Transcript Interstitial Lung Disease

Interstitial Lung Disease
Julye N. Carew, M.D.
January 12, 2007
Interstitial Lung Diseases
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Definition
Clinical Presentation and evaluation
Radiographic Features
Classification
Treatment
Prognosis
Definition
• “Interstitial lung disease”- a misnomer
• Few cells in the interstitium of the normal lung
• Injury to basement membrane shared by
epithelium and endothelium
• Increased alveolar permeability and spillage of
serum contents into the alveolar space and
recruitment of fibroblasts
• Collagen deposition
• Also injury to small airways=respiratory
bronchioles, alveolar ducts and terminal
bronchioles
Alveolar/Interstitial Space
Matrix
Connective tissue
Murray and Nadel, Text of Resp. Medicine
Pathogenesis
Epithelial cell apoptosis with loss of basement membrane integrity: production of growth factors
in response to alveolar epithelial injury with hyperplastic type II cells and myofibroblast recruitment
Noble, et al. Clinics in Chest Med, Dec 2004
Pathogenesis
• UNKNOWN!!!
• Some understanding of the mechanism of
injury
• Initiating injuries are likely multiple=
inhaled, sensitization to allergens,
circulatory
• With continued injury, “repair” process
continues with additional fibroproliferation
that is unchecked
ILD
• 81 in 100,000 prevalence in men
• 67 in 100,000 in women
• 32.5 in 100,000 incidence in men
• 26 in 100,000 in women
• 200 in 100,000 incidence in age >75
• 30-40% of all ILD “IPF”
ILD
• Due to increasing numbers of cytotoxic
drugs, increased detection of occupational
lung disease and increasing life
expectancy, as well as better imaging and
diagnostic testing the incidence of these
diseases is expected to rise
Evaluation of ILD
• EXTENSIVE HISTORY
• AGE, GENDER, UNDERLYING
COMORBIDITIES, DRUGS, SMOKING,
OCCUPATIONAL HISTORY, HOBBIES, PETS,
FAMHX
• DURATION OF SYMPTOMS
• PHYSICAL EXAM
• LABORATORIES
• IMAGING
• SPIROMETRY, LUNG VOLUMES AND DLCO
Laboratories
• LFTs, CBC
• ANA, RF, hypersensitivity panels, ANCA,
anti-GBM
• ?CRP, ESR
Pulmonary function
• Spirometry
• Lung volumes
• Diffusion capacity
Spirometry
UpToDate, 2007
Lung Volumes
UpToDate, 2007
Diffusion capacity
UpToDate, 2007
Diffusion
Matrix
Connective tissue
Murray and Nadel, Text of Resp. Medicine
Imaging
• PA/LAT CXR
• HRCT
GROUND GLASS
Schwarz, ILD, 2003, RB
NODULAR GROUND GLASS
Schwarz, ILD, 2003, HP
INTRALOBULAR SEPTAL THICKENING
Schwarz, ILD, 2003, LC
RETICULAR INFILTRATES
Schwarz, ILD, 2003, HP
HONEYCOMB LUNG
Schwarz, ILD, 2003
HONEYCOMB LUNG
Clinical Classification
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Connective Tissue Diseases
Drug-induced
Primary Unclassified
Occupational
Idiopathic Disorders
Clinical Classification-- CTD
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Scleroderma
Polymyositis-dermatomyositis
Systemic lupus erythematosus
Rheumatoid arthritis**
Mixed connective tissue disease
Ankylosing spondylitis
Behcet’s
Sjogren’s syndrome
RA
Rheumatoid Arthritis
• Interstitial fibrosis
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Male predominance 3:1
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High titers of RF and rheumatoid
nodules
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Occurs in 33% of all RA patients
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Usually patients are dyspneic, but also
limited by joint disease
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Therapies may cause fibrosis (gold,
methotrexate, penicillamine)
RA
Schwarz and King, ILD 2003
Drugs
• Antibiotics--nitrofurantoin,
sulfasalazine, ethambutol
• Antiarrhythmics--amiodarone,
tocainide, propranolol
• Anti-inflammatories--gold,
penicillamine
• Anticonvulsants--dilantin
• Chemotherapeutic agents-mitomycin C, bleomycin,
busulfan, cyclophosphamide,
chlorambucil, methotrexate,
azathioprine, BCNU
[carmustine], procarbazine
• Therapeutic radiation
• Oxygen toxicity
• Narcotics
• Cocaine Paraquat
Primary- Unclassified
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Sarcoidosis
Eosinophilic granuloma
Amyloidosis
Lipoid pneumonia
Lymphangitic
carcinomatosis
Broncholaveolar
carcinoma
Pulmonary lymphoma
Gaucher's disease
Niemann-Pick disease
Hermansky-Pudlak
syndrome
Neurofibromatosis
• LAM
• Tuberous sclerosis
• Acute respiratory distress
syndrome
• AIDS
• Bone marrow
transplantation
• Postinfectious
• Eosinophilic pneumonia
• Alveolar proteinosis
• Diffuse alveolar
hemorrhage syndromes
• Alveolar microlithiasis
• Metastatic calcification
Occupational
