ilds for medical students
TRANSCRIPT
Interstitial Lung Diseases How not to freak out over all those acronyms
Dr Laura-Jane SmithRespiratory Registrar
Honorary Clinical Lecturer in Medical Education, UCL@drlaurajane
http://www.slideshare.net/_elljay_
May 2015
Objectives
• Describe what ILDs are• Explain the basis of the classification of ILDs• List the steps in diagnosis of ILDs• List the specific features of some interesting
ILDs
pneumonia ≠ infection
Task 1
Interstitial Lung Diseases – what are they?
ILD = DPLDNon-infective infiltrations
of interstitium and alveoli
Progressive
breathlessness
Restrictive lung function
Reduced
transfer factor
Clinical
RadiologicalPathological
Speed of progressionSymptoms
Associated conditionsAgeSex
Ethnicity
UIP vs NSIPGranuloma
FibrosisInflammation
UIP-like patternNSIP-like patternDistributionHoneycombingGround glassNodulesCysts
UIP NSIP
Interstitial lung diseases
Sarcoidosis
Idiopathic(IPF)
Associated with
connective tissue
disease
RadiotherapyDrugs Post-ARDS
Pulmonary fibrosis Hypersensitivity pneumonitis Rare / infiltrations
Lymphangitis carcinomatosis
LIP
Eosinophilicpneumonias
Organising pneumonia
LAMHistiocytosis X
Pneumoconiosis
amyloid
Histology can be UIP or NSIPEnd stage of many ILDs have similar appearances to UIP Alveolar
proteinosis
ILD: classification
Other
RB-ILDDIP
Task 2
Dear colleague,
I’d be grateful if you would see this 76 year old actor who has a 7 month history of breathlessness and cough.
Heart sounds are normal and he has no peripheral oedema. Chest expansion equal. There are bibasal crackles. Sats 95% on air.
PMH: HTNMeds: amlodipine 5mg ODLives with husband. Smokes occasional cigar but no cigarettes.
Best wishes, Dr GP
Investigations
FEV1 2.25L (9% predicted) FVC 2.74L (65% predicted) ratio 0.82Total lung volume 79% predicted, TLCO 48% predicted.
CXRCT
Interstitial lung diseases
Sarcoidosis
Idiopathic(IPF)
Associated with
connective tissue
disease
RadiotherapyDrugs Post-ARDS
Pulmonary fibrosis Hypersensitivity pneumonitis Rare / infiltrations
RB-ILD
Eosinophilicpneumonias
Organising pneumonia
LAMHistiocytosis X
Pneumoconiosis
Alveolar proteinosis
ILD: classification
60% ILDs
LIP10-20% ILDs
Usually UIP Usually NSIPAsbestosis
End stage of many ILDs is fibrosis
5-15% RTX pts within 1-3/12, progresses over 6-12/12
Lymphangitis carcinomatosis
Other
Eosinophilicpneumonias
Chronic aspiration
Organising pneumonia
LAMHistiocytosis X
amyloid
Alveolar proteinosis
DIP
Idiopathic Pulmonary Fibrosis
• Incidence 14-43/100000 worldwide• 2000 new cases/yr in UK• Median age of presentation 70yrs• Progressive breathlessness over months-yrs• Dry cough• Finger clubbing 15-20%• Fine, late inspiratory ‘Velcro’ crackles
Idiopathic Pulmonary Fibrosis
Genes and epigenetics
Environment
Abberant
response to
injury
Inflammation Abnormal repair
Repeated injury
Fibroblast proliferation and migration
Alveolar
epithelium
damage
Activation of coagulation
Extracellular matrix deposition
Epithelial
mesenchymal
transition
Adapted from: Camelo, Ana, et al. "The epithelium in idiopathic pulmonary fibrosis: breaking the barrier." Frontiers in pharmacology 4 (2013).
