Idiopathic Interstitial Pneumonia
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Transcript of Idiopathic Interstitial Pneumonia
Idiopathic Interstitial Pneumonia
Trying to make sense of the letters
Michelle Thompson, MS4February 2006
Idiopathic Interstitial Pneumonias (IIP’s)
Group of uncommon parenchymal lung diseases
Similar pattern of lung injury to those seen in collagen vascular disease, drug reactions, asbestosis and chronic hypersensitivity pneumonitis
“Idiopathic” reserved for conditions in which the cause of lung injury pattern is unknown
Classification
“So diverse are the different forms and so varied the conditions under which this change occurs that a proper classification is extremely difficult”
Osler speaking of IIP (1892)
Classification A number of classification schemes, names and definitions have been
associated with the IIP’s over the years leading to a great deal of confusion (and article titles referring to “alphabet soup”)
American Thoracic Society and European Respiratory Society (ATS/ERS) met in 2002 to clarify nomenclature and describe the clinical, radiologic and histologic patterns of these conditions
Participants included thoracic radiologists, pulmonologists and pulmonary pathologists
Idiopathic Interstitial Pneumonias(clinical nomenclature as proposed by ATS/ERS)
Include (in order of frequency): Usual Interstitial Pneumonia (UIP) Non-specific Interstitial Pneumonia (NSIP) Cryptogenic Organizing pneumonia (COP) Acute Interstitial Pneumonia (AIP) Respiratory Bronchiolitis-Associated Interstitial Lung
Disease (RB-ILD) Desquamative Interstital Pneumonia (DIP) Lymphoid Interstitial Pneumonia (LIP)
Diagnosis of IIP
ATS/ERS guidelines emphasize the importance of combined clinical, radiologic and histologic diagnosis of IIP’s
The MOST IMPORTANT distinction is between UIP and the other IIP’s due to prognostic and therapeutic implications
Diagnosis of IIP
HIGHLIGHTS:
If HRCT gives confident diagnosis of UIP, no lung biopsy needed and diagnostic process is done
If equivocal findings on HRCT, then surgical lung biopsy considered
Figure from UpToDate, adapted from ATS/ERS guidelines
Usual Interstitial Pneumonia (UIP)
Also known as Idiopathic pulmonary fibrosis (IPF)
Most common IIP Primarily a fibrotic condition
Clinical Findings in UIP
Age >50 Slight male predominance Symptoms usually present 6 months prior to
presentation Progressive shortness of breath, non-productive
cough Physical exam: end-inspiratory crackles at lung bases
“velcro” lung Lung function tests: restrictive pattern Decreased DLCO
Histologic Findings in UIP
Histology: Fibroblastic foci at the edge of dense scars Subpleural, paraseptal and/or peribronchovascular distribution Dense fibrosis causes remodeling of lung architecture and frequent
honeycomb fibrosis
Two distinguishing characteristics from other IIP’s1. Temporal heterogeneity: fibrotic lesions of different stages
within same biopsy specimen
2. Spatial heterogeneity: patchy lung involvement
Histology of UIP
Left to right: 1. Patchy fibrosis, subpleural distribution. Some lymphoid aggregates (black arrow). Areas of normal
lung also present.
2. Fibroblastic focus (white arrow) adjacent to dense collagenous scar.
Figures from Lynch et al. 2005
Radiographic features of UIP
Radiographs Bilateral and basilar irregular linear opacities
(close to 100% of cases) Ground glass opacities Honeycombing Loss of lung volumes Normal radiograph in 2-8% of cases
Early changes UIP: peripheral, irregular linear opacities and normal lung volumes
Late features UIP: same patient 2 years later. Peripheral, irregular linear opacities and progressive loss of lung volume
Images from McAdams et al., 1996
Late features UIP showing bilateral, coarse, reticular opacities with architectural distortion, volume loss and honeycombing
Images from McAdams et al., 1996
CT features of UIP
Reticular opacities with traction bronchiectasis Honeycombing (96% of cases) Ground glass opacity (less extensive than reticular
pattern) Architectural distortion reflecting fibrosis Distribution: basal/peripheral and patchy
CT features of UIP
Left: left lower lobe shows peripheral ground-glass opacity and reticular patterns with traction bronchiectasis (arrow)
Right: same patient two years later with progression of ground-glass to reticular pattern and honeycombing and progression of traction bronchiectasis
Images from Lynch et al., 2005
Clinical Course in UIP
Gradual deterioration, with possible periods of rapid decline
Mean survival is 2.5-3.5 years from time of diagnosis
As UIP is predominantly a fibrotic condition, does not typically respond to steroid treatment
Non-specific Interstitial Pneumonia (NSIP)
Second most frequently diagnosed IIP
more favorable prognosis than IPF/UIP
ATS/ERS guidelines stress that a finding of an NSIP pattern on biopsy should “prompt the clinician to redouble efforts to find potential causes” (collagen vascular disease, exposures)
Clinical findings in NSIP
Mean age of onset is 40-50 No sexual predominance No association with cigarette smoking Gradual onset, some patients may have subacute course The median duration of symptoms before diagnosis is 6-31 mo
in different series Symptoms: progressive SOB, cough, fatigue Half present with history of weight loss Physical Exam: crackles at lung bases Lung function tests: restrictive pattern with decreased DLCO
Histology of NSIP
Because features are “non-specific”, histology is difficult to define
Spatially homogenous alveolar wall thickening Temporal homogenous pattern
Two main types:1. Fibrotic: dense or loose interstitial fibrosis lacking temporal heterogeneity or
patchy features
2. Cellular: Mild-moderate interstitial chronic inflammation Type II pneumocyte hyperplasia in areas of inflammation
Fibrotic NSIP
NSIP with fibrosing pattern. Alveolar walls (arrows) show thickening caused by fibrosis. No fibroblastic foci are present.
