Transcript Diffuse Parynchmal Lung Disease ,How to approach?

Diffuse Parynchmal Lung Disease
,How to approach?
Dr. Abdelhaleem Bella
Assistant Professor of Medicine, Dammam University
Consultant Pulmonologist ,King Fahad Hospital of the University.
Layout of the Presentation
DPLD : A&C
•Radiological Characteristics
•Other Fibrotic Lung Diseases
•Basic Science
•Phenotypes
•Diagnostic Approach and
Therapy
ILD
•IIP
•Other
IPF
DPLD : Acute
DPLD : Chronic
Chronic DPLD : Occupational Lung
Disease
Chronic DPLD : Drug Induced
Chronic DPLD : Systemic Disease
Related
Where is the Honey?
Understanding the Anatomy of the
Honey combing
Pulmonary Fibrosis isn’t that
simple!
Pictorial review of alternative
diagnosis
Post TB Pulmonary Fibrosis
Drugs: Nitrofurantoin Induced
Pulmonary Fibrosis
High resolution computed
tomography (HR-CT) of the lung
showing characteristics of fibrosis.
(A) HR-CT at the level of the main
carina.
(B) HR-CT at the basal parts of the
lungs 1 cm above the diaphragm.
Inter- and intralobular septal
thickening (IST),
traction Bronchiectasis (TB),
honeycombing cysts (HC) and ground
glass (GG) are indicated.
Occupational :Asbestosis
Late asbestosis in a patient
with calcified pleural
plaques.
HRCT shows extensive
fibrosis and honeycombing
in the lung periphery at the
lung bases.
Except for the presence of
pleural abnormalities typical
of asbestos exposure, this
appearance is
indistinguishable from IPF.
Radiation Fibrosis
CTD related Pulmonary Fibrosis
The major fissures are displaced posteriorly
(red arrows) as a result of fibrosis and volume
loss.
These findings are consistent with fibrotic NSIP
associated with scleroderma.
Note that the oesophagus is dilated (blue
arrow), a finding typical of scleroderma.
Sarcoidosis
Types of Idiopathic Interstitial
Pneumonia
IPF : UIP
HRCT: Honeycombing consisting of
multilayered thick-walled cysts.
Architectural distortion with traction
bronchiectasis due to fibrosis.
Predominance in basal and subpleural
region.
In the presence of a surgical biopsy showing
a UIP pattern the diagnosis of IPF requires
exclusion of other known causes of UIP
including drug toxicities, environmental
exposures (asbestos), and collagen vascular
diseases like RA, SLE, polyarteritis nodosa
and scleroderma.
Diagnostic Criteria of IPF
Probable IPF
Definite IPF
How helpful is a HRCT
NSIP:NSIP
NSIP is by far the most common interstitial
lung disease in patients with connective
tissue disease
The diagnosis of NSIP requires histological
proof
HRCT: varying combination of GGO and
fibrosis (traction bronchiectasis), but relative
lack of honeycombing (less peripheral)
IPF vs NSIP
Lymphocytic Interstitial Pneumonia
Aetiology: Autoimmune disease ,
HIV etc
Acute Interstitial Pneumonia (AIP)
Diffuse alveolar damage with subsequent
fibrosis.
It has a fatal outcome in many cases.
Looks similar to acute respiratory distress
syndrome (ARDS).
The HRCT characteristics are diffuse or patchy
consolidation, often with a crazy paving.
There are areas of consolidation and extensive
areas of ground-glass density with a crazypaving appearance.
These abnormalities developed in several days
and this rapid progression of disease combined
with these imaging findings are very suggestive
of the diagnosis AIP.
COP
peripheral and peribronchiolar distribution. Axial HRCT imaging shows
consolidation in a peripheral (arrowheads) and peribronchiolar
(arrows) distribution.
Smoking Related Interstitial Lung
Disease
DIP
IPF
RB-ILD
PLCH
Goodpasture Syndrome
RA associated pulmonary fibrosis
Acute Esinophilic Pneumonia
RB-ILD
ground glass attenuation centrilobular nodules. Axial HRCT image
shows multiple ground glass attenuation nodules (arrows) and patchy
areas of ground glass opacity.
Desquamative Interstitial Pneumonia
The HRCT shows diffuse areas of ground-glass density in the lower lobes and some mosaic
pattern as the sole abnormality.
Reticular abnormalities and signs of fibrosis are typically absent.
These abnormalities are usually reversible and will disappear upon cessation of smoking.
