1. Diffuse Parynchmal Lung Disease ,How to approach?
Dr. Abdelhaleem Bella
Assistant Professor of Medicine, Dammam University
Consultant Pulmonologist ,King Fahad Hospital of the University.

2. Layout of the Presentation
DPLD : A&C
ILD
IIP IPF
Other
Radiological Characteristics
Other Fibrotic Lung Diseases
Basic Science
Phenotypes
Diagnostic Approach and Therapy

3. DPLD : Acute

4. DPLD : Chronic

5. Chronic DPLD : Occupational Lung Disease

6. Chronic DPLD : Drug Induced

7. Chronic DPLD : Systemic Disease Related

8. Where is the Honey?

9. Understanding the Anatomy of the Honey combing

10. Pulmonary Fibrosis isn’t that simple!
Pictorial review of alternative diagnosis

11. Post TB Pulmonary Fibrosis

12. 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.

13. 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.

14. Radiation Fibrosis

15. 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.

16. Sarcoidosis

17. Types of Idiopathic Interstitial Pneumonia

18. 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.

19. Diagnostic Criteria of IPF
Probable IPF
Definite IPF

20. How helpful is a HRCT

21. 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)

22. IPF vs NSIP

23. Lymphocytic Interstitial Pneumonia
Aetiology: Autoimmune disease , HIV etc

24. 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 crazy-paving 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.

25. COP
peripheral and peribronchiolar distribution. Axial HRCT imaging shows consolidation in a peripheral (arrowheads) and peribronchiolar (arrows) distribution.

26. Smoking Related Interstitial Lung Disease
DIP
IPF
RB-ILD
PLCH
Goodpasture Syndrome
RA associated pulmonary fibrosis
Acute Esinophilic Pneumonia

27. RB-ILD  
 Respiratory bronchiolitis-interstitial lung disease (RB-ILD) on high resolution (HR) CT imaging: ground glass attenuation centrilobular nodules. Axial HRCT image shows multiple ground glass attenuation nodules (arrows) and patchy areas of ground glass opacity.
ground glass attenuation centrilobular nodules. Axial HRCT image shows multiple ground glass attenuation nodules (arrows) and patchy areas of ground glass opacity.

28. 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.

29. 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
Original Research: 5
Case Reports/Series : 8
Reviews : 5

30. 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):
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):
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

31. Basic Science in IPF

32. IPF is a progressive disease with a median survival of 2-4 years after diagnosis
Methods:
Intratracheal Bleomycin
Gene Over expression: TGF-B1 ,IL-1B etc, Osteopontin and PDGF
Irradiation
Particulate material: asbestos and silica

33. Pathways for progression of Fibrosis

34. 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

35. Compounds that have shown activity as antifibrotic drugs in Bleomycin animal models (rat & mouse)

36. 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

37. Poor Prognostic Features

38. IPF Management Guidelines

39. Management of IPF-General

40. 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

41. Management of ILD presenting acutely

43. ATS/ERS 2011 Treatment Guidelines

44. Phenotypes in IPF

45. Phenotypes I: CPFE IPF associated emphysema (CPFE): Cottin 2005
(30%-55%)
FVC <50% & Pulmonary Hypertension are poor prognosis

46. 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

47. 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)

48. 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

49. 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

50. The future starts now Pathology Radiology Registry MDT : CPR Meeting
Medical Team
Registry
Further research

51. Thank You