Image from Lynch et al., 2005
Cellular NSIP
Photomicrograph showing NSIP with cellular pattern. Alveolar walls (arrows) are infiltrated by a chronic inflammatory infiltrate.
Image from Lynch et al., 2005
Fibrotic vs. Cellular NSIP Main importance is prognostic. Patients with predominant fibrosis have a poorer
prognosis than those with cellular NSIP
Figure below shows survival curves for patients with UIP, fibrotic NSIP (FNSIP) and Cellular NSIP (CNSIP). Those with CNSIP are shown to have the best survival.
Figure from Lynch et al., 2005
Radiographic Features of NSIP
Irregular linear opacities Air space consolidation Bilateral and basilar pattern Radiograph normal in 14% of cases
Radiographic features of NSIP
Basilar opacities and normal lung volumes
Image from McAdams et al., 1996
CT features of NSIP
Scattered ground glass opacities Basal predominance Consolidation uncommon and honeycombing
rare Irregular linear opacities Fibrosis (lobar volume loss, reticular pattern,
and/or traction bronchiectasis)
CT features of NSIP
Top: Fibrotic NSIP. Ground glass opacity with traction bronchiectasis (arrows) Arrowhead indicating posterior displacement of left major fissure denoting volume loss
Bottom: Cellular NSIP. Ground glass opacity with reticular pattern.
Images from Lynch et al., 2005
Clinical Course of NSIP
Significantly better prognosis than UIP
Evidence for corticosteroid efficacy is from retrospective reviews of observational studies. (25-30% of patients improved)*
Relapse may occur
*Collard et al., 2003
Cryptogenic Organizing Pneumonia (COP)(IIP formerly known as BOOP)
Third most common IIP
Although process is primarily intraalveolar, it is included with IIP’s because of its idiopathic nature and because its appearance may overlap with other IIP’s
Organizing Pneumonia: (COP or BOOP)
Histology: Organizing pneumonia-intraluminal organization in distal
air spaces Patchy distribution Preservation of lung architecture Uniform temporal appearance Mild chronic interstitial inflammation Edematous granulation-type tissue within airspaces:
bronchioles and alveolar ducts and alveoli
Clinical findings in COP
Cough and shortness of breath Relatively short duration of symptoms (1-6 months) Patients often diagnosed first with pneumonia but fail to respond to
antibiotics as not infectious etiology Physical exam: PFT’s: restrictive pattern equal sex distribution but nonsmokers outnumber smokers by 2:1. Mean age of onset is 55 yr Continuing weight loss, sweats, chills, intermittent fever, and myalgia are common. Localized or more widespread crackles are frequently present,
Histology of COP
Patchy areas of consolidation Polypoid plugs of loose organizing connective
tissue Architecture of lung is preserved All the connective tissue is the same age Mild to moderate inflammation
COP histology
From left to right: 1. low-power photomicrograph shows scattered areas of organizing pneumonia. Fibroblast plugs are identified as
pale, round structures (arrows)2. High power photomicrograph shows fibroblast plug in small brochiole3. High power photomicrograph shows fibroblast plugs streaming from one alveolus to another 4. gross specimen showing branching fibroblast plugs (arrowheads)
Images from McAdams et al., 1996
Radiographic features of COP
Bilateral or unilateral areas of consolidation Patchy distribution, but in minority of cases may be
confined to the subpleural region Small nodular opacities are seen in 10–50% of cases. Lung volumes are normal in up to 75% of cases
Radiographic Features in COP
Multifocal, bilateral, basilar consolidations
Bilateral multifocal consolidations
Images from McAdams et al, 1996
CT features of COP
Consolidation present in 90% of patients Lower lung zones frequently involved Air bronchograms present with consolidation Mild bronchial dilatation in areas of
consolidation
CT features in COP
Bilateral pulmonary consolidation with subpleural and perbronchovascular predominance and right pleural effusion
Images from Lynch et al., 2005
Clinical Course (COP)
Majority of patients recover completely with oral corticosteroids
Relapse common with steroid taper and/or cessation
Acute Interstitial Pneumonia (AIP)
Rapidly evolving lesion (days-weeks) Histological findings of diffuse alveolar
damage. Therefore, diagnosis of AIP should only be considered after the other causes of DAD (sepsis, shock, etc.) are ruled out.