InvestigationsBloods: exclude specific causes
Lung function tests: restrictive defect, small lung volumes, reduced transfer factor
Imaging: thickened interlobular septa, ground glass infiltration, and honeycombing in a sub-pleural and basal distribution
Bronchoscopy: BAL/EBUS helps exclude other diagnoses and infection
Lung biopsy: Surgical/VATS biopsy is considered only if the diagnosis is unclear and will change management
Table from Eureka: Respiratory Medicine. Smith, Brown, Quint. 2015.
Prognosis
• Insidious disease progression– Rate of decline in FVC ~150-200mL/yr– Periods of acute deterioration, unpredictable
• Prognosis very poor– Most die within 5-10 years– 20-30% alive at 5 years after diagnosis
Treatment
Treatment
• Stop smoking• Treat contributors – drugs, reflux • Oral corticosteroids• NAC• Immunosuppresion: azathioprine,
cyclophosphamide• Newer drugs: perfenidone, nintedanib
Treatment
• 1999 ATS/ERS statement recommended ‘standard therapy’ for IPF based on expert opinion and several small cohort studies – Azathioprine and Prednisolone
• IFIGENIA – Idiopathic Pulmonary Fibrosis International Group exploring N-acetylcysteine I Annual– 3 Drug Regimen (PAN) preserved Pulmonary
Function > 2 Drug Regimen (PN)
N Engl J Med 2005;353:2229-42.
Prednisone, Azathioprine, and N-Acetylcysteine for Pulmonary Fibrosis. (2012). New England Journal of Medicine, 366(21), 1968–1977. doi:10.1056/NEJMoa1113354
https://adventuresofabluegirl.wordpress.com/2015/05/27/adventures-galore/
“It's frightening, life changing. Life becomes very small, stuck in house. Breathlessness is
terrifying.”
Interstitial lung diseases
Sarcoidosis
Idiopathic(IPF)
Associated with
connective tissue
disease
RadiotherapyDrugs Post-ARDS
Pulmonary fibrosis Hypersensitivity pneumonitis Rare / infiltrations
RB-ILD
Eosinophilicpneumonias
Organising pneumonia
LAMHistiocytosis X
Pneumoconiosis
Alveolar proteinosis
ILD: classification
60% ILDs10-20% ILDs
Usually UIP Usually NSIP
End stage of many ILDs is fibrosis
5-15% RTX pts within 1-3/12, progresses over 6-12/12
Lymphangitis carcinomatosis
Other
LIPChronic
aspiration
Asbestosis
Eosinophilicpneumonias
Organising pneumonia
LAMHistiocytosis X
amyloid
Alveolar proteinosis
DIP
Table from Eureka: Respiratory Medicine. Smith, Brown, Quint. 2015.
Task 3
Dear colleague,
I’d be grateful if you would see this 34 year old singer and activist who has a 3 week history of dry cough, fatigue and aching knees and ankles. She has also developed an unusual rash.
Heart sounds are normal. Chest expansion is equal. Chest sounds clear. Sats are 97% on air. Knees and ankles are swollen and red but with no effusions.
PMH: None. No recent travel. Born in Dublin. No meds. Lives alone.Social smoker.
