Idiopathic Interstitial Pneumonias – Insights in ILD

 

Idiopathic ILDs – Insights in ILD

Idiopathic ILD

Major IIPs
  • Chronic fibrosing
    • Idiopathic Pulmonary Fibrosis (IPF)
    • Nonspecific Interstitial Pneumonia (NSIP)
  • Smoking related
    • Respiratory Bronchiolitis Associated Interstitial Lung Disease (RB-ILD)
    • Desquamative Interstitial Pneumonia (DIP)
  • Acute/subacute
    • Cryptogenic Organizing Pneumonia (COP)
    • Acute Interstitial Pneumonia (AIP)
Rare IIPs
  • Lymphoid Interstitial Pneumonia (LIP)
  • Idiopathic Pleuroparenchymal Fibroelastosis (PPFE)
IIPs, idiopathic interstitial pneumonias; ILD, interstitial lung disease.1. Travis WD et al. Am J Respir Crit Care Med. 2013;188(6):733-748.

Idiopathic Interstitial Pneumonias Overview – Insights in ILD

  • IIPs are a class of ILDs of unknown etiology characterized by varying degrees of inflammation and fibrosis1
  • Clinical history, HRCT findings, and pathology results should be taken into consideration when diagnosing patients with IIPs2
HRCT, high-resolution computed tomography.
1. Lee J. Overview of Idiopathic Interstitial Pneumonias. Merck Manual Professional Version website. https://www.merckmanuals.com/professional/pulmonary-disorders/interstitial-lung-diseases/overview-of-idiopathic-interstitial-pneumonias. May 2018. Accessed August 2, 2018. 2. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304.
 

Idiopathic Pulmonary Fibrosis – Insights in ILD

 

Idiopathic Pulmonary Fibrosis Overview – Insights in ILD

  • Fibrosis is limited to the lung alveoli and interstitium1
  • IPF is a progressive, fatal lung disease of unknown etiology1
IPF, idiopathic pulmonary fibrosis.1. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824.

IPF Epidemiology and Risk Factors – Insights in ILD

  • Although IPF does not have a direct known cause, many environmental and genetic risk factors have been identified, including smoking, male sex, older age (>65), and mutations in genes associated with mucus clearance andinflammatory pathways1  
    • As many as 132,000 people in the United States have IPF1,2
  • Approximately 50,000 new cases are diagnosed annually1,2
    • IPFmakes up approximately 55%of IIPs3

1. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824. 2. U.S. Census Bureau, Population Division. Annual Estimate of the Population for the United States, Regions, States, and Puerto Rico: April 1, 2011. 3. European Respiratory Society. Interstitial Lung Diseases. In: J Gibson, R Loddenkemper, Y Sibille, B Lundbäck, editors. The European Lung White Book: Respiratory Health and Disease in Europe. 2nd Ed. Sheffield: Eur Respir Soc; 2013.

IPF Clinical Presentation – Insights in ILD

  • The most common symptoms of IPF are dyspnea and dry cough1,2
  • Patients may present with digital clubbing3-5
  • Crackles are another common sign of IPF1
    • In IPF, these crackles have a distinctive VelcroTM-like character6
  
1. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824. 2. van Manen MJG et al. Eur Respir Rev. 2016;25(141):278-286. 3. Bjoraker JA et al. Am J Respir Crit Care Med. 1998;157(1):199-203. 4. King TE et al. Am J Respir Crit Care Med. 2001;164(7):1171-1181. 5. Douglas WW et al. Am J Respir Crit Care Med. 2000;161(4 pt 1):1172-1178. 6. Cottin V et al. Eur Respir J. 2012;40(3):519-521.
 

IPF Diagnostic Tests – Insights in ILD

  • Detailed medical history
    • Past medical history1,2
    • Current and past chronic medications1,2
    • Social history1,2
    • Family history1-3
IPF is a diagnosis of exclusion, making a complete history essential to identifying potential causes of dyspnea and cough1
  • Serologic testing to exclude CTDs4
  • A common way to assess pulmonary function is by conducting the 6MWT1
  • Complementary ways to determine a patient’s pulmonary function include5:
    • FEV1
    • FVC
    • DLco
IPF shows a restrictive defect6,7

CTD, connective tissue disease; 6MWT, 6-minute walk test; FEV1, forced expiratory volume; FVC, forced vital capacity; DLCO, diffusing capacity of the lung for carbon monoxide.
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. Garcia-Sancho C et al. Respir Med. 2011;105(12):1902-1907. 4. Vij R et al. Chest. 2013;143(3):814-824. 5. Ley B et al. Am J Respir Crit Care Med. 2011;183(4):431-440.  6. Meltzer EB et al. Orphanet J Rare Dis. 2008;3:1-15. 7. Pellegrino R et al. Eur Respir J. 2005;26(5):948-968.

