Interstitial Lung Disease

 

Interstitial Lung Diseases Are a Diverse Group of Conditions That Cause Lung Fibrosis1

150+ ILDs

Many ILDs share similar symptoms, physiology, and radiologic findings1

ILD, interstitial lung disease.
1. Raghu G et al. Clin Chest Med. 2004;25(3):409-419.

ILDs Are Often Characterized by Dyspnea and Cough1

Signs and symptoms shared by most ILDs include2-6:
  • Dyspnea
  • Cough
  • Fatigue
  • Restrictive pattern on PFTsa
  • Diffuse lung infiltration on chest imaging
  
aPatients can have other pathologies that could result in mixed or sometimes pure obstructive patterns
PFT, pulmonary function test
1. Raghu G et al. Clin Chest Med 2004;25(3):409-419. 2. Raghu G et al. Am J Respir Crit Care Med 2011;183(6):788-824. 3. Van Manen MJG et al. Eur Respir Rev. 2016;25:278-286. 4. European Respiratory Society. Interstitial Lung Diseases in European Lung White Book. 256-269. 5. Cosgrove G et al.
BMC Pulm Med 2018; 18:9. 6. Nathan S et al. Paed Respir Rev. 2015;16(4):219-224.

Signs and Symptoms of ILDs may Be Mistaken for More Common Disorders1,2

ILDs may be mistaken for more common disorders, such as1,2:
 
Pulmonary
Bronchitis
Pneumonia
COPD
Asthma

Cardiac
CHF
Cardiac Ischemia

Psychogenic Conditions
 

CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease.
1. Karnani NG et al. Am Fam Physician. 2005;71(8):1529-1537. 2. Cosgrove G et al. BMC Pulm Med 2018; 18:9.

ILD Misdiagnosis Affects Patient Care as Well as Qualityof Life

In one study of patients with ILD, 55% of respondents had at least 1 misdiagnosis and 38% had 2 or more misdiagnoses

75% consulted 3 or more physicians
  • 68% of respondents stated that consulting a specialist with expertise in ILD was the most important factor in obtaining an accurate diagnosis

34% had a delay of 2 or more years in diagnosis
  • Misdiagnosis affected amount of time spent with friends and family, and some patients reported that it influenced their decision to retire or apply for disability

1. Cosgrove G et al. BMC Pulm Med. 2018; 18:9.

ILDs can Result From Acute or Chronic Processes

  • Some ILDs are associated with infection, exposure to dust or other particles, or an underlying genetic predisposition1
  • The cause may also be unknown (idiopathic interstitial pneumonias)1
Used with permission from the American Thoracic Society.  http://www.thoracic.org/patients/patient-resources/resources/idiopathic-pulmonary-fibrosis.pdf
1. Raghu G et al. Clin Chest Med. 2004;25(3):409-419.

ILDs Are Classified by the Originating Factor1

ILDa
Exposure-related
Systemic rheumatic disease-related*
Idiopathic
Sarcoidosis
Other

ILDs often share dyspnea and cough as presenting symptoms, but the underlying associated disease will also produce additional signs and symptoms2

a
Adapted from Ryerson et al. 2013.
*Systemic rheumatic disease is also called connective tissue disease and collagen-vascular disease.
1. Ryerson CJ et al. Curr Opin Pulm Med. 2013;19(5):453-459. 2. Raghu G et al. Clin Chest Med. 2004;25(3):409-419.
 

Progression and Survival Varies Based on the Type of ILD

  • Many ILDs have high rates of morbidity and mortality1
  • ILDs are commonly observed in patients of all ages but more frequently affect adults1
  • Most unretired patients with ILD are unable to work due to breathlessness upon exertion2
  • Patients with occupational or exposure-related ILD should avoid further exposure and transfer to another job2
1. Nathan S et al. Paed Respir Rev. 2015;16(4):219-224. 2. Eur Respir Society White Book ILD

Evaluating Patients for Potential ILD

 

A Checklist for Evaluating a Patient With Dyspnea And Dry Cough for Potential ILD

  • Comprehensive patient history
  • Comprehensive physical exam
  • Pulmonary function testing
  • Laboratory analyses
  • Imaging
  • Other modalities (as indicated)
 
 
 
 
 
 
 
 
 
 
 
