Diagnosing IPF: Clinical features of IPF

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Diagnosing IPF: Clinical features of IPF

A patient with suspected IPF should have a full workup performed

Clinical signs of IPF may be found during1-4:

–Physical examination
–Pulmonary function testing
–A full medical history

 

1. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 2. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824. 3. Meltzer EB et al. Orphanet J Rare Dis. 2008;3:1-15. 4. Pellegrino R et al. Eur Respir J. 2005;26(5):948-968.

2

Physical examination

Signs of IPF are often present on physical examination

Common signs of IPF1,5-8

üDyspnea
üDry, nonproductive cough
üCrackles on auscultation
üDigital clubbing

1. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 5. Bjoraker JA et al. Am J Respir Crit Care Med. 1998;157(1):199-203. 6. King TE Jr. et al. Am J Respir Crit Care Med. 2001;164(7):1171-1181. 7. Douglas WW et al. Am J Respir Crit Care Med. 2000;161(4 Pt 1):1172-1178. 8. American Thoracic Society. Am J Respir Crit Care Med. 2000;161(2 Pt 1):646-664.

4

Signs of IPF are often present on physical examination (cont.)

9. Kim DS et al. Proc Am Thorac Soc. 2006;3(4):285-292. 10. Panos RJ et al. Am J Med. 1990;88(4):396-404.

Rare signs of IPF9,10

üCyanosis
üSigns of right heart failure

5

Signs of IPF are often present on physical examination (cont.)

3. Meltzer EB et al. Orphanet J Rare Dis. 2008;3:1-15. 9. Kim DS et al. Proc Am Thorac Soc. 2006;3(4):285-292.

Constitutional signs and CTDs are rare in IPF3,9

xFever
xWeight loss
xArthritis or other CTDs

These signs should prompt investigation into secondary causes of pulmonary fibrosis3

CTD, connective tissue disorder.

6

Dyspnea is nearly universal in IPF8

Dyspnea is one of the prominent and disabling symptoms of IPF8

 

8. American Thoracic Society. Am J Respir Crit Care Med. 2000;161(2 Pt 1):646-664.

7

Most patients have experienced dyspnea for more than 6 months before presentation5,8

Some patients expect shortness of breath to be part of normal aging, especially during or after physical activity, and may not seek medical attention until much later11

 

IPF should be considered in all patients with unexplained, gradual onset of chronic dyspnea (either exertional or at rest)5,8

5. Bjoraker JA et al. Am J Respir Crit Care Med. 1998;157(1):199-203. 8. American Thoracic Society. Am J Respir Crit Care Med. 2000;161(2 Pt 1):646-664. 11. Castriotta RJ et al. Chest. 2010;138(3):693-703.

8

Cough is a nearly universal symptom of IPF

  • Most – if not all – patients with IPF have a chronic, dry/nonproductive cough8,12
  •  

  • Wheezing is not common in IPF and suggests airway disease rather than interstitial disease13
  •  

    8. American Thoracic Society. Am J Respir Crit Care Med. 2000;161(2 Pt 1):646-664. 12. Ryerson CJ et al. Respirology. 2011;16(6):969-975.13. Kritek P, Choi MK. In: Longo DL, Fauco AS, Kasper DL et al, eds. Harrison’s Principles of Internal Medicine. 18th ed. New York, NY: McGraw-Hill Companies, Inc. 2012:2094-2101.

    9

    Cough is a nearly universal symptom of IPF (cont.)

  • Chronic cough significantly impairs patients’ QOL14
  •  

  • Persistent and excessive cough may cause serious complications, including15:
  • –Cough-related syncope
    –Pneumothorax
    –Cardiac arrhythmias
    –Seizures

     

    14. Swigris JJ et al. Health Qual Life Outcomes. 2005;3:61. 15. Irwin RS et al. Chest .1998;114(2):133S-181S.

    QOL, quality of life.

