Diffuse Parenchymal Lung Disease

Zunaira Islam MD Pgy2Dr Eugene Go

Diffuse Parenchymal Lung Disease

Also previously called Interstitial lung disease (ILD) and Diffuse Infiltrative Lung disease (DILD)

Describes 100s of diseases

no good classification exists, except one that divides them into Known Cause and Unknown Cause

Diffuse … parenchymal… interstitial…

Diffuse: refers to the nonspecific radiological patterns

Parenchyma refers to the functioning part of an organ (nephron, hepatocyte, myocytes) … and Stroma refers to the connective tissue and supporting structures

Lung parenchyma in its strictest sense refers solely to alveolar tissue, respiratory bronchioles, alveolar ducts, terminal bronchioles. However, the term is often used loosely to refer to any form of lung tissue

Many of these diseases involve the alveoli air space as well.

Interstitium of lung: Airspace Compartment – respiratory

bronchioles, alveolar ducts and alveoli

Interstitial Compartment – intervening supportive framework; contains alveolar septa, perivascular and peribronchial connective tissue

Cells within the interstitium – fibroblasts, mast cells, tissue macrophages, lymphocytesType I Pneumocyte – flat and region of

gaseous diffusion; vulnerable to injuryType II Pneumocyte – polygonal and site of

surfactant synthesis; can proliferate and reform alveolar epithelial surface

Pathogenesis of interstitial disease:

Often at the end stage most disease processes end in fibrosis from different often unknown causes. Pathogenesis of Interstitial Fibrosis – fibrous widening of interstitium is hallmark of chronic interstitial lung diseaseTwo Mechanisms: (1) Primary interstitial widening – edema and fibrosis

formation directly within the interstitial compartmenteg: interstitial edema, sarcoidosis (thickening of interstitium initially by granuloma formation)

(2) Accretion – organization of exudate within the alveolar space that is converted to fibrous connective tissue and is incorporated into the interstitium; in some cases the exudate is cleared with resolution. eg: organizing pneumonia

Hence you see why DPLD is found in the interstitium as well as the alveolar air-space This explains the any different radiological findings we will see.

Classification of DPLD based on KNOWN vs UNKNOWN cause (only one so far agreed upon by American and European Societies)

Connective Tissue Disease

Hypersensitivity Pneumonitis

Drug Induced (MTX, nitrofurantoin, amiodarone)

Smoking related::

1- Pulmonary Langerhans ell Histiocytosis 2- Resp Bronchiolitis Interstitial Lung disease . 3- Desquamative interstitial pneumonia

Acute eosinophillic pneumonia

Radiation idued

Toxic inhalations (cocaine,zinc in smoke bombs, amonia)

idiopathic interstitial pneumonias:

- Idiopathic pulm fibrosis IPF

-Nonspecific interstitial pna NIP

- Cryptogenic organizing pna COP (BOOP)

- Lymphocytic interstitial pna LIP

- Acute interstitial pnemonia

Other eosinophilic pnas

Pulm vasculitides

Pulm lympangioleiomyomatosis

Pulm alveolar proteinosis

Diagnostic approach1- CINICAL CONTEXT

2- TEMPORAL PROGRESSION

3- RADIOLOGICAL FINDINGS

4- HISTOPATHOLOGICAL FINDINGS

1- CLINICAL CONTEXT

Age , sex , occupation, drugs, radiation exposure , CTD , physical exam – usually dry crackles

2- TEMPORAL PROGRESSION

Most are slow

Acute ones:

1- usually those that cause alveolar hemorrhage: Vasculitides, Wegeners , Churg Strauss , microscopic polyangitis

2- Eosinophillic pneumnias – can present as ARDS

3- Acute Interstitial Pna can also present as ARDS without known cause – called Hamman Rich Syndrome. (Path just shows Diffuse Alveolar Destruction)

4- Acute exacerbation of known I.P.F (Path will also show Diffuse Alveolar Damage)

3- RADIOLOGICAL FINDINGS By this we mean HIGH RESOLUTION CT SCAN (HRCT)

Pattern:

- Both interstitial and alveolar abnormalities can be seen.

- Interstitial shows up as reticular and reticulonodular /linear /lattice like presentation

- Alveolr shows up as either consolidation (complete) or ground glass (partial filling - can still see architecture) opacification

- May have Cystic spaces – specially Langerhans Cell Histocytosis

- May have Nodules – in central lung zone , along perivascular bundle – Sarcoidosis

Radiological findings .. continued

Distribution:

Upper lobes: hypersensitivity, sarcoidosis

Central: pulm alveolar proteinosis , sarcoidosis

Lower lobes: IPF , Asbestosis (As-BASE-tosis)

MOSAIC distribution: nonspecific, ground glass, involving neighboring lobules, -Due to Vascular disease or Air trapping - eg. obliterating pnas

Mosaic patterns can be GEOGRAPHICAL: patchy areas of ground glass, with sharp edges contrasting normal and abnormal – seen in Resp Bronchiolitis assciated Interstitial Lung Disease (RBILD)

IPF: HRCT of advanced stage of pulmonary fibrosis demonstrating reticular opacities with honeycombing,

with predominant subpleural distribution.

Hypersensitivity pneumonitis: Note the ground-glass appearance and small nodules.