 
  1. Raghu G et al. Clin Chest Med. 2004;25(3):409-419.

A Comprehensive History Helps Narrow the List of Potential ILDs

Past Medical History1,2
  • Gastroesophageal reflux disease
  • Cancer, chemotherapy, and/or radiation therapy
  • Cardiac arrhythmias and amiodarone use
  • Prostate, urinary, kidney infections, and nitrofurantoin use

1. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824. 2. Lederer DJ. http://www.pfdoc.org/2014/07/a-pulmonary-fibrosis-primer-for-doctors.html. Accessed December 5, 2017. 3. Schwaiblmair M et al. Open Respir Med J. 2012;6:63-74. 4. Camus P. The drug-induced respiratory disease website. 2012. Pneumotox website. www.pneumotox.com. Accessed December 12, 2017. 5. Garcia-Sancho C et al. Respir Med. 2011;105(12):1902-1907.

 

A Comprehensive History Helps Narrow the List of Potential ILDs

Current and Past Chronic Medications3,4
  • Cancer, chemotherapy, and/or radiation therapy
  • Amiodarone use
  • Nitrofurantoin use

1. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824. 2. Lederer DJ. http://www.pfdoc.org/2014/07/a-pulmonary-fibrosis-primer-for-doctors.html. Accessed December 5, 2017. 3. Schwaiblmair M et al. Open Respir Med J. 2012;6:63-74. 4. Camus P. The drug-induced respiratory disease website. 2012. Pneumotox website. www.pneumotox.com. Accessed December 12, 2017. 5. Garcia-Sancho C et al. Respir Med. 2011;105(12):1902-1907

A Comprehensive History Helps Narrow the List of Potential ILDs

Exposure History1
  • Tobacco use
  • Drug use
  • Occupational
  • Environmental
  • Avocational
1. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824. 2. Lederer DJ. http://www.pfdoc.org/2014/07/a-pulmonary-fibrosis-primer-for-doctors.html. Accessed December 5, 2017. 3. Schwaiblmair M et al. Open Respir Med J. 2012;6:63-74. 4. Camus P. The drug-induced respiratory disease website. 2012. Pneumotox website. www.pneumotox.com. Accessed December 12, 2017. 5. Garcia-Sancho C et al. Respir Med. 2011;105(12):1902-1907

A Comprehensive History Helps Narrow the List of Potential ILDs

Family History1-3
  • Pulmonary fibrosis
  • ILD
  • Sarcoidosis
  • Autoimmune disease
  • Oxygen use
1. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824. 2. Lederer DJ. http://www.pfdoc.org/2014/07/a-pulmonary-fibrosis-primer-for-doctors.html. Accessed December 5, 2017. 3. Schwaiblmair M et al. Open Respir Med J. 2012;6:63-74. 4. Camus P. The drug-induced respiratory disease website. 2012. Pneumotox website. www.pneumotox.com. Accessed December 12, 2017. 5. Garcia-Sancho C et al. Respir Med. 2011;105(12):1902-1907

Auscultation Primer

  • Both anterior and posterior auscultation are necessary for detecting sounds of ILDs, particularly posterior basilar auscultation1,2
  • Patients may exhibit signs of ILD with concomitant sounds of other pulmonary complications (eg, wheeze)2
  • Careful auscultation in areas 6 and 7 should be performed when ILD is suspected1
    • Auscultating areas 4 and 5 (anterior) can be more difficult to access on women, but they are also important to examine. These areas may be more accessible when a patient is lying down

1. Lederer DJ. http://www.pfdoc.org/2014/07/a-pulmonary-fibrosis-primer-for-doctors.html. Accessed December 5, 2017.
2. Sarkar M et al. Ann Thorac Med. 2015;10(3):158-68.
 
 
Posterior
Anterior
1
2
3
4
5
6
7
2
3
4
5
6
7
0
1

Specific Sounds and Their Timing Can Help Narrow Down Possible ILDs

Crackles
  • Many ILDs exhibit fine, bibasilar crackles1,2
  • However, crackles are not specific to ILDs. The timing and location of the crackles can vary, which further distinguishes the specific cause, such as COPD, pneumonia, asbestosis, chronic bronchitis, and pulmonary edema secondary to heart failure1
  • Crackles may occur alongside other breath sounds, providing further clues to the potential cause(s) of dyspnea and/or cough1,3,4
 
1. Sarkar M et al. Ann Thorac Med. 2015;10(3):158-168.  2.Cottin V et al. Eur Respir J. 2012;40(3):519-521. 3.Cottin V et al. Eur Respir J. 2005;26:586-593. 4. Castelino FV et al. Arthr Res Ther. 2010;12:213.