IPF Diagnostic Tests (Continued) – Insights in ILD

HRCT
  • UIP pattern1
    • Subpleural, basal predominance
    • Reticulation
    • Honeycombing with/without traction bronchiectasis
    • Absence of features inconsistent with UIP 
UIP, usual interstitial pneumonia.
1. Raghu G et al. Am J Respir Crit Care Med. 2011;183(6):788-824.
 

IPF Disease and Symptom Management – Insights in ILD

The following strategies are typically implemented to manage the disease in patients with IPF1,2:
 
Smoking cessation
Managing comorbidities
Pulmonary rehabilitation
Supplemental oxygen
FDA-approved pharmacologic therapies
Lung transplant

1. Lee JS et al. Curr Opin Pulm Med. 2011;17(5):348-354. 2. Raghu G et al. Respir Med. 2017;129:24-30.
 

Idiopathic Nonspecific Interstitial Pneumonia – Insights in ILD

 

Idiopathic NSIP Overview – Insights in ILD

NSIP pattern is associated with many nonneoplastic disorders such as1,2:
  • Connective tissue disorders
  • Drug-induced lung diseases
  • Viral infections
  • Prior acute lung injury
  • Recurrent organizing pneumonia
  • Hypersensitivity pneumonitis
  • Other rare diseases
A diagnosis of idiopathic NSIP requires exclusion of these other causes1,2

NSIP, nonspecific interstitial pneumonia.
1. Tomassetti S et al. Semin Respir Crit Care Med. 2016; 37(3):378-94. 2. Batra K et al. Hum Pathol. 2018;72:1-17.
 

Idiopathic NSIP Overview (Continued) – Insights in ILD

Idiopathic NSIP presents as 2 different forms1:
  • The fibrotic pattern is more commonly diagnosed
  • The cellular pattern is rare and has the potential for complete resolution with treatment
1. Batra K et al. Hum Pathol. 2018;72:1-17.

Idiopathic NSIP Epidemiology and Risk Factors – Insights in ILD

  • Primarily affects middle-aged women who werenever smokers1
  • The median age of onset is 52 years2
  • Prognosis for the majority of patients is good with 5- and 10-year survival rates of 82.3% and 73.2%, respectively1
    • NSIP makes up approximately 25% of IIPs3
 
1. Travis WD et al. Am J Respir Crit Care Med. 2008;177(12):1338-47. 2. Tomassetti S et al. Semin Respir Crit Care Med. 2016; 37(3):378-94. 3. European Respiratory Society. Interstitial Lung Diseases. In: J Gibson, R Loddenkemper, Y Sibille, B Lundbäck, editors. The European Lung White Book: Respiratory Health and Disease in Europe. 2nd Ed. Sheffield: Eur Respir Soc; 2013.

 
 
Middle Age

Idiopathic NSIP Clinical Presentation – Insights in ILD

  • Patients typically present with breathlessness and cough of usually 6 to 7 months duration1
  • Inspiratory crackles are common2
  • Hypoxia may be seen in patients with more advanced disease2
  • Some patients may experience systemic signs or symptoms2
Weight Loss (25%)
Fever (22%)
Arthralgias (14%)
Raynaud phenomenon (8%)
Myalgias (7%)
Skin rash (5%)
Arthritis (3%)

1. Travis WD et al. Am J Respir Crit Care Med. 2008;177(12):1338-47. 2. Tomassetti S et al. Semin Respir Crit Care Med. 2016; 37(3):378-94.

Idiopathic NSIP Diagnosis and Misdiagnosis – Insights in ILD

NSIP is similar in clinical, radiologic, and pathologic presentation to chronic organizing pneumonia, IPF, and RB-ILD1

RB-ILD, respiratory bronchiolitis associated interstitial lung disease
1. Travis WD et al. Am J Respir Crit Care Med. 2008;177(12):1338-47.

Idiopathic NSIP Diagnostic Tests – Insights in ILD

  • Pulmonary function tests1:
    • FVC
    • DLCO
Restrictive ventilatory patterns are observed on pulmonary function tests2
  • HRCT
    • Features: Ground-glass opacities, reticular opacities with lower lung zone predominance, micronodules, consolidation, minimal honeycombing2,3
      • A predominant finding of ground-glass abnormality is suggestive of cellular NSIP4
      • A predominant finding of reticulation in combination with ground glass opacity, traction bronchiectasis, and minimal honeycombing is indicative of fibrotic NSIP5
    • Distribution: Predominantly diffuse or subpleural,symmetric distribution2,3
1. Tomassetti S et al. Semin Respir Crit Care Med. 2016; 37(3):378-94. 2. Travis WD et al. Am J Respir Crit Care Med. 2008;177(12):1338-47. 3. Mueller-Mang C et al. Radiographics. 2007;27(3):595-615. 4. Batra K et al. Hum Pathol. 2018;72:1-17. 5. Johkoh T et al. Radiology. 2002;225(1):199-204.