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Silicosis- tile, glass
Asbestosis
Hard-metal pneumoconiosis
Coal worker's pneumoconiosis
Berylliosis-fluorescent bulbs, dental, electronics
Aluminum oxide fibrosis-abrasives
Talc pneumoconiosis
Siderosis (arc welder)-iron foundry, welders
Stannosis (tin)
Idiopathic
Acute interstitial pneumonitis (Hamman-Rich syndrome)
Idiopathic pulmonary fibrosis “IPF”
Familial idiopathic pulmonary fibrosis
Desquamative interstitial pneumonitis
Respiratory bronchiolitis
Cryptogenic organizing pneumonia
Nonspecific interstitial pneumonitis
Lymphocytic interstitial pneumonia (Sjögren's syndrome, connective tissue
disease, AIDS, Hashimoto's thyroiditis)
Autoimmune pulmonary fibrosis (inflammatory bowel disease, primary biliary
cirrhosis, idiopathic thrombocytopenic purpura, autoimmune hemolytic
anemia)
Idiopathic ILD
• Diagnosis is made based upon clinical
history, radiographic findings and
pathology
• Some pathologic findings are
pathognomonic for a particular disease,
while others are suggestive in the correct
clinical setting
IPF
• Major Criteria
– • Exclusion of other known causes of ILD, such as certain drug
toxicities, environmental exposures, and connective tissue diseases
– • Abnormal pulmonary function studies that include evidence of
restriction (reduced VC often with an increased FEV1 /FVC ratio) and
impaired gas exchange [increased AaPo2 with rest or exercise or
decreased DLCO ]
– • Bibasilar reticular abnormalities with minimal ground glass opacities on
HRCT scans
– • Transbronchial lung biopsy or bronchoalveolar lavage (BAL) showing
no features to support an alternative diagnosis
• Minor Criteria
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• Age > 50 yr
• Insidious onset of otherwise unexplained dyspnea on exertion
• Duration of illness 3 mo
• Bibasilar, inspiratory crackles (dry or “Velcro” type in quality)
IPF consensus statement, 2000, AJRCCM
Idiopathic pulmonary fibrosis
• Pathology=UIP
Schwarz, ILD, 2003
Treatment
• Very limited literature, NO RANDOMIZED
TRIALS
• ATS recommendations:
• Prednisone 60 mg daily tapering or 20 mg
plus Cytoxan 100-120 mg/day
• Retrospective case review (n=78 with
OLB), UIP=38, NSIP=28, RB/DIP=13
• At 6 months, 11% UIP, 29% NSIP, 80%
RB/DIP improved
Nicholson, AJRCCM, 2000
Treatment of IPF
• Azathioprine
Treatment of IPF
• Colchicine 1998 and 2000 studies
(Douglas et al., AJRCCM) compared
colchicine to prednisone and other
combinations and showed no difference in
survival in any of the groups but with fewer
side effects with Colchicine
• NAC
Treatment of IPF
• Gamma interferon
• Th-1 cytokine that induces CD4 cells to the Th1
phenotype, inhibits the proliferation of fibroblasts
and downregulates TGF-β
• Administered subcu three times weekly
• Flu-like symptoms
• Mixed results with this drug in trials, but may be
due to the fact that it needs to be used earlier in
disease
Treatment of IPF
• Pirfenidone
• Pyridone molecule that inhibits TGF-βstimulated collagen production
• Ameliorates bleomycin-induced fibrosis in
hamsters
• Undergoing stage III trials
IPF
King, et al., AJRCCM, 2001
DIP
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Clinical classification=pathology
DISEASE OF SMOKERS!!
4th-5th decades
Subacute cough and dyspnea
CT shows diffuse GG infiltrates
Smoking cessation
DIP
Schwarz, ILD, 2003
DIP
Leslie, Clinics in Chest Med, 2006
RB-ILD
• SMOKING DISEASE!!
• Similar to DIP, but pathology slightly
different, in peribronchiolar distribution
• Smoking cessation +/- steroids
RB-ILD
Schwarz, ILD, 2003
LIP
• Characterized by monotonous sheets of
polyclonal lymphocytes
• Clinical=pathology
• Uncommon
• Associated with Sjogren’s and AIDS
• May remit with steroids and other ISD,
progress to fibrosis, lead to infectious
complications, or develop lymphoma
LIP
Leslie, Clinics in Chest Med, 2006
NSIP
• Originally represented “difficult to characterize”
• Clearly represents a separate disease from IPF
• Primary and secondary forms (HP, drugs, CVD,
AIDS and transplants)
• Second most common diagnosis
• Middle-aged, majority smoker’s
• Surgical biopsy required to make diagnosis
• HOMOGENEOUS
• ?? Early UIP
NSIP
Leslie, Chest, 128:5, 2005
Interstitial pneumonias
American Thoracic Society/European Respiratory Society
classification of the idiopathic interstitial pneumonias
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Histologic pattern
Clinico-radiologic-pathologic
UIP
IPF
NSIP
NSIP
Organizing pneumonia
COP
Diffuse alveolar damage (DAD)
AIP
Respiratory bronchiolitis pattern
RBILD
Desquamative pattern
DIP
Lymphoid pattern
LIP