Pulmonary Fibrosis & Bronchiectasis Omer Alamoudi, MD, FRCP, FCCP, FACP Professor, consultant Pulmonologist Department of Medicine, KAUH Email: dramoudi@yahoo.com

Pulmonary fibrosis, Idiopathic (IPF) Definition Causes Clinical presentation pathology Diagnosis Management

Idiopathic Pulmonary fibrosis (IPF) Definition Chronic progressive disease of unknown etiology Characterized by inflammation and fibrosis of the lung parenchyma Lung interstitium and alveoli Slide 3 IPF: Definition and Diagnosis

Pulmonary fibrosis, Idiopathic (IPF) Definition Causes Clinical presentation Pathology Diagnosis Management

IPF Causes PCP Radiation pneumonitis Unknown (90%) Recurrent Intraalveolar hemorrhages Chronic aspiration pneumonia Smoking, wood, metal dust exposure Granulomatosis (Sarcoidosis, histoplasmosis) Unknown (90%) Familial (AD) Viral (Epstein Barr virus) Collagen vascular disorder (RA, scleroderma, SLE, dermatomyositis) Asbestosis Drugs (Amiodarone, Busulphan, Bleomycin)

Pulmonary fibrosis, Idiopathic (IPF) Definition Causes Clinical presentation pathology Diagnosis Management

Pulmonary fibrosis, Idiopathic (IPF) Clinical presentation Onset: Usually between 50 and 70 yr Clinical presentation Progressive dyspnea on exertion Paroxysmal cough, usually nonproductive Clubbing of the fingers (50%) Fine inspiratory basal crackles chest auscultation Abnormal chest x-ray or HRCT Restrictive pulmonary physiology with reduced lung volumes and DLCO and widened AaPO2

Pulmonary fibrosis, Idiopathic (IPF) Clinical presentation Signs of pulmonary hypertension Loud P 2 Right ventricular heave RBBB Signs of Corpulmonale and Rt heart failure Raised JVP Hepatomegaly, ascitis Lower limb edema Signs of underlying causes (RA, scleroderma)

Pulmonary fibrosis, Idiopathic (IPF) Definition Classification pathogenesis Causes Clinical presentation Pathology Diagnosis Management

IPF: Pathology UIP is essential to diagnosis of IPF Idiopathic, progressive, diffuse fibrosing inflammatory process Involves lung parenchyma Surgical lung biopsy suspected IPF Atypical clinical or radiographic features Major purpose of histologic examination is to distinguish UIP from other histologic subsets of IIP

HISTOPATHOLOGIC ELEMENTS OF UIP

CHRONIC INTERSTITIAL INFLAMMATION IN UIP

Pulmonary fibrosis, Idiopathic (IPF) Definition Causes Clinical presentation Pathology Diagnosis Management

IPF Diagnosis Major criteria Exclusion of other known causes of ILD Restrictive pulmonary function studies Bibasilar reticular abnormalities on HRCT scan No histologic or cytologic features on transbronchial lung biopsy or BAL analysis supporting another diagnosis Minor criteria Age >50 yr Insidious onset of otherwise unexplained exertional dyspnea Duration of illness 3 mo Bibasilar, dry (“Velcro”) inspiratory crackles

Diagnosis IPF Chest radiograph Early: ground glass appearance Late: reticular, reticulonodular, honeycombing at the periphery Deviation of trachea to the right Bilateral lower lobe opacities and possible mild decrease in lung volumes.

Diagnosis IPF Chest radiograph Reduction of the lung volume Pleural involvement, adenopathy, localized parenchymal densities (very rare)

Diagnosis IPF High Resolution CT (HRCT) Useful to differentiate IPF from other ILD Determine the severity and extent of the disease Select the place for biopsy Findings Patchy, ground glass attenuation, thickened interlobular septae Traction bronchiectasis Reticular pattern, honeycombing

Diagnosis IPF HRCT Distortion of the pulmonary architecture Thickening of pulmonary interstitium Ground-glass attenuation. No obvious honeycombing is present

Diagnosis IPF HRCT Advanced stage of pulmonary fibrosis Reticular opacities Honeycombing, predominantly subpleural distribution.

