Pulmonary Fibrosis & Bronchiectasis Omer Alamoudi, MD, FRCP, FCCP, FACP Professor, consultant Pulmonologist Department of Medicine, KAUH Email: [email protected]

Pulmonary Fibrosis &Pulmonary Fibrosis & BronchiectasisBronchiectasis

Omer Alamoudi, MD, FRCP, FCCP, FACPOmer Alamoudi, MD, FRCP, FCCP, FACP

Professor, consultant PulmonologistProfessor, consultant Pulmonologist

Department of Medicine, KAUHDepartment of Medicine, KAUH

Email: [email protected]: [email protected]

Pulmonary fibrosis, Idiopathic (IPF)Pulmonary fibrosis, Idiopathic (IPF)

DefinitionDefinition

CausesCauses

Clinical presentationClinical presentation

pathologypathology

DiagnosisDiagnosis

ManagementManagement

Idiopathic Pulmonary fibrosis (IPF)Idiopathic Pulmonary fibrosis (IPF)DefinitionDefinition

Chronic progressive Chronic progressive disease of unknown disease of unknown etiologyetiology

Characterized by Characterized by inflammation and fibrosis inflammation and fibrosis of the lung parenchymaof the lung parenchyma

Lung interstitium and Lung interstitium and alveolialveoli



CausesCauses


PathologyPathology

DiagnosisDiagnosis


IPFIPFCausesCauses

Unknown (90%)Unknown (90%)Familial (AD)Familial (AD)Viral (Epstein Barr virus)Viral (Epstein Barr virus)Collagen vascular disorder Collagen vascular disorder (RA, scleroderma, SLE, (RA, scleroderma, SLE, dermatomyositis)dermatomyositis)AsbestosisAsbestosis Drugs (Amiodarone, Drugs (Amiodarone, Busulphan, Bleomycin)Busulphan, Bleomycin)

PCPPCPRadiation pneumonitisRadiation pneumonitisRecurrent Intraalveolar Recurrent Intraalveolar hemorrhageshemorrhagesChronic aspiration Chronic aspiration pneumoniapneumoniaSmoking, wood, metal dust Smoking, wood, metal dust exposureexposureGranulomatosis Granulomatosis (Sarcoidosis, (Sarcoidosis, histoplasmosis)histoplasmosis)



CausesCauses


pathologypathology

DiagnosisDiagnosis


Pulmonary fibrosis, Idiopathic (IPF)Pulmonary fibrosis, Idiopathic (IPF)Clinical presentationClinical presentation

Onset:Onset: Usually between 50 and 70 yr Usually between 50 and 70 yr

Clinical presentationClinical presentation– Progressive dyspnea on exertionProgressive dyspnea on exertion– Paroxysmal cough, usually nonproductiveParoxysmal cough, usually nonproductive– Clubbing of the fingers (50%)Clubbing of the fingers (50%)– Fine inspiratory basal crackles chest auscultation Fine inspiratory basal crackles chest auscultation – Abnormal chest x-ray or HRCTAbnormal chest x-ray or HRCT– Restrictive pulmonary physiology with reduced Restrictive pulmonary physiology with reduced

lung volumes and DLCO and widened AaPOlung volumes and DLCO and widened AaPO22

Pulmonary fibrosis, Idiopathic (IPF)Pulmonary fibrosis, Idiopathic (IPF) Clinical presentationClinical presentation

Signs of pulmonary hypertensionSigns of pulmonary hypertension– Loud P 2Loud P 2– Right ventricular heaveRight ventricular heave– RBBBRBBB

Signs of Corpulmonale and Rt heart failureSigns of Corpulmonale and Rt heart failure– Raised JVPRaised JVP– Hepatomegaly, ascitisHepatomegaly, ascitis– Lower limb edemaLower limb edema

Signs of underlying causes (RA, scleroderma)Signs of underlying causes (RA, scleroderma)



ClassificationClassification

pathogenesispathogenesis

CausesCauses


PathologyPathology

DiagnosisDiagnosis


IPF: IPF: PathologyPathology

UIP is essential to diagnosis of IPFUIP is essential to diagnosis of IPF– Idiopathic, progressive, diffuse fibrosing Idiopathic, progressive, diffuse fibrosing

inflammatory process inflammatory process – Involves lung parenchymaInvolves lung parenchyma

