Skip to main content

Risk factors for ILDs

There are a number of risk factors for the development of ILD that should prompt suspicion of pulmonary fibrosis1,2

ILD patients with the HRCT scans in their hands.

OLDER AGE IS HIGHLY ASSOCIATED WITH RISK OF ILD, WITH THE MOST COMMON ILD IN OLDER PEOPLE BEING IPF3

IPF typically occurs between 60 and 70 years of age,2,4 but older age brings greater risk of IPF3

  • Age ≥70 years: 95% positive predictive value for IPF

  • Age ≥75 years: ~100% positive predictive value for IPF

In a study of 920 patients with IPF, 62% were men5


There is a strong association between smoking and IPF, especially for those with a greater than 20 pack-years history6


A number of environmental and occupational exposures have been associated with increased risk for IPF, including silica, sand or stone7,8

Risk factors for development of IPF

Age

  • Old age2

  • 60–70 years1,4

Sex

Exposure

  • Smoking6

  • Silica, sand, stone7

  • Livestock/farming8

Other conditions

  • GERD2

  • Epstein-Barr virus2

  • Hepatitis C2

Genetics
  • Familial history2

RISK FACTORS FOR DEVELOPMENT OF NON-IPF ILDs

IDIOPATHIC NON-SPECIFIC INTERSTITIAL PNEUMONIA (iNSIP)

iNSIP is characterized by an NSIP pattern on HRCT with no known cause. Risk factors for development of iNSIP include female sex and middle age,10 with the median age of onset being 52 years11

Male patient with fibrotic iNSIP

HYPERSENSITIVITY PNEUMONITIS (HP) 

HP is characterized by pulmonary disease accompanied by systemic manifestations, such as fever or weight loss, and is caused by inhalation of an antigen to which the patient has been sensitized.12

Environmental antigens from occupations or hobbies associated with HP include activities involving birds, farming, cheese, fur and malt.13

Female patient with fibrotic cHP

What sources of environmental antigens are associated with HP?

Sources of environmental antigens associated with HP12

Bacteria

  • Moldy hay and grain (farmer’s lung)

Fungi/yeasts

  • Moldy hay and grain (farmer’s lung)

  • Moldy compost and mushrooms (mushroom worker’s lung)

  • Contaminated houses (Japanese summer-type HP)

  • Moldy cork (suberosis)

  • Moldy cheese or cheese casings (cheese washer’s lung)

  • Contaminated wood pulp or dust (woodworker’s lung)

Mycobacteria

  • Mold on ceiling; tub water (hot tub lung)

  • Mist from pool water, sprays and fountains (swimming pool lung)

Animal proteins

  • Proteins in avian droppings and serum on feathers (pigeon breeder’s lung; bird fancier’s lung)

  • Avian proteins in feather beds, pillows and duvets (feather duvet lung)

  • Silkworm proteins in dust from silkworm larvae and cocoons (silk production HP)

Chemicals

  • Diisocyanates and trimellitic anyhydride from polyurethane foams, spray paints, dyes and glues (chemical worker’s lung)

SARCOIDOSIS-RELATED INTERSTITIAL LUNG DISEASE

Sarcoidosis-associated interstitial lung disease is the pulmonary manifestation of a multisystem granulomatous disease of unknown cause that primarily affects the respiratory and lymphatic systems.14

Female patient with sarcoidosis-associated interstitial lung disease

What are the risk factors for the development of sarcoidosis-associated interstitial lung disease?

Risk factors for development of sarcoidosis-associated interstitial lung disease

Age

20–40 years14–16

Sex

Female17

Race

African American14

Genetics

Familial clustering14,15

SYSTEMIC SCLEROSIS-ASSOCIATED INTERSTITIAL LUNG DISEASE (SSc-ILD) 

SSc-ILD is the pulmonary manifestation of a systemic autoimmune disease that affects multiple organs, including the skin. Risk of developing ILD in patients with SSc is higher in those who are:18–22

  • >65 years old

  • Male

  • African or Native American heritage

  • Diagnosed with diffuse cutaneous systemic sclerosis (dcSSc)

  • Smoking or have a history of smoking

  • Serologically positive for anti-topoisomerase I antibody

RHEUMATOID ARTHRITIS-ASSOCIATED INTERSTITIAL LUNG DISEASE (RA-ILD)

RA-ILD is the pulmonary manifestation of a systemic autoimmune disease that affects the joints. Risk of developing ILD in RA patients is higher in those who are:23–33 

  • >65 years old

  • Male

  • Experiencing longer disease duration or higher disease activity 

  • Smoking or have a history of smoking

  • Serologically positive for RF or anti-CCP antibody

What should you consider after identifying risk factors for fibrotic ILDs in your patients?