Clinical Findings in AIP
Patients often have prior illness suggestive of viral URI Constitutional symptoms: myalgias, arthralgias, fever, chills, malaise Severe dyspnea on exertion developing over days Median time from first symptom to presentation is 3 weeks Hypoxemia progressing rapidly to respiratory failure Mean age of 50 No sex predominance No association with smoking Physical exam: diffuse crackles Lung function tests: restrictive pattern Mechanical ventilation is usually required The majority of patients fulfill the diagnostic clinical criteria for ARDS
Histology of AIP
Histology: Diffuse alveolar damage Acute phase: Edema and hyaline membranes Organizing phase: Organizing alveolar septal
fibrosis and pneumocyte hyperplasia Uniform temporal appearance
Histology of AIP
Left to right1. High power photomicrograph demonstrating interstitial widening by edema and inflammatory
cells. Hyaline membrane formation also apparent.
2. High power photomicrograph shows organization of the intraalveolar exudate and immature collagen deposition
Images from Lynch et al., 2005
Radiographic features of AIP
Diffuse bilateral opacities Left: Initial radiograph shows bilateral and basilar consolidation Right: Two weeks later with progressive, diffuse consolidation.
Images from McAdams et al., 1996
CT features of AIP
Early exudation phase: Ground glass opacity-bilateral and patchy Consolidation also evident
Organizing stage: Distortion of bronchovascular bundles Traction bronchiectasis
Although CT findings in AIP and ARDS overlap, patients with AIP are more likely to have symmetric lower lobe distribution and a greater prevelance of honeycombing
CT features of AIP
Diffuse consolidation and air bronchograms
Image from McAdams et al., 1996
Clinical Course AIP
No proven treatment, corticosteroids often used
Mortality rates high (>50%)
Those patients who recover may experience recurrence and/or chronic, progressive lung disease
Respiratory Bronchiolitis Interstitial Disease (RB-ILD)
Respiratory Bronchiolitis: Lesion found in cigarette smokers Characterized by pigmented macrophages in respiratory
bronchioles Rarely symptomatic, minor airway dysfunction
RB-ILD is defined as the combination of clinically significant pulmonary symptoms, abnormal pulmonary function and imaging abnormalities associated with the pathologic lesion of respiratory bronchiolitis
Clinical Findings in RB-ILD
Heavy smokers with average exposure of more than 30 pack-years
Gradual onset 40-50 years of age Generally mild symptoms of sob and cough (new or
changed) Some patients may present with significant dyspnea
and hypoxemia Male to female ratio of 2:1
Histology: RB-ILD Histology:
Bronchiolocentric alveolar macrophage accumulation Mild bronchiolar/peribronchiolar fibrosis and chronic inflammation Macrophages with “dusty-brown” appearance
Figure below: faintly pigmented alveolar macrophages (arrows) fill the lumen of respiratory bronchiole. Mild thickening of respiratory bronchiole wall.
Image from Lynch et al., 1996
Radiographic Features of RB-ILD
Wall thickening of central or peripheral bronchi (75% of patients)
Ground glass opacity (60% of patients) Normal radiograph (14%) Centrilobular emphysema also commonly
seen as patients are heavy smokers
Radiographic features of RB-ILD
Linear opacities in lung bases with atelectasis in right lower lung
Image from McAdams et al., 1996
CT features of RB-ILD
Centrilobular nodules Patchy ground glass Thickening of central and peripheral airways Upper lobe centrilobular emphysema Air trapping
**CT findings in RB-ILD are similar to those seen in other, asymptommatic smokers. However, findings in patients with RB-ILD are usually more extensive
CT features in RB-ILD
RB-ILD in 41 year old with 30 pack-year smoking history. Widespread gound-glass opacification, with some poorly defined centrilobular nodules (arrowheads)
Image from Lynch et al., 2005
Clinical Course RB-ILD
Many patients improve after cessation of smoking
No reports of progression to dense pulmonary fibrosis
Desquamative Interstitial Pneumonia (DIP)
Considered to be most likely part of a spectrum of RB-ILD as is associated with smoking and has similar pathology
Very rare Named desquamative because the primary finding
on histology was thought to be desquamation of epithelial cells.