Idiopathic NSIP Diagnostic Tests (Continued) – Insights in ILD

  • Surgical Lung Biopsy
    • Used when HRCT suggests NSIP as NSIP pattern overlaps with organizing pneumonia and desquamative interstitial pneumonia1
    • The key histopathologic feature of NSIP is the uniformity of interstitial involvement2
      • Pattern indicative of cellular NSIP shows mild to moderate interstitial chronic inflammation3
      • In cases of fibrosing NSIP, dense or loose interstitial fibrosis is observed3
  • Bronchoalveolar Lavage4
    • Microbiologic studies should be performed to exclude infections
    • Cellular analysis should be performed to exclude malignancy
    • A differential cell count: >15% lymphocytes correlates with increased likelihoodof NSIP5
 
1. Lynch DA et al. Radiology. 2005 ;236(1):10-21. 2. Travis WD et al. Am J Respir Crit Care Med. 2008;177(12):1338-47. 3. Mueller-Mang C et al. Radiographics. 2007;27(3):595-615. 4. Tomassetti S et al. Semin Respir Crit Care Med. 2016; 37(3):378-94. 5. Meyer KC et al. Am J Respir Crit Care Med. 2012;185(9):1004-14.

Idiopathic NSIP Diagnostic Process – Insights in ILD

  • When HRCT or biopsy is believed to show features of NSIP but there are incomplete data or the potential for an alternative diagnosis, the term NSIP pattern should be used1
  • A multidisciplinary discussion involving pulmonologists, radiologists, and pathologists is advised in cases where the clinical, radiologic, and pathologic features are not definite or probable for NSIP1
 
1. Travis WD et al. Am J Respir Crit Care Med. 2008;177(12):1338-47.

Idiopathic NSIP Disease and Symptom Management – Insights in ILD

  • Pulmonary function tests (FVC, DLCO, 6MWT) should be used throughout the disease course to evaluate1:
    • Disease progression
    • Response to treatment
    • Prognosis
  • Treatment1:
    • Steroids and immunosuppressives are often used to treat patients with NSIP although these treatments appear to be more effective in patients with cellular NSIP
    • Lung transplant, pulmonary rehabilitation, and oxygen therapy should be considered for patients with progressive disease1
 1. Tomassetti S et al. Semin Respir Crit Care Med. 2016; 37(3):378-94.

Respiratory Bronchiolitis - Associated Interstitial Lung Disease – Insightsin ILD

 

Respiratory Bronchiolitis ILD Overview – Insights in ILD

All current smokers present with histologic respiratory bronchiolitis, which may become extensive enough to result in development of an ILD termed RB-ILD1

Currently, RB-ILD has not been reported to progress to dense pulmonary fibrosis2

1. Travis WD et al. Am J Respir Crit Care Med. 2013;188(6):733-48. 2. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304.

Respiratory Bronchiolitis ILD Epidemiology and Risk Factors – Insights in ILD

  • The majority of patients are current or former smokers with more than 30 pack-years of cigarette smoking1-3
  • RB-ILD predominantly affects middle-aged males3
  • The incidence and prevalence of RB-ILD is not yet known4
    • RB-ILDmakes up approximately 10%of IIPs5

​​​​​​​1. Travis WD et al. Am J Respir Crit Care Med. 2013;188(6):733-48. 2. Margaritopoulos GA et al. Respirology. 2016;21(1):57-64. 3. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304. 4. Sieminska A et al. Orphanet J Rare Dis. 2014; 9:106. 5. European Respiratory Society. Interstitial Lung Diseases. In: J Gibson, R Loddenkemper, Y Sibille, B Lundbäck, editors. The European Lung White Book: Respiratory Health and Disease in Europe. 2nd Ed. Sheffield: Eur Respir Soc; 2013.

Respiratory Bronchiolitis ILD Clinical Presentation – Insights in ILD

  • Patients with RB-ILD are typically asymptomatic with some patients experiencing a subclinical decline in lung function1
  • In cases where patients are symptomatic, they typically present with mild dyspnea and cough2
  • Bibasilar end-inspiratory crackles are one of the most common signs of RB-ILD although they are not observed in all patients3
1. Margaritopoulos GA et al. Respirology. 2016;21(1):57-64. 2. Mueller-Mang C et al. Radiographics. 2007;27(3):595-615. 3. Sieminska A et al. Orphanet J Rare Dis. 2014; 9:106.

Respiratory Bronchiolitis ILD Diagnostic Tests – Insights in ILD

Pulmonary function tests
In patients with moderate symptoms there may be a mild to moderate reduction in DLCO1
For patients with more severe disease, features of both airway obstruction and restriction may be observed due to concomitant emphysema1
 
HRCT
Features: Ground-glass opacities and centrilobular nodules with bronchial wall thickening2,3
Distribution: Diffuse or upper lung predominance3
 
Bronchoalveolar lavage
Smoker’s macrophages and absence of lymphocytosis2

Surgical lung biopsy is not needed if HRCT and BAL criteria are met2
Pattern of bronchiocentric accumulation of macrophages containing brown particles with mild bronchiolar fibrosis3
​​​​​​​

There is histologic overlap between RB, DIP, bronchiolitis and NSIP with RB and DIP representing either end of the spectrum1

DIP, desquamative interstitial pneumonia; BAL, bronchoalveolar lavage; RB, respiratory bronchiolitis.
1. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304. 2. Travis WD et al. Am J Respir Crit Care Med. 2013;188(6):733-48. 3. Mueller-Mang C et al. Radiographics. 2007;27(3):595-615.