    10

    CHANGE_ME

    At least 80% of patients with IPF have crackles on auscultation5-7
    3. Meltzer EB et al. Orphanet J Rare Dis. 2008;3:1-15. 5. Bjoraker JA et al. Am J Respir Crit Care Med. 1998;157(1):199-203. 6. King TE, Jr. et al. Am J Respir Crit Care Med. 2001;164(7):1171-1181. 7. Douglas WW et al. Am J Respir Crit Care Med. 2000;161(4 Pt 1):1172-1178. 16. Kraman SS. Arch Intern Med. 1986;146(7):1411-1412. 17. Cottin V et al. Eur Respir J. 2012;40(3):519-521.
    Icon created by Freepik from flaticon.com.
    11

    Some experts believe that crackles are essentially universal in the diagnosis of IPF17

    However, the correlation of crackles and IPF has not been validated in the current diagnostic criteria1,17

    If crackles are absent, other forms of lung disease (eg, granulomatous disease) should be considered18

    1. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 17. Cottin V et al. Eur Respir J. 2012;40(3):519-521. 18. Epler GR et al. Chest. 1978;73(3):333-339.

    12

    Digital clubbing may be present in up to 50% of patients with IPF5-7

    Clubbing is commonly seen in other pulmonary diseases, including lung cancer and pulmonary tuberculosis, as well as in congestive heart failure19

    5. Bjoraker JA et al. Am J Respir Crit Care Med. 1998;157(1):199-203. 6. King TE Jr. et al. Am J Respir Crit Care Med. 2001;164(7):1171-1181. 7. Douglas WW et al. Am J Respir Crit Care Med. 2000;161(4 Pt 1):1172-1178. 19. Spicknall KE et al. J Am Acad Dermatol 2005; 52(6):1020. 20. NHLBI. Signs and Symptoms of IPF. Available at https://www.nhlbi.nih.gov/health/health-topics/topics/ipf/signs. Accessed June 7, 2017.

    Source: National Heart, Lung, and Blood Institute, National Institutes of Health. Available at https://www.nhlbi.nih.gov/health/health-topics/topics/ipf/signs. Accessed August 28, 2017.20

    13

    Pulmonary function testing

    Patients with suspected IPF should undergo full pulmonary function testing21

    21. Ley B et al. Am J Respir Crit Care Med. 2011;183(4):431-440.

    üSpirometry
    üComplete lung volume assessment
  • TLC
  • FVC
  • FEV1
  • üEvaluation of DLco

    TLC, total lung capacity; FVC, forced vital capacity; FEV1, forced expiratory volume in 1 second; DLco, diffusing capacity of carbon monoxide.

    15

    Patients with IPF generally show reduced total lung capacity

    TLC generally decreases in IPF because parenchymal scar tissue accumulates, resulting in reduced intrinsic elasticity and subsequent distortion of normal lung architecture3

     

    3. Meltzer EB et al. Orphanet J Rare Dis. 2008;3:1-15.

    16

    Patients with IPF often show a restrictive pattern on spirometry3

    3. Meltzer EB et al. Orphanet J Rare Dis. 2008;3:1-15. 4. Pellegrino R et al. Eur Respir J. 2005;26(5):948-968.

    Restrictive defect

    Volume (L)

    Flow (L/sec)

    Obstructive defect

    Volume (L)

    Flow (L/sec)

    Used with permission from Pellegrino R et al. Eur Respir J 2005;26(5):948-968.

    PEF, peak expiratory flow.

  • TLC is normal
  • Normal FVC but lower FEV1
  • Lower FEV1/FVC ratio
  • Flows are lower than expected over the entire volume range
  • TLC is low
  • Low FVC
  • Higher FEV1/FVC ratio
  • Flows are higher than expected at a given             lung volume
  • Inspiration

    Expiration

    Observed

    Predicted

    Observed

    Predicted

    Inspiration

    Expiration

    17

    Patients with IPF also tend to have impaired gas exchange

    Fibrosis during IPF affects how well the lungs exchange gases, which can be seen by measuring the diffusion capacity of the lungs, particularly carbon monoxide (DLco)3

     

    3. Meltzer EB et al. Orphanet J Rare Dis. 2008;3:1-15.

    18

    Reduced DLco may occur before reduced lung volumes

    Reduced DLco can be found during the early stages of IPF3,8

     

     

     

     

    3. Meltzer EB et al. Orphanet J Rare Dis. 2008;3:1-15. 8. American Thoracic Society. Am J Respir Crit Care Med. 2000;161(2 Pt 1):646-664. 22. Portillo CK et al. Arch Bronconeumol. 2010;46(12):646-651. 23. Cottin V et al. Eur Respir J. 2005;26(4):586-593.