Footnotes
  • Anti-CCP, anti–citrullinated protein antibody; dsSSc, diffuse cutaneous systemic sclerosis; GERD, gastroesophageal reflux disease; HP, hypersensitivity pneumonitis; HRCT, high-resolution computed tomography; ILD, interstitial lung disease; iNSIP, idiopathic non-specific interstitial; IPF, idiopathic pulmonary fibrosis; NSIP, non-specific interstitial pneumonia; RA, rheumatoid arthritis; RA-ILD, rheumatoid arthritis-associated interstitial lung disease; RF, rheumatoid factor; SSc, systemic sclerosis; SSc-ILD, systemic sclerosis-associated interstitial lung disease.

  1. Raghu G, Collard HR, Egan JJ, et al; on behalf of the ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183(6):788–824.

  2. Raghu G, Remy-Jardin M, Myers JL, et al; on behalf of the ATS/ERS/JRS/ALAT. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198(5):e44–e68. 

  3. Fell CD, Martinez FJ, Liu LX, et al. Clinical predictors of a diagnosis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2010;181:832–837. 
  4. Castriotta RJ, Eldadah BA, Foster WM, et al. Workshop on idiopathic pulmonary fibrosis in older adults. Chest. 2010;138:693–703. 
  5. Gribbin J, Hubbard RB, Jeune IL, et al. Incidence and mortality of idiopathic pulmonary fibrosis and sarcoidosis in the UK. Thorax. 2006;61:980–985. 
  6. Baumgartner KB, Samet JM, Stidley CA, et al. Cigarette smoking: a risk factor for idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 1997;155:242–248. 
  7. Taskar VS, Coultas DB. Is idiopathic pulmonary fibrosis an environmental disease? Proc Am Thorac Soc. 2006;3:293–298. 
  8. Baumgartner KB, Samet JM, Coultas DB, et al. Occupational and environmental risk factors for idiopathic pulmonary fibrosis: a multicenter case-control study. Collaborating Centers. Am J Epidemiol. 2000;152:307–315.
  9. Coultas DB, Zumwalt RE, Black WC, et al. The epidemiology of interstitial lung diseases. Am J Respir Crit Care Med. 1994;150:967–972. 
  10. Travis WD, Hunninghake G, King, Jr., TE, et al. Idiopathic Nonspecific Interstitial Pneumonia. Am J Respir Crit Care Med. 2008;177:1338–1347. 
  11. Tomassetti S, Ryu JH, Piciucchi, et al. Nonspecific Interstitial Pneumonia: What Is the Optimal Approach to Management? Semin Respir Crit Care Med. 2016;37:378–394. 
  12. Spagnolo P, Rossi G, Cavazza A, et al. Hypersensitivity Pneumonitis: A Comprehensive Review. J Investig Allergol Clin Immunol. 2015;25:237–250. 
  13. Hirschmann JV, Pipavath SNJ, Godwin JD. Hypersensitivity Pneumonitis: A Historical, Clinical, and Radiologic Review. Radiographics. 2009;29:1921–1938. 
  14. American Thoracic Society. Statement on Sarcoidosis. Am J Respir Crit Care Med. 1999;160:736–755.
  15. Ianuzzi MC, Sah BP. Sarcoidosis. Merck Manual Professional Version website. Available at: https://www.merckmanuals.com/professional/pulmonary-disorders/sarcoidosis/sarcoidosis. August 2017. Accessed: November 2020. 
  16. Coker RK. Management strategies for pulmonary sarcoidosis. Ther Clin Risk Manag. 2009;5:575–584. 
  17. Baughman RP, Field S, Costabel U, et al. Sarcoidosis in America. Analysis Based on Health Care Use. Ann Am Thorac Soc. 2016;13:1244–1252.
  18. Fan Y, Bender S, Shi W, et al. Incidence and prevalence of systemic sclerosis and systemic sclerosis with interstitial lung disease in the United States. JMCP. 2020;1–9.
  19. Hoffmann-Vold AM, Maher TM, Philpot EE, et al. The identification and management of interstitial lung disease in systemic sclerosis: evidence-based European consensus statements. The Lancet Rheumatology. 2020b;2: e71–e83.
  20. Al-Sheikh H, Ahmad Z, Johnson SR. Ethnic Variations in Systemic Sclerosis Disease Manifestations, Internal Organ Involvement, and Mortality. J Rheumatol. 2019;46:1103–1108. 