Best wishes, Dr GP
Imaging
Interstitial lung diseases
Sarcoidosis
Idiopathic(IPF)
Associated with
connective tissue
disease
RadiotherapyDrugs Post-ARDS
Pulmonary fibrosis Hypersensitivity pneumonitis Rare / infiltrations
Lymphangitis carcinomatosis
LIP
Eosinophilicpneumonias
Organising pneumonia
LAMHistiocytosis X
Pneumoconiosis
amyloid
Alveolar proteinosis
ILD: classification
Other
RB-ILDDIP
Sarcoidosis
• Inflammatory disorder of unknown cause• Infiltration of affected tissues by non-
caseating granulomas +/- fibrosis• Cell-mediated immunological response • Associated with HLA-DRB1*0301 allele• 5-10/100000 in UK (higher in Irish, West
Indian, African-American)• Age of presentation 20-40yrs
Asymptomatic (30%)
Acute sarcoidosis (Lofgrens)• Erythema nodosum• Bihilar lymphadenopathy• Low grade fever• Arthralgia
Chronic sarcoidosis• Insidious onset• Relapsing/remitting• Progressive in 30%
Spectrum of disease in Sarcoidosis
InvestigationsBloods: serum ACE (increased in up to 80%), hypercalcaemia in 2-5%, increased ALP if liver infiltration
Lung function tests: mixed obstructive/restrictive defect, reduced transfer factor
Imaging: bihilar and mediastinal lymphadenopathy, micronodular infiltrates (peri-lymphatic), airspace-like opacities, ground-glass opacities, peripheral cavitation, fibrosis
Bronchoscopy: EBUS to sample lymph nodes, bronchial and transbronchial biopsies
Tissue biopsy: skin lesions, parotids, extrathoracic lymph nodes, liver
Treatment
• No treatment• Oral corticosteroids• Immunosuppression: hydroxychloroquine and
others eg methotrexate, infliximab
Interstitial lung diseases
Sarcoidosis
Idiopathic(IPF)
Associated with
connective tissue
disease
RadiotherapyDrugs Post-ARDS
Pulmonary fibrosis Hypersensitivity pneumonitis Rare / infiltrations
Lymphangitis carcinomatosis
LIP
Eosinophilicpneumonias
Organising pneumonia
LAMHistiocytosis X
Pneumoconiosis
amyloid
Alveolar proteinosis
ILD: classification
Other
RB-ILDDIP
acute vs chronic
Examples
Interstitial lung diseases
Sarcoidosis
Idiopathic(IPF)
Associated with
connective tissue
disease
RadiotherapyDrugs Post-ARDS
Pulmonary fibrosis Hypersensitivity pneumonitis Rare / infiltrations
Lymphangitis carcinomatosis
LIP
Eosinophilicpneumonias
Organising pneumonia
LAMHistiocytosis X
Pneumoconiosis
amyloid
Alveolar proteinosis
ILD: classification
Other
RB-ILDDIP
Interstitial lung diseases
Sarcoidosis
Idiopathic(IPF)
Associated with
connective tissue
disease
RadiotherapyDrugs Post-ARDS
Pulmonary fibrosis Hypersensitivity pneumonitis Rare / infiltrations
Lymphangitis carcinomatosis
LIP
Eosinophilicpneumonias
Organising pneumonia
LAMHistiocytosis X
Pneumoconiosis
amyloid
Alveolar proteinosis
ILD: classification
Other
RB-ILDDIP
Consolidation
Cysts
Infiltration with lymphocytes
Diffuse or nodular infiltrates
Alveolar infiltrates
Smoking related
Micronodular infiltrates
Examples
QUESTIONS?
Key points
• Interstitial lung diseases are a heterogenous group of diseases featuring non-infective infiltrations of the interstitium and alveoli
• Patients present with breathlessness and cough• Patients have a restrictive deficit on spirometry and
reduced transfer factor• Some patterns on HRCT are characteristic • The key to diagnosis is clinical, radiological and
histological correlation • IPF is a distinct disease which is incurable and often has
a poor prognosis, but new treatments are emerging
Dr Laura-Jane Smith@drlaurajane
http://www.slideshare.net/_elljay_
Task 1
UIP: usual interstitial pneumoniaILD: interstitial lung diseaseIPF: idiopathic pulmonary fibrosisNSIP: non-specific interstitial pneumoniaDPLD: diffuse parenchymal lung diseaseCFA: cryptogenic fibrosing alveolitis
LIP: lymphocytic interstitial pneumoniaDIP: desquamative interstitial pneumoniaCOP: chronic organising pneumoniaHP: hypersensitivity pneumonitisRB-ILD: respiratory bronchiolitis ILDARDS: acute resp distress syndrome
UIPILDIPF
LIPDIPCOP
HPNSIP
ARDSRB-ILD
CFADPLD
Task 2Three differential diagnoses1. 2. 3. Three questions from the history1. 2. 3. Three investigations1. 2. 3.
Task 3Three differential diagnoses1. 2. 3. Three questions from the history1. 2. 3. Three investigations1. 2. 3.