Respiratory Bronchiolitis ILD Diagnostic Tests (Continued) – Insights inILD

  • The most common findings on chest X-ray are thickening of the walls of central or peripheral bronchi and ground-glass opacity1
1. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304.
 

Respiratory Bronchiolitis ILD Disease & Symptom Management –Insights in ILD

  • Smoking cessation will typically prevent disease progression1
    • Many patients’ conditions improve after smoking cessation2
  • However, the respiratory bronchiolitis histologic pattern may persist in patients even after cessation of smoking3
    • 1/3 of patients still presented with RB-ILD even 5 years after smoking cessation
  • Patients are often treated with corticosteroids2
1. Travis WD et al. Am J Respir Crit Care Med. 2013;188(6):733-48. 2. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304. 3. Fraig M et al. Am J Surg Pathol. 2002;26(5):647-53.

Desquamative Interstitial Pneumonia – Insights in ILD

Desquamative Interstitial Pneumonia Overview – Insights in ILD

  • DIP is an IIP common in smokers and characterized by the accumulation of pigmented macrophages1,2
  • Prognosis is generally good with overall survival of at least 70% after10 years3,4
    • Follow-up HRCTs of patients receiving treatment typically show partial or complete resolution of areas of ground glass opacification3
    • Infrequently, progression to a reticular pattern on HRCT is observed3,4
 DIP, desquamative interstitial pneumonia
1. Godbert B et al. Eur Respir Rev. 2013;22(128):117-23. 2. Batra K et al. Hum Pathol. 2018;72:1-17. 3. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304. 4. Kawabata Y et al. Respirology. 2012;17(8):1214-21.
 

DIP Epidemiology and Risk Factors – Insights in ILD

  • Primarily affects smokers in their 50s and 60s1
  • More common in men than women1
  • In rare cases, DIP may occur in nonsmokers who have had exposure to environmental inhalation exposures1-3
    • Inorganic particles
    • Dust
    • Nylon filaments
DIP makes up approximately 5% of IIPs4

1. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304. 2. Godbert B et al. Eur Respir Rev. 2013;22(128):117-23. 3. Abraham JL et al. Chest. 1981;80(1 Suppl):67-70. 4. European Respiratory Society. Interstitial Lung Diseases. In: J Gibson, R Loddenkemper, Y Sibille, B Lundbäck, editors. The European Lung White Book: Respiratory Health and Disease in Europe. 2nd Ed. Sheffield: Eur Respir Soc; 2013.
 

 
50s & 60s

Desquamative Interstitial Pneumonia Clinical Presentation – Insights inILD

  • Gradual onset of dyspnea and dry cough over weeks or months1
  • Cyanosis is a common presenting symptom2
  • About ½ of patients with DIP will develop clubbing1
1. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304. 2. Godbert B et al. Eur Respir Rev. 2013;22(128):117-23.
 

Desquamative Interstitial Pneumonia Diagnostic Tests – Insights in ILD

  • Pulmonary function tests
    • DLCO is moderately decreased1,2
    • Normal lung volumes or a mild restrictive abnormality1
  • HRCT
    • Features: ground-glass opacities, irregular linear or reticular opacities, sometimes cysts3
    • Distribution: apicobasal gradient, peripheral predominance3
RB-ILD, acute or subacute hypersensitivity pneumonitis, sarcoidosis, and infections such as Pneumocystis carinii pneumonia may not be distinguishable from DIP on HRCT1

1. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304. 2. Ryu JH et al. Chest. 2005;127:178–184. 3. Mueller-Mang C et al. Radiographics. 2007;27(3):595-615.
 

Desquamative Interstitial Pneumonia Diagnostic Tests (Cont’d) – Insightsin ILD

  • Surgical lung biopsy should be used in certain cases1
    • Histopathology results featuring diffuse accumulation of macrophages in distal airspaces, mild interstitial fibrosis, mild chronic inflammation indicate a diagnosis of DIP2
  • Bronchoalveolar lavage findings are not usually very specific3
    • Features:
      • Increased number of alveolar macrophages
      • Large number of which have granules of smoker’s-pigment consisting of intracellular yellow, gold, brown, or black smoke particulates4
  • Chest X-ray is not sensitive enough for detection of DIP and appears normal in 3%-22% of biopsy-proven cases4
    • Features:
      • Widespread patchy ground glass opacification
      • Lower zone predilection
      • Sometimes a peripheral predominance
1. Lee J. Desquamative Interstitial Pneumonia. Merck Manual Professional Version website. https://www.merckmanuals.com/professional/pulmonary-disorders/interstitial-lung-diseases/desquamative-interstitial-pneumonia. May 2018. Accessed July 25, 2018. 2. Mueller-Mang C et al. Radiographics. 2007;27(3):595-615. 3. Godbert B et al. Eur Respir Rev.2013;22(128):117-23. 4. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304.

