ILDs for CMTs
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Transcript of ILDs for CMTs
Interstitial Lung Diseases for CMTs
Dr Laura-Jane SmithRespiratory Registrar, Whittington Hospital
Honorary Clinical Lecturer in Medical Education, UCL@drlaurajane
http://www.slideshare.net/_elljay_
June 2015
Objectives
• Describe what ILDs are• Explain the basis of the classification of ILDs• List the steps in diagnosis of ILDs• Update evidence for treatment of IPF• 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
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 (59% 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
Task 2
Treatment
• Stop smoking• Treat contributors – drugs, reflux • Oral corticosteroids• NAC• Immunosuppresion: azathioprine,
cyclophosphamide• Newer drugs: perfenidone, nintedanib
Specialist ILD MDT decision-making
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
RCT of NAC
Martinez, Fernando J., et al. "Randomized Trial of N-acetylcysteine in Idiopathic Pulmonary Fibrosis." The New England journal of medicine 370.22 (2014): 2093.
Recent trials• The ASCEND trial: A Phase 3 Trial of Pirfenidone in Patients with
Idiopathic Pulmonary Fibrosis; N Engl J Med 2014;370:2083-92.– Oral Anti-fibrotic Therapy– Reduced Disease Progression (Lung Function, Exercise Tolerance,
Progression Free Survival)– Fewer Deaths
• Efficacy & Safety of Nintedanib in Idiopathic Pulmonary Fibrosis; N Engl J Med 2014;370:2071-82.– Intracellular Inhibitor of Multiple Tyrosine Kinases– Reduced Decline in FVC – Slowing of Disease Progression– Associated with Diarrhoea, < 5% Drop Out
From: Adamali, Huzaifa I., and Toby M. Maher. "Current and novel drug therapies for idiopathic pulmonary fibrosis." Drug design, development and therapy 6 (2012): 261.
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
Task 3
Table from Eureka: Respiratory Medicine. Smith, Brown, Quint. 2015.
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
Examples of rare ILDs
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