Epidemiology of Pulmonary Fibrosis- KSA
• Search Strategy : I used Endnote X3 searching
PubMed database
while keeping the author affiliation as Saudi
Arabia the following search terms were used:
(Title): ILD, Interstitial Lung Disease,
Pulmonary fibrosis, Pneumonitis, organizing
pneumonia
(Abstract): pulmonary fibrosis, Interstitial Lung disease ,pneumonitis
, organizing pneumonia.
Excluded :Paediatric population , Infective causes
of lung disease and Sarcoidosis papers.
Basic Research : 3
Case Reports/Series : 8
Original Research: 5
Reviews : 5
122 patients , 30% had surgical Bx 98% diagnostic,30%
no diagnosis
al-Mobeireek A. Management of interstitial lung disease: an audit at a university teaching hospital in Saudi Arabia. Indian J Chest Dis
Allied Sci. Oct-Dec 1998;40(4):235-241.
61 patients , mixed group , survival 92 months, clubbing
worsens survival
Alhamad EH etal. Clinical and functional outcomes in Middle Eastern patients with idiopathic pulmonary fibrosis. Clin Respir J. Oct
2008;2(4):220-226
118 patients , three groups ,LD-CTD CTD and IPF,
Hypoxia and low albumin poor prognosis
Alhamad EH, Al-Kassimi FA, Alboukai AA, et al. Comparison of three groups of patients with usual interstitial pneumonia. Respir Med.
Aug 4 2012.
Basic Science in IPF
• IPF is a progressive disease with a median
survival of 2-4 years after diagnosis
• Methods:
1. Intratracheal Bleomycin
2. Gene Over expression: TGF-B1 ,IL-1B etc,
Osteopontin and PDGF
3. Irradiation
4. Particulate material: asbestos and silica
Pathways for progression of Fibrosis
Targeting Fibrosis in Respiratory
Diseases
• Uncontrolled extracellular matrix (ECM) accumulation ,
often associated with loss of function and possibly
morbidity and mortality
• Initiating factors may not be the ones which sustain the
fibrotic process
• Most of our knowledge comes from animal models (
NB Bleomycin: Disappointing)
• Fibrosis can develop around : airways, pulmonary
vessels, pleura and lung parenchyma
• Transforming Growth Factor-B (TGF-B1) and related
pathway ( Early vs Late)
• Gene profile studies
Compounds that have shown activity as antifibrotic
drugs in Bleomycin animal models (rat & mouse)
Approach to Diagnosing IPF
History :
Symptoms ( Cough and Breathlessness) ,
Smoking and Occupation
Examination : General , Clubbing , Bilateral end inspiratory Velcro
crackles
Co morbidity
Radiology : CXR ,CT & HRCT
Pulmonary Physiology : PFT & 6 MWT
Bronchoscopy and Surgical Biopsy
Other Tests : autoimmune screen , Tuberculosis exclusion
Poor Prognostic Features
IPF Management Guidelines
Management of IPF-General
Acute Exacerbation of IPF
• Acute worsening of
dyspnea(<1 month) with
hypoxia and lung
infiltrate in absence of
infection or heart failure
• 8%-15%
• Diagnostic approach
• Therapy
Management of ILD presenting acutely
ATS/ERS 2011 Treatment Guidelines
Phenotypes in IPF
Phenotypes I: CPFE
• IPF associated emphysema (CPFE): Cottin 2005
• (30%-55%)
• FVC <50% & Pulmonary Hypertension are poor prognosis
Phenotypes II:Disp-Pulmonary
Hypertension
• 31%-85% of patients
with IPF have PHT (NB
awaiting LTx)
• mPAP >17mm Hg is
the best predictor of
mortality
• Mechanisms???
• Disproportionate
Phenotype III: Rapidly Progressive IPF
• Genetic Studies: up regulation of genes involved
in cell motility, myofibroblasts proliferation etc
• Tissue biopsies: Adenosine A2B receptor ( Lung
fibroblasts to myofibroblasts)
Phenotype IV or Comorbidites???
• GERD :33%-60%:animal , BAL , Nissen post
lung Tx
• Cardiovascular and Thromboembolic disease
• Lung Cancer :RR 7.31 , Prevalence 5-10%.
commoner in male , smokers.
• Depression : 23% are clinically depressed
Randomised , double blind placebo controlled
Mild to moderate lung Function impairment
Three groups: Prednisolone+ Azathioprine+NAC OR NAC OR Placebo
1:1:1
FVC over 60 weeks follow up
Terminated at 32 weeks
The future starts now
Pathology
Radiology
MDT : CPR Meeting
Registry
Medical Team
Further research
Thank You