    In patients with concomitant IPF and emphysema, spirometric measures and lung volumes may be normal, but DL will invariably be low22,23

    19

    Most patients with IPF will experience hypoxemia on exertion3

    Patients may or may not show decreased blood gas exchange/oxygen saturation at rest3

     

    3. Meltzer EB et al. Orphanet J Rare Dis. 2008;3:1-15.

    20

    Other clinical evaluations

    Patients with IPF or suspected IPF should have a cardiovascular workup

  • Pulmonary hypertension is a common comorbidity in IPF24
  •  

  • Patients with IPF or suspected IPF should be evaluated for potential pulmonary vascular abnormalities, such as right ventricular hypertrophy or right bundle branch block patterns25
  • 24. Collard HR et al. J Med Econ. 2012;15(5);829-835. 25. Han MK et al. Circulation. 2007;116(25):2992-3005.

    22

    Patients should be evaluated for signs and symptoms of CTD

    The ATL/ERS/JRS/ALAT 2018 guidelines recommend evaluating patients with suspected IPF for1:

    –Rheumatoid factor
    –Anti-CCP
    –Anti-CRP
    –ANA titer and pattern
    –Others on a case-by-case basis

    Patients with ILD and clinical signs or symptoms that meet the diagnostic criteria for CTD do not have IPF1

    1. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68.

    ANA, anti-nuclear antibody; CCP, cyclic citrullinated peptide; CRP, C-reactive protein; ILD, interstitial lung disease.

    23

    Other tests should be ordered based on the patient’s specific symptoms

    Possible symptoms and associated tests include2,26-28:

     

    2. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824. 26. Kinder BW et al. Am J Respir Crit Care Med. 2007;176(7):691-697. 27. Vij R et al. Chest. 2013;143(3):814-824. 28. Satoh M, et al. Mod Rheumatol. 2009;19:219-228.

    CK, creatine kinase; RF, rheumatoid factor; SS-A/SS-B, Sjögren’s antibodies.

    CK

    Aldolase

    Anti-Jo1

    ANA

    RF

    Anti-CCP

    SS-A

    SS-B

    Scl-70

     

    Morning stiffness

    Arthritis

    Rash

    Dry mouth (Sicca syndrome)

    Dry eyes

    Skin thickening

    Esophageal symptoms

    Raynaud’s phenomenon

     

     

    Mechanic’s hands

    Proximal muscle pain/weakness

    Heliotrope rash

    Raynaud’s phenomenon

     

    24

    High titers of autoantibodies suggest the presence of CTD8

    Approximately 10%-20% of patients with IPF have low-level titers of ANA ( <1:160) or rheumatoid factor8 

    –Such patients should be screened for signs and symptoms of CTD (eg, arthritis, Raynaud's phenomenon, skin changes, abnormal esophageal motility)2

     

    2. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824. 8. American Thoracic Society. Am J Respir Crit Care Med. 2000;161(2 Pt 1):646-664.

    25

    Patients with suspected CTD but low titers should be retested

    If CTD is strongly suspected but the tests do not show strong evidence of CTD, the panel may be repeated after initial testing2,29 

     

    2. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824. 29. British Columbia Medical Association. Antinuclear antibody (ANA) testing protocol. Available at www.bcguidelines.ca. Accessed June 7, 2017. 

    26

    Medical history

    A detailed medical history is essential to diagnosing IPF

    In all cases of potential ILD, a detailed medical history should be taken that covers1,2:

     

    1. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 2.Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824.

    üComorbidities
    üSocial history
    üOccupational and environmental exposures
    üDrug exposures
    üFamily history

     

    28

    IPF has several common comorbidities

  • Common comorbidities seen with IPF include24:
  • –GERD
    –Emphysema
    –Coronary artery disease
    –Congestive heart failure
    –Obstructive sleep apnea 
    –Pulmonary hypertension, either due to chronic hypoxia or as a result of ILD
    –Lung cancer

     

  • See Managing IPF: Comorbidities for more information
  •  

    GERD, gastroesophageal reflux disease.

