Diffuse Parenchymal Lung Disease Zunaira Islam MD Pgy2 Dr 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, lymphocytes Type I Pneumocyte – flat and region of gaseous diffusion; vulnerable to injury Type 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 fromdifferent often unknown causes. Pathogenesis of Interstitial Fibrosis –fibrous widening of interstitium is hallmark of chronic interstitial lungdiseaseTwo Mechanisms: (1) Primary interstitial widening – edema and fibrosis formation directly within the interstitial compartment eg: 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 pneumoniaHence you see why DPLD is found in the interstitium as well as thealveolar air-spaceThis 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 idiopathic interstitial pneumonias: Hypersensitivity Pneumonitis - Idiopathic pulm fibrosis IPF Drug Induced (MTX, -Nonspecific interstitial pna NIP nitrofurantoin, amiodarone) - Cryptogenic organizing pna COP (BOOP) Smoking related:: - Lymphocytic interstitial pna LIP 1- Pulmonary Langerhans ellHistiocytosis 2- Resp Bronchiolitis - Acute interstitial pnemoniaInterstitial Lung disease . 3-Desquamative interstitial pneumonia Other eosinophilic pnas Acute eosinophillic pneumonia Pulm vasculitides Radiation idued Pulm lympangioleiomyomatosis Pulm alveolar proteinosis Toxic inhalations (cocaine,zinc in smoke bombs, amonia)
1- CLINICAL CONTEXTAge , sex , occupation, drugs, radiation exposure , CTD ,physical exam – usually dry crackles
2- TEMPORAL PROGRESSIONMost are slowAcute ones:1- usually those that cause alveolar hemorrhage: Vasculitides,Wegeners , Churg Strauss , microscopic polyangitis2- Eosinophillic pneumnias – can present as ARDS3- Acute Interstitial Pna can also present as ARDS without knowncause – called Hamman Rich Syndrome. (Path just shows DiffuseAlveolar Destruction)4- Acute exacerbation of known I.P.F (Path will also show DiffuseAlveolar 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 .. continuedDistribution:Upper lobes: hypersensitivity, sarcoidosisCentral: pulm alveolar proteinosis , sarcoidosisLower lobes: IPF , Asbestosis (As-BASE-tosis)MOSAIC distribution: nonspecific, ground glass, involvingneighboring lobules, -Due to Vascular disease or Airtrapping - eg. obliterating pnasMosaic patterns can be GEOGRAPHICAL: patchy areasof ground glass, with sharp edges contrasting normal andabnormal – seen in Resp Bronchiolitis assciatedInterstitial Lung Disease (RBILD)
IPF: HRCT of advanced stage of pulmonary fibrosisdemonstrating 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 ofnodules 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 spaceslined by bronchiolar epithelium with thickened walls composed ofdense 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. Thiscombination 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.
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%
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 infiltrate may be more responsive to steroids Lymphoid Interstitial Pneumonitis (LIP) – lymphocytes and plasma cells dominate the cellular infiltrate and rare much more numerous than in UIP often associated with Sjogrens’s syndrome and dysglobulinemias often 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 pressureBronchiolitis obliterans : fibrous tissue occlusion of respiratorybronchioles . Histology – similar to proliferative phase of DAD, butinflammation is often more intense.Diffuse alveolar damage (DAD), organizing pneumonia and usualinterstitial pneumonitis (UIP) have similar histological appearancesreflective of the stereotyped response of the lung to a variety ofinsults
Classification of DPLD based on KNOWN vs UNKNOWN cause (only one so far agreed upon by American and European Societies) Connective Tissue Disease idiopathic interstitial pneumonias: Hypersensitivity Pneumonitis - Idiopathic pulm fibrosis IPF Drug Induced (MTX, -Nonspecific interstitial pna NIP nitrofurantoin, amiodarone) - Cryptogenic organizing pna COP Smoking related:: (BOOP) 1- Pulmonary Langerhans ell - Lymphocytic interstitial pna LIPHistiocytosis - Acute interstitial pnemonia 2- Resp Bronchiolitis InterstitialLung disease Other eosinophilic pnas 3- Desquamative interstitial Pulm vasculitidespneumonia Pulm lympangioleiomyomatosis Acute eosinophillic pneumonia Pulm alveolar proteinosis Radiation idued Toxic inhalations (cocaine,zinc in smoke bombs, amonia)
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.)