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 ILD IIP IPF Other Radiological Characteristics Other Fibrotic Lung Diseases Basic Science Phenotypes Diagnostic Approach and Therapy

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 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.

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    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.

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 Original Research: 5 Case Reports/Series : 8 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: Intratracheal Bleomycin Gene Over expression: TGF-B1 ,IL-1B etc, Osteopontin and PDGF Irradiation 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 Registry MDT : CPR Meeting Medical Team Registry Further research

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