Specific Sounds and Their Timing Can Help Narrow Down Possible ILDs

Wheezes
Squeaks
Pops
Rhonchi
  • Sounds heard at initial inspiration and those heard primarily at the tops of the lungs should prompt investigation of causes other than ILDs, although these can also be characteristic of some forms of ILD1,2
  • Thorough auscultation of all regions is the best way to ensure that the signs of all potential explanations of dyspnea and/or cough are explored2

1. 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. 2. Sarkar M et al. Ann Thorac Med 2015;10(3):158-168.17

 

Patients Reporting Dyspnea Should Undergo Complete Pulmonary Function Tests1,2

  • PFTs allow the physician to3:
    • Evaluate lung function
    • Differentiate amon pulmonary disorders
    • Guide initial management strategies
  • Pulmonary function can be assessed using spirometry parameters such as1,4,5:
    • Lung volumes (FEV1, FVC)
    • Gas exchange (DLCO)
    • Dyspnea on exertion (6MWT)
    • A quicker way to assess dyspnea on exertion is to use the hallway or staircase
6MWT, 6-minute walk test; DLco,diffusing capacity of the lungs for carbon monoxide; FEV1,forced expiratory volume in 1 minute; FVC, forced vital capacity.
1. Lederer DJ. http://www.pfdoc.org/2014/07/a-pulmonary-fibrosis-primer-for-doctors.html. Accessed November 17,2017. 2. Meyer KC. Trans Respir Med. 2014;2:4. 3. Ranu H et al. Ulster Med J. 2011;80(2):84-90. 4. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824. 5. Ley B et al. Am J Respir Crit Care Med. 2011;183(4):431-440.

PFTs Help Determine the Type of Respiratory Defect Present1

Restrictive defect2
  • TLC is low
  • Low FVC
  • Higher FEV1/FVC ratio
  • Flows are higher than expected at a given lung volume
Obstructive defect2
  • TLC is normal
  • Normal FVC
  • Lower FEV1
  • Lower FEV1/FVC ratio
  • Flows are lower than expected over the entire volume range
Restrictive defects are common in ILDs1

Used with permission from Pellegrino R et al. Eur Respir J. 2005;26(5):948-968.
TLC, total lung capacity.
1. Ranu H et al. Ulster Med J. 2011;80(2):84-90. 2. Pellegrino R et al. Eur Respir J. 2005;26(5):948-968.

PFT Results Can Show Signs of Restrictive, Obstructive, or Mixed Disease1,2

FVC
FEV1 
FEV1/FVC 
DLco
TLC  
 
Obtaining complete PFTs is important because it allows determination of the nature of the respiratory defect1
 
1. Ranu H et al. Ulster Med J. 2011;80(2):84-90. 2. Lin H et al. J Thorac Dis. 2015;7(4):767-779.
 

Other Investigations for Evaluating Potential ILDs1-3

  • Laboratory workups
  • Chest X-ray
  • HRCT
  • Lung biopsy
  • BAL
BAL, bronchoalveolar lavage; HRCT, high resolution computed tomography.
1. Jo HE et al. Respirology. 2016;21(8):1438-1444. 2. Vij R et al. Chest. 2013;143(3):814-824. 3. Meyer KC et al. Eur Respir J. 2011;38:761-769.

Laboratory Workup

  • Basic blood tests (eg, CBC) are generally a first step in evaluating a patient, although many ILDs will not have specific abnormalities1
  • Some ILDs – particularly those associated with systemic rheumatic diseasesa – will often exhibit characteristic antibody signatures2
aSystemic rheumatic diseases have also been called connective tissue disease or collagen-vascular diseases.
CBC, complete blood count. 
1. Bradley B et al. Thorax. 2008; 63(suppl V):v1-v58. 2. Vij R et al. Chest. 2013;143(3):814-824.