Surgical lung biopsy Surgical lung biopsy – suspected IPFsuspected IPF

– Atypical clinical or radiographic featuresAtypical clinical or radiographic features

Major purpose of histologic examination is to Major purpose of histologic examination is to distinguish UIP from other histologic subsets of IIPdistinguish UIP from other histologic subsets of IIP

HISTOPATHOLOGIC ELEMENTS HISTOPATHOLOGIC ELEMENTS OF UIPOF UIP

CHRONIC INTERSTITIAL INFLAMMATION CHRONIC INTERSTITIAL INFLAMMATION IN UIPIN UIP



CausesCauses


PathologyPathology

DiagnosisDiagnosis


IPFIPFDiagnosisDiagnosis

Major criteriaMajor criteria

– Exclusion of other known causes of ILDExclusion of other known causes of ILD

– Restrictive pulmonary function studiesRestrictive pulmonary function studies

– Bibasilar reticular abnormalities on HRCT scanBibasilar reticular abnormalities on HRCT scan

– No histologic or cytologic features on transbronchial lung No histologic or cytologic features on transbronchial lung biopsy or BAL analysis supporting another diagnosisbiopsy or BAL analysis supporting another diagnosis

Minor criteriaMinor criteria

– Age >50 yrAge >50 yr

– Insidious onset of otherwise unexplained exertional Insidious onset of otherwise unexplained exertional dyspneadyspnea

– Duration of illness Duration of illness 3 mo3 mo

– Bibasilar, dry (“Velcro”) inspiratory cracklesBibasilar, dry (“Velcro”) inspiratory crackles

Diagnosis IPFDiagnosis IPF

Chest radiographChest radiograph– Early: ground glass Early: ground glass

appearance appearance– Late: reticular, Late: reticular,

reticulonodular, reticulonodular, honeycombing at the honeycombing at the peripheryperiphery

– Deviation of trachea Deviation of trachea to the rightto the right Bilateral lower lobe opacities Bilateral lower lobe opacities

and possible mild decrease in and possible mild decrease in lung volumeslung volumes. .


Chest radiographChest radiograph

– Reduction of the Reduction of the lung volumelung volume

– Pleural involvement, Pleural involvement, adenopathy, adenopathy, localized localized parenchymal parenchymal densities (very rare)densities (very rare)

Diagnosis IPFDiagnosis IPFHigh Resolution CT (HRCT)High Resolution CT (HRCT)

HRCTHRCT– Useful to differentiate IPF from other ILDUseful to differentiate IPF from other ILD– Determine the severity and extent of the diseaseDetermine the severity and extent of the disease– Select the place for biopsySelect the place for biopsy

FindingsFindings– Patchy, ground glass attenuation, thickened Patchy, ground glass attenuation, thickened

interlobular septaeinterlobular septae– Traction bronchiectasisTraction bronchiectasis– Reticular pattern, honeycombingReticular pattern, honeycombing

Diagnosis IPFDiagnosis IPFHRCTHRCT

Distortion of the Distortion of the pulmonary pulmonary architecture architecture

Thickening of Thickening of pulmonary pulmonary interstitiuminterstitium

Ground-glass Ground-glass attenuation. attenuation.

No obvious No obvious honeycombing is honeycombing is present present

Diagnosis IPFDiagnosis IPF HRCTHRCT

Advanced stage Advanced stage of pulmonary of pulmonary fibrosisfibrosis

Reticular Reticular opacitiesopacities

Honeycombing, Honeycombing, predominantly predominantly subpleural subpleural distribution. distribution.