    29

    24. Collard HR et al. J Med Econ. 2012;15(5);829-835.

    Many patients are former smokers at the time of IPF diagnosis5,30

    Cigarette smoking is strongly associated with IPF, especially among patients with a history of smoking more than 20 pack-years30

    5. Bjoraker JA, et al. Am J Respir Crit Care Med. 1998;157(1):199-203. 30. Baumgartner KB et al. Am J  Respir Crit Care Med. 1997;155(1):242-248.

     

    30

    Certain occupational and environmental exposures are associated with IPF

  • Occupational and environmental exposures that are associated with increased risk of IPF include31:
  • –Varied sources of dust and/or particulate matter
    –Agriculture-related and livestock-related exposures
    –Raising birds

     

  • Although these exposures are associated with IPF, they have not been found to be causative32
  •  

  • See About IPF: Risk Factors for more information
  • 31. Baumgartner KB et al. Am J Epidemiol 2000;152(4):307-315. 32. Taskar VS et al. Proc Am Thorac Soc. 2006;3:293–298.

    31

    IPF can look like hypersensitivity pneumonitis but differs by environmental exposures

  • HP is typically caused by an inflammatory reaction to inhaled organic particles33
  •  

  • Specific fungi33:
  • –Bird feathers (eg, household bedding)
    –Atypical mycobacterium (eg, those that colonize hot tubs) 

     

    33. Selman M et al. Am J Respir Crit Care Med. 2012;186(4):314-324.

    32

    HP, hypersensitivity pneumonitis.

    It is essential to distinguish between IPF and HP

  • The workup and treatment for IPF and HP are vastly different33,34
  •  

  • HP is treated with systemic corticosteroids,33 which is strongly discouraged when treating IPF2
  •  

     

    2. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824. 33. Selman M et al. Am J Respir Crit Care Med. 2012;186(4):314-324. 34. Morell F. Lancet Respir Med. 2013;1(9):685-694.

    33

    Serologic workup should be performed for suspected cases of HP

    Patients whose exposure history suggests HP should undergo a serologic workup including fungal antigen panels and immunoglobulin G levels toward the suspected offending antigen33

     

    33. Selman M et al. Am J Respir Crit Care Med. 2012;186(4):314-324.

    34

    Numerous drugs have been associated with development of ILD35,36

    The website Pneumotox (www.pneumotox.com) is freely available and accessible to help in diagnosing potential drug-induced ILD by drug name or pathologic condition35

    35. Camus P. The drug-induced respiratory disease website. 2012.  Pneumotox website. www.pneumotox.com. Accessed December 12, 2017. 36. Schwaiblmair M et al. Open Respir Med J. 2012;6:63-74.

    35

    Family history of IPF or young age should lead to suspicion of familial IPF

  • Familial IPF is generally indistinguishable from sporadic cases based on clinical and/or histologic characteristics37,38
  •  

     

     

     

  • For more information on the genetic mutations associated with IPF, see About IPF: Molecular Understanding
  •  

    Both familial and sporadic cases of IPF have been linked with genetic mutations39-42

    37. Marshall RP et al. Thorax. 2000;55(2):143-146. 38. Hodgson U et al. Thorax. 2002;57(4):338-342. 39. Thomas AQ et al. Am J Respir Crit Care Med. 2002;165(9):1322-1328.

    36

    40. van Moorsel CH et al. Am J Respir Crit Care Med. 2010;182(11):1419-1425. 41. Wang Y et al. Am J Hum Genet. 2009;84(1):52-59. 42. Seibold MA et al. N Engl J Med. 2011;364(16):1503-1512.

    Summary

  • Patients with suspected IPF should undergo a full set of examinations1-4
  • –Physical exam, respiratory evaluation, full medical history
  • Pulmonary function tests will often show abnormalities that add evidence to support a diagnosis of IPF2,3
  • Taking a detailed medical history is essential for identifying risk factors and potential alternative diagnoses1,2
  • 1. Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68. 2. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824. 3. Meltzer EB et al. Orphanet J Rare Dis. 2008;3:1-15. 4. Pellegrino R et al. Eur Respir J. 2005;26(5):948-968.

