Practical approach to Idiopathic Pulmonary Fibrosis

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Practical approach to Idiopathic Pulmonary Fibrosis Dr .Heba AshebaniGeneral practitionerAbusetta hospital.What is the Pulmonary Interstitium ?

The interstitial space is defined as continuum of loose connective tissue throughout the lung .composed of three subdivisions:the Broncho vascular (axial), surrounding the bronchi, arteries, and veins from the lung root to the level of the respiratory bronchiole.the parenchymal ( acinar ), situated between the alveolar and capillary membranes.the subpleural , situated beneath the pleura, as well as in the interlobular spate .NOTE : The interstitium of the lung is not normally visible radiographically; it becomes visible only when disease (e.g., edema, fibrosis, tumor).

Subdivisions of interstitiumSubdivisions of interstitium


IPF25-35%DrugsAutoimmune diseaseOccupation NSIPSarcoidCause of IPF is UNKNOWN

Incidence : 10 15 / 100,000 . Male > Female (2 : 1) . 5000 new cases IPF per year in UK . Number of cases are increasing worldwide . Onset: Usually between 70 and 80 years . Etiology : Uncertain , but a single cause appears unlikely , even in patients with biopsy-proven IPF .

10Risk factors for developing IPF:Smoking (2.8 fold increased risk).Occupational exposures. -Hard woods, metals, asbestos.Family history of pulmonary fibrosis.Possibly gastro-oesophageal reflux disease (GORD).

All major criteria and at least 3 of the 4 minor criteria are requirEDMajor criteria :Absence of other known causes of interstitial lung disease. A restrictive lung function profile . HRCT appearance of predominantly basal reticular abnormalities with honeycombing and little or no ground-glass appearance.

Diagnostic criteriaD) No features of an alternative diagnosis in transbronchial lung biopsy ( granulomas ) Or Broncho alveolar lavage ( in lymphocytes ).Minor criteria : Age > 50 years . Insidious unexplained exertional dyspnea .duration of illness > 3 months .Predominantly basal or widespread crackles on auscultation .

Multiple microscopic foci of injury occurring over many years Pathogenesis Focal fibroblast proliferation (fibroblastic foci)Collagen depositionProgressive clinical courseDeath

Histological pattern underlying IPF is USUAL INTERSTITIAL PNEUMONIA (UIP).-Temporal heterogonous areas of end stage fibrosis and honeycombing , with areas of active proliferation of fibroblast (suggesting diffuse ongoing microscopic alveolar epithelial injury).-Fibroblastic foci: subepethelial foci of proliferating fibroblasts.

Histological features- A patchy chronic inflammatory cells infiltrate is variably present .-Honey combing (common) cystic space is lined by bronchial epithelium.

TemporalheterogeneityPeripheral accentuation of fibrosisInterstitial inflammation and fibrosis with alveolar wall thickening Clinical assessment : Evaluate symptoms.Occupational exposures.Medications.Family history.Examination:Oxygen saturationClubbing of finger nailsListen to chest for crackles

Establishing Diagnosis Clinical features Progressive exertional dyspnea without wheeze .A nonproductive cough , although sputum production is present in few patients. Chest discomfort , fatigue, and weight loss are occasional features . Digital clubbing is present in over 50% of patients and has been Presentation and Features of IPFAn adverse prognostic determinant in some series .

On auscultation : very fine end-inspiratory crackles are typically heard bilaterally at the lung bases and become widespread in advanced disease . Central cyanosis and clinical evidence of pulmonary hypertension , with or without right ventricular failure , are late features .

Chest radiography :Typically shows small lung volumes and predominantly peripheral and basal reticulonodular shadowing .Obscuration of the hart borders and diaphragms in advanced disease Overt honeycombing in 10 % of cases .The heart may appear to be enlarged in the absence of cardiovascular disease .

This profile is very nonspecific , occurring in many other fibrotic processes .Normal CXR does not exclude IPF .

High-resolution CT HRCT are pathognomonic in up to 70% of patients.The disease is predominantly postero-basal and peripheral , becoming widespread in advanced disease . Reticular pattern , with or without honey-combing .A minor component of ground glass attenuation .Traction bronchiectasis in lower lobes .

Reactive mediastinal lymphadenopathy is usual on HRCT and is not indecative of coexisting disease process unless also present CXR.Prone HRCT sections maybe required in early disease .