DIP Disease and Symptom Management – Insights in ILD

Smoking cessation is recommended in patients with DIP1
 
Corticosteroids are often used to treat patients with DIP1
 
Lung transplantation is recommended in severe cases2

1. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304. 2. Godbert B et al. Eur Respir Rev. 2013;22(128):117-23.
 

Cryptogenic Organizing Pneumonia – Insights in ILD

 

Cryptogenic Organizing Pneumonia Overview – Insights in ILD

  • COP is characterized by the observation of a pattern of organizing pneumonia with no cause or etiologic context1
  • Previously referred to as bronchiolitis obliterans organizing pneumonia or idiopathic BOOP2
  • A small proportion of patients will experience spontaneous resolution2
Few cases of COP progress to respiratory failure and death2 

COP, cryptogenic organizing pneumonia.
1. Cottin V et al. Semin Respir Crit Care Med. 2012;33(5):462-75. 2. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304.
 

Cryptogenic Organizing Pneumonia Overview (Continued) – Insights in ILD

  • Diagnosis is often delayed 6-12 months1
  • Patients typically present with symptoms of a lower respiratory tract infection and are often given multiple courses of antibiotics before they are diagnosed with COP2
COP is most commonly misdiagnosed as infectious pneumonia1

1. Cottin V et al. Semin Respir Crit Care Med. 2012;33(5):462-75. 2. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304. 

COP Epidemiology and Risk Factors – Insights in ILD

  • Affects men and women equally1
  • More common in nonsmokers1
  • Mean age of onset 55 years old1 
COP makes up approximately 3% of IIPs2

1. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304. 2. European Respiratory Society. Interstitial Lung Diseases. In: J Gibson, R Loddenkemper, Y Sibille, B Lundbäck, editors. The European Lung White Book: Respiratory Health and Disease in Europe. 2nd Ed. Sheffield: Eur Respir Soc; 2013.

Cryptogenic Organizing Pneumonia Clinical Presentation – Insights in ILD

  • Productive cough1
  • Progressive or mild dyspnea2
  • Other common symptoms1,2:
    • Anorexia
    • Weight loss
    • Sweats
    • Chills
    • Intermittent fever
    • Myalgia
1. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304. 2. Cottin V et al. Semin Respir Crit Care Med. 2012;33(5):462-75.

Cryptogenic Organizing Pneumonia Clinical Presentation (Cont’d) –Insights in ILD

  • Crackles may be localized or widespread throughout the lungs1,2
1. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304. 2. Cottin V et al. Semin Respir Crit Care Med. 2012;33(5):462-75.
 

Cryptogenic Organizing Pneumonia Diagnostic Tests – Insights in ILD

Clinical history1
  • Infections 
  • Drugs 
  • Comorbid diseases 
    • CTD
    • Cancer
    • Thoracic radiotherapy for breast cancer
    • Exposure to drugs
    • Inflammatory bowel disease
    • Aspiration
    • Common variable immune deficiency (less common)
    • Toxic exposures (less common)

CTD, connective tissue disease.
1. Cottin V et al. Semin Respir Crit Care Med. 2012;33(5):462-75.
 

Cryptogenic Organizing Pneumonia Diagnostic Tests (Cont’d) – Insightsin ILD

  • CBC1
    • Raised erythrocyte sedimentation rate
    • Elevated C-reactive protein
    • Peripheral blood neutrophilia
  • Pulmonary function tests1
    • Lung volumes are normal in about 75% of patients
    • Restrictive pattern (mild to moderate)
    • Reduced DLCO
    • Mild resting hypoxemia
CBC, complete blood count.
1. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304.

Cryptogenic Organizing Pneumonia Diagnostic Tests (Cont’d) 1 – Insightsin ILD

  • HRCT1
    • Features: Airspace consolidation, mild bronchial dilatation, ground-glass opacities, large nodules are rare
    • Distribution: Patchy, peripheral or peribronchial, basal predominance, sometimes sparing of subpleural space, migration tendency
  • Bronchoalveolar lavage2
    • Increased number and proportion of lymphocytes
    • Decreased ratio of CD4+ to CD8+ cells
    • Increased number of neutrophils and eosinophils
1. Mueller-Mang C et al. Radiographics. 2007;27(3):595-615. 2. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304.

Cryptogenic Organizing Pneumonia Diagnostic Tests (Cont’d) 2 – Insightsin ILD

  • Surgical lung biopsy is not always necessary1
    • Only typical cases at imaging with compatible clinical and BAL features should be treated without biopsy1
    • Patchy distribution of intraluminal organizing fibrosis in distal airspaces, preservation of lung architecture, uniform temporal appearance2
  • Chest X-ray
    • Bilateral or unilateral areas of consolidation with patchy distribution3
 
1. Cottin V et al. Semin Respir Crit Care Med. 2012;33(5):462-75. 2. Mueller-Mang C et al. Radiographics. 2007;27(3):595-615. 3. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304.