  21. Greidinger EL, Flaherty, KT, White B, et al. African-American race and anitibodies to topoisomerase I are associated with increased severity of scleroderma lung disease. Chest. 1998:114:801–807. 

  22. Hoffmann-Vold AM, Fretheim H, Halse AK, et al. Tracking impact of interstitial lung disease in systemic sclerosis in a complete nationwide cohort. Am J Respir Crit Care Med. 2019;200:1258–1266.  

  23. Mori S, Koga Y, Sugimoto M. Different risk factors between interstitial lung disease and airway disease in rheumatoid arthritis. Respir Med. 2012;106(11):1591–1599.
  24. Esposito AJ, Chu SG, Madan R, et al. Thoracic manifestations of rheumatoid arthritis. Clin Chest Med. 2019;40(3):545–560. 
  25. Koo SM, Kim SY, Choi SM, et al. Korean guidelines for diagnosis and management of interstitial lung diseases: part 5. Connective tissue disease associated interstitial lung disease. Tuberc Respir Dis (Seoul). 2019;82(4):285–297. 
  26. Ha YJ, Lee YJ, Kang EH. Lung involvements in rheumatic diseases: update on the epidemiology, pathogenesis, clinical features, and treatment. Biomed Res Int. 2018:6930297. 
  27. Bongartz T, Nannini C, Medina-Velasquez YF, et al. Incidence and mortality of interstitial lung disease in rheumatoid arthritis: a population-based study. Arthritis Rheum. 2010;62(6):1583–1591.
  28. Habib HM, Eisa AA, Arafat WR, et al. Pulmonary involvement in early rheumatoid arthritis patients. Clin Rheumatol. 2011;30:217–221. 
  29. Kelly CA, Saravanan V, Nisar M, et al. Rheumatoid arthritis-related interstitial lung disease: associations, prognostic factors and physiological and radiological characteristics – a large multicentre UK study. Rheumatology (Oxford). 2014;53(9):1676–1682. 
  30. Gochuico BR, Avila NA, Chow CK, et al. Progressive preclinical interstitial lung disease in rheumatoid arthritis. Arch Intern Med. 2008;168(2):159–166. 
  31. Doyle TJ, Patel AS, Hatabu H, et al. Detection of rheumatoid arthritis-interstitial lung disease is enhanced by serum biomarkers. Am J Respir Crit Care Med. 2015;191(12):1403–1412. 
  32. Giles JT, Danoff SK, Sokolove J, et al. Association of fine specificity and repertoire expansion of anticitrullinated peptide antibodies with rheumatoid arthritis associated interstitial lung disease. Ann Rheum Dis. 2014;73:1487–1494.
  33. Yin Y, Liang D, Zhao L, et al. Anti-cyclic citrullinated peptide antibody is associated with interstitial lung disease in patients with rheumatoid arthritis. PLoS ONE. 2014;9(4):e92449. doi:10.1371/journal.pone.0092449.
  34. Chaudhuri N, Spencer L, Greaves M, et al. A Review of the Multidisciplinary Diagnosis of Interstitial Lung Diseases: A Retrospective Analysis in a Single UK Specialist Centre. J Clin Med. 2016;5(66):1–9. 
  35. Cottin V, Hirani N, Hotchkin D, et al. Presentation, diagnosis and clinical course of the spectrum of progressive-fibrosing interstitial lung diseases. Eur Respir Rev. 2018;27(150):180076. 
  36. Cottin V, Brown KK. Interstitial lung disease associated with systemic sclerosis (SSc–ILD). Respir Res. 2019a;20(1):13.
  37. Wong AW, Ryerson C, Guler S. Progression of fibrosing interstitial lung disease. Respir Res. 2020:29;21(1):32.
  38. Flaherty KR, Brown KK, Wells AU, et al. Design of the PF-ILD trial: A double-blind, randomised, placebo-controlled phase III trial of nintedanib in patients with progressive fibrosing interstitial lung disease. BMJ Open Resp Res. 2017;4(1):e000212. 
  39. Theodore AC, Tseng C-H, Li N, Elashoff RM, Tashkin DP. Correlation of cough with disease activity and treatment with cyclophosphamide in scleroderma interstitial lung disease: findings from the Scleroderma Lung Study. Chest. 2012;142(3):614–621.
  40. Asano Y, Jinnin M, Kawaguchi Y, et al. Diagnostic criteria, severity classification and guidelines of systemic sclerosis: Guideline of SSc. J Dermatol. 2018;45, 633–691.

Resources for patients