Lung function tests Restrictive ventilatory defect in VC , TLC , RV , sometimes appears normal in early disease. in DLco levels even in early disease . ABG could be normal in early disease .

Mild arterial hypoxia with widening of the alveolar-arterial gradient.Sever hypoxia is a late feature .Increased Paco2 levels occur in terminal disease .6 minutes walk test + oximetry easier ,better for disease progression and regression.

Blood testsBlood tests contribute little to management of IPF .Secondary polycythemia my occur in sever disease.

IF diagnosis is uncertain..Some circumstances the CT scan has unusual features which are not typical for IPF.

May need a bronchoscopy.

May need a surgical lung biopsy.

Broncho-alveolar lavageBAL is useful diagnostic test when a surgical biopsy is not performedIn IPF , Typically there is an increase in total cell counts with an excess of neutrophils and/or eosinophils .A mild lymphocytosis is infrequent , but striking rises lymphocyte counts suggest an alternative disorder such as NSIP .Useful in excluding infections.

Surgical lung biopsy A surgical lung biopsy is the histological diagnostic procedure of choice .Video-assisted thoracoscopic biopsy is the most widely advanced procedure .Strongly recommended that at least two sites are biopsied .Larger biopsies are required to determine whether abnormalities Are heterogeneous or homogenous .Echocardiography Routine echocardiography is warranted at presentation and in patients subsequently developing disproportionate hypoxia or a selective serial reduction in Dlco . PrognosisThe 5 years survival is approximately 10 to 15 % in IPF .

IPF is a progressive disease.Median survival is 3 years from diagnosisFeatures are associated with a worse outcomeGrade of evidence Increasing age. ++Resting hypoxia. ++Major desaturation on during 6-min walk test 50% , Dlco > 30%).60 weeks of treatment with either placebo or acetylcystiene 600 mg three times daily .NO difference in change in FVC.NO difference in acute exacerbations of IPF .NO survival advantage.The study only assessed acetylcysteine in mild and moderate IPF.It is not known if acetylcysteine is of benefit in people with more sever IPF (FVC < 50%). Published by IPF clinical research network , NEJM 2014.

Outcome on Pirfenidone (antifibrotic) :Pirfenidone is antifibrotic therapy , but how it works Unknown.3 previous clinical trials had let to the treatment being approve in 30 Countries in Europe in including UK , and Canada .ASCEND study 555 patients with IPF ( FVC 50-90 % , Dlco 30-90%) 277 placebo , 278 Pirfenidone .

KEY FINDINGS OF STUDY Pirfinedone reduced progression of IPF by almost 50%.Perfinidone reduced risk of death from IPF at 1 year by 68%.Pirfenedone does not affect symptoms of breathlessness .S/E : skin rash ( 28 %) , GIT symptoms such as acid reflux ( 11.9 %)And loss of appetite (15%).

NEW TREATMENT : Ninetdanib Inhibits growth factors ( tyrosine kinase inhibitor )that have been implicated in the development of pulmonary fibrosis .INPULSIS trial were 2 studies conducted, simultaneously ,enrolled 1066 patients ,(placebo 423 ,Nintedanib 638 ).Mild to moderate IPF ( FVC > 50% , dlCO 30-79% ).Key findings of the study The drug slowed decline in FVC over 52 weeks .Trend towards a reduced rate of death .The effect on acute exacerbations of IPF was not consisted across the studies .Diarrhea is the most common side effect .Approved by the U.S FDA in OCTOBER 2014.

Lung transplantation suitable for those patients physically eligible to undergo a major transplant operation. lung transplant has been shown to reduce the risk of death by 75% as compared with patients who remain on the waiting list.Symptomatic patients with IPF younger than 65 years of age and witha body mass index (BMI) 26 kg/m2 should be referred for lung transplantation.

53the most recent data suggest that bilateral lung transplantation is superior to single lung transplantation in patients with IPF.Five-year survival rates after lung transplantation in IPF are estimated at between 50 to 56%.

Supportive TreatmentsSmoking cessationPulmonary Rehab and exercise -Improves strength and walk distancePalliative Care Services

55Oxygen therapyNot for everyone with IPF.People who are limited by low blood oxygen: -walking outside / gardening -around the house -at night -all or most of the time

Different types of oxygen -Long term oxygen therapy (LTOT). -Oxygen for exercise (ambulatory). -Short burst.

Preventing chest infectionsVaccination: Annual flu vaccine. Pneumonia vaccine.

Prompt treatment of infections with antibiotics.