COP Disease and Symptom Management – Insights in ILD

  • Oral corticosteroids are commonly used to treat patients with COP1
  • Immunosuppressives may be used in patients who experience relapse2
1. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304. 2. Cottin V et al. Semin Respir Crit Care Med. 2012;33(5):462-75.

Acute Interstitial Pneumonia – Insights in ILD

  • AIP is a rapidly progressive interstitial pneumonia with pathology indistinguishable from the pattern found in acute respiratorydistress syndrome1
  • Most patients die within 3 months of diagnosis2
    • Prognosis is poor with mortality rates of 50% or more1
  • Survivors may experience recurrence and chronic progressive ILD1​​​​​​​
AIP, acute interstitial pneumonia. 1. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304. 2. Bouros D et al. Eur Respir J. 2000;15(2):412-8.

Acute Interstitial Pneumonia Overview – Insights in ILD

  • Mean age of onset is 50 years old1
  • No association with smoking1
  • No sex predominance1
AIP makes up approximately 1% of IIPs2

1. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304. 2. European Respiratory Society. Interstitial Lung Diseases. In: J Gibson, R Loddenkemper, Y Sibille, B Lundbäck, editors. The European Lung White Book: Respiratory Health and Disease in Europe. 2nd Ed. Sheffield: Eur Respir Soc; 2013.

AIP Epidemiology and Risk Factors – Insights in ILD

Prominent diffuse crackles1
Severe exertional dyspnea that develops over a short period of time1

Median time from first symptom to presentation is 3 weeks 
 
Fever, cough, shortness of breath that increase in severity over 7-14 days, progressing to respiratory failure2
 
1. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304. 2. Lee J. Acute Interstitial Pneumonia. Merck Manual Professional Version website. https://www.merckmanuals.com/professional/pulmonary-disorders/interstitial-lung-diseases/acute-interstitial-pneumonia. May 2018. Accessed July 27, 2018.

Acute Interstitial Pneumonia Clinical Presentation – Insights in ILD

  • Pulmonary function tests1
    • Restrictive pattern
    • Reduced DLCO
  • HRCT
    • Features: Exudative phase shows ground-glass opacities, airspace consolidation; organizing phase shows bronchial dilatation, architectural distortion2
    • Distribution: Lower lung predominance, symmetric, bilateral2
1. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304. 2. Mueller-Mang C et al. Radiographics. 2007;27(3):595-615.
 

Acute Interstitial Pneumonia Diagnostic Tests – Insights in ILD

  • Surgical lung biopsy is typically used to diagnose AIP1
    • Histopathology pattern shows diffuse alveolar damage2
      • Exudative early phase shows hyaline membranes and diffuse alveolar infiltration by lymphocytes2
      • Proliferating phase shows alveolar wall thickening due to fibrosis and pneumocyte hyperplasia2
  • Chest X-ray3
    • Most common findings on chest X-ray are bilateral airspace opacification with air bronchograms
    • The distribution is often patchy, with sparing of the costophrenic angles
1. Lee J. Acute Interstitial Pneumonia. Merck Manual Professional Version website. https://www.merckmanuals.com/professional/pulmonary-disorders/interstitial-lung-diseases/acute-interstitial-pneumonia. May 2018. Accessed July 27, 2018. 2. Mueller-Mang C et al. Radiographics. 2007;27(3):595-615. 3. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304.

Acute Interstitial Pneumonia Diagnostic Tests (Continued) – Insights inILD

  • Mechanical ventilation is usually required1
  • Patients with respiratory failure may not respond tosupplemental oxygen1
  • Corticosteroid therapy is used although its effectiveness has not been established2
No proven treatment method exists for patients with AIP1

1. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304. 2. Lee J. Acute Interstitial Pneumonia. Merck Manual Professional Version website. https://www.merckmanuals.com/professional/pulmonary-disorders/interstitial-lung-diseases/acute-interstitial-pneumonia. May 2018. Accessed July 27, 2018.

AIP Disease and Symptom Management – Insights in ILD

 

Idiopathic Lymphoid Interstitial Pneumonia – Insights in ILD

  • Idiopathic LIP is a lymphocytic infiltration of the alveolar interstitium and airspaces with no known cause1
  • Classified as a rare interstitial pneumonia2
 Patients with LIP rarely experience progression of the disease to pulmonary fibrosis3
 
LIP, lymphoid interstitial pneumonia.
1. Lee J. Lymphocytic Interstitial Pneumonia. Merck Manual Professional Version website. https://www.merckmanuals.com/professional/pulmonary-disorders/interstitial-lung-diseases/lymphocytic-interstitial-pneumonia. May 2018. Accessed July 31, 2018. 2. Travis WD et al. Am J Respir Crit Care Med. 2013;188(6):733-748. 3. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304.
 

