identify fibrotic ILD early in your patients with CTDs?

 

Footnotes

6MWD, six-minute walking distance; CADM, clinically amyopathic dermatomyositis; CTD, connective tissue disease; CTD-ILD, connective tissue disease-associated interstitial lung disease; DLCO, diffusing capacity of the lung for carbon monoxide; DM, dermatomyositis; FVC, forced vital capacity; HRCT, high-resolution computed tomography; ILD, interstitial lung disease; PM, polymyositis; RA, rheumatoid arthritis; rheumatoid arthritis-associated interstitial lung disease; SSc, systemic sclerosis; SSc-ILD, systemic sclerosis-associated interstitial lung disease.

  1. Fischer A and Distler J. Progressive fibrosing interstitial lung disease associated with systemic autoimmune diseases. Clin Rheumatol. 2019;38(10):2673–2681. 

  2. Mathai SC and Danoff SK. Management of interstitial lung disease associated with connective tissue disease. BMJ. 2016;352:h6819.

  3. Wallace B, Vummidi D, Khanna D. Management of connective tissue diseases associated interstitial lung disease: a review of the published literature. Curr Opin Rheumatol. 2016;28(3):236–245.

  4. Spagnolo P, Cordier JF, Cottin V. Connective tissue diseases, multimorbidity and the ageing lung. Eur Respir J. 2016;47(5):1535–1558.

  5. Vacchi C, Sebastiani M, Cassone G, et al. Therapeutic options for the treatment of interstitial lung disease related to connective tissue diseases. A narrative review. J Clin Med. 2020;9(2):407. doi: 10.3390/jcm9020407. 

  6. Maher TM, Wuyts W. Management of fibrosing interstitial lung diseases. Adv Ther. 2019;36(7):1518–1531.

  7. Hyldgaard C, Hilberg O, Pedersen AB, et al. A population-based cohort study of rheumatoid arthritis-associated interstitial lung disease: comorbidity and mortality. Ann Rheum Dis. 2017;76(10):1700–1706.

  8. Raimundo K, Solomon JJ, Olson AL, et al. Rheumatoid arthritis – interstitial lung disease in the United States: prevalence, incidence, and healthcare costs and mortality. J Rheumatol. 2019;46(4):360–369.

  9. Bouros D, Wells AU, Nicholson AG, et al. Histopathologic Subsets of Fibrosing Alveolitis in Patients with Systemic Sclerosis and Their Relationship to Outcome. Am J Respir Crit Care Med. 2002;165:1581–1586.

  10. Palm Ø, Garen T, Enger TV, et al. Clinical pulmonary involvement in primary Sjögren’s syndrome: prevalence, quality of life and mortality—a retrospective study based on registry data. Rheumatology. 2013;52:173-179.

  11. Ito I, Nagai S, Kitaichi M, et al. Pulmonary Manifestations of Primary Sjögren’s Syndrome: A Clinical, Radiologic, and Pathologic Study. Am J Respir Crit Care Med. 2005;171:632–638.

  12. Enomoto Y, Takemura T, Hagiwara E, et al. Prognostic Factors in Interstitial Lung Disease Associated with Primary Sjögren’s Syndrome: A Retrospective Analysis of 33 Pathologically–Proven Cases. PLoS One. 2013;8:e73774.

  13. Ji S-Y, Zeng F-Q, Guo Q, et al. Predictive factors and unfavourable prognostic factors of interstitial lung disease in patients with polymyositis or dermatomyositis: a retrospective study. Chin Med J (Engl). 2010;123(5):517–522.

  14. Tyndall AJ, et al. Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis. 2010;69(10):1809-1815. doi:10.1136/ ard.2009.114264.

  15. Cassone G, Manfredi A, Vacchi C, et al. Treatment of rheumatoid arthritis-associated interstitial lung disease: lights and shadows. J Clin Med. 2020;9(4):1082.

  16. Olson AL, Swigris JJ, Sprunger DB, et al. Rheumatoid Arthritis–Interstitial Lung Disease–associated Mortality. Am J Respir Crit Care Med. 2011;183:372–378.

  17. Yazisiz V, Göçer M, Erbasan F, et al. Survival analysis of patients with Sjögren’s syndrome in Turkey: a tertiary hospital-based study. Clin Rheumatol. 2020;39(1):233–241.

  18. Chan C, Ryerson CJ, Dunne JV, et al. Demographic and clinical predictors of progression and mortality in connective tissue disease-associated interstitial lung disease: a retrospective cohort study. BMC Pulm Med. 2019;19(1):192. doi: 10.1186/ s12890-019-0943-2.