HRCT FINDINGS IN IPF

Diagnosis IPF Pulmonary function tests Restrictive pattern ↓ FVC ↓ FEV1 ↑FEV1/FVC

Diagnosis IPF Pulmonary function tests Restrictive pattern Lung volumes ( TLC, RV, FRC ↓), DLCO ↓

Diagnosis IPF ABG PO2 Reduced (V/Q mismatch) PCO2 Normal or Reduced Increased (End stage)

Diagnosis IPF Bronchoscopy & Bronchoalveolar lavage (BAL) Assess progression of disease Assess response to therapy Assess prognosis of disease Lymphocyte Good prognosis/ respond to therapy Eosinophil & neutrophils Poor prognosis/ no response to steroid

Diagnosis IPF Other tests Lung biopsy (open vs TBBB) most important Gallium-67 increased (not useful) PET (position emission tomography) Glucose uptake increased ESR, ANA, RF

Pulmonary fibrosis, Idiopathic (IPF) Definition Causes Clinical presentation Pathology Diagnosis Management

THERAPEUTIC APPROACHES TO IPF Corticosteroids Other immunosuppressives Azathioprine Cyclophosphamide Antifibrotic agents Colchicine D-Penicillamine IFN- IFN- Pirfenidone Antioxidant agents Glutathione N-acetylcysteine Others Agents that block neutrophil adhesion molecules Inhibitors of specific fibrogenic cytokines and growth factors

IPF Management Should started as early as possible Duration of therapy 3-6 months Corticosteroids Prednisone tablets Dose 1-1.5mg/kg (30Mg) Methyl prednisone (pulse therapy 3-5 days) Dose 1 gm/day

How to assess the response to therapy IPF Management How to assess the response to therapy Reduction of symptoms Improvement of lung function tests Improvement of DLCO Improvement of chest x ray (alveolitis)

IPF Management Cyclophosphamide Dose 2 mg/kg/day (max 200 mg/day) Leucopenia (WBC < 3000) Opportunistic infection Ca bladder Hemorrhagic cystitis

IPF Management Azathioprine 1-2mg/kg/day (max 200Mg/day) GIT symptoms Bone marrow suppression Increase liver enzymes Leucopenia, and thrombocytopenia (WBC< 3000) Colchicine (anti-inflammatory) Dose 0.5mg BID

IPF Management Oxygen supply (rest and exercise) if PO2< 55 mmHg Lung transplantation Age <60 Progressive disease Lack of response to therapy Psychosocial support Influenza vaccine

CAUSE OF DEATH IPF [N=543] 1-7 year FU 60% Died [N=326] Respiratory failure 39% Lung cancer 10% Pulmonary embolism 3% Pulmonary infection 3% Cardiovascular disease 27% Other 18%

RISK FACTORS FOR PROGRESSIVE DISEASE Age: >50 yr Gender: male Dyspnea: moderate to severe with exertion History of cigarette smoking Lung function: moderate to severe loss (especially gas exchange with exercise) BAL fluid: neutrophilia or eosinophilia at presentation HRCT scan: reticular opacities or honeycomb changes Response to corticosteroids: poor Pathology: more fibrosis, fibroblastic foci

Bronchiectasis

Bronchiectasis Definition Etiology Clinical findings Diagnosis Management

Bronchiectasis Definition Acquired disorder affecting the major bronchi and bronchioles Permanent dilatation and destruction of bronchial wall

Bronchiectasis Definition Etiology Pathophysiology Clinical findings Diagnosis Management

Bronchiectasis Factors trigger bronchiectasis Infection Impairment of drainage Airway obstruction Defect of host defense