Chest X-rays Are Important to Rule Out Other Possible Causes of Shortness of Breath

  • Chest X-rays cannot solely diagnose most ILDs, but they can help rule out other causes of dyspnea, including heart disease, pneumonia, collapsed lung, emphysema, and lung cancer1,2
  • When possible, previous chest X-rays should be included in the evaluation to determine whether the disease process is acute or chronic3
If an X-ray report states ILD, interstitial findings, or reticulation, the patient should be referred to a pulmonologist for an HRCT scan and further workup3

1. National Heart, Lung, and Blood Institute. Chest X Ray.  http://www.nhlbi.nih.gov/health/health-topics/topics/cxray/whoneeds. Accessed December 11, 2017. 2. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824. 3. Meyer KC. Trans Respir Med. 2014;2:4.

HRCTs Are an Essential Piece of Diagnosing Many ILDs

  • HRCT creates high-resolution stacked X-ray slices to visualize internal organs1,2
  • HRCT allows physicians to3,4:
    • Differentiate features that help distinguish among various ILDs
    • Assess progression of disease and to exclude concomitant processes such as emphysema, edema, or infection
 1. FDA Medical X ray Imaging. http://www.fda.gov/RadiationEmittingProducts/RadiationEmittingProductsandProcedures/
MedicalImaging /MedicalX-rays/ucm115318.htm. Accessed December 11, 2017. 2. Verschakelen JA. Curr Opin Pulm Med. 2010;16(5):503-510.
3. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824.  4. Suh RD et al. Semin Respir Crit Care Med. 2006;27(6):623-633.

Patients With Dyspnea and/or Cough Should Have an HRCT to Look for Signs of ILD Because Chest X-rays May Appear Normal

PLACEHOLDER - Faculty to provide image set of X-ray and HRCT
 
1. Walsh SL et al. Semin Respir Crit Care Med. 2014;35(1):129-144.

Lung Biopsy Can Add Additional Information for Making an Accurate Diagnosis

  • Depending on the specific ILD suspected and the outcome of other evaluations, such as serologies and/or HRCT, lung biopsy may be recommended to accurately diagnose the patient’s condition1,2
  • Types of lung biopsy procedures3,4:
    • Open lung biopsy
    • Video-assisted thoracoscopic surgery
    • Cryobiopsy
Patients with suspected acute exacerbations of ILD should not be referred for lung biopsy due to higher risk of mortality1,5
 
1. Cottin V. Eur Respir J. 2016;48(5):1274-1277. 2. Lynch DA et al. Lancet Respir Med. 2018;6(20:138-153. 3. Tomassetti S et al. Am J Respir Crit Care Med. 2016;193(7):745-752. 4. Colby TV et al. Arch Pathol Lab Med. 2016;141(7):891-900. 5. Hutchinson JP et al. Am J Respir Crit Care Med. 2016;193(10):1161-1167

Bronchoalveolar Lavage May Provide Information That Can Reduce the Need for Lung Biopsy1

  • Performing BAL can rule out opportunistic infections and is useful in diagnosing hypersensitivity pneumonitis and sarcoidosis1
  • However, BAL results are generally nonspecific (consistent with or suggestive of a given condition) rather than pathognomonic for ILD1
~500%
The amount smoking increases cell count in BAL2,3

1. Meyer KC et al. Eur Respir J. 2011;38:761-769. 2. Karimi R et al. PLoS One. 2012;7(3):e34232. 3. BAL Cooperative Group Steering Committee. Am Rev Respir Dis. 1990;141(5 Pt 2):S169-S202.
 

Diagnosing ILDs Involves a Diverse Team of HCPs1,2

  • PCPs are often the first ones to recognize the initial signs of ILD and/or diseases that have ILD manifestations1
  • Referral to a pulmonologist, rheumatologist, or other specialist may be required, depending on the presenting symptoms1,2
  • Once pulmonary symptoms occur, patients should be evaluated and potentially referred to an ILD Center of Excellence1
 
PCP, primary care physician.
1. Cosgrove G et al. BMC Pulm Med. 2018; 18:9. 2. Lynch DA et al. Lancet Respir Med. 2018;6(20:138-153.

Early Referral to an ILD Center Can Improve Time to Diagnosis

  • Multidisciplinary discussions are recommended for diagnosing ILDs1-3
  • ILD centers have the resources and experience to manage a multidisciplinary approach to diagnosing ILDs2,3
 
MDD, multidisciplinary discussion
1. Cosgrove G et al. BMC Pulm Med. 2018; 18:9. 2. Flaherty K et al. Am J Respir Crit Care Med. 2007;175(10):1054-1060. 3. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824. 4. Lynch DA et al. Lancet Respir Med. 2018;6(20:138-153.