     

    37

    References

    1.Raghu G et al. Am J Respir Crit Care Med. 2018;198(5):e44-e68.
    2.Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824.
    3.Meltzer EB et al. Orphanet J Rare Dis. 2008;3:1-15.
    4.Pellegrino R et al. Eur Respir J. 2005;26(5):948-968.
    5.Bjoraker JA et al. Am J Respir Crit Care Med. 1998;157(1):199-203.
    6.King TE Jr. et al. Am J Respir Crit Care Med. 2001;164(7):1171-1181.
    7.Douglas WW et al. Am J Respir Crit Care Med. 2000;161(4 Pt 1):1172-1178.
    8.American Thoracic Society. Am J Respir Crit Care Med. 2000;161(2 Pt 1):646-664.
    9.Kim DS et al. Proc Am Thorac Soc. 2006;3(4):285-292.
    10.Panos RJ et al. Am J Med. 1990;88(4):396-404.
    11.Castriotta RJ et al. Chest. 2010;138(3):693-703.
    12.Ryerson CJ et al. Respirology. 2011;16(6):969-975.
    13.Kritek P, Choi MK. In: Longo DL, Fauco AS, Kasper DL et al, eds. Harrison’s Principles of Internal Medicine. 18th ed. New York, NY: McGraw-Hill Companies, Inc. 2012:2094-2101.
    14.Swigris JJ et al. Health Qual Life Outcomes. 2005;3:61.
    15.Irwin RS et al. Chest. 1998;114(2):133S-181S.
    16.Kraman SS. Arch Intern Med. 1986;146(7):1411-1412.
    17.Cottin V et al. Eur Respir J. 2012;40(3):519-521.
    18.Epler GR et al. Chest. 1978;73(3):333-339.
    19.Spicknall KE et al. J Am Acad Dermatol 2005; 52(6):1020.
    20.NHLBI. Signs and Symptoms of IPF. Available at https://www.nhlbi.nih.gov/health/health-topics/topics/ipf/signs. Accessed June 7, 2017.
    21.Ley B et al. Am J Respir Crit Care Med. 2011;183(4):431-440.
    22.Portillo CK et al. Arch Bronconeumol. 2010;46(12):646-651.
    23.Cottin V et al. Eur Respir J. 2005;26(4):586-593.
    24.Collard HR et al. J Med Econ. 2012;15(5);829-835.
    25.Han MK et al. Circulation. 2007;116(25):2992-3005.

     

     

     

    38

    References

    39

    26.Kinder BW et al. Am J Respir Crit Care Med. 2007;176(7):691-697.
    27.Vij R et al. Chest. 2013;143(3):814-824.
    28.Satoh M, et al. Mod Rehumatol. 2009;19:219-228.
    29.British Columbia Medical Association. Antinuclear antibody (ANA) testing protocol. Available at www.bcguidelines.ca. Accessed June 7, 2017. 
    30.Baumgartner KB et al. Am J  Respir Crit Care Med. 1997;155(1):242-248.
    31.Baumgartner KB et al. Am J Epidemiol. 2000;152(4):307-315.
    32.Taskar VS et al. Proc Am Thorac Soc. 2006;3:293-298.
    33.Selman M et al. Am J Respir Crit Care Med. 2012;186(4):314-324.
    34.Morell F. Lancet Respir Med. 2013;1(9):685-694.
    35.Camus P. The drug-induced respiratory disease website. Pneumotox website. 2012. Available at www.pneumotox.com. Accessed June 21, 2017.
    36.Schwaiblmair M et al. Open Respir Med J. 2012;6:63-74.
    37.Marshall RP et al. Thorax. 2000;55(2):143-146.
    38.Hodgson U et al. Thorax. 2002;57(4):338-342.
    39.Thomas AQ et al. Am J Respir Crit Care Med. 2002;165(9):1322-1328.
    40.van Moorsel CH et al. Am J Respir Crit Care Med. 2010;182(11):1419-1425.
    41.Wang Y et al. Am J Hum Genet. 2009;84(1):52-59.
    42.Seibold MA et al. N Engl J Med. 2011;364(16):1503-1512.