Ill defined centrilobular nodules of ground glass density in a patient with hypersensitivity pneumonitis

Langerhans cell histiocytosis: early nodular stage before the typical cysts appear

 

Sarcoidosis: Nodules along the fissures indicating a perilymphatic distribution (red arrows) , with majority of nodules located along the bronchovascular bundle (yellow arrow) Nodules in the subpleural region and

along the fissures, specially in upper lobe and perihilar regions -

Honeycombing is defined by the presence of small cystic spaces lined by bronchiolar epithelium with thickened walls

composed of dense fibrous tissue. Honeycombing is the typical feature of usual interstitial pneumonia UIP – eg seen in IPF

Alveolar Proteinosis: Both septal thickening and ground glass opacity in a patchy distribution. Some lobules are affected and

others are not. This combination of findings is called 'crazy paving'.Crazy paving was thought to be specific for alveolar

proteinosis, but is also seen in many other diseases such as PCP, bronchoalveolar carcinoma, sarcoidosis, nonspecific interstitial

pneumonia (NSIP), organizing pneumonia (COP), adult respiratory distress syndrome and pulmonary hemorrhage.

Mosaic pattern showing air trapping

4- HISTOPATHOLOGY

Do only if need to – if it will change the treatment (steroid vs no steroid)

Common Methods used:

Bronchoscopy usually provides TINY sample – cannot see architecture, but CAN still be very helpful in reaching diagnosis

VATS video assisted thorascopic surgery: Can be used if needed , but keep in mind: Mortality rate is high at 2% . Complication ate is 5-10%

Histo-pathological findings:

Usual interstitial pneumonia (UIP)

Nonspecific Interstitial Pneumonia (NIP)

Organising pneumonia

Diffuse Alveolar Damage (DAD)

Respiratory bronchiolitis

Lymphoid Interstitial Pneumonia

Idiopathic pulm fibrosis, CTD associated DPLD , radiation induced DPLD, Cryptogenic fibrosis Alveolitis

Nonspecific interstitial pneumonia – a group with poorly characterized HRCT findings – needs further study

Crytogenic Organizing Pneumonia

Acute Interstitial Pneumonia,

Acute exacerbations of IDP

Resp Bronchiolitis associated ILD

Lymphoid Interstitial pna

Usual Interstitial Pneumonitis (UIP) – interstitial inflammatory infiltrate composed predominantly of lymphocytes and plasma cells

Desquamative Interstitial Pneumonitis (DIP) – characterized by numbers of pigmented macrophages within alveolar spaces in addition to a usually mild chronic interstitial infiltratemay be more responsive to steroids

Lymphoid Interstitial Pneumonitis (LIP) – lymphocytes and plasma cells dominate the cellular infiltrate and rare much more numerous than in UIPoften associated with Sjogrens’s syndrome and

dysglobulinemiasoften difficult to distinguish between LIP and lymphoma

involving the lung; LIP can progress to lymphoma

Diffuse Alveolar Damage (DAD) – in acute interstitial injury

seen in Adult respiratory Distress Syndrome (ARDS), Shock Lung

sudden onset of respiratory failure with hypoxemia, capillary permeability and diffuse alveolar infiltrates of CXR

pts require inspired oxygen concentrations and ventilatory pressure

Bronchiolitis obliterans : fibrous tissue occlusion of respiratory bronchioles . Histology – similar to proliferative phase of DAD, but inflammation is often more intense.

Diffuse alveolar damage (DAD), organizing pneumonia and usual interstitial pneumonitis (UIP) have similar histological appearances reflective of the stereotyped response of the lung to a variety of insults

Classification of DPLD based on KNOWN vs UNKNOWN cause (only one so far agreed upon by American and European Societies)

Connective Tissue Disease

Hypersensitivity Pneumonitis

Drug Induced (MTX, nitrofurantoin, amiodarone)

Smoking related::

1- Pulmonary Langerhans ell Histiocytosis

2- Resp Bronchiolitis Interstitial Lung disease

3- Desquamative interstitial pneumonia

Acute eosinophillic pneumonia

Radiation idued

Toxic inhalations (cocaine,zinc in smoke bombs, amonia)

idiopathic interstitial pneumonias:

- Idiopathic pulm fibrosis IPF

-Nonspecific interstitial pna NIP

- Cryptogenic organizing pna COP (BOOP)

- Lymphocytic interstitial pna LIP

- Acute interstitial pnemonia

Other eosinophilic pnas

Pulm vasculitides

Pulm lympangioleiomyomatosis

Pulm alveolar proteinosis

CTD: about 50% pt with RA more common in men, and 75% patients with scleroderma have chest involvement.

DRUGS: nitrofurantoin , amiodarone, methotrexate -> care in pts with RA

RADIATION: Can happen on other side, not necessary in same area, 1-6 months later

HYPERSENSITIVITY: mold, mold, mold. Mycobacteria in hot-tubs , bird feathers n droppings, meat serum.

Lymphangioleiomyomatosis: rare , <1%. Exclusively in women, associated with tuberous sclerosis in 15%, spontaneous pneumothorax in 55%. Thought to be estrogen relater but hormonal therapies fail.

SMOKING RELATED:

1- Pulm Langerhans cell Histioctosis (histiocytosis x /eosinophilic Granuloma) – young. 25% have pneumothorax. May stabilize.

2- Resp brnchiolitis RBILD: most smokers, occaisionally severe, mixed obsrtuctive/restrictive pattern

3- Desquamative Interstitial pna: rare, overlap with RBLID. Steroids may help. Have to stop smoking

IDIOPATHIC INTERSTITIAL PNEUMONIAS:

Nonspecific Interstitial pna (NIP): (Histo-path classification) rare, overlap with IPF, requires open lung biopsy.

Cryptogenic Organizing Pna: COP / BOOP : middle aged nonsmokers. A pneumonia that is not improving – think COP! Biopsy is usually done with Bronch or VATS. Resolves on its own , steroids may help – or may recurr durng steroid taper.

Acute Interstitial Pneumonia: Hamman Rich Syndrome

(This is different cos its acute and can present with fulminant Resp Failure. Histopath will show Diffuse Alveolar Damage. Poor prognosis – 50% mortality , no effective therapy so far.)

Thanks !!