Causes of Bronchiectasis Etiology Pulmonary infections Tuberculosis Viral, Mycoplasma Pneumonia Pertussis (whooping cough) Mycobacterium Avium intracellulare (MAI)

Causes of Bronchiectasis Airway obstruction FB aspiration Rt lung, lower lobes Obstructive pneumonia, focal bronchiectasis LN enlargement Rt middle lobe syndrome

Causes of Bronchiectasis Defective host defenses Local Ciliary Dyskinesia Systemic Hypogammaglobulinemia AIDS

Causes of Bronchiectasis Rheumatic diseases Rheumatoid arthritis Sjogren’s syndrome Inflammatory bowel diseases Ulcerative colitis Crohns disease

Causes of Bronchiectasis Kartagener’s syndrome Immotile cilia (Dextrocardia, Sinusitis, Bronchiectasis) Young’s Syndrome (Sinusitis, Obstructive azoospermia, Bronchiectasis) Cystic fibrosis

Causes of Bronchiectasis Allergic bronchopulmonary aspergillosis (ABPA) Central bronchiectasis High IgE level Precipitating, specific antibodies to Aspergillus Long standing asthma Cigarette smoking Idiopathic (50%)

Bronchiectasis Definition Etiology Clinical findings Diagnosis Management

Bronchiectasis Clinical findings Symptoms Cough Daily sputum production Dyspnea Hemoptysis Recurrent pleurisy

Bronchiectasis Clinical findings Signs Coarse crackles Finger Clubbing (50%) Rhonchi

Bronchiectasis Definition Etiology Clinical findings Diagnosis Management

Bronchiectasis Diagnostic evaluation Complete blood count, differential Immunoglobulin levels (IgG, IgM, IgA) Sputum culture, smear (TB, Fungi)

Bronchiectasis Diagnostic evaluation Chest radiography (PA, lateral) Abnormal in most patients Linear atelectasis Dilated , thickened airways (tram, parallel lines, ring shadows) Central → ABPA Upper lobe (TB, cystic fibrosis)

Bronchiectasis Diagnostic evaluation High resolution CT scanning (HRCT) Airway dilatation Bronchial wall thickening Cystic changes

Bronchiectasis Definition Etiology Clinical findings Diagnosis Management

Bronchiectasis Treatment of infection Acute exacerbation Streptococcus pn., H. influenzae Amoxycillin-clavulinic acid Clarithromycin Cefuroxime Duration 10-14 days

Bronchiectasis Pseudomonas Extensive bronchiectasis Difficult to eradicate Poor quality of life Increased no of hospitalization Ciprofloxacin orally or IV, aerosolized Bronchodilator

Bronchiectasis Aspergillus Itraconazole 400mg/day

Bronchiectasis Bronchial hygiene Hydration and mucus clearance Oral liquids Nebulization with saline solution, mucolytic agents (DNase) Physiotherapy Chest percussion technique Mechanical vibrator 15-30 min/session, 2-3 times/day

Bronchiectasis Bronchodilators Airway reactivity Nebulized Salbutamol Anti-inflammatory medications Inhaled corticosteroids Beclomethasone, budesonide

Bronchiectasis Surgery Indications Removal destroyed lung Reduction in overwhelming purulent sputum production Uncontrolled hemorrhage Removal of area harboring resistant organism

Bronchiectasis Bronchial artery embolization Intractable bleeding Preserve lung tissue Avoid thoracotomy Lung transplantation Controversial

IPF vs Bronchiectasis Bilateral, Basal Sputum –ve Dry cough Alveoli / interstitium Hypoxemia ++ Fine crackles Restrictive pattern Unilateral or bilateral Sputum ++++ Productive cough Airways Hypoxemia ± Coarse crackles Obstructive/restrictive

Quiz 1

Quiz 2: What is the diagnosis

Thank you

Suggested Text book to read Davidson’s principle of internal medicine