HRCT FINDINGS IN IPFHRCT FINDINGS IN IPF

Diagnosis IPFDiagnosis IPFPulmonary function testsPulmonary function tests

Restrictive patternRestrictive pattern– ↓ ↓ FVCFVC– ↓ ↓ FEV1FEV1– ↑↑FEV1/FVCFEV1/FVC

Diagnosis IPFDiagnosis IPFPulmonary function tests Pulmonary function tests

Restrictive patternRestrictive pattern

Lung volumes ( TLC, RV, FRC Lung volumes ( TLC, RV, FRC ↓↓), DLCO ), DLCO ↓↓


ABG ABG – PO2PO2 Reduced (V/Q mismatch)Reduced (V/Q mismatch)– PCO2PCO2 Normal or ReducedNormal or Reduced

Increased (End stage)Increased (End stage)


Bronchoscopy & Bronchoalveolar lavage (BAL)Bronchoscopy & Bronchoalveolar lavage (BAL)– Assess progression of diseaseAssess progression of disease– Assess response to therapyAssess response to therapy– Assess prognosis of diseaseAssess prognosis of disease

LymphocyteLymphocyte Good prognosis/ Good prognosis/ respond to therapyrespond to therapy

Eosinophil &Eosinophil & neutrophilsneutrophils Poor prognosis/ Poor prognosis/

no response to steroidno response to steroid


Other testsOther tests– Lung biopsy (open vs TBBB) most importantLung biopsy (open vs TBBB) most important– Gallium-67 increased (not useful)Gallium-67 increased (not useful)– PET (position emission tomography)PET (position emission tomography)

Glucose uptake increasedGlucose uptake increased

– ESR, ANA, RFESR, ANA, RF



CausesCauses


PathologyPathology

DiagnosisDiagnosis


THERAPEUTIC APPROACHES TO IPFTHERAPEUTIC APPROACHES TO IPF

CorticosteroidsCorticosteroids

Other immunosuppressivesOther immunosuppressives

– AzathioprineAzathioprine

– CyclophosphamideCyclophosphamide

Antifibrotic agentsAntifibrotic agents

– ColchicineColchicine

– D-PenicillamineD-Penicillamine

– IFN-IFN-– IFN-IFN-– PirfenidonePirfenidone

Antioxidant agentsAntioxidant agents

– GlutathioneGlutathione

– N-acetylcysteineN-acetylcysteine

– OthersOthers

Agents that block neutrophil Agents that block neutrophil adhesion moleculesadhesion molecules

Inhibitors of specific Inhibitors of specific fibrogenic cytokines and fibrogenic cytokines and growth factors growth factors

IPFIPFManagementManagement

Should started as early as possibleShould started as early as possible

Duration of therapy 3-6 monthsDuration of therapy 3-6 months

CorticosteroidsCorticosteroids– Prednisone tabletsPrednisone tablets

Dose 1-1.5mg/kg (30Mg)Dose 1-1.5mg/kg (30Mg)– Methyl prednisone (pulse therapy 3-5 days)Methyl prednisone (pulse therapy 3-5 days)

Dose 1 gm/dayDose 1 gm/day


How to assess the response to therapyHow to assess the response to therapy– Reduction of symptomsReduction of symptoms– Improvement of lung function testsImprovement of lung function tests– Improvement of DLCOImprovement of DLCO– Improvement of chest x ray (alveolitis)Improvement of chest x ray (alveolitis)


CyclophosphamideCyclophosphamide– Dose 2 mg/kg/day (max 200 mg/day)Dose 2 mg/kg/day (max 200 mg/day)– Leucopenia (WBC < 3000)Leucopenia (WBC < 3000)– Opportunistic infectionOpportunistic infection– Ca bladderCa bladder– Hemorrhagic cystitisHemorrhagic cystitis


AzathioprineAzathioprine– 1-2mg/kg/day (max 200Mg/day)1-2mg/kg/day (max 200Mg/day)– GIT symptomsGIT symptoms– Bone marrow suppressionBone marrow suppression– Increase liver enzymesIncrease liver enzymes– Leucopenia, and thrombocytopenia (WBC< 3000)Leucopenia, and thrombocytopenia (WBC< 3000)

Colchicine (anti-inflammatory)Colchicine (anti-inflammatory)– Dose 0.5mg BIDDose 0.5mg BID


Oxygen supply (rest and exercise) if PO2< 55 mmHgOxygen supply (rest and exercise) if PO2< 55 mmHg

Lung transplantation Lung transplantation – Age <60Age <60– Progressive diseaseProgressive disease– Lack of response to therapyLack of response to therapy