Now recognized as intra-alveolar macrophages
Clinical findings in DIP
Uncommon Male to female ratio of 2:1 Progressive dyspnea, dry cough May progress to respiratory failure Digital clubbing (40%)
Histology of DIP
Histology: Uniform involvement of lung parenchyma Accumulation of alveolar macrophages Mild-moderate fibrotic thickening of alveolar septa Mild interstitial chronic inflammation Modest infiltrate including lymphocytes, plasma cells Feature distinguishing DIP from RB is that DIP affects the
lung in a uniform diffuse manner and lacks the bronchiolocentric distribution seen in RB.
Histology of DIP
Photomicrograph shows DIP pattern. Alveolar spaces show diffuse alveolar macrophage accumulation and mild interstitial thickening caused by fibrous connective tissue (arrows)
Image from Lynch et al., 2005
Radiographic features of DIP
Normal in 3-22% of biopsy-proven cases
Patchy ground glass opacification Lower zone/peripheral
predominance Figure: bilateral, basilar
consolidations with no honeycombing or volume loss
Image from McAdams et al., 1996
CT features of DIP
Ground glass opacification Lower zone distribution (73%), peripheral
(59%) Irregular linear opacities and reticular pattern
are frequent (59%), usually seen at lung bases Honeycombing (33%) is peripheral and limited
CT features of DIP
Basal ground glass opacification with multiple peribronchovascular cysts (arrows)
Image from Lynch et al., 2005
Clinical Course of DIP
The prognosis of DIP is generally good.
Most patients improve with smoking cessation and corticosteroids
Overall survival is about 70% after 10 yr
Lymphoid Interstital Pneumonia (LIP)
Very rare condition
regarded as a histologic variant of diffuse pulmonary lymphoid hyperplasia
Because of its’ rarity, important to do thorough investigation for collagen vascular disease and immunodeficiency
Clinical features of LIP
Poorly defined clinical presentation More common in women Usually diagnosed in fifth decade Gradual onset over 3 years Symptoms include SOB, fever, weight loss Physical exam: crackles Monoclonal increase in IgG or IgM (75%)
Histology of LIP Histology
Diffuse interstitial infiltration Alveolar septal distribution Infiltrates mostly t-cells, plasma cells and macrophages Lymphoid hyperplasia frequent Photomicrograph shows LIP. Alveolar walls (arrows) are markedly
infiltrated by lymphocytes and plasma cells.
Image from Lynch et al., 2005
Radiographic features of LIP
Two radiographic patterns:1. Basilar with alveolar component2. Diffuse with honeycombing
CT features of LIP Dominant finding: ground glass opacity Perivascular cysts or perivascular honeycombing Reticular abnormality (50%) lung nodules Widespread consolidation may occur
Diffuse ground glass opacification and multiple lung cysts
Image from Lynch et al., 2005
Clinical Course of LIP
Corticosteroids used for treatment: 2/3 of patients respond to therapy either with improvement or no progression of disease
1/3 of patients progress to diffuse fibrosis
Summary of IIP
Most important distinction is between UIP and other IIP’s as prognosis is greatly different
Start with thorough history and physical exam looking for possible etiologies of parenchymal lung disease before labeling “idiopathic”
Surgical lung biopsy not necessary if confident diagnosis of UIP possible with HRCT
Corticosteroids not useful in UIP as it is a fibrotic condition
References
1. American Thoracic Society, European Respiratory society Consensus Classification of the Idiopathic Interstitial Pneumonias. American Journal of Respiratory and Critical Care Medicine 2002; 165:277-304
2. Lynch, D., Travis, W., Muller, N., Galvin, J., Hansell, D., Grenier, P., King, T. Idiopathic Interstitial Pneumonias: CT features. Radiology 2005; 236:10-21
3. Collard, H., King, T. Demystifying idiopathic interstitial pneumonia. Archives of Internal Medicine 2003; 163:17-29
4. McAdams, H., Rosado-de-Christenson, M., Wehunt, W., Fishback, N. The alphabet soup revisited: the chronic interstitial pneumonias in the 1990’s. Radiographics 1996; 16:1009-1033
5. MacDonald, S., Rubens, M., Hansell, D., Copley, S., Desai, S., M. du Bois, R., Nicholson, A., Colby, T., Wells, A. Non-specific interstitial pneumonia and usual interstitial pneumonia: comparative appearances and diagnostic accuracy of thin-section CT. Radiology 2001; 221:600-605
6. Colby, T. Pathological approach to idiopathic interstitial pneumonias: useful points for clinicians. Breathe 2004; 1:43-49.
7. UpToDate