Idiopathic LIP Overview – Insights in ILD

  • More common in women1,2
  • Mostly diagnosed in individuals in their 50s1
LIP makes up approximately 1% of IIPs3

1. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304. 2. Cha SI et al. Eur Respir J. 2006;28(2):364-9. 3. European Respiratory Society. Interstitial Lung Diseases. In: J Gibson, R Loddenkemper, Y Sibille, B Lundbäck, editors. The European Lung White Book: Respiratory Health and Disease in Europe. 2nd Ed. Sheffield: Eur Respir Soc; 2013.

Idiopathic LIP Epidemiology and Risk Factors – Insights in ILD

  • Patients present with gradually increasing cough and dyspnea over 3 or more years1
  • Patients occasionally present with1:
    • Joint Pain
    • Fever
    • Chest Pain
    • Weight Loss
  • Crackles may be detected as the disease progresses1
 
1. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304.

Idiopathic LIP Clinical Presentation – Insights in ILD

Thorough clinical history to exclude known causes such as1:
Rheumatoid arthritis
Sjögren’s syndrome
Hashimoto’s disease
Pernicious anemia
Chronic active hepatitis
Systemic lupus erythematosus
Autoimmune hemolytic anemia
Primary biliary cirrhosis
Myasthenia gravis
Hypogammaglobulinemia
Human immunodeficiency virus

Routine laboratory tests and serum protein electrophoresis2:
Polyclonal gammopathy
Hypogammaglobulinemia

1. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304. 2. Lee J. Lymphocytic Interstitial Pneumonia. Merck Manual Professional Version website. https://www.merckmanuals.com/professional/pulmonary-disorders/interstitial-lung-diseases/lymphocytic-interstitial-pneumonia. May 2018. Accessed July 31, 2018.

Idiopathic LIP Diagnostic Tests – Insights in ILD

Pulmonary function tests1
  • Reduced FVC and FEV1
  • Elevated FEV1/FVC
  • Decreased DLCO 
HRCT2
  • Features: Ground-glass opacities, perivascular cysts, septal thickening, centrilobular nodules
  • Distribution: Basilar predominance or diffuse
Lung biopsy is required for diagnosis in adults3
  • Diffuse infiltration of alveolar septa by lymphoid cells, lymphoid hyperplasia frequent2
  • Histopathology pattern of LIP is similar to diffuse lymphoid hyperplasia, nodular lymphoid hyperplasia, lymphoma and the patterns of OP, NSIP, hypersensitivity pneumonitis, and UIP4

OP, organizing pneumonia.
1. Cha SI et al. Eur Respir J. 2006;28(2):364-9. 2. Mueller-Mang C et al. Radiographics. 2007;27(3):595-615. 3. Lee J. Lymphocytic Interstitial Pneumonia. Merck Manual Professional Version website. https://www.merckmanuals.com/professional/pulmonary-disorders/interstitial-lung-diseases/lymphocytic-interstitial-pneumonia. May 2018. Accessed July 31, 2018. 4. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304.

Idiopathic LIP Diagnostic Tests (Continued) – Insights in ILD

  • Bronchoalveolar lavage should be performed to rule out infection1
    • Fluid reveals many lymphocytes but immunophenotyping should not reveal any clonality2
  • 2 patterns on chest X-ray have been described2
    • Basilar with an alveolar component
    • Diffuse with associated honeycombing
 
1. Lee J. Lymphocytic Interstitial Pneumonia. Merck Manual Professional Version website. https://www.merckmanuals.com/professional/pulmonary-disorders/interstitial-lung-diseases/lymphocytic-interstitial-pneumonia. May 2018. Accessed July 31, 2018. 2. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304.
 

Idiopathic LIP Diagnostic Tests (Continued) 1 – Insights in ILD

  • Corticosteroids and cytotoxic drugs are used to treat patients with idiopathic LIP1,2
 
1. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304. 2. Lee J. Lymphocytic Interstitial Pneumonia. Merck Manual Professional Version website. https://www.merckmanuals.com/professional/pulmonary-disorders/interstitial-lung-diseases/lymphocytic-interstitial-pneumonia. May 2018. Accessed July 31, 2018.
 

Idiopathic LIP Disease and Symptom Management – Insights in ILD

 

Idiopathic Pleuroparenchymal Fibroelastosis – Insights in ILD

  • Idiopathic PPFE is a rare and relatively new condition that consists of fibrosis of the pleura and subpleural lung parenchyma, predominantly in the upper lobes1
60% experience disease progression1
40% die from PPFE1

PPFE, pleuroparenchymal fibroelastosis.
1. Travis WD et al. Am J Respir Crit Care Med. 2013;188(6):733-748.

Idiopathic Pleuroparenchymal Fibroelastosis Overview – Insights in ILD

  • Rare disease with only 100+ cases reported in the literature to date1
  • Affects both men and women equally2
  • 57 years2 - Median age of onset

1. Bonifazi M et al. Curr Pulmonol Rep. 2017;6(1):9-15. 2. Travis WD et al. Am J Respir Crit Care Med. 2013;188(6):733-748.