Psychosocial supportPsychosocial support

Influenza vaccineInfluenza vaccine

CAUSE OF DEATHCAUSE OF DEATH

IPF[N=543]

1-7 year FU

60% Died[N=326]

Respiratory failure39%

Lung cancer

10%

Pulmonaryembolism

3%

Pulmonary infection

3%

Cardiovasculardisease

27%

Other18%

RISK FACTORS FOR PROGRESSIVE DISEASERISK FACTORS FOR PROGRESSIVE DISEASE

Age: >50 yrGender: maleDyspnea: moderate to severe with exertionHistory of cigarette smokingLung function: moderate to severe loss (especially gas exchange with exercise)BAL fluid: neutrophilia or eosinophilia at presentationHRCT scan: reticular opacities or honeycomb changesResponse to corticosteroids: poorPathology: more fibrosis, fibroblastic foci

BronchiectasisBronchiectasis



EtiologyEtiology

Clinical findingsClinical findings

DiagnosisDiagnosis




– Acquired disorder disorder affecting the major affecting the major bronchi and bronchiolesbronchi and bronchioles

– Permanent dilatation and Permanent dilatation and destruction of bronchial destruction of bronchial wallwall



EtiologyEtiology

PathophysiologyPathophysiology


DiagnosisDiagnosis



Factors trigger bronchiectasisFactors trigger bronchiectasis

InfectionInfection

Impairment of drainageImpairment of drainage

Airway obstructionAirway obstruction

Defect of host defenseDefect of host defense

Causes of BronchiectasisCauses of Bronchiectasis

Etiology Etiology

Pulmonary infectionsPulmonary infections– TuberculosisTuberculosis– Viral, Mycoplasma PneumoniaViral, Mycoplasma Pneumonia– Pertussis (whooping cough)Pertussis (whooping cough)– Mycobacterium Avium intracellulare (MAI)Mycobacterium Avium intracellulare (MAI)


Airway obstructionAirway obstruction– FB aspirationFB aspiration

Rt lung, lower lobesRt lung, lower lobes

Obstructive pneumonia, focal bronchiectasisObstructive pneumonia, focal bronchiectasis

– LN enlargementLN enlargement

Rt middle lobe syndromeRt middle lobe syndrome


Defective host defensesDefective host defenses– LocalLocal

Ciliary DyskinesiaCiliary Dyskinesia– SystemicSystemic

HypogammaglobulinemiaHypogammaglobulinemia

AIDSAIDS


Rheumatic diseasesRheumatic diseases

Rheumatoid arthritisRheumatoid arthritis

Sjogren’s syndromeSjogren’s syndrome

Inflammatory bowel diseasesInflammatory bowel diseases

Ulcerative colitisUlcerative colitis

Crohns diseaseCrohns disease


Kartagener’s syndromeKartagener’s syndrome– Immotile ciliaImmotile cilia

(Dextrocardia, Sinusitis, Bronchiectasis)(Dextrocardia, Sinusitis, Bronchiectasis)

Young’s SyndromeYoung’s Syndrome(Sinusitis, Obstructive azoospermia, (Sinusitis, Obstructive azoospermia, Bronchiectasis)Bronchiectasis)

Cystic fibrosisCystic fibrosis


Allergic bronchopulmonary aspergillosis (ABPA)Allergic bronchopulmonary aspergillosis (ABPA)

Central bronchiectasisCentral bronchiectasis

High IgE levelHigh IgE level

Precipitating, specific antibodies to AspergillusPrecipitating, specific antibodies to Aspergillus

Long standing asthmaLong standing asthma

Cigarette smokingCigarette smoking

Idiopathic (50%)Idiopathic (50%)



EtiologyEtiology


DiagnosisDiagnosis



Clinical findingsClinical findings– SymptomsSymptoms

CoughCough

Daily sputum production Daily sputum production

DyspneaDyspnea

HemoptysisHemoptysis

Recurrent pleurisyRecurrent pleurisy



– SignsSigns

Coarse cracklesCoarse crackles

Finger ClubbingFinger Clubbing (50%)(50%)

RhonchiRhonchi



EtiologyEtiology


DiagnosisDiagnosis



Diagnostic evaluationDiagnostic evaluation

Complete blood count, differential

Immunoglobulin levels (IgG, IgM, IgA)

Sputum culture, smear (TB, Fungi)


Diagnostic evaluationDiagnostic evaluation– Chest radiography (PA, lateral)Chest radiography (PA, lateral)

Abnormal in most patientsAbnormal in most patients

Linear atelectasisLinear atelectasis

Dilated , thickened airways (tram, parallel lines, Dilated , thickened airways (tram, parallel lines, ring shadows)ring shadows)

Central Central →→ ABPA ABPA

Upper lobe (TB, cystic fibrosis)Upper lobe (TB, cystic fibrosis)


Diagnostic evaluationDiagnostic evaluation

– High resolution CT scanning (HRCT)High resolution CT scanning (HRCT)

Airway dilatationAirway dilatation

Bronchial wall thickeningBronchial wall thickening

Cystic changesCystic changes



EtiologyEtiology


DiagnosisDiagnosis



Treatment of infectionTreatment of infection– Acute exacerbationAcute exacerbation

Streptococcus pn., H. influenzaeStreptococcus pn., H. influenzae

Amoxycillin-clavulinic acidAmoxycillin-clavulinic acid

ClarithromycinClarithromycin

CefuroximeCefuroxime

Duration 10-14 daysDuration 10-14 days


PseudomonasPseudomonas– Extensive bronchiectasisExtensive bronchiectasis– Difficult to eradicateDifficult to eradicate– Poor quality of lifePoor quality of life– Increased no of hospitalizationIncreased no of hospitalization

Ciprofloxacin orally or IV, aerosolized Ciprofloxacin orally or IV, aerosolized

BronchodilatorBronchodilator


AspergillusAspergillus

– Itraconazole 400mg/dayItraconazole 400mg/day


Bronchial hygieneBronchial hygiene– Hydration and mucus clearanceHydration and mucus clearance

Oral liquidsOral liquids

Nebulization with saline solution, mucolytic Nebulization with saline solution, mucolytic agents (DNase)agents (DNase)

– PhysiotherapyPhysiotherapy

Chest percussion techniqueChest percussion technique

Mechanical vibratorMechanical vibrator

15-30 min/session, 2-3 times/day15-30 min/session, 2-3 times/day


BronchodilatorsBronchodilators– Airway reactivityAirway reactivity

Nebulized SalbutamolNebulized Salbutamol

Anti-inflammatory medicationsAnti-inflammatory medications

Inhaled corticosteroids Inhaled corticosteroids

Beclomethasone, budesonideBeclomethasone, budesonide


SurgerySurgery– IndicationsIndications

Removal destroyed lungRemoval destroyed lung

Reduction in overwhelming purulent sputum Reduction in overwhelming purulent sputum productionproduction

Uncontrolled hemorrhageUncontrolled hemorrhage

Removal of area harboring resistant organism Removal of area harboring resistant organism


Bronchial artery embolizationBronchial artery embolization– Intractable bleedingIntractable bleeding

Preserve lung tissuePreserve lung tissue

Avoid thoracotomyAvoid thoracotomy

Lung transplantationLung transplantation– Controversial Controversial

IPF vs BronchiectasisIPF vs Bronchiectasis

Bilateral, BasalBilateral, Basal

Sputum –veSputum –ve

Dry coughDry cough

Alveoli / interstitiumAlveoli / interstitium

Hypoxemia ++Hypoxemia ++

Fine cracklesFine crackles

Restrictive patternRestrictive pattern

Unilateral or bilateralUnilateral or bilateral

Sputum ++++Sputum ++++

Productive coughProductive cough

AirwaysAirways

Hypoxemia ±Hypoxemia ±

Coarse cracklesCoarse crackles

Obstructive/restrictiveObstructive/restrictive

Quiz 1Quiz 1

Quiz 2: What is the diagnosis

Thank youThank you

Suggested Text book to readSuggested Text book to read

Davidson’s principle of internal medicineDavidson’s principle of internal medicine

Documents

Pulmonary Fibrosis & Bronchiectasis Omer Alamoudi, MD, FRCP, FCCP, FACP Professor, consultant Pulmonologist Department of Medicine, KAUH Email: [email protected]