  19. Walsh SLF, Sverzellati N, Devaraj A, et al. Connective tissue disease related fibrotic lung disease: high resolution computed tomographic and pulmonary function indices as prognostic determinants. Thorax. 2014;69(3):216–222.

  20. Adegunsoye A, Oldham JM, Bellam SK, et al. Computed Tomography Honeycombing Identifies a Progressive Fibrotic Phenotype with Increased Mortality across Diverse Interstitial Lung Diseases. Ann Am Thorac Soc. 2019;16:580–588.

  21. Paschalaki KE, Jacob J, Wells AU, et al. Monitoring of Lung Involvement in Rheumatologic Disease. Respiration. 2016;91:89–98. 

  22. Geerts S, Wuyts W, de Langhe E, et al. Connective tissue disease associated interstitial pneumonia: a challenge for both rheumatologists and pulmonologists. Sarcoidosis Vasc Dif. 2017;34:326–335.

  23. Kolb M, Bondue B, Pesci A, et al. Acute exacerbations of progressive-fibrosing interstitial lung diseases. Eur Respir Rev. 2018;27(150):pii:180071.

  24. Song JW, Hong S-B, Lim C-M, et al. Acute exacerbation of idiopathic pulmonary fibrosis: incidence, risk factors and outcome. Eur Respir J. 2011;37(2):356–363.

  25. Song JW, Lee H, Lee C, et al. Clinical Course and outcome of rheumatoid arthritis-related usual interstitial pneumonia. Sarcoidosis Vasc Dif. 2013;30:103–112.

  26. Tomiyama F, Watanabe R, Ishii T, et al. High Prevalence of Acute Exacerbation of Interstitial Lung Disease in Japanese Patients with Systemic Sclerosis. Tohoku J Exp Med. 2016;239, 297–305.

  27. Okamoto M, Fujimoto K, Sadohara J, et al. A retrospective cohort study of outcome in systemic sclerosis-associated interstitial lung disease. Respiratory Investigation. 2016;54, 445–453.

  28. Collard HR, Ryerson CJ, Corte TJ, et al. Acute Exacerbation of Idiopathic Pulmonary Fibrosis – An International Working Group Report. Am J Respir Crit Care Med. 2016;194:265–275.

  29. Suda T, Kaida Y, Nakamura Y, et al. Acute exacerbation of interstitial pneumonia associated with collagen vascular diseases. Resp Med. 2009;103:846–853. 

  30. Cao M, Sheng J, Qiu X, et al. Acute exacerbations of fibrosing interstitial lung disease associated with connective tissue diseases: a population-based study. BMC Pulm Med. 2019;19:215. 

  31. Mittoo S, Frankel S, LeSage D, et al. Patient perspectives in OMERACT provide an anchor for future metric development and improved approaches to healthcare delivery in connective tissue disease related interstitial lung disease (CTD-ILD). Curr Respir Med Rev. 2015;11:175–183.

  32. Saketkoo LA, MMittoo S, Huscher D, et al. Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials. Thorax. 2014;69(5):428–436.

  33. Saketkoo LA, Scholand MB, Lammi MR, et al. Patient-reported outcome measures in systemic sclerosis–related interstitial lung disease for clinical practice and clinical trials. Scleroderma Relat Disord. 2020;5(2 Suppl):48–60. 

  34. Morisset J, Dubé B, Garvey C, et al. The Unmet Educational Needs of Patients with Interstitial Lung Disease: Setting the Stage for Tailored Pulmonary Rehabilitation. Ann Am Thorac Soc. 2016;13:1026–1033.

  35. Swigris JJ, Brown KK, Abdulqawi R, et al. Patients’ perceptions and patient-reported outcomes in progressive-fibrosing interstitial lung diseases. Eur Respir Rev. 2018;27(150):180075. doi: 10.1183/16000617.0075-2018.

  36. Chowaniec M, Skoczyńska M, Sokolik R, Wiland P. Interstitial lung disease in systemic sclerosis: challenges in early diagnosis and management. Reumatologia. 2018;56(4):249–254.

  37. Cottin V, Brown KK. Interstitial lung disease associated with systemic sclerosis (SSc–ILD). Respir Res. 2019a;20(1):13.

  38. Wells AU, Denton CP. Interstitial lung disease in connective tissue disease— mechanisms and management. Nat Rev Rheumatol. 2014;10:728–739.

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