Idiopathic PPFE Epidemiology and Risk Factors – Insights in ILD

  • Risk factors:
    • Lung, bone marrow, and hematopoietic cell transplantations1,2
    • Chemotherapy2
    • Occupational exposures such as aluminosilicate dust3
    • History of recurrent lower respiratory tract infections4
    • Genetics/familial history5
1. Mariani F et al. Diagn Interv Radiol. 2016;22(5):400-6. 2. Beynat-Mouterde C et al. Eur Respir J. 2014;44(2):523-7. 3. Huang Z et al. Int J Clin Exp Pathol. 2015;8(7):8676-9. 4. Reddy TL et al. Eur Respir J. 2012;40(2):377-85. 5. Azoulay E et al. Eur Respir J. 1999;14(4):971-3.
 

Idiopathic PPFE Epidemiology and Risk Factors (Continued) – Insights inILD

  • The most common symptoms of PPFE are:
    • Dyspnea1
    • Nonproductive cough1
    • Weight loss1
    • Pneumothorax1,2
    • Chest pain3
    • Thoracic cage deformity1
  • Crackles are occasionally audible3
1. Portillo K et al. Case Rep Pulmonol. 2015;2015:810515. 2. Travis WD et al. Am J Respir Crit Care Med. 2013;188(6):733-748. 3. Watanabe K et al. Curr Respir Med Rev. 2013;9:299-237.
 

Idiopathic PPFE Clinical Presentation – Insights in ILD

Pulmonary function tests1
  • Decreased FVC
  • Increased FEV1/FVC
  • Decreased TLC
  • Increased RV/TLC
  • Decreased DLCO
  • Normal or minimally decreased DLCO/VA
 
HRCT2
  • Dense subpleural consolidation with traction bronchiectasis, architectural distortion, and upper lobe volume loss
Surgical lung biopsy is required to confirm the diagnosis3
  • Intra-alveolar fibrosis with prominent elastosis of the alveolar walls and dense fibrous thickening of the visceral pleura
RV, residual volume; TLC, total lung capacity; VA, alveolar volume.
1. Watanabe K et al. Curr Respir Med Rev. 2013;9:299-237. 2. Travis WD et al. Am J Respir Crit Care Med. 2013;188(6):733-748. 3. Lee J. Idiopathic Pleuroparenchymal Fibroelastosis. Merck Manual Professional Version website. https://www.merckmanuals.com/professional/pulmonary-disorders/interstitial-lung-diseases/idiopathic-pleuroparenchymal-fibroelastosis. May 2018. Accessed August 1, 2018.
 

Idiopathic PPFE Diagnostic Tests – Insights in ILD

Chest X-ray1
  • Abnormally narrowed anterior-posterior thoracic dimension (flattened thoracic cage)
  • Elevated hilar opacities
  • Reticular and nodular opacities in the bilateral upper lung fields
  • Fibrocystic opacities in the upper lung fields and occasional reticular opacities in the lower lung fields in the advanced stage

Serum tests1
  • KL-6 levels that are normal or around the upper limit of normal
  • Elevated Surfactant protein D
  • Autoantibodies may be elevated
KL-6, Krebs von den Lungen-6.
1. Watanabe K et al. Curr Respir Med Rev. 2013;9:299-237.
 

Idiopathic PPFE Diagnostic Tests (Continued) – Insights in ILD

  • Corticosteroids are typically used to treat patients with PPFE but have no proven effectiveness1,2
1. Lee J. Idiopathic Pleuroparenchymal Fibroelastosis. Merck Manual Professional Version website. https://www.merckmanuals.com/professional/pulmonary-disorders/interstitial-lung-diseases/idiopathic-pleuroparenchymal-fibroelastosis. May 2018. Accessed August 1, 2018. 2. Watanabe K et al. Curr Respir Med Rev. 2013;9:229-237.
 

Idiopathic PPFE Disease and Symptom Management – Insights in ILD

 

Unclassifiable Interstitial Pneumonia – Insights in ILD

  • Even after extensive clinical, radiologic, and/or pathologic examination physicians may still be unable to classify a patient’s IIP1
  • In these cases, the pulmonologist should determine the best course of treatment based on the most probable diagnosis after a detailed discussion with the pathologist and radiologist1
This category designation should not be used for cases in which the distinction between the UIP and fibrosing NSIP patterns is difficult1

1. American Thoracic Society. Am J Respir Crit Care Med. 2002;165(2):277-304.

Unclassifiable Interstitial Pneumonia Overview – Insights in ILD

Unclassifiable Interstitial Pneumonia Overview (Continued) – Insights inILD

5 Main Reasons for an Unclassifiable IIP Diagnosis – Insights in ILD

Unclassifiable IIP Survival and Mortality – Insights in ILD

Unclassifiable IIP